Have a language expert improve your writing

Run a free plagiarism check in 10 minutes, generate accurate citations for free.

  • Knowledge Base

Methodology

  • How to Write a Literature Review | Guide, Examples, & Templates

How to Write a Literature Review | Guide, Examples, & Templates

Published on January 2, 2023 by Shona McCombes . Revised on September 11, 2023.

What is a literature review? A literature review is a survey of scholarly sources on a specific topic. It provides an overview of current knowledge, allowing you to identify relevant theories, methods, and gaps in the existing research that you can later apply to your paper, thesis, or dissertation topic .

There are five key steps to writing a literature review:

  • Search for relevant literature
  • Evaluate sources
  • Identify themes, debates, and gaps
  • Outline the structure
  • Write your literature review

A good literature review doesn’t just summarize sources—it analyzes, synthesizes , and critically evaluates to give a clear picture of the state of knowledge on the subject.

Instantly correct all language mistakes in your text

Upload your document to correct all your mistakes in minutes

upload-your-document-ai-proofreader

Table of contents

What is the purpose of a literature review, examples of literature reviews, step 1 – search for relevant literature, step 2 – evaluate and select sources, step 3 – identify themes, debates, and gaps, step 4 – outline your literature review’s structure, step 5 – write your literature review, free lecture slides, other interesting articles, frequently asked questions, introduction.

  • Quick Run-through
  • Step 1 & 2

When you write a thesis , dissertation , or research paper , you will likely have to conduct a literature review to situate your research within existing knowledge. The literature review gives you a chance to:

  • Demonstrate your familiarity with the topic and its scholarly context
  • Develop a theoretical framework and methodology for your research
  • Position your work in relation to other researchers and theorists
  • Show how your research addresses a gap or contributes to a debate
  • Evaluate the current state of research and demonstrate your knowledge of the scholarly debates around your topic.

Writing literature reviews is a particularly important skill if you want to apply for graduate school or pursue a career in research. We’ve written a step-by-step guide that you can follow below.

Literature review guide

Here's why students love Scribbr's proofreading services

Discover proofreading & editing

Writing literature reviews can be quite challenging! A good starting point could be to look at some examples, depending on what kind of literature review you’d like to write.

  • Example literature review #1: “Why Do People Migrate? A Review of the Theoretical Literature” ( Theoretical literature review about the development of economic migration theory from the 1950s to today.)
  • Example literature review #2: “Literature review as a research methodology: An overview and guidelines” ( Methodological literature review about interdisciplinary knowledge acquisition and production.)
  • Example literature review #3: “The Use of Technology in English Language Learning: A Literature Review” ( Thematic literature review about the effects of technology on language acquisition.)
  • Example literature review #4: “Learners’ Listening Comprehension Difficulties in English Language Learning: A Literature Review” ( Chronological literature review about how the concept of listening skills has changed over time.)

You can also check out our templates with literature review examples and sample outlines at the links below.

Download Word doc Download Google doc

Before you begin searching for literature, you need a clearly defined topic .

If you are writing the literature review section of a dissertation or research paper, you will search for literature related to your research problem and questions .

Make a list of keywords

Start by creating a list of keywords related to your research question. Include each of the key concepts or variables you’re interested in, and list any synonyms and related terms. You can add to this list as you discover new keywords in the process of your literature search.

  • Social media, Facebook, Instagram, Twitter, Snapchat, TikTok
  • Body image, self-perception, self-esteem, mental health
  • Generation Z, teenagers, adolescents, youth

Search for relevant sources

Use your keywords to begin searching for sources. Some useful databases to search for journals and articles include:

  • Your university’s library catalogue
  • Google Scholar
  • Project Muse (humanities and social sciences)
  • Medline (life sciences and biomedicine)
  • EconLit (economics)
  • Inspec (physics, engineering and computer science)

You can also use boolean operators to help narrow down your search.

Make sure to read the abstract to find out whether an article is relevant to your question. When you find a useful book or article, you can check the bibliography to find other relevant sources.

You likely won’t be able to read absolutely everything that has been written on your topic, so it will be necessary to evaluate which sources are most relevant to your research question.

For each publication, ask yourself:

  • What question or problem is the author addressing?
  • What are the key concepts and how are they defined?
  • What are the key theories, models, and methods?
  • Does the research use established frameworks or take an innovative approach?
  • What are the results and conclusions of the study?
  • How does the publication relate to other literature in the field? Does it confirm, add to, or challenge established knowledge?
  • What are the strengths and weaknesses of the research?

Make sure the sources you use are credible , and make sure you read any landmark studies and major theories in your field of research.

You can use our template to summarize and evaluate sources you’re thinking about using. Click on either button below to download.

Take notes and cite your sources

As you read, you should also begin the writing process. Take notes that you can later incorporate into the text of your literature review.

It is important to keep track of your sources with citations to avoid plagiarism . It can be helpful to make an annotated bibliography , where you compile full citation information and write a paragraph of summary and analysis for each source. This helps you remember what you read and saves time later in the process.

The only proofreading tool specialized in correcting academic writing - try for free!

The academic proofreading tool has been trained on 1000s of academic texts and by native English editors. Making it the most accurate and reliable proofreading tool for students.

literature review including cases

Try for free

To begin organizing your literature review’s argument and structure, be sure you understand the connections and relationships between the sources you’ve read. Based on your reading and notes, you can look for:

  • Trends and patterns (in theory, method or results): do certain approaches become more or less popular over time?
  • Themes: what questions or concepts recur across the literature?
  • Debates, conflicts and contradictions: where do sources disagree?
  • Pivotal publications: are there any influential theories or studies that changed the direction of the field?
  • Gaps: what is missing from the literature? Are there weaknesses that need to be addressed?

This step will help you work out the structure of your literature review and (if applicable) show how your own research will contribute to existing knowledge.

  • Most research has focused on young women.
  • There is an increasing interest in the visual aspects of social media.
  • But there is still a lack of robust research on highly visual platforms like Instagram and Snapchat—this is a gap that you could address in your own research.

There are various approaches to organizing the body of a literature review. Depending on the length of your literature review, you can combine several of these strategies (for example, your overall structure might be thematic, but each theme is discussed chronologically).

Chronological

The simplest approach is to trace the development of the topic over time. However, if you choose this strategy, be careful to avoid simply listing and summarizing sources in order.

Try to analyze patterns, turning points and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred.

If you have found some recurring central themes, you can organize your literature review into subsections that address different aspects of the topic.

For example, if you are reviewing literature about inequalities in migrant health outcomes, key themes might include healthcare policy, language barriers, cultural attitudes, legal status, and economic access.

Methodological

If you draw your sources from different disciplines or fields that use a variety of research methods , you might want to compare the results and conclusions that emerge from different approaches. For example:

  • Look at what results have emerged in qualitative versus quantitative research
  • Discuss how the topic has been approached by empirical versus theoretical scholarship
  • Divide the literature into sociological, historical, and cultural sources

Theoretical

A literature review is often the foundation for a theoretical framework . You can use it to discuss various theories, models, and definitions of key concepts.

You might argue for the relevance of a specific theoretical approach, or combine various theoretical concepts to create a framework for your research.

Like any other academic text , your literature review should have an introduction , a main body, and a conclusion . What you include in each depends on the objective of your literature review.

The introduction should clearly establish the focus and purpose of the literature review.

Depending on the length of your literature review, you might want to divide the body into subsections. You can use a subheading for each theme, time period, or methodological approach.

As you write, you can follow these tips:

  • Summarize and synthesize: give an overview of the main points of each source and combine them into a coherent whole
  • Analyze and interpret: don’t just paraphrase other researchers — add your own interpretations where possible, discussing the significance of findings in relation to the literature as a whole
  • Critically evaluate: mention the strengths and weaknesses of your sources
  • Write in well-structured paragraphs: use transition words and topic sentences to draw connections, comparisons and contrasts

In the conclusion, you should summarize the key findings you have taken from the literature and emphasize their significance.

When you’ve finished writing and revising your literature review, don’t forget to proofread thoroughly before submitting. Not a language expert? Check out Scribbr’s professional proofreading services !

This article has been adapted into lecture slides that you can use to teach your students about writing a literature review.

Scribbr slides are free to use, customize, and distribute for educational purposes.

Open Google Slides Download PowerPoint

If you want to know more about the research process , methodology , research bias , or statistics , make sure to check out some of our other articles with explanations and examples.

  • Sampling methods
  • Simple random sampling
  • Stratified sampling
  • Cluster sampling
  • Likert scales
  • Reproducibility

 Statistics

  • Null hypothesis
  • Statistical power
  • Probability distribution
  • Effect size
  • Poisson distribution

Research bias

  • Optimism bias
  • Cognitive bias
  • Implicit bias
  • Hawthorne effect
  • Anchoring bias
  • Explicit bias

A literature review is a survey of scholarly sources (such as books, journal articles, and theses) related to a specific topic or research question .

It is often written as part of a thesis, dissertation , or research paper , in order to situate your work in relation to existing knowledge.

There are several reasons to conduct a literature review at the beginning of a research project:

  • To familiarize yourself with the current state of knowledge on your topic
  • To ensure that you’re not just repeating what others have already done
  • To identify gaps in knowledge and unresolved problems that your research can address
  • To develop your theoretical framework and methodology
  • To provide an overview of the key findings and debates on the topic

Writing the literature review shows your reader how your work relates to existing research and what new insights it will contribute.

The literature review usually comes near the beginning of your thesis or dissertation . After the introduction , it grounds your research in a scholarly field and leads directly to your theoretical framework or methodology .

A literature review is a survey of credible sources on a topic, often used in dissertations , theses, and research papers . Literature reviews give an overview of knowledge on a subject, helping you identify relevant theories and methods, as well as gaps in existing research. Literature reviews are set up similarly to other  academic texts , with an introduction , a main body, and a conclusion .

An  annotated bibliography is a list of  source references that has a short description (called an annotation ) for each of the sources. It is often assigned as part of the research process for a  paper .  

Cite this Scribbr article

If you want to cite this source, you can copy and paste the citation or click the “Cite this Scribbr article” button to automatically add the citation to our free Citation Generator.

McCombes, S. (2023, September 11). How to Write a Literature Review | Guide, Examples, & Templates. Scribbr. Retrieved April 1, 2024, from https://www.scribbr.com/dissertation/literature-review/

Is this article helpful?

Shona McCombes

Shona McCombes

Other students also liked, what is a theoretical framework | guide to organizing, what is a research methodology | steps & tips, how to write a research proposal | examples & templates, "i thought ai proofreading was useless but..".

I've been using Scribbr for years now and I know it's a service that won't disappoint. It does a good job spotting mistakes”

Purdue Online Writing Lab Purdue OWL® College of Liberal Arts

Writing a Literature Review

OWL logo

Welcome to the Purdue OWL

This page is brought to you by the OWL at Purdue University. When printing this page, you must include the entire legal notice.

Copyright ©1995-2018 by The Writing Lab & The OWL at Purdue and Purdue University. All rights reserved. This material may not be published, reproduced, broadcast, rewritten, or redistributed without permission. Use of this site constitutes acceptance of our terms and conditions of fair use.

A literature review is a document or section of a document that collects key sources on a topic and discusses those sources in conversation with each other (also called synthesis ). The lit review is an important genre in many disciplines, not just literature (i.e., the study of works of literature such as novels and plays). When we say “literature review” or refer to “the literature,” we are talking about the research ( scholarship ) in a given field. You will often see the terms “the research,” “the scholarship,” and “the literature” used mostly interchangeably.

Where, when, and why would I write a lit review?

There are a number of different situations where you might write a literature review, each with slightly different expectations; different disciplines, too, have field-specific expectations for what a literature review is and does. For instance, in the humanities, authors might include more overt argumentation and interpretation of source material in their literature reviews, whereas in the sciences, authors are more likely to report study designs and results in their literature reviews; these differences reflect these disciplines’ purposes and conventions in scholarship. You should always look at examples from your own discipline and talk to professors or mentors in your field to be sure you understand your discipline’s conventions, for literature reviews as well as for any other genre.

A literature review can be a part of a research paper or scholarly article, usually falling after the introduction and before the research methods sections. In these cases, the lit review just needs to cover scholarship that is important to the issue you are writing about; sometimes it will also cover key sources that informed your research methodology.

Lit reviews can also be standalone pieces, either as assignments in a class or as publications. In a class, a lit review may be assigned to help students familiarize themselves with a topic and with scholarship in their field, get an idea of the other researchers working on the topic they’re interested in, find gaps in existing research in order to propose new projects, and/or develop a theoretical framework and methodology for later research. As a publication, a lit review usually is meant to help make other scholars’ lives easier by collecting and summarizing, synthesizing, and analyzing existing research on a topic. This can be especially helpful for students or scholars getting into a new research area, or for directing an entire community of scholars toward questions that have not yet been answered.

What are the parts of a lit review?

Most lit reviews use a basic introduction-body-conclusion structure; if your lit review is part of a larger paper, the introduction and conclusion pieces may be just a few sentences while you focus most of your attention on the body. If your lit review is a standalone piece, the introduction and conclusion take up more space and give you a place to discuss your goals, research methods, and conclusions separately from where you discuss the literature itself.

Introduction:

  • An introductory paragraph that explains what your working topic and thesis is
  • A forecast of key topics or texts that will appear in the review
  • Potentially, a description of how you found sources and how you analyzed them for inclusion and discussion in the review (more often found in published, standalone literature reviews than in lit review sections in an article or research paper)
  • Summarize and synthesize: Give an overview of the main points of each source and combine them into a coherent whole
  • Analyze and interpret: Don’t just paraphrase other researchers – add your own interpretations where possible, discussing the significance of findings in relation to the literature as a whole
  • Critically Evaluate: Mention the strengths and weaknesses of your sources
  • Write in well-structured paragraphs: Use transition words and topic sentence to draw connections, comparisons, and contrasts.

Conclusion:

  • Summarize the key findings you have taken from the literature and emphasize their significance
  • Connect it back to your primary research question

How should I organize my lit review?

Lit reviews can take many different organizational patterns depending on what you are trying to accomplish with the review. Here are some examples:

  • Chronological : The simplest approach is to trace the development of the topic over time, which helps familiarize the audience with the topic (for instance if you are introducing something that is not commonly known in your field). If you choose this strategy, be careful to avoid simply listing and summarizing sources in order. Try to analyze the patterns, turning points, and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred (as mentioned previously, this may not be appropriate in your discipline — check with a teacher or mentor if you’re unsure).
  • Thematic : If you have found some recurring central themes that you will continue working with throughout your piece, you can organize your literature review into subsections that address different aspects of the topic. For example, if you are reviewing literature about women and religion, key themes can include the role of women in churches and the religious attitude towards women.
  • Qualitative versus quantitative research
  • Empirical versus theoretical scholarship
  • Divide the research by sociological, historical, or cultural sources
  • Theoretical : In many humanities articles, the literature review is the foundation for the theoretical framework. You can use it to discuss various theories, models, and definitions of key concepts. You can argue for the relevance of a specific theoretical approach or combine various theorical concepts to create a framework for your research.

What are some strategies or tips I can use while writing my lit review?

Any lit review is only as good as the research it discusses; make sure your sources are well-chosen and your research is thorough. Don’t be afraid to do more research if you discover a new thread as you’re writing. More info on the research process is available in our "Conducting Research" resources .

As you’re doing your research, create an annotated bibliography ( see our page on the this type of document ). Much of the information used in an annotated bibliography can be used also in a literature review, so you’ll be not only partially drafting your lit review as you research, but also developing your sense of the larger conversation going on among scholars, professionals, and any other stakeholders in your topic.

Usually you will need to synthesize research rather than just summarizing it. This means drawing connections between sources to create a picture of the scholarly conversation on a topic over time. Many student writers struggle to synthesize because they feel they don’t have anything to add to the scholars they are citing; here are some strategies to help you:

  • It often helps to remember that the point of these kinds of syntheses is to show your readers how you understand your research, to help them read the rest of your paper.
  • Writing teachers often say synthesis is like hosting a dinner party: imagine all your sources are together in a room, discussing your topic. What are they saying to each other?
  • Look at the in-text citations in each paragraph. Are you citing just one source for each paragraph? This usually indicates summary only. When you have multiple sources cited in a paragraph, you are more likely to be synthesizing them (not always, but often
  • Read more about synthesis here.

The most interesting literature reviews are often written as arguments (again, as mentioned at the beginning of the page, this is discipline-specific and doesn’t work for all situations). Often, the literature review is where you can establish your research as filling a particular gap or as relevant in a particular way. You have some chance to do this in your introduction in an article, but the literature review section gives a more extended opportunity to establish the conversation in the way you would like your readers to see it. You can choose the intellectual lineage you would like to be part of and whose definitions matter most to your thinking (mostly humanities-specific, but this goes for sciences as well). In addressing these points, you argue for your place in the conversation, which tends to make the lit review more compelling than a simple reporting of other sources.

Grad Coach

How To Write An A-Grade Literature Review

3 straightforward steps (with examples) + free template.

By: Derek Jansen (MBA) | Expert Reviewed By: Dr. Eunice Rautenbach | October 2019

Quality research is about building onto the existing work of others , “standing on the shoulders of giants”, as Newton put it. The literature review chapter of your dissertation, thesis or research project is where you synthesise this prior work and lay the theoretical foundation for your own research.

Long story short, this chapter is a pretty big deal, which is why you want to make sure you get it right . In this post, I’ll show you exactly how to write a literature review in three straightforward steps, so you can conquer this vital chapter (the smart way).

Overview: The Literature Review Process

  • Understanding the “ why “
  • Finding the relevant literature
  • Cataloguing and synthesising the information
  • Outlining & writing up your literature review
  • Example of a literature review

But first, the “why”…

Before we unpack how to write the literature review chapter, we’ve got to look at the why . To put it bluntly, if you don’t understand the function and purpose of the literature review process, there’s no way you can pull it off well. So, what exactly is the purpose of the literature review?

Well, there are (at least) four core functions:

  • For you to gain an understanding (and demonstrate this understanding) of where the research is at currently, what the key arguments and disagreements are.
  • For you to identify the gap(s) in the literature and then use this as justification for your own research topic.
  • To help you build a conceptual framework for empirical testing (if applicable to your research topic).
  • To inform your methodological choices and help you source tried and tested questionnaires (for interviews ) and measurement instruments (for surveys ).

Most students understand the first point but don’t give any thought to the rest. To get the most from the literature review process, you must keep all four points front of mind as you review the literature (more on this shortly), or you’ll land up with a wonky foundation.

Okay – with the why out the way, let’s move on to the how . As mentioned above, writing your literature review is a process, which I’ll break down into three steps:

  • Finding the most suitable literature
  • Understanding , distilling and organising the literature
  • Planning and writing up your literature review chapter

Importantly, you must complete steps one and two before you start writing up your chapter. I know it’s very tempting, but don’t try to kill two birds with one stone and write as you read. You’ll invariably end up wasting huge amounts of time re-writing and re-shaping, or you’ll just land up with a disjointed, hard-to-digest mess . Instead, you need to read first and distil the information, then plan and execute the writing.

Free Webinar: Literature Review 101

Step 1: Find the relevant literature

Naturally, the first step in the literature review journey is to hunt down the existing research that’s relevant to your topic. While you probably already have a decent base of this from your research proposal , you need to expand on this substantially in the dissertation or thesis itself.

Essentially, you need to be looking for any existing literature that potentially helps you answer your research question (or develop it, if that’s not yet pinned down). There are numerous ways to find relevant literature, but I’ll cover my top four tactics here. I’d suggest combining all four methods to ensure that nothing slips past you:

Method 1 – Google Scholar Scrubbing

Google’s academic search engine, Google Scholar , is a great starting point as it provides a good high-level view of the relevant journal articles for whatever keyword you throw at it. Most valuably, it tells you how many times each article has been cited, which gives you an idea of how credible (or at least, popular) it is. Some articles will be free to access, while others will require an account, which brings us to the next method.

Method 2 – University Database Scrounging

Generally, universities provide students with access to an online library, which provides access to many (but not all) of the major journals.

So, if you find an article using Google Scholar that requires paid access (which is quite likely), search for that article in your university’s database – if it’s listed there, you’ll have access. Note that, generally, the search engine capabilities of these databases are poor, so make sure you search for the exact article name, or you might not find it.

Method 3 – Journal Article Snowballing

At the end of every academic journal article, you’ll find a list of references. As with any academic writing, these references are the building blocks of the article, so if the article is relevant to your topic, there’s a good chance a portion of the referenced works will be too. Do a quick scan of the titles and see what seems relevant, then search for the relevant ones in your university’s database.

Method 4 – Dissertation Scavenging

Similar to Method 3 above, you can leverage other students’ dissertations. All you have to do is skim through literature review chapters of existing dissertations related to your topic and you’ll find a gold mine of potential literature. Usually, your university will provide you with access to previous students’ dissertations, but you can also find a much larger selection in the following databases:

  • Open Access Theses & Dissertations
  • Stanford SearchWorks

Keep in mind that dissertations and theses are not as academically sound as published, peer-reviewed journal articles (because they’re written by students, not professionals), so be sure to check the credibility of any sources you find using this method. You can do this by assessing the citation count of any given article in Google Scholar. If you need help with assessing the credibility of any article, or with finding relevant research in general, you can chat with one of our Research Specialists .

Alright – with a good base of literature firmly under your belt, it’s time to move onto the next step.

Need a helping hand?

literature review including cases

Step 2: Log, catalogue and synthesise

Once you’ve built a little treasure trove of articles, it’s time to get reading and start digesting the information – what does it all mean?

While I present steps one and two (hunting and digesting) as sequential, in reality, it’s more of a back-and-forth tango – you’ll read a little , then have an idea, spot a new citation, or a new potential variable, and then go back to searching for articles. This is perfectly natural – through the reading process, your thoughts will develop , new avenues might crop up, and directional adjustments might arise. This is, after all, one of the main purposes of the literature review process (i.e. to familiarise yourself with the current state of research in your field).

As you’re working through your treasure chest, it’s essential that you simultaneously start organising the information. There are three aspects to this:

  • Logging reference information
  • Building an organised catalogue
  • Distilling and synthesising the information

I’ll discuss each of these below:

2.1 – Log the reference information

As you read each article, you should add it to your reference management software. I usually recommend Mendeley for this purpose (see the Mendeley 101 video below), but you can use whichever software you’re comfortable with. Most importantly, make sure you load EVERY article you read into your reference manager, even if it doesn’t seem very relevant at the time.

2.2 – Build an organised catalogue

In the beginning, you might feel confident that you can remember who said what, where, and what their main arguments were. Trust me, you won’t. If you do a thorough review of the relevant literature (as you must!), you’re going to read many, many articles, and it’s simply impossible to remember who said what, when, and in what context . Also, without the bird’s eye view that a catalogue provides, you’ll miss connections between various articles, and have no view of how the research developed over time. Simply put, it’s essential to build your own catalogue of the literature.

I would suggest using Excel to build your catalogue, as it allows you to run filters, colour code and sort – all very useful when your list grows large (which it will). How you lay your spreadsheet out is up to you, but I’d suggest you have the following columns (at minimum):

  • Author, date, title – Start with three columns containing this core information. This will make it easy for you to search for titles with certain words, order research by date, or group by author.
  • Categories or keywords – You can either create multiple columns, one for each category/theme and then tick the relevant categories, or you can have one column with keywords.
  • Key arguments/points – Use this column to succinctly convey the essence of the article, the key arguments and implications thereof for your research.
  • Context – Note the socioeconomic context in which the research was undertaken. For example, US-based, respondents aged 25-35, lower- income, etc. This will be useful for making an argument about gaps in the research.
  • Methodology – Note which methodology was used and why. Also, note any issues you feel arise due to the methodology. Again, you can use this to make an argument about gaps in the research.
  • Quotations – Note down any quoteworthy lines you feel might be useful later.
  • Notes – Make notes about anything not already covered. For example, linkages to or disagreements with other theories, questions raised but unanswered, shortcomings or limitations, and so forth.

If you’d like, you can try out our free catalog template here (see screenshot below).

Excel literature review template

2.3 – Digest and synthesise

Most importantly, as you work through the literature and build your catalogue, you need to synthesise all the information in your own mind – how does it all fit together? Look for links between the various articles and try to develop a bigger picture view of the state of the research. Some important questions to ask yourself are:

  • What answers does the existing research provide to my own research questions ?
  • Which points do the researchers agree (and disagree) on?
  • How has the research developed over time?
  • Where do the gaps in the current research lie?

To help you develop a big-picture view and synthesise all the information, you might find mind mapping software such as Freemind useful. Alternatively, if you’re a fan of physical note-taking, investing in a large whiteboard might work for you.

Mind mapping is a useful way to plan your literature review.

Step 3: Outline and write it up!

Once you’re satisfied that you have digested and distilled all the relevant literature in your mind, it’s time to put pen to paper (or rather, fingers to keyboard). There are two steps here – outlining and writing:

3.1 – Draw up your outline

Having spent so much time reading, it might be tempting to just start writing up without a clear structure in mind. However, it’s critically important to decide on your structure and develop a detailed outline before you write anything. Your literature review chapter needs to present a clear, logical and an easy to follow narrative – and that requires some planning. Don’t try to wing it!

Naturally, you won’t always follow the plan to the letter, but without a detailed outline, you’re more than likely going to end up with a disjointed pile of waffle , and then you’re going to spend a far greater amount of time re-writing, hacking and patching. The adage, “measure twice, cut once” is very suitable here.

In terms of structure, the first decision you’ll have to make is whether you’ll lay out your review thematically (into themes) or chronologically (by date/period). The right choice depends on your topic, research objectives and research questions, which we discuss in this article .

Once that’s decided, you need to draw up an outline of your entire chapter in bullet point format. Try to get as detailed as possible, so that you know exactly what you’ll cover where, how each section will connect to the next, and how your entire argument will develop throughout the chapter. Also, at this stage, it’s a good idea to allocate rough word count limits for each section, so that you can identify word count problems before you’ve spent weeks or months writing!

PS – check out our free literature review chapter template…

3.2 – Get writing

With a detailed outline at your side, it’s time to start writing up (finally!). At this stage, it’s common to feel a bit of writer’s block and find yourself procrastinating under the pressure of finally having to put something on paper. To help with this, remember that the objective of the first draft is not perfection – it’s simply to get your thoughts out of your head and onto paper, after which you can refine them. The structure might change a little, the word count allocations might shift and shuffle, and you might add or remove a section – that’s all okay. Don’t worry about all this on your first draft – just get your thoughts down on paper.

start writing

Once you’ve got a full first draft (however rough it may be), step away from it for a day or two (longer if you can) and then come back at it with fresh eyes. Pay particular attention to the flow and narrative – does it fall fit together and flow from one section to another smoothly? Now’s the time to try to improve the linkage from each section to the next, tighten up the writing to be more concise, trim down word count and sand it down into a more digestible read.

Once you’ve done that, give your writing to a friend or colleague who is not a subject matter expert and ask them if they understand the overall discussion. The best way to assess this is to ask them to explain the chapter back to you. This technique will give you a strong indication of which points were clearly communicated and which weren’t. If you’re working with Grad Coach, this is a good time to have your Research Specialist review your chapter.

Finally, tighten it up and send it off to your supervisor for comment. Some might argue that you should be sending your work to your supervisor sooner than this (indeed your university might formally require this), but in my experience, supervisors are extremely short on time (and often patience), so, the more refined your chapter is, the less time they’ll waste on addressing basic issues (which you know about already) and the more time they’ll spend on valuable feedback that will increase your mark-earning potential.

Literature Review Example

In the video below, we unpack an actual literature review so that you can see how all the core components come together in reality.

Let’s Recap

In this post, we’ve covered how to research and write up a high-quality literature review chapter. Let’s do a quick recap of the key takeaways:

  • It is essential to understand the WHY of the literature review before you read or write anything. Make sure you understand the 4 core functions of the process.
  • The first step is to hunt down the relevant literature . You can do this using Google Scholar, your university database, the snowballing technique and by reviewing other dissertations and theses.
  • Next, you need to log all the articles in your reference manager , build your own catalogue of literature and synthesise all the research.
  • Following that, you need to develop a detailed outline of your entire chapter – the more detail the better. Don’t start writing without a clear outline (on paper, not in your head!)
  • Write up your first draft in rough form – don’t aim for perfection. Remember, done beats perfect.
  • Refine your second draft and get a layman’s perspective on it . Then tighten it up and submit it to your supervisor.

Literature Review Course

Psst… there’s more!

This post is an extract from our bestselling Udemy Course, Literature Review Bootcamp . If you want to work smart, you don't want to miss this .

You Might Also Like:

How To Find a Research Gap (Fast)

38 Comments

Phindile Mpetshwa

Thank you very much. This page is an eye opener and easy to comprehend.

Yinka

This is awesome!

I wish I come across GradCoach earlier enough.

But all the same I’ll make use of this opportunity to the fullest.

Thank you for this good job.

Keep it up!

Derek Jansen

You’re welcome, Yinka. Thank you for the kind words. All the best writing your literature review.

Renee Buerger

Thank you for a very useful literature review session. Although I am doing most of the steps…it being my first masters an Mphil is a self study and one not sure you are on the right track. I have an amazing supervisor but one also knows they are super busy. So not wanting to bother on the minutae. Thank you.

You’re most welcome, Renee. Good luck with your literature review 🙂

Sheemal Prasad

This has been really helpful. Will make full use of it. 🙂

Thank you Gradcoach.

Tahir

Really agreed. Admirable effort

Faturoti Toyin

thank you for this beautiful well explained recap.

Tara

Thank you so much for your guide of video and other instructions for the dissertation writing.

It is instrumental. It encouraged me to write a dissertation now.

Lorraine Hall

Thank you the video was great – from someone that knows nothing thankyou

araz agha

an amazing and very constructive way of presetting a topic, very useful, thanks for the effort,

Suilabayuh Ngah

It is timely

It is very good video of guidance for writing a research proposal and a dissertation. Since I have been watching and reading instructions, I have started my research proposal to write. I appreciate to Mr Jansen hugely.

Nancy Geregl

I learn a lot from your videos. Very comprehensive and detailed.

Thank you for sharing your knowledge. As a research student, you learn better with your learning tips in research

Uzma

I was really stuck in reading and gathering information but after watching these things are cleared thanks, it is so helpful.

Xaysukith thorxaitou

Really helpful, Thank you for the effort in showing such information

Sheila Jerome

This is super helpful thank you very much.

Mary

Thank you for this whole literature writing review.You have simplified the process.

Maithe

I’m so glad I found GradCoach. Excellent information, Clear explanation, and Easy to follow, Many thanks Derek!

You’re welcome, Maithe. Good luck writing your literature review 🙂

Anthony

Thank you Coach, you have greatly enriched and improved my knowledge

Eunice

Great piece, so enriching and it is going to help me a great lot in my project and thesis, thanks so much

Stephanie Louw

This is THE BEST site for ANYONE doing a masters or doctorate! Thank you for the sound advice and templates. You rock!

Thanks, Stephanie 🙂

oghenekaro Silas

This is mind blowing, the detailed explanation and simplicity is perfect.

I am doing two papers on my final year thesis, and I must stay I feel very confident to face both headlong after reading this article.

thank you so much.

if anyone is to get a paper done on time and in the best way possible, GRADCOACH is certainly the go to area!

tarandeep singh

This is very good video which is well explained with detailed explanation

uku igeny

Thank you excellent piece of work and great mentoring

Abdul Ahmad Zazay

Thanks, it was useful

Maserialong Dlamini

Thank you very much. the video and the information were very helpful.

Suleiman Abubakar

Good morning scholar. I’m delighted coming to know you even before the commencement of my dissertation which hopefully is expected in not more than six months from now. I would love to engage my study under your guidance from the beginning to the end. I love to know how to do good job

Mthuthuzeli Vongo

Thank you so much Derek for such useful information on writing up a good literature review. I am at a stage where I need to start writing my one. My proposal was accepted late last year but I honestly did not know where to start

SEID YIMAM MOHAMMED (Technic)

Like the name of your YouTube implies you are GRAD (great,resource person, about dissertation). In short you are smart enough in coaching research work.

Richie Buffalo

This is a very well thought out webpage. Very informative and a great read.

Adekoya Opeyemi Jonathan

Very timely.

I appreciate.

Norasyidah Mohd Yusoff

Very comprehensive and eye opener for me as beginner in postgraduate study. Well explained and easy to understand. Appreciate and good reference in guiding me in my research journey. Thank you

Maryellen Elizabeth Hart

Thank you. I requested to download the free literature review template, however, your website wouldn’t allow me to complete the request or complete a download. May I request that you email me the free template? Thank you.

Submit a Comment Cancel reply

Your email address will not be published. Required fields are marked *

Save my name, email, and website in this browser for the next time I comment.

  • Print Friendly

Have a language expert improve your writing

Run a free plagiarism check in 10 minutes, automatically generate references for free.

  • Knowledge Base
  • Dissertation
  • What is a Literature Review? | Guide, Template, & Examples

What is a Literature Review? | Guide, Template, & Examples

Published on 22 February 2022 by Shona McCombes . Revised on 7 June 2022.

What is a literature review? A literature review is a survey of scholarly sources on a specific topic. It provides an overview of current knowledge, allowing you to identify relevant theories, methods, and gaps in the existing research.

There are five key steps to writing a literature review:

  • Search for relevant literature
  • Evaluate sources
  • Identify themes, debates and gaps
  • Outline the structure
  • Write your literature review

A good literature review doesn’t just summarise sources – it analyses, synthesises, and critically evaluates to give a clear picture of the state of knowledge on the subject.

Instantly correct all language mistakes in your text

Be assured that you'll submit flawless writing. Upload your document to correct all your mistakes.

upload-your-document-ai-proofreader

Table of contents

Why write a literature review, examples of literature reviews, step 1: search for relevant literature, step 2: evaluate and select sources, step 3: identify themes, debates and gaps, step 4: outline your literature review’s structure, step 5: write your literature review, frequently asked questions about literature reviews, introduction.

  • Quick Run-through
  • Step 1 & 2

When you write a dissertation or thesis, you will have to conduct a literature review to situate your research within existing knowledge. The literature review gives you a chance to:

  • Demonstrate your familiarity with the topic and scholarly context
  • Develop a theoretical framework and methodology for your research
  • Position yourself in relation to other researchers and theorists
  • Show how your dissertation addresses a gap or contributes to a debate

You might also have to write a literature review as a stand-alone assignment. In this case, the purpose is to evaluate the current state of research and demonstrate your knowledge of scholarly debates around a topic.

The content will look slightly different in each case, but the process of conducting a literature review follows the same steps. We’ve written a step-by-step guide that you can follow below.

Literature review guide

The only proofreading tool specialized in correcting academic writing

The academic proofreading tool has been trained on 1000s of academic texts and by native English editors. Making it the most accurate and reliable proofreading tool for students.

literature review including cases

Correct my document today

Writing literature reviews can be quite challenging! A good starting point could be to look at some examples, depending on what kind of literature review you’d like to write.

  • Example literature review #1: “Why Do People Migrate? A Review of the Theoretical Literature” ( Theoretical literature review about the development of economic migration theory from the 1950s to today.)
  • Example literature review #2: “Literature review as a research methodology: An overview and guidelines” ( Methodological literature review about interdisciplinary knowledge acquisition and production.)
  • Example literature review #3: “The Use of Technology in English Language Learning: A Literature Review” ( Thematic literature review about the effects of technology on language acquisition.)
  • Example literature review #4: “Learners’ Listening Comprehension Difficulties in English Language Learning: A Literature Review” ( Chronological literature review about how the concept of listening skills has changed over time.)

You can also check out our templates with literature review examples and sample outlines at the links below.

Download Word doc Download Google doc

Before you begin searching for literature, you need a clearly defined topic .

If you are writing the literature review section of a dissertation or research paper, you will search for literature related to your research objectives and questions .

If you are writing a literature review as a stand-alone assignment, you will have to choose a focus and develop a central question to direct your search. Unlike a dissertation research question, this question has to be answerable without collecting original data. You should be able to answer it based only on a review of existing publications.

Make a list of keywords

Start by creating a list of keywords related to your research topic. Include each of the key concepts or variables you’re interested in, and list any synonyms and related terms. You can add to this list if you discover new keywords in the process of your literature search.

  • Social media, Facebook, Instagram, Twitter, Snapchat, TikTok
  • Body image, self-perception, self-esteem, mental health
  • Generation Z, teenagers, adolescents, youth

Search for relevant sources

Use your keywords to begin searching for sources. Some databases to search for journals and articles include:

  • Your university’s library catalogue
  • Google Scholar
  • Project Muse (humanities and social sciences)
  • Medline (life sciences and biomedicine)
  • EconLit (economics)
  • Inspec (physics, engineering and computer science)

You can use boolean operators to help narrow down your search:

Read the abstract to find out whether an article is relevant to your question. When you find a useful book or article, you can check the bibliography to find other relevant sources.

To identify the most important publications on your topic, take note of recurring citations. If the same authors, books or articles keep appearing in your reading, make sure to seek them out.

You probably won’t be able to read absolutely everything that has been written on the topic – you’ll have to evaluate which sources are most relevant to your questions.

For each publication, ask yourself:

  • What question or problem is the author addressing?
  • What are the key concepts and how are they defined?
  • What are the key theories, models and methods? Does the research use established frameworks or take an innovative approach?
  • What are the results and conclusions of the study?
  • How does the publication relate to other literature in the field? Does it confirm, add to, or challenge established knowledge?
  • How does the publication contribute to your understanding of the topic? What are its key insights and arguments?
  • What are the strengths and weaknesses of the research?

Make sure the sources you use are credible, and make sure you read any landmark studies and major theories in your field of research.

You can find out how many times an article has been cited on Google Scholar – a high citation count means the article has been influential in the field, and should certainly be included in your literature review.

The scope of your review will depend on your topic and discipline: in the sciences you usually only review recent literature, but in the humanities you might take a long historical perspective (for example, to trace how a concept has changed in meaning over time).

Remember that you can use our template to summarise and evaluate sources you’re thinking about using!

Take notes and cite your sources

As you read, you should also begin the writing process. Take notes that you can later incorporate into the text of your literature review.

It’s important to keep track of your sources with references to avoid plagiarism . It can be helpful to make an annotated bibliography, where you compile full reference information and write a paragraph of summary and analysis for each source. This helps you remember what you read and saves time later in the process.

You can use our free APA Reference Generator for quick, correct, consistent citations.

Prevent plagiarism, run a free check.

To begin organising your literature review’s argument and structure, you need to understand the connections and relationships between the sources you’ve read. Based on your reading and notes, you can look for:

  • Trends and patterns (in theory, method or results): do certain approaches become more or less popular over time?
  • Themes: what questions or concepts recur across the literature?
  • Debates, conflicts and contradictions: where do sources disagree?
  • Pivotal publications: are there any influential theories or studies that changed the direction of the field?
  • Gaps: what is missing from the literature? Are there weaknesses that need to be addressed?

This step will help you work out the structure of your literature review and (if applicable) show how your own research will contribute to existing knowledge.

  • Most research has focused on young women.
  • There is an increasing interest in the visual aspects of social media.
  • But there is still a lack of robust research on highly-visual platforms like Instagram and Snapchat – this is a gap that you could address in your own research.

There are various approaches to organising the body of a literature review. You should have a rough idea of your strategy before you start writing.

Depending on the length of your literature review, you can combine several of these strategies (for example, your overall structure might be thematic, but each theme is discussed chronologically).

Chronological

The simplest approach is to trace the development of the topic over time. However, if you choose this strategy, be careful to avoid simply listing and summarising sources in order.

Try to analyse patterns, turning points and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred.

If you have found some recurring central themes, you can organise your literature review into subsections that address different aspects of the topic.

For example, if you are reviewing literature about inequalities in migrant health outcomes, key themes might include healthcare policy, language barriers, cultural attitudes, legal status, and economic access.

Methodological

If you draw your sources from different disciplines or fields that use a variety of research methods , you might want to compare the results and conclusions that emerge from different approaches. For example:

  • Look at what results have emerged in qualitative versus quantitative research
  • Discuss how the topic has been approached by empirical versus theoretical scholarship
  • Divide the literature into sociological, historical, and cultural sources

Theoretical

A literature review is often the foundation for a theoretical framework . You can use it to discuss various theories, models, and definitions of key concepts.

You might argue for the relevance of a specific theoretical approach, or combine various theoretical concepts to create a framework for your research.

Like any other academic text, your literature review should have an introduction , a main body, and a conclusion . What you include in each depends on the objective of your literature review.

The introduction should clearly establish the focus and purpose of the literature review.

If you are writing the literature review as part of your dissertation or thesis, reiterate your central problem or research question and give a brief summary of the scholarly context. You can emphasise the timeliness of the topic (“many recent studies have focused on the problem of x”) or highlight a gap in the literature (“while there has been much research on x, few researchers have taken y into consideration”).

Depending on the length of your literature review, you might want to divide the body into subsections. You can use a subheading for each theme, time period, or methodological approach.

As you write, make sure to follow these tips:

  • Summarise and synthesise: give an overview of the main points of each source and combine them into a coherent whole.
  • Analyse and interpret: don’t just paraphrase other researchers – add your own interpretations, discussing the significance of findings in relation to the literature as a whole.
  • Critically evaluate: mention the strengths and weaknesses of your sources.
  • Write in well-structured paragraphs: use transitions and topic sentences to draw connections, comparisons and contrasts.

In the conclusion, you should summarise the key findings you have taken from the literature and emphasise their significance.

If the literature review is part of your dissertation or thesis, reiterate how your research addresses gaps and contributes new knowledge, or discuss how you have drawn on existing theories and methods to build a framework for your research. This can lead directly into your methodology section.

A literature review is a survey of scholarly sources (such as books, journal articles, and theses) related to a specific topic or research question .

It is often written as part of a dissertation , thesis, research paper , or proposal .

There are several reasons to conduct a literature review at the beginning of a research project:

  • To familiarise yourself with the current state of knowledge on your topic
  • To ensure that you’re not just repeating what others have already done
  • To identify gaps in knowledge and unresolved problems that your research can address
  • To develop your theoretical framework and methodology
  • To provide an overview of the key findings and debates on the topic

Writing the literature review shows your reader how your work relates to existing research and what new insights it will contribute.

The literature review usually comes near the beginning of your  dissertation . After the introduction , it grounds your research in a scholarly field and leads directly to your theoretical framework or methodology .

Cite this Scribbr article

If you want to cite this source, you can copy and paste the citation or click the ‘Cite this Scribbr article’ button to automatically add the citation to our free Reference Generator.

McCombes, S. (2022, June 07). What is a Literature Review? | Guide, Template, & Examples. Scribbr. Retrieved 1 April 2024, from https://www.scribbr.co.uk/thesis-dissertation/literature-review/

Is this article helpful?

Shona McCombes

Shona McCombes

Other students also liked, how to write a dissertation proposal | a step-by-step guide, what is a theoretical framework | a step-by-step guide, what is a research methodology | steps & tips.

  • USC Libraries
  • Research Guides

Organizing Your Social Sciences Research Paper

  • 5. The Literature Review
  • Purpose of Guide
  • Design Flaws to Avoid
  • Independent and Dependent Variables
  • Glossary of Research Terms
  • Reading Research Effectively
  • Narrowing a Topic Idea
  • Broadening a Topic Idea
  • Extending the Timeliness of a Topic Idea
  • Academic Writing Style
  • Choosing a Title
  • Making an Outline
  • Paragraph Development
  • Research Process Video Series
  • Executive Summary
  • The C.A.R.S. Model
  • Background Information
  • The Research Problem/Question
  • Theoretical Framework
  • Citation Tracking
  • Content Alert Services
  • Evaluating Sources
  • Primary Sources
  • Secondary Sources
  • Tiertiary Sources
  • Scholarly vs. Popular Publications
  • Qualitative Methods
  • Quantitative Methods
  • Insiderness
  • Using Non-Textual Elements
  • Limitations of the Study
  • Common Grammar Mistakes
  • Writing Concisely
  • Avoiding Plagiarism
  • Footnotes or Endnotes?
  • Further Readings
  • Generative AI and Writing
  • USC Libraries Tutorials and Other Guides
  • Bibliography

A literature review surveys prior research published in books, scholarly articles, and any other sources relevant to a particular issue, area of research, or theory, and by so doing, provides a description, summary, and critical evaluation of these works in relation to the research problem being investigated. Literature reviews are designed to provide an overview of sources you have used in researching a particular topic and to demonstrate to your readers how your research fits within existing scholarship about the topic.

Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . Fourth edition. Thousand Oaks, CA: SAGE, 2014.

Importance of a Good Literature Review

A literature review may consist of simply a summary of key sources, but in the social sciences, a literature review usually has an organizational pattern and combines both summary and synthesis, often within specific conceptual categories . A summary is a recap of the important information of the source, but a synthesis is a re-organization, or a reshuffling, of that information in a way that informs how you are planning to investigate a research problem. The analytical features of a literature review might:

  • Give a new interpretation of old material or combine new with old interpretations,
  • Trace the intellectual progression of the field, including major debates,
  • Depending on the situation, evaluate the sources and advise the reader on the most pertinent or relevant research, or
  • Usually in the conclusion of a literature review, identify where gaps exist in how a problem has been researched to date.

Given this, the purpose of a literature review is to:

  • Place each work in the context of its contribution to understanding the research problem being studied.
  • Describe the relationship of each work to the others under consideration.
  • Identify new ways to interpret prior research.
  • Reveal any gaps that exist in the literature.
  • Resolve conflicts amongst seemingly contradictory previous studies.
  • Identify areas of prior scholarship to prevent duplication of effort.
  • Point the way in fulfilling a need for additional research.
  • Locate your own research within the context of existing literature [very important].

Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper. 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Jesson, Jill. Doing Your Literature Review: Traditional and Systematic Techniques . Los Angeles, CA: SAGE, 2011; Knopf, Jeffrey W. "Doing a Literature Review." PS: Political Science and Politics 39 (January 2006): 127-132; Ridley, Diana. The Literature Review: A Step-by-Step Guide for Students . 2nd ed. Los Angeles, CA: SAGE, 2012.

Types of Literature Reviews

It is important to think of knowledge in a given field as consisting of three layers. First, there are the primary studies that researchers conduct and publish. Second are the reviews of those studies that summarize and offer new interpretations built from and often extending beyond the primary studies. Third, there are the perceptions, conclusions, opinion, and interpretations that are shared informally among scholars that become part of the body of epistemological traditions within the field.

In composing a literature review, it is important to note that it is often this third layer of knowledge that is cited as "true" even though it often has only a loose relationship to the primary studies and secondary literature reviews. Given this, while literature reviews are designed to provide an overview and synthesis of pertinent sources you have explored, there are a number of approaches you could adopt depending upon the type of analysis underpinning your study.

Argumentative Review This form examines literature selectively in order to support or refute an argument, deeply embedded assumption, or philosophical problem already established in the literature. The purpose is to develop a body of literature that establishes a contrarian viewpoint. Given the value-laden nature of some social science research [e.g., educational reform; immigration control], argumentative approaches to analyzing the literature can be a legitimate and important form of discourse. However, note that they can also introduce problems of bias when they are used to make summary claims of the sort found in systematic reviews [see below].

Integrative Review Considered a form of research that reviews, critiques, and synthesizes representative literature on a topic in an integrated way such that new frameworks and perspectives on the topic are generated. The body of literature includes all studies that address related or identical hypotheses or research problems. A well-done integrative review meets the same standards as primary research in regard to clarity, rigor, and replication. This is the most common form of review in the social sciences.

Historical Review Few things rest in isolation from historical precedent. Historical literature reviews focus on examining research throughout a period of time, often starting with the first time an issue, concept, theory, phenomena emerged in the literature, then tracing its evolution within the scholarship of a discipline. The purpose is to place research in a historical context to show familiarity with state-of-the-art developments and to identify the likely directions for future research.

Methodological Review A review does not always focus on what someone said [findings], but how they came about saying what they say [method of analysis]. Reviewing methods of analysis provides a framework of understanding at different levels [i.e. those of theory, substantive fields, research approaches, and data collection and analysis techniques], how researchers draw upon a wide variety of knowledge ranging from the conceptual level to practical documents for use in fieldwork in the areas of ontological and epistemological consideration, quantitative and qualitative integration, sampling, interviewing, data collection, and data analysis. This approach helps highlight ethical issues which you should be aware of and consider as you go through your own study.

Systematic Review This form consists of an overview of existing evidence pertinent to a clearly formulated research question, which uses pre-specified and standardized methods to identify and critically appraise relevant research, and to collect, report, and analyze data from the studies that are included in the review. The goal is to deliberately document, critically evaluate, and summarize scientifically all of the research about a clearly defined research problem . Typically it focuses on a very specific empirical question, often posed in a cause-and-effect form, such as "To what extent does A contribute to B?" This type of literature review is primarily applied to examining prior research studies in clinical medicine and allied health fields, but it is increasingly being used in the social sciences.

Theoretical Review The purpose of this form is to examine the corpus of theory that has accumulated in regard to an issue, concept, theory, phenomena. The theoretical literature review helps to establish what theories already exist, the relationships between them, to what degree the existing theories have been investigated, and to develop new hypotheses to be tested. Often this form is used to help establish a lack of appropriate theories or reveal that current theories are inadequate for explaining new or emerging research problems. The unit of analysis can focus on a theoretical concept or a whole theory or framework.

NOTE : Most often the literature review will incorporate some combination of types. For example, a review that examines literature supporting or refuting an argument, assumption, or philosophical problem related to the research problem will also need to include writing supported by sources that establish the history of these arguments in the literature.

Baumeister, Roy F. and Mark R. Leary. "Writing Narrative Literature Reviews."  Review of General Psychology 1 (September 1997): 311-320; Mark R. Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Kennedy, Mary M. "Defining a Literature." Educational Researcher 36 (April 2007): 139-147; Petticrew, Mark and Helen Roberts. Systematic Reviews in the Social Sciences: A Practical Guide . Malden, MA: Blackwell Publishers, 2006; Torracro, Richard. "Writing Integrative Literature Reviews: Guidelines and Examples." Human Resource Development Review 4 (September 2005): 356-367; Rocco, Tonette S. and Maria S. Plakhotnik. "Literature Reviews, Conceptual Frameworks, and Theoretical Frameworks: Terms, Functions, and Distinctions." Human Ressource Development Review 8 (March 2008): 120-130; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016.

Structure and Writing Style

I.  Thinking About Your Literature Review

The structure of a literature review should include the following in support of understanding the research problem :

  • An overview of the subject, issue, or theory under consideration, along with the objectives of the literature review,
  • Division of works under review into themes or categories [e.g. works that support a particular position, those against, and those offering alternative approaches entirely],
  • An explanation of how each work is similar to and how it varies from the others,
  • Conclusions as to which pieces are best considered in their argument, are most convincing of their opinions, and make the greatest contribution to the understanding and development of their area of research.

The critical evaluation of each work should consider :

  • Provenance -- what are the author's credentials? Are the author's arguments supported by evidence [e.g. primary historical material, case studies, narratives, statistics, recent scientific findings]?
  • Methodology -- were the techniques used to identify, gather, and analyze the data appropriate to addressing the research problem? Was the sample size appropriate? Were the results effectively interpreted and reported?
  • Objectivity -- is the author's perspective even-handed or prejudicial? Is contrary data considered or is certain pertinent information ignored to prove the author's point?
  • Persuasiveness -- which of the author's theses are most convincing or least convincing?
  • Validity -- are the author's arguments and conclusions convincing? Does the work ultimately contribute in any significant way to an understanding of the subject?

II.  Development of the Literature Review

Four Basic Stages of Writing 1.  Problem formulation -- which topic or field is being examined and what are its component issues? 2.  Literature search -- finding materials relevant to the subject being explored. 3.  Data evaluation -- determining which literature makes a significant contribution to the understanding of the topic. 4.  Analysis and interpretation -- discussing the findings and conclusions of pertinent literature.

Consider the following issues before writing the literature review: Clarify If your assignment is not specific about what form your literature review should take, seek clarification from your professor by asking these questions: 1.  Roughly how many sources would be appropriate to include? 2.  What types of sources should I review (books, journal articles, websites; scholarly versus popular sources)? 3.  Should I summarize, synthesize, or critique sources by discussing a common theme or issue? 4.  Should I evaluate the sources in any way beyond evaluating how they relate to understanding the research problem? 5.  Should I provide subheadings and other background information, such as definitions and/or a history? Find Models Use the exercise of reviewing the literature to examine how authors in your discipline or area of interest have composed their literature review sections. Read them to get a sense of the types of themes you might want to look for in your own research or to identify ways to organize your final review. The bibliography or reference section of sources you've already read, such as required readings in the course syllabus, are also excellent entry points into your own research. Narrow the Topic The narrower your topic, the easier it will be to limit the number of sources you need to read in order to obtain a good survey of relevant resources. Your professor will probably not expect you to read everything that's available about the topic, but you'll make the act of reviewing easier if you first limit scope of the research problem. A good strategy is to begin by searching the USC Libraries Catalog for recent books about the topic and review the table of contents for chapters that focuses on specific issues. You can also review the indexes of books to find references to specific issues that can serve as the focus of your research. For example, a book surveying the history of the Israeli-Palestinian conflict may include a chapter on the role Egypt has played in mediating the conflict, or look in the index for the pages where Egypt is mentioned in the text. Consider Whether Your Sources are Current Some disciplines require that you use information that is as current as possible. This is particularly true in disciplines in medicine and the sciences where research conducted becomes obsolete very quickly as new discoveries are made. However, when writing a review in the social sciences, a survey of the history of the literature may be required. In other words, a complete understanding the research problem requires you to deliberately examine how knowledge and perspectives have changed over time. Sort through other current bibliographies or literature reviews in the field to get a sense of what your discipline expects. You can also use this method to explore what is considered by scholars to be a "hot topic" and what is not.

III.  Ways to Organize Your Literature Review

Chronology of Events If your review follows the chronological method, you could write about the materials according to when they were published. This approach should only be followed if a clear path of research building on previous research can be identified and that these trends follow a clear chronological order of development. For example, a literature review that focuses on continuing research about the emergence of German economic power after the fall of the Soviet Union. By Publication Order your sources by publication chronology, then, only if the order demonstrates a more important trend. For instance, you could order a review of literature on environmental studies of brown fields if the progression revealed, for example, a change in the soil collection practices of the researchers who wrote and/or conducted the studies. Thematic [“conceptual categories”] A thematic literature review is the most common approach to summarizing prior research in the social and behavioral sciences. Thematic reviews are organized around a topic or issue, rather than the progression of time, although the progression of time may still be incorporated into a thematic review. For example, a review of the Internet’s impact on American presidential politics could focus on the development of online political satire. While the study focuses on one topic, the Internet’s impact on American presidential politics, it would still be organized chronologically reflecting technological developments in media. The difference in this example between a "chronological" and a "thematic" approach is what is emphasized the most: themes related to the role of the Internet in presidential politics. Note that more authentic thematic reviews tend to break away from chronological order. A review organized in this manner would shift between time periods within each section according to the point being made. Methodological A methodological approach focuses on the methods utilized by the researcher. For the Internet in American presidential politics project, one methodological approach would be to look at cultural differences between the portrayal of American presidents on American, British, and French websites. Or the review might focus on the fundraising impact of the Internet on a particular political party. A methodological scope will influence either the types of documents in the review or the way in which these documents are discussed.

Other Sections of Your Literature Review Once you've decided on the organizational method for your literature review, the sections you need to include in the paper should be easy to figure out because they arise from your organizational strategy. In other words, a chronological review would have subsections for each vital time period; a thematic review would have subtopics based upon factors that relate to the theme or issue. However, sometimes you may need to add additional sections that are necessary for your study, but do not fit in the organizational strategy of the body. What other sections you include in the body is up to you. However, only include what is necessary for the reader to locate your study within the larger scholarship about the research problem.

Here are examples of other sections, usually in the form of a single paragraph, you may need to include depending on the type of review you write:

  • Current Situation : Information necessary to understand the current topic or focus of the literature review.
  • Sources Used : Describes the methods and resources [e.g., databases] you used to identify the literature you reviewed.
  • History : The chronological progression of the field, the research literature, or an idea that is necessary to understand the literature review, if the body of the literature review is not already a chronology.
  • Selection Methods : Criteria you used to select (and perhaps exclude) sources in your literature review. For instance, you might explain that your review includes only peer-reviewed [i.e., scholarly] sources.
  • Standards : Description of the way in which you present your information.
  • Questions for Further Research : What questions about the field has the review sparked? How will you further your research as a result of the review?

IV.  Writing Your Literature Review

Once you've settled on how to organize your literature review, you're ready to write each section. When writing your review, keep in mind these issues.

Use Evidence A literature review section is, in this sense, just like any other academic research paper. Your interpretation of the available sources must be backed up with evidence [citations] that demonstrates that what you are saying is valid. Be Selective Select only the most important points in each source to highlight in the review. The type of information you choose to mention should relate directly to the research problem, whether it is thematic, methodological, or chronological. Related items that provide additional information, but that are not key to understanding the research problem, can be included in a list of further readings . Use Quotes Sparingly Some short quotes are appropriate if you want to emphasize a point, or if what an author stated cannot be easily paraphrased. Sometimes you may need to quote certain terminology that was coined by the author, is not common knowledge, or taken directly from the study. Do not use extensive quotes as a substitute for using your own words in reviewing the literature. Summarize and Synthesize Remember to summarize and synthesize your sources within each thematic paragraph as well as throughout the review. Recapitulate important features of a research study, but then synthesize it by rephrasing the study's significance and relating it to your own work and the work of others. Keep Your Own Voice While the literature review presents others' ideas, your voice [the writer's] should remain front and center. For example, weave references to other sources into what you are writing but maintain your own voice by starting and ending the paragraph with your own ideas and wording. Use Caution When Paraphrasing When paraphrasing a source that is not your own, be sure to represent the author's information or opinions accurately and in your own words. Even when paraphrasing an author’s work, you still must provide a citation to that work.

V.  Common Mistakes to Avoid

These are the most common mistakes made in reviewing social science research literature.

  • Sources in your literature review do not clearly relate to the research problem;
  • You do not take sufficient time to define and identify the most relevant sources to use in the literature review related to the research problem;
  • Relies exclusively on secondary analytical sources rather than including relevant primary research studies or data;
  • Uncritically accepts another researcher's findings and interpretations as valid, rather than examining critically all aspects of the research design and analysis;
  • Does not describe the search procedures that were used in identifying the literature to review;
  • Reports isolated statistical results rather than synthesizing them in chi-squared or meta-analytic methods; and,
  • Only includes research that validates assumptions and does not consider contrary findings and alternative interpretations found in the literature.

Cook, Kathleen E. and Elise Murowchick. “Do Literature Review Skills Transfer from One Course to Another?” Psychology Learning and Teaching 13 (March 2014): 3-11; Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Jesson, Jill. Doing Your Literature Review: Traditional and Systematic Techniques . London: SAGE, 2011; Literature Review Handout. Online Writing Center. Liberty University; Literature Reviews. The Writing Center. University of North Carolina; Onwuegbuzie, Anthony J. and Rebecca Frels. Seven Steps to a Comprehensive Literature Review: A Multimodal and Cultural Approach . Los Angeles, CA: SAGE, 2016; Ridley, Diana. The Literature Review: A Step-by-Step Guide for Students . 2nd ed. Los Angeles, CA: SAGE, 2012; Randolph, Justus J. “A Guide to Writing the Dissertation Literature Review." Practical Assessment, Research, and Evaluation. vol. 14, June 2009; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016; Taylor, Dena. The Literature Review: A Few Tips On Conducting It. University College Writing Centre. University of Toronto; Writing a Literature Review. Academic Skills Centre. University of Canberra.

Writing Tip

Break Out of Your Disciplinary Box!

Thinking interdisciplinarily about a research problem can be a rewarding exercise in applying new ideas, theories, or concepts to an old problem. For example, what might cultural anthropologists say about the continuing conflict in the Middle East? In what ways might geographers view the need for better distribution of social service agencies in large cities than how social workers might study the issue? You don’t want to substitute a thorough review of core research literature in your discipline for studies conducted in other fields of study. However, particularly in the social sciences, thinking about research problems from multiple vectors is a key strategy for finding new solutions to a problem or gaining a new perspective. Consult with a librarian about identifying research databases in other disciplines; almost every field of study has at least one comprehensive database devoted to indexing its research literature.

Frodeman, Robert. The Oxford Handbook of Interdisciplinarity . New York: Oxford University Press, 2010.

Another Writing Tip

Don't Just Review for Content!

While conducting a review of the literature, maximize the time you devote to writing this part of your paper by thinking broadly about what you should be looking for and evaluating. Review not just what scholars are saying, but how are they saying it. Some questions to ask:

  • How are they organizing their ideas?
  • What methods have they used to study the problem?
  • What theories have been used to explain, predict, or understand their research problem?
  • What sources have they cited to support their conclusions?
  • How have they used non-textual elements [e.g., charts, graphs, figures, etc.] to illustrate key points?

When you begin to write your literature review section, you'll be glad you dug deeper into how the research was designed and constructed because it establishes a means for developing more substantial analysis and interpretation of the research problem.

Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1 998.

Yet Another Writing Tip

When Do I Know I Can Stop Looking and Move On?

Here are several strategies you can utilize to assess whether you've thoroughly reviewed the literature:

  • Look for repeating patterns in the research findings . If the same thing is being said, just by different people, then this likely demonstrates that the research problem has hit a conceptual dead end. At this point consider: Does your study extend current research?  Does it forge a new path? Or, does is merely add more of the same thing being said?
  • Look at sources the authors cite to in their work . If you begin to see the same researchers cited again and again, then this is often an indication that no new ideas have been generated to address the research problem.
  • Search Google Scholar to identify who has subsequently cited leading scholars already identified in your literature review [see next sub-tab]. This is called citation tracking and there are a number of sources that can help you identify who has cited whom, particularly scholars from outside of your discipline. Here again, if the same authors are being cited again and again, this may indicate no new literature has been written on the topic.

Onwuegbuzie, Anthony J. and Rebecca Frels. Seven Steps to a Comprehensive Literature Review: A Multimodal and Cultural Approach . Los Angeles, CA: Sage, 2016; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016.

  • << Previous: Theoretical Framework
  • Next: Citation Tracking >>
  • Last Updated: Apr 1, 2024 9:56 AM
  • URL: https://libguides.usc.edu/writingguide

Harvey Cushing/John Hay Whitney Medical Library

  • Collections
  • Research Help

YSN Doctoral Programs: Steps in Conducting a Literature Review

  • Biomedical Databases
  • Global (Public Health) Databases
  • Soc. Sci., History, and Law Databases
  • Grey Literature
  • Trials Registers
  • Data and Statistics
  • Public Policy
  • Google Tips
  • Recommended Books
  • Steps in Conducting a Literature Review

What is a literature review?

A literature review is an integrated analysis -- not just a summary-- of scholarly writings and other relevant evidence related directly to your research question.  That is, it represents a synthesis of the evidence that provides background information on your topic and shows a association between the evidence and your research question.

A literature review may be a stand alone work or the introduction to a larger research paper, depending on the assignment.  Rely heavily on the guidelines your instructor has given you.

Why is it important?

A literature review is important because it:

  • Explains the background of research on a topic.
  • Demonstrates why a topic is significant to a subject area.
  • Discovers relationships between research studies/ideas.
  • Identifies major themes, concepts, and researchers on a topic.
  • Identifies critical gaps and points of disagreement.
  • Discusses further research questions that logically come out of the previous studies.

APA7 Style resources

Cover Art

APA Style Blog - for those harder to find answers

1. Choose a topic. Define your research question.

Your literature review should be guided by your central research question.  The literature represents background and research developments related to a specific research question, interpreted and analyzed by you in a synthesized way.

  • Make sure your research question is not too broad or too narrow.  Is it manageable?
  • Begin writing down terms that are related to your question. These will be useful for searches later.
  • If you have the opportunity, discuss your topic with your professor and your class mates.

2. Decide on the scope of your review

How many studies do you need to look at? How comprehensive should it be? How many years should it cover? 

  • This may depend on your assignment.  How many sources does the assignment require?

3. Select the databases you will use to conduct your searches.

Make a list of the databases you will search. 

Where to find databases:

  • use the tabs on this guide
  • Find other databases in the Nursing Information Resources web page
  • More on the Medical Library web page
  • ... and more on the Yale University Library web page

4. Conduct your searches to find the evidence. Keep track of your searches.

  • Use the key words in your question, as well as synonyms for those words, as terms in your search. Use the database tutorials for help.
  • Save the searches in the databases. This saves time when you want to redo, or modify, the searches. It is also helpful to use as a guide is the searches are not finding any useful results.
  • Review the abstracts of research studies carefully. This will save you time.
  • Use the bibliographies and references of research studies you find to locate others.
  • Check with your professor, or a subject expert in the field, if you are missing any key works in the field.
  • Ask your librarian for help at any time.
  • Use a citation manager, such as EndNote as the repository for your citations. See the EndNote tutorials for help.

Review the literature

Some questions to help you analyze the research:

  • What was the research question of the study you are reviewing? What were the authors trying to discover?
  • Was the research funded by a source that could influence the findings?
  • What were the research methodologies? Analyze its literature review, the samples and variables used, the results, and the conclusions.
  • Does the research seem to be complete? Could it have been conducted more soundly? What further questions does it raise?
  • If there are conflicting studies, why do you think that is?
  • How are the authors viewed in the field? Has this study been cited? If so, how has it been analyzed?

Tips: 

  • Review the abstracts carefully.  
  • Keep careful notes so that you may track your thought processes during the research process.
  • Create a matrix of the studies for easy analysis, and synthesis, across all of the studies.
  • << Previous: Recommended Books
  • Last Updated: Jan 4, 2024 10:52 AM
  • URL: https://guides.library.yale.edu/YSNDoctoral
  • Franklin University |
  • Help & Support |
  • Locations & Maps |

Franklin University logo

  • | Research Guides

To access Safari eBooks,

  • Select not listed in the Select Your Institution drop down menu.
  • Enter your Franklin email address and click Go
  • click "Already a user? Click here" link
  • Enter your Franklin email and the password you used to create your Safari account.

Continue Close

Literature Review

What is a literature review.

  • Literature Reviews: An Overview
  • Literature Review Ebooks
  • Structure and Development
  • Mistakes to Avoid & Additional Help

A Literature Review is Not:

  • just a summary of sources
  • a grouping of broad, unrelated sources
  • a compilation of  everything  that has been written on a particular topic
  • literature criticism (think English) or a book review

So, what is it?

A literature review is an integrated analysis - not just a summary - of scholarly writings that are related directly to your research question. That is, it represents the literature that provides background information on your topic and shows a correspondence between those writings and your research question. In contrast to an academic research paper, t he focus of a literature review is to summarize and synthesize the arguments and ideas of others without adding new contributions.

According to the APA 7th Manual, literature review articles “provide narrative summaries and evaluations of the findings or theories within a literature base” and “capture trends in the literature” (2020, p. 8).

Why is it important?

A literature review is important because it:

  • Explains the background of research on a topic
  • Demonstrates why a topic is significant to a subject area
  • Discovers relationships between research studies/ideas
  • Identifies major themes, concepts, and researchers on a topic
  • Identifies critical gaps, contradictions, inconsistencies, and points of disagreement
  • Points the way in fulfilling a need for additional research
  • Discusses further research questions that logically come out of the previous studies

The analytical features of a literature review might:

  • Give a new interpretation of old material or combine new with old interpretations
  • Trace the intellectual progression of the field, including major debates
  • Depending on the situation, evaluate the sources and advise the reader on the most pertinent or relevant
  • Identify where gaps exist in how a problem has been researched to date
  • Sample Literature Review (APA Format) This sample paper was provided by the APA Blog (https://apastyle.apa.org/) as an example student literature review. However, APA does not set formal requirements for the nature or contents of an APA Style student papers. Students should follow the guidelines and requirements of their instructor, when writing papers. For instance, an abstract and keywords are not required for APA Style student papers, although an instructor may request them in student papers that are longer or more complex. Talk to your instructor and view your assignment directions for more information

Yellow, green, and orange cubes with white ltext and a green bottom banner

  • Next: Structure and Development >>
  • Last Updated: Oct 3, 2023 2:44 PM
  • URL: https://guides.franklin.edu/LITREVIEW

University Libraries      University of Nevada, Reno

  • Skill Guides
  • Subject Guides

Systematic, Scoping, and Other Literature Reviews: Overview

  • Project Planning

What Is a Systematic Review?

Regular literature reviews are simply summaries of the literature on a particular topic. A systematic review, however, is a comprehensive literature review conducted to answer a specific research question. Authors of a systematic review aim to find, code, appraise, and synthesize all of the previous research on their question in an unbiased and well-documented manner. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) outline the minimum amount of information that needs to be reported at the conclusion of a systematic review project. 

Other types of what are known as "evidence syntheses," such as scoping, rapid, and integrative reviews, have varying methodologies. While systematic reviews originated with and continue to be a popular publication type in medicine and other health sciences fields, more and more researchers in other disciplines are choosing to conduct evidence syntheses. 

This guide will walk you through the major steps of a systematic review and point you to key resources including Covidence, a systematic review project management tool. For help with systematic reviews and other major literature review projects, please send us an email at  [email protected] .

Getting Help with Reviews

Organization such as the Institute of Medicine recommend that you consult a librarian when conducting a systematic review. Librarians at the University of Nevada, Reno can help you:

  • Understand best practices for conducting systematic reviews and other evidence syntheses in your discipline
  • Choose and formulate a research question
  • Decide which review type (e.g., systematic, scoping, rapid, etc.) is the best fit for your project
  • Determine what to include and where to register a systematic review protocol
  • Select search terms and develop a search strategy
  • Identify databases and platforms to search
  • Find the full text of articles and other sources
  • Become familiar with free citation management (e.g., EndNote, Zotero)
  • Get access to you and help using Covidence, a systematic review project management tool

Doing a Systematic Review

  • Plan - This is the project planning stage. You and your team will need to develop a good research question, determine the type of review you will conduct (systematic, scoping, rapid, etc.), and establish the inclusion and exclusion criteria (e.g., you're only going to look at studies that use a certain methodology). All of this information needs to be included in your protocol. You'll also need to ensure that the project is viable - has someone already done a systematic review on this topic? Do some searches and check the various protocol registries to find out. 
  • Identify - Next, a comprehensive search of the literature is undertaken to ensure all studies that meet the predetermined criteria are identified. Each research question is different, so the number and types of databases you'll search - as well as other online publication venues - will vary. Some standards and guidelines specify that certain databases (e.g., MEDLINE, EMBASE) should be searched regardless. Your subject librarian can help you select appropriate databases to search and develop search strings for each of those databases.  
  • Evaluate - In this step, retrieved articles are screened and sorted using the predetermined inclusion and exclusion criteria. The risk of bias for each included study is also assessed around this time. It's best if you import search results into a citation management tool (see below) to clean up the citations and remove any duplicates. You can then use a tool like Rayyan (see below) to screen the results. You should begin by screening titles and abstracts only, and then you'll examine the full text of any remaining articles. Each study should be reviewed by a minimum of two people on the project team. 
  • Collect - Each included study is coded and the quantitative or qualitative data contained in these studies is then synthesized. You'll have to either find or develop a coding strategy or form that meets your needs. 
  • Explain - The synthesized results are articulated and contextualized. What do the results mean? How have they answered your research question?
  • Summarize - The final report provides a complete description of the methods and results in a clear, transparent fashion. 

Adapted from

Types of reviews, systematic review.

These types of studies employ a systematic method to analyze and synthesize the results of numerous studies. "Systematic" in this case means following a strict set of steps - as outlined by entities like PRISMA and the Institute of Medicine - so as to make the review more reproducible and less biased. Consistent, thorough documentation is also key. Reviews of this type are not meant to be conducted by an individual but rather a (small) team of researchers. Systematic reviews are widely used in the health sciences, often to find a generalized conclusion from multiple evidence-based studies. 

Meta-Analysis

A systematic method that uses statistics to analyze the data from numerous studies. The researchers combine the data from studies with similar data types and analyze them as a single, expanded dataset. Meta-analyses are a type of systematic review.

Scoping Review

A scoping review employs the systematic review methodology to explore a broader topic or question rather than a specific and answerable one, as is generally the case with a systematic review. Authors of these types of reviews seek to collect and categorize the existing literature so as to identify any gaps.

Rapid Review

Rapid reviews are systematic reviews conducted under a time constraint. Researchers make use of workarounds to complete the review quickly (e.g., only looking at English-language publications), which can lead to a less thorough and more biased review. 

Narrative Review

A traditional literature review that summarizes and synthesizes the findings of numerous original research articles. The purpose and scope of narrative literature reviews vary widely and do not follow a set protocol. Most literature reviews are narrative reviews. 

Umbrella Review

Umbrella reviews are, essentially, systematic reviews of systematic reviews. These compile evidence from multiple review studies into one usable document. 

Grant, Maria J., and Andrew Booth. “A Typology of Reviews: An Analysis of 14 Review Types and Associated Methodologies.” Health Information & Libraries Journal , vol. 26, no. 2, 2009, pp. 91-108. doi: 10.1111/j.1471-1842.2009.00848.x .

  • Next: Project Planning >>

Banner

CC0006 Basics of Report Writing

Structure of a report (case study, literature review or survey).

  • Structure of report (Site visit)
  • Citing Sources
  • Tips and Resources

The information in the report has to be organised in the best possible way for the reader to understand the issue being investigated, analysis of the findings and recommendations or implications that relate directly to the findings. Given below are the main sections of a standard report. Click on each section heading to learn more about it.

  • Tells the reader what the report is about
  • Informative, short, catchy

Example - Sea level rise in Singapore : Causes, Impact and Solution

The title page must also include group name, group members and their matriculation numbers.

Content s Page

  • Has headings and subheadings that show the reader where the various sections of the report are located
  • Written on a separate page
  • Includes the page numbers of each section
  • Briefly summarises the report, the process of research and final conclusions
  • Provides a quick overview of the report and describes the main highlights
  • Short, usually not more than 150 words in length
  • Mention briefly why you choose this project, what are the implications and what kind of problems it will solve

Usually, the abstract is written last, ie. after writing the other sections and you know the key points to draw out from these sections. Abstracts allow readers who may be interested in the report to decide whether it is relevant to their purposes.

Introduction

  • Discusses the background and sets the context
  • Introduces the topic, significance of the problem, and the purpose of research
  • Gives the scope ie shows what it includes and excludes

In the introduction, write about what motivates your project, what makes it interesting, what questions do you aim to answer by doing your project. The introduction lays the foundation for understanding the research problem and should be written in a way that leads the reader from the general subject area of the topic to the particular topic of research.

Literature Review

  • Helps to gain an understanding of the existing research in that topic
  • To develop on your own ideas and build your ideas based on the existing knowledge
  • Prevents duplication of the research done by others

Search the existing literature for information. Identify the data pertinent to your topic. Review, extract the relevant information for eg how the study was conducted and the findings. Summarise the information. Write what is already known about the topic and what do the sources that you have reviewed say. Identify conflicts in previous studies, open questions, or gaps that may exist. If you are doing

  • Case study - look for background information and if any similar case studies have been done before.
  • Literature review - find out from literature, what is the background to the questions that you are looking into
  • Site visit - use the literature review to read up and prepare good questions before hand.
  • Survey - find out if similar surveys have been done before and what did they find?

Keep a record of the source details of any information you want to use in your report so that you can reference them accurately.

Methodology

Methodology is the approach that you take to gather data and arrive at the recommendation(s). Choose a method that is appropriate for the research topic and explain it in detail.

In this section, address the following: a) How the data was collected b) How it was analysed and c) Explain or justify why a particular method was chosen.

Usually, the methodology is written in the past tense and can be in the passive voice. Some examples of the different methods that you can use to gather data are given below. The data collected provides evidence to build your arguments. Collect data, integrate the findings and perspectives from different studies and add your own analysis of its feasibility.

  • Explore the literature/news/internet sources to know the topic in depth
  • Give a description of how you selected the literature for your project
  • Compare the studies, and highlight the findings, gaps or limitations.
  • An in-depth, detailed examination of specific cases within a real-world context.
  • Enables you to examine the data within a specific context.
  • Examine a well defined case to identify the essential factors, process and relationship.
  • Write the case description, the context and the process involved.
  • Make sense of the evidence in the case(s) to answer the research question
  • Gather data from a predefined group of respondents by asking relevant questions
  • Can be conducted in person or online
  • Why you chose this method (questionnaires, focus group, experimental procedure, etc)
  • How you carried out the survey. Include techniques and any equipment you used
  • If there were participants in your research, who were they? How did you select them and how may were there?
  • How the survey questions address the different aspects of the research question
  • Analyse the technology / policy approaches by visiting the required sites
  • Make a detailed report on its features and your understanding of it

Results and Analysis

  • Present the results of the study. You may consider visualising the results in tables and graphs, graphics etc.
  • Analyse the results to obtain answer to the research question.
  • Provide an analysis of the technical and financial feasibility, social acceptability etc

Discussion, Limitation(s) and Implication(s)

  • Discuss your interpretations of the analysis and the significance of your findings
  • Explain any new understanding or insights that emerged as a result of your research
  • Consider the different perspectives (social, economic and environmental)in the discussion
  • Explain the limitation(s)
  • Explain how could what you found be used to make a difference for sustainability

Conclusion and Recommendations

  • Summarise the significance and outcome of the study highlighting the key points.
  • Come up with alternatives and propose specific actions based on the alternatives
  • Describe the result or improvement it would achieve
  • Explain how it will be implemented

Recommendations should have an innovative approach and should be feasible. It should make a significant difference in solving the issue under discussion.

  • List the sources you have referred to in your writing
  • Use the recommended citation style consistently in your report

Appendix (if necessary/any)

Include any material relating to the report and research that does not fit in the body of the report, in the appendix. For example, you may include survey questionnaire and results in the appendix.

  • << Previous: Structure of a report
  • Next: Structure of report (Site visit) >>
  • Last Updated: Jan 12, 2024 11:52 AM
  • URL: https://libguides.ntu.edu.sg/report-writing

You are expected to comply with University policies and guidelines namely, Appropriate Use of Information Resources Policy , IT Usage Policy and Social Media Policy . Users will be personally liable for any infringement of Copyright and Licensing laws. Unless otherwise stated, all guide content is licensed by CC BY-NC 4.0 .

Jump to navigation

Home

Cochrane Training

Chapter 3: defining the criteria for including studies and how they will be grouped for the synthesis.

Joanne E McKenzie, Sue E Brennan, Rebecca E Ryan, Hilary J Thomson, Renea V Johnston, James Thomas

Key Points:

  • The scope of a review is defined by the types of population (participants), types of interventions (and comparisons), and the types of outcomes that are of interest. The acronym PICO (population, interventions, comparators and outcomes) helps to serve as a reminder of these.
  • The population, intervention and comparison components of the question, with the additional specification of types of study that will be included, form the basis of the pre-specified eligibility criteria for the review. It is rare to use outcomes as eligibility criteria: studies should be included irrespective of whether they report outcome data, but may legitimately be excluded if they do not measure outcomes of interest, or if they explicitly aim to prevent a particular outcome.
  • Cochrane Reviews should include all outcomes that are likely to be meaningful and not include trivial outcomes. Critical and important outcomes should be limited in number and include adverse as well as beneficial outcomes.
  • Review authors should plan at the protocol stage how the different populations, interventions, outcomes and study designs within the scope of the review will be grouped for analysis.

Cite this chapter as: McKenzie JE, Brennan SE, Ryan RE, Thomson HJ, Johnston RV, Thomas J. Chapter 3: Defining the criteria for including studies and how they will be grouped for the synthesis. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.4 (updated August 2023). Cochrane, 2023. Available from www.training.cochrane.org/handbook .

3.1 Introduction

One of the features that distinguishes a systematic review from a narrative review is that systematic review authors should pre-specify criteria for including and excluding studies in the review (eligibility criteria, see MECIR Box 3.2.a ).

When developing the protocol, one of the first steps is to determine the elements of the review question (including the population, intervention(s), comparator(s) and outcomes, or PICO elements) and how the intervention, in the specified population, produces the expected outcomes (see Chapter 2, Section 2.5.1 and Chapter 17, Section 17.2.1 ). Eligibility criteria are based on the PICO elements of the review question plus a specification of the types of studies that have addressed these questions. The population, interventions and comparators in the review question usually translate directly into eligibility criteria for the review, though this is not always a straightforward process and requires a thoughtful approach, as this chapter shows. Outcomes usually are not part of the criteria for including studies, and a Cochrane Review would typically seek all sufficiently rigorous studies (most commonly randomized trials) of a particular comparison of interventions in a particular population of participants, irrespective of the outcomes measured or reported. It should be noted that some reviews do legitimately restrict eligibility to specific outcomes. For example, the same intervention may be studied in the same population for different purposes; or a review may specifically address the adverse effects of an intervention used for several conditions (see Chapter 19 ).

Eligibility criteria do not exist in isolation, but should be specified with the synthesis of the studies they describe in mind. This will involve making plans for how to group variants of the PICO elements for synthesis. This chapter describes the processes by which the structure of the synthesis can be mapped out at the beginning of the review, and the interplay between the review question, considerations for the analysis and their operationalization in terms of eligibility criteria. Decisions about which studies to include (and exclude), and how they will be combined in the review’s synthesis, should be documented and justified in the review protocol.

A distinction between three different stages in the review at which the PICO construct might be used is helpful for understanding the decisions that need to be made. In Chapter 2, Section 2.3 , we introduced the ideas of a review PICO (on which eligibility of studies is based), the PICO for each synthesis (defining the question that each specific synthesis aims to answer) and the PICO of the included studies (what was actually investigated in the included studies). In this chapter, we focus on the review PICO and the PICO for each synthesis as a basis for specifying which studies should be included in the review and planning its syntheses. These PICOs should relate clearly and directly to the questions or hypotheses that are posed when the review is formulated (see Chapter 2 ) and will involve specifying the population in question, and a set of comparisons between the intervention groups.

An integral part of the process of setting up the review is to specify which characteristics of the interventions (e.g. individual compounds of a drug), populations (e.g. acute and chronic conditions), outcomes (e.g. different depression measurement scales) and study designs, will be grouped together. Such decisions should be made independent of knowing which studies will be included and the methods of synthesis that will be used (e.g. meta-analysis). There may be a need to modify the comparisons and even add new ones at the review stage in light of the data that are collected. For example, important variations in the intervention may be discovered only after data are collected, or modifying the comparison may facilitate the possibility of synthesis when only one or few studies meet the comparison PICO. Planning for the latter scenario at the protocol stage may lead to less post-hoc decision making ( Chapter 2, Section 2.5.3 ) and, of course, any changes made during the conduct of the review should be recorded and documented in the final report.

3.2 Articulating the review and comparison PICO

3.2.1 defining types of participants: which people and populations.

The criteria for considering types of people included in studies in a review should be sufficiently broad to encompass the likely diversity of studies and the likely scenarios in which the interventions will be used, but sufficiently narrow to ensure that a meaningful answer can be obtained when studies are considered together; they should be specified in advance (see MECIR Box 3.2.a ). As discussed in Chapter 2, Section 2.3.1 , the degree of breadth will vary, depending on the question being asked and the analytical approach to be employed. A range of evidence may inform the choice of population characteristics to examine, including theoretical considerations, evidence from other interventions that have a similar mechanism of action, and in vitro or animal studies. Consideration should be given to whether the population characteristic is at the level of the participant (e.g. age, severity of disease) or the study (e.g. care setting, geographical location), since this has implications for grouping studies and for the method of synthesis ( Chapter 10, Section 10.11.5 ). It is often helpful to consider the types of people that are of interest in three steps.

MECIR Box 3.2.a Relevant expectations for conduct of intervention reviews

First, the diseases or conditions of interest should be defined using explicit criteria for establishing their presence (or absence). Criteria that will force the unnecessary exclusion of studies should be avoided. For example, diagnostic criteria that were developed more recently – which may be viewed as the current gold standard for diagnosing the condition of interest – will not have been used in earlier studies. Expensive or recent diagnostic tests may not be available in many countries or settings, and time-consuming tests may not be practical in routine healthcare settings.

Second, the broad population and setting of interest should be defined . This involves deciding whether a specific population group is within scope, determined by factors such as age, sex, race, educational status or the presence of a particular condition such as angina or shortness of breath. Interest may focus on a particular setting such as a community, hospital, nursing home, chronic care institution, or outpatient setting. Box 3.2.a outlines some factors to consider when developing population criteria.

Whichever criteria are used for defining the population and setting of interest, it is common to encounter studies that only partially overlap with the review’s population. For example, in a review focusing on children, a cut-point of less than 16 years might be desirable, but studies may be identified with participants aged from 12 to 18. Unless the study reports separate data from the eligible section of the population (in which case data from the eligible participants can be included in the review), review authors will need a strategy for dealing with these studies (see MECIR Box 3.2.a ). This will involve balancing concerns about reduced applicability by including participants who do not meet the eligibility criteria, against the loss of data when studies are excluded. Arbitrary rules (such as including a study if more than 80% of the participants are under 16) will not be practical if detailed information is not available from the study. A less stringent rule, such as ‘the majority of participants are under 16’ may be sufficient. Although there is a risk of review authors’ biases affecting post-hoc inclusion decisions (which is why many authors endeavour to pre-specify these rules), this may be outweighed by a common-sense strategy in which eligibility decisions keep faith with the objectives of the review rather than with arbitrary rules. Difficult decisions should be documented in the review, checked with the advisory group (if available, see Chapter 1 ), and sensitivity analyses can assess the impact of these decisions on the review’s findings (see Chapter 10, Section 10.14 and MECIR Box 3.2.b ).

Box 3.2.a Factors to consider when developing criteria for ‘Types of participants’

MECIR Box 3.2.b Relevant expectations for conduct of intervention reviews

Third, there should be consideration of whether there are population characteristics that might be expected to modify the size of the intervention effects (e.g. different severities of heart failure). Identifying subpopulations may be important for implementation of the intervention. If relevant subpopulations are identified, two courses of action are possible: limiting the scope of the review to exclude certain subpopulations; or maintaining the breadth of the review and addressing subpopulations in the analysis.

Restricting the review with respect to specific population characteristics or settings should be based on a sound rationale. It is important that Cochrane Reviews are globally relevant, so the rationale for the exclusion of studies based on population characteristics should be justified. For example, focusing a review of the effectiveness of mammographic screening on women between 40 and 50 years old may be justified based on biological plausibility, previously published systematic reviews and existing controversy. On the other hand, focusing a review on a particular subgroup of people on the basis of their age, sex or ethnicity simply because of personal interests, when there is no underlying biologic or sociological justification for doing so, should be avoided, as these reviews will be less useful to decision makers and readers of the review.

Maintaining the breadth of the review may be best when it is uncertain whether there are important differences in effects among various subgroups of people, since this allows investigation of these differences (see Chapter 10, Section 10.11.5 ). Review authors may combine the results from different subpopulations in the same synthesis, examining whether a given subdivision explains variation (heterogeneity) among the intervention effects. Alternatively, the results may be synthesized in separate comparisons representing different subpopulations. Splitting by subpopulation risks there being too few studies to yield a useful synthesis (see Table 3.2.a and Chapter 2, Section 2.3.2 ). Consideration needs to be given to the subgroup analysis method, particularly for population characteristics measured at the participant level (see Chapter 10 and Chapter 26 , Fisher et al 2017). All subgroup analyses should ideally be planned a priori and stated as a secondary objective in the protocol, and not driven by the availability of data.

In practice, it may be difficult to assign included studies to defined subpopulations because of missing information about the population characteristic, variability in how the population characteristic is measured across studies (e.g. variation in the method used to define the severity of heart failure), or because the study does not wholly fall within (or report the results separately by) the defined subpopulation. The latter issue mainly applies for participant characteristics but can also arise for settings or geographic locations where these vary within studies. Review authors should consider planning for these scenarios (see example reviews Hetrick et al 2012, Safi et al 2017; Table 3.2.b , column 3).

Table 3.2.a Examples of population attributes and characteristics

3.2.2 Defining interventions and how they will be grouped

In some reviews, predefining the intervention ( MECIR Box 3.2.c ) may be straightforward. For example, in a review of the effect of a given anticoagulant on deep vein thrombosis, the intervention can be defined precisely. A more complicated definition might be required for a multi-component intervention composed of dietary advice, training and support groups to reduce rates of obesity in a given population.

The inherent complexity present when defining an intervention often comes to light when considering how it is thought to achieve its intended effect and whether the effect is likely to differ when variants of the intervention are used. In the first example, the anticoagulant warfarin is thought to reduce blood clots by blocking an enzyme that depends on vitamin K to generate clotting factors. In the second, the behavioural intervention is thought to increase individuals’ self-efficacy in their ability to prepare healthy food. In both examples, we cannot assume that all forms of the intervention will work in the same way. When defining drug interventions, such as anticoagulants, factors such as the drug preparation, route of administration, dose, duration, and frequency should be considered. For multi-component interventions (such as interventions to reduce rates of obesity), the common or core features of the interventions must be defined, so that the review authors can clearly differentiate them from other interventions not included in the review.

MECIR Box 3.2.c Relevant expectations for conduct of intervention reviews

In general, it is useful to consider exactly what is delivered, who delivers it, how it is delivered, where it is delivered, when and how much is delivered, and whether the intervention can be adapted or tailored , and to consider this for each type of intervention included in the review (see the TIDieR checklist (Hoffmann et al 2014)). As argued in Chapter 17 , separating interventions into ‘simple’ and ‘complex’ is a false dichotomy; all interventions can be complex in some ways. The critical issue for review authors is to identify the most important factors to be considered in a specific review. Box 3.2.b outlines some factors to consider when developing broad criteria for the ‘Types of interventions’ (and comparisons).

Box 3.2.b Factors to consider when developing criteria for ‘Types of interventions’

Once interventions eligible for the review have been broadly defined, decisions should be made about how variants of the intervention will be handled in the synthesis. Differences in intervention characteristics across studies occur in all reviews. If these reflect minor differences in the form of the intervention used in practice (such as small differences in the duration or content of brief alcohol counselling interventions), then an overall synthesis can provide useful information for decision makers. Where differences in intervention characteristics are more substantial (such as delivery of brief alcohol counselling by nurses versus doctors), and are expected to have a substantial impact on the size of intervention effects, these differences should be examined in the synthesis. What constitutes an important difference requires judgement, but in general differences that alter decisions about how an intervention is implemented or whether the intervention is used or not are likely to be important. In such circumstances, review authors should consider specifying separate groups (or subgroups) to examine in their synthesis.

Clearly defined intervention groups serve two main purposes in the synthesis. First, the way in which interventions are grouped for synthesis (meta-analysis or other synthesis) is likely to influence review findings. Careful planning of intervention groups makes best use of the available data, avoids decisions that are influenced by study findings (which may introduce bias), and produces a review focused on questions relevant to decision makers. Second, the intervention groups specified in a protocol provide a standardized terminology for describing the interventions throughout the review, overcoming the varied descriptions used by study authors (e.g. where different labels are used for the same intervention, or similar labels used for different techniques) (Michie et al 2013). This standardization enables comparison and synthesis of information about intervention characteristics across studies (common characteristics and differences) and provides a consistent language for reporting that supports interpretation of review findings.

Table 3.2.b   outlines a process for planning intervention groups as a basis for/precursor to synthesis, and the decision points and considerations at each step. The table is intended to guide, rather than to be prescriptive and, although it is presented as a sequence of steps, the process is likely to be iterative, and some steps may be done concurrently or in a different sequence. The process aims to minimize data-driven approaches that can arise once review authors have knowledge of the findings of the included studies. It also includes principles for developing a flexible plan that maximizes the potential to synthesize in circumstances where there are few studies, many variants of an intervention, or where the variants are difficult to anticipate. In all stages, review authors should consider how to categorize studies whose reports contain insufficient detail.

Table 3.2.b A process for planning intervention groups for synthesis

3.2.3 Defining which comparisons will be made

When articulating the PICO for each synthesis, defining the intervention groups alone is not sufficient for complete specification of the planned syntheses. The next step is to define the comparisons that will be made between the intervention groups. Setting aside for a moment more complex analyses such as network meta-analyses, which can simultaneously compare many groups ( Chapter 11 ), standard meta-analysis ( Chapter 10 ) aims to draw conclusions about the comparative effects of two groups at a time (i.e. which of two intervention groups is more effective?). These comparisons form the basis for the syntheses that will be undertaken if data are available. Cochrane Reviews sometimes include one comparison, but most often include multiple comparisons. Three commonly identified types of comparisons include the following (Davey et al 2011).

  • newer generation antidepressants versus placebo (Hetrick et al 2012); and
  • vertebroplasty for osteoporotic vertebral compression fractures versus placebo (sham procedure) (Buchbinder et al 2018).
  • chemotherapy or targeted therapy plus best supportive care (BSC) versus BSC for palliative treatment of esophageal and gastroesophageal-junction carcinoma (Janmaat et al 2017); and
  • personalized care planning versus usual care for people with long-term conditions (Coulter et al 2015).
  • early (commenced at less than two weeks of age) versus late (two weeks of age or more) parenteral zinc supplementation in term and preterm infants (Taylor et al 2017);
  • high intensity versus low intensity physical activity or exercise in people with hip or knee osteoarthritis (Regnaux et al 2015);
  • multimedia education versus other education for consumers about prescribed and over the counter medications (Ciciriello et al 2013).

The first two types of comparisons aim to establish the effectiveness of an intervention, while the last aims to compare the effectiveness of two interventions. However, the distinction between the placebo and control is often arbitrary, since any differences in the care provided between trials with a control arm and those with a placebo arm may be unimportant , especially where ‘usual care’ is provided to both. Therefore, placebo and control groups may be determined to be similar enough to be combined for synthesis.

In reviews including multiple intervention groups, many comparisons are possible. In some of these reviews, authors seek to synthesize evidence on the comparative effectiveness of all their included interventions, including where there may be only indirect comparison of some interventions across the included studies ( Chapter 11, Section 11.2.1 ). However, in many reviews including multiple intervention groups, a limited subset of the possible comparisons will be selected. The chosen subset of comparisons should address the most important clinical and research questions. For example, if an established intervention (or dose of an intervention) is used in practice, then the synthesis would ideally compare novel or alternative interventions to this established intervention, and not, for example, to no intervention.

3.2.3.1 Dealing with co-interventions

Planning is needed for the special case where the same supplementary intervention is delivered to both the intervention and comparator groups. A supplementary intervention is an additional intervention delivered alongside the intervention of interest, such as massage in a review examining the effects of aromatherapy (i.e. aromatherapy plus massage versus massage alone). In many cases, the supplementary intervention will be unimportant and can be ignored. In other situations, the effect of the intervention of interest may differ according to whether participants receive the supplementary therapy. For example, the effect of aromatherapy among people who receive a massage may differ from the effect of the aromatherapy given alone. This will be the case if the intervention of interest interacts with the supplementary intervention leading to larger (synergistic) or smaller (dysynergistic/antagonistic) effects than the intervention of interest alone (Squires et al 2013). While qualitative interactions are rare (where the effect of the intervention is in the opposite direction when combined with the supplementary intervention), it is possible that there will be more variation in the intervention effects (heterogeneity) when supplementary interventions are involved, and it is important to plan for this. Approaches for dealing with this in the statistical synthesis may include fitting a random-effects meta-analysis model that encompasses heterogeneity ( Chapter 10, Section 10.10.4 ), or investigating whether the intervention effect is modified by the addition of the supplementary intervention through subgroup analysis ( Chapter 10, Section 10.11.2 ).

3.2.4 Selecting, prioritizing and grouping review outcomes

3.2.4.1 selecting review outcomes.

Broad outcome domains are decided at the time of setting up the review PICO (see Chapter 2 ). Once the broad domains are agreed, further specification is required to define the domains to facilitate reporting and synthesis (i.e. the PICO for comparison) (see Chapter 2, Section 2.3 ). The process for specifying and grouping outcomes largely parallels that used for specifying intervention groups.

Reporting of outcomes should rarely determine study eligibility for a review. In particular, studies should not be excluded because they do not report results of an outcome they may have measured, or provide ‘no usable data’ ( MECIR Box 3.2.d ). This is essential to avoid bias arising from selective reporting of findings by the study authors (see Chapter 13 ). However, in some circumstances, the measurement of certain outcomes may be a study eligibility criterion. This may be the case, for example, when the review addresses the potential for an intervention to prevent a particular outcome, or when the review addresses a specific purpose of an intervention that can be used in the same population for different purposes (such as hormone replacement therapy, or aspirin).

MECIR Box 3.2.d Relevant expectations for conduct of intervention reviews

In general, systematic reviews should aim to include outcomes that are likely to be meaningful to the intended users and recipients of the reviewed evidence. This may include clinicians, patients (consumers), the general public, administrators and policy makers. Outcomes may include survival (mortality), clinical events (e.g. strokes or myocardial infarction), behavioural outcomes (e.g. changes in diet, use of services), patient-reported outcomes (e.g. symptoms, quality of life), adverse events, burdens (e.g. demands on caregivers, frequency of tests, restrictions on lifestyle) and economic outcomes (e.g. cost and resource use). It is critical that outcomes used to assess adverse effects as well as outcomes used to assess beneficial effects are among those addressed by a review (see Chapter 19 ).

Outcomes that are trivial or meaningless to decision makers should not be included in Cochrane Reviews. Inclusion of outcomes that are of little or no importance risks overwhelming and potentially misleading readers. Interim or surrogate outcomes measures, such as laboratory results or radiologic results (e.g. loss of bone mineral content as a surrogate for fractures in hormone replacement therapy), while potentially helpful in explaining effects or determining intervention integrity (see Chapter 5, Section 5.3.4.1 ), can also be misleading since they may not predict clinically important outcomes accurately. Many interventions reduce the risk for a surrogate outcome but have no effect or have harmful effects on clinically relevant outcomes, and some interventions have no effect on surrogate measures but improve clinical outcomes.

Various sources can be used to develop a list of relevant outcomes, including input from consumers and advisory groups (see Chapter 2 ), the clinical experiences of the review authors, and evidence from the literature (including qualitative research about outcomes important to those affected (see Chapter 21 )). A further driver of outcome selection is consideration of outcomes used in related reviews. Harmonization of outcomes across reviews addressing related questions facilitates broader evidence synthesis questions being addressed through the use of Overviews of reviews (see Chapter V ).

Outcomes considered to be meaningful, and therefore addressed in a review, may not have been reported in the primary studies. For example, quality of life is an important outcome, perhaps the most important outcome, for people considering whether or not to use chemotherapy for advanced cancer, even if the available studies are found to report only survival (see Chapter 18 ). A further example arises with timing of the outcome measurement, where time points determined as clinically meaningful in a review are not measured in the primary studies. Including and discussing all important outcomes in a review will highlight gaps in the primary research and encourage researchers to address these gaps in future studies.

3.2.4.2 Prioritizing review outcomes

Once a full list of relevant outcomes has been compiled for the review, authors should prioritize the outcomes and select the outcomes of most relevance to the review question. The GRADE approach to assessing the certainty of evidence (see Chapter 14 ) suggests that review authors separate outcomes into those that are ‘critical’, ‘important’ and ‘not important’ for decision making.

The critical outcomes are the essential outcomes for decision making, and are those that would form the basis of a ‘Summary of findings’ table or other summary versions of the review, such as the Abstract or Plain Language Summary. ‘Summary of findings’ tables provide key information about the amount of evidence for important comparisons and outcomes, the quality of the evidence and the magnitude of effect (see Chapter 14, Section 14.1 ). There should be no more than seven outcomes included in a ‘Summary of findings’ table, and those outcomes that will be included in summaries should be specified at the protocol stage. They should generally not include surrogate or interim outcomes. They should not be chosen on the basis of any anticipated or observed magnitude of effect, or because they are likely to have been addressed in the studies to be reviewed. Box 3.2.c summarizes the principal factors to consider when selecting and prioritizing review outcomes.

Box 3.2.c Factors to consider when selecting and prioritizing review outcomes

3.2.4.3 Defining and grouping outcomes for synthesis

Table 3.2.c outlines a process for planning for the diversity in outcome measurement that may be encountered in the studies included in a review and which can complicate, and sometimes prevent, synthesis. Research has repeatedly documented inconsistency in the outcomes measured across trials in the same clinical areas (Harrison et al 2016, Williamson et al 2017). This inconsistency occurs across all aspects of outcome measurement, including the broad domains considered, the outcomes measured, the way these outcomes are labelled and defined, and the methods and timing of measurement. For example, a review of outcome measures used in 563 studies of interventions for dementia and mild cognitive impairment found that 321 unique measurement methods were used for 1278 assessments of cognitive outcomes (Harrison et al 2016). Initiatives like COMET ( Core Outcome Measures in Effectiveness Trials ) aim to encourage standardization of outcome measurement across trials (Williamson et al 2017), but these initiatives are comparatively new and review authors will inevitably encounter diversity in outcomes across studies.

The process begins by describing the scope of each outcome domain in sufficient detail to enable outcomes from included studies to be categorized ( Table 3.2.c Step 1). This step may be straightforward in areas for which core outcome sets (or equivalent systems) exist ( Table 3.2.c Step 2). The methods and timing of outcome measurement also need to be specified, giving consideration to how differences across studies will be handled ( Table 3.2.c Steps 3 and 4). Subsequent steps consider options for dealing with studies that report multiple measures within an outcome domain ( Table 3.2.c Step 5), planning how outcome domains will be used in synthesis ( Table 3.2.c Step 6), and building in contingencies to maximize potential to synthesize ( Table 3.2.c Step 7).

Table 3.2.c A process for planning outcome groups for synthesis

3.3 Determining which study designs to include

Some study designs are more appropriate than others for answering particular questions. Authors need to consider a priori what study designs are likely to provide reliable data with which to address the objectives of their review ( MECIR Box 3.3.a ). Sections 3.3.1 and 3.3.2 cover randomized and non-randomized designs for assessing treatment effects; Chapter 17, Section 17.2.5  discusses other study designs in the context of addressing intervention complexity.

MECIR Box 3.3.a Relevant expectations for conduct of intervention reviews

3.3.1 Including randomized trials

Because Cochrane Reviews address questions about the effects of health care, they focus primarily on randomized trials and randomized trials should be included if they are feasible for the interventions of interest ( MECIR Box 3.3.b ). Randomization is the only way to prevent systematic differences between baseline characteristics of participants in different intervention groups in terms of both known and unknown (or unmeasured) confounders (see Chapter 8 ), and claims about cause and effect can be based on their findings with far more confidence than almost any other type of study. For clinical interventions, deciding who receives an intervention and who does not is influenced by many factors, including prognostic factors. Empirical evidence suggests that, on average, non-randomized studies produce effect estimates that indicate more extreme benefits of the effects of health care than randomized trials. However, the extent, and even the direction, of the bias is difficult to predict. These issues are discussed at length in Chapter 24 , which provides guidance on when it might be appropriate to include non-randomized studies in a Cochrane Review.

Practical considerations also motivate the restriction of many Cochrane Reviews to randomized trials. In recent decades there has been considerable investment internationally in establishing infrastructure to index and identify randomized trials. Cochrane has contributed to these efforts, including building up and maintaining a database of randomized trials, developing search filters to aid their identification, working with MEDLINE to improve tagging and identification of randomized trials, and using machine learning and crowdsourcing to reduce author workload in identifying randomized trials ( Chapter 4, Section 4.6.6.2 ). The same scale of organizational investment has not (yet) been matched for the identification of other types of studies. Consequently, identifying and including other types of studies may require additional efforts to identify studies and to keep the review up to date, and might increase the risk that the result of the review will be influenced by publication bias. This issue and other bias-related issues that are important to consider when defining types of studies are discussed in detail in Chapter 7 and Chapter 13 .

Specific aspects of study design and conduct should be considered when defining eligibility criteria, even if the review is restricted to randomized trials. For example, whether cluster-randomized trials ( Chapter 23, Section 23.1 ) and crossover trials ( Chapter 23, Section 23.2 ) are eligible, as well as other criteria for eligibility such as use of a placebo comparison group, evaluation of outcomes blinded to allocation sequence, or a minimum period of follow-up. There will always be a trade-off between restrictive study design criteria (which might result in the inclusion of studies that are at low risk of bias, but very few in number) and more liberal design criteria (which might result in the inclusion of more studies, but at a higher risk of bias). Furthermore, excessively broad criteria might result in the inclusion of misleading evidence. If, for example, interest focuses on whether a therapy improves survival in patients with a chronic condition, it might be inappropriate to look at studies of very short duration, except to make explicit the point that they cannot address the question of interest.

MECIR Box 3.3.b Relevant expectations for conduct of intervention reviews

3.3.2 Including non-randomized studies

The decision of whether non-randomized studies (and what type) will be included is decided alongside the formulation of the review PICO. The main drivers that may lead to the inclusion of non-randomized studies include: (i) when randomized trials are unable to address the effects of the intervention on harm and long-term outcomes or in specific populations or settings; or (ii) for interventions that cannot be randomized (e.g. policy change introduced in a single or small number of jurisdictions) (see Chapter 24 ). Cochrane, in collaboration with others, has developed guidance for review authors to support their decision about when to look for and include non-randomized studies (Schünemann et al 2013).

Non-randomized designs have the commonality of not using randomization to allocate units to comparison groups, but their different design features mean that they are variable in their susceptibility to bias. Eligibility criteria should be based on explicit study design features, and not the study labels applied by the primary researchers (e.g. case-control, cohort), which are often used inconsistently (Reeves et al 2017; see Chapter 24 ).

When non-randomized studies are included, review authors should consider how the studies will be grouped and used in the synthesis. The Cochrane Non-randomized Studies Methods Group taxonomy of design features (see Chapter 24 ) may provide a basis for grouping together studies that are expected to have similar inferential strength and for providing a consistent language for describing the study design.

Once decisions have been made about grouping study designs, planning of how these will be used in the synthesis is required. Review authors need to decide whether it is useful to synthesize results from non-randomized studies and, if so, whether results from randomized trials and non-randomized studies should be included in the same synthesis (for the purpose of examining whether study design explains heterogeneity among the intervention effects), or whether the effects should be synthesized in separate comparisons (Valentine and Thompson 2013). Decisions should be made for each of the different types of non-randomized studies under consideration. Review authors might anticipate increased heterogeneity when non-randomized studies are synthesized, and adoption of a meta-analysis model that encompasses heterogeneity is wise (Valentine and Thompson 2013) (such as a random effects model, see Chapter 10, Section 10.10.4 ). For further discussion of non-randomized studies, see Chapter 24 .

3.4 Eligibility based on publication status and language

Chapter 4 contains detailed guidance on how to identify studies from a range of sources including, but not limited to, those in peer-reviewed journals. In general, a strategy to include studies reported in all types of publication will reduce bias ( Chapter 7 ). There would need to be a compelling argument for the exclusion of studies on the basis of their publication status ( MECIR Box 3.4.a ), including unpublished studies, partially published studies, and studies published in ‘grey’ literature sources. Given the additional challenge in obtaining unpublished studies, it is possible that any unpublished studies identified in a given review may be an unrepresentative subset of all the unpublished studies in existence. However, the bias this introduces is of less concern than the bias introduced by excluding all unpublished studies, given what is known about the impact of reporting biases (see Chapter 13 on bias due to missing studies, and Chapter 4, Section 4.3 for a more detailed discussion of searching for unpublished and grey literature).

Likewise, while searching for, and analysing, studies in any language can be extremely resource-intensive, review authors should consider carefully the implications for bias (and equity, see Chapter 16 ) if they restrict eligible studies to those published in one specific language (usually English). See Chapter 4, Section 4.4.5 , for further discussion of language and other restrictions while searching.

MECIR Box 3.4.a Relevant expectations for conduct of intervention reviews

3.5 Chapter information

Authors: Joanne E McKenzie, Sue E Brennan, Rebecca E Ryan, Hilary J Thomson, Renea V Johnston, James Thomas

Acknowledgements: This chapter builds on earlier versions of the Handbook . In particular, Version 5, Chapter 5 , edited by Denise O’Connor, Sally Green and Julian Higgins.

Funding: JEM is supported by an Australian National Health and Medical Research Council (NHMRC) Career Development Fellowship (1143429). SEB and RER’s positions are supported by the NHMRC Cochrane Collaboration Funding Program. HJT is funded by the UK Medical Research Council (MC_UU_12017-13 and MC_UU_12017-15) and Scottish Government Chief Scientist Office (SPHSU13 and SPHSU15). RVJ’s position is supported by the NHMRC Cochrane Collaboration Funding Program and Cabrini Institute. JT is supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care North Thames at Barts Health NHS Trust. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

3.6 References

Bailey JV, Murray E, Rait G, Mercer CH, Morris RW, Peacock R, Cassell J, Nazareth I. Interactive computer-based interventions for sexual health promotion. Cochrane Database of Systematic Reviews 2010; 9 : CD006483.

Bender R, Bunce C, Clarke M, Gates S, Lange S, Pace NL, Thorlund K. Attention should be given to multiplicity issues in systematic reviews. Journal of Clinical Epidemiology 2008; 61 : 857–865.

Buchbinder R, Johnston RV, Rischin KJ, Homik J, Jones CA, Golmohammadi K, Kallmes DF. Percutaneous vertebroplasty for osteoporotic vertebral compression fracture. Cochrane Database of Systematic Reviews 2018; 4 : CD006349.

Caldwell DM, Welton NJ. Approaches for synthesising complex mental health interventions in meta-analysis. Evidence-Based Mental Health 2016; 19 : 16–21.

Chamberlain C, O’Mara-Eves A, Porter J, Coleman T, Perlen S, Thomas J, McKenzie J. Psychosocial interventions for supporting women to stop smoking in pregnancy. Cochrane Database of Systematic Reviews 2017; 2 : CD001055.

Ciciriello S, Johnston RV, Osborne RH, Wicks I, deKroo T, Clerehan R, O’Neill C, Buchbinder R. Multimedia educational interventions for consumers about prescribed and over-the-counter medications. Cochrane Database of Systematic Reviews 2013; 4 : CD008416.

Cochrane Consumers & Communication Group. Outcomes of Interest to the Cochrane Consumers & Communication Group: taxonomy. http://cccrg.cochrane.org/ .

COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) initiative. COSMIN database of systematic reviews of outcome measurement instruments. https://database.cosmin.nl/ .

Coulter A, Entwistle VA, Eccles A, Ryan S, Shepperd S, Perera R. Personalised care planning for adults with chronic or long-term health conditions. Cochrane Database of Systematic Reviews 2015; 3 : CD010523.

Davey J, Turner RM, Clarke MJ, Higgins JPT. Characteristics of meta-analyses and their component studies in the Cochrane Database of Systematic Reviews: a cross-sectional, descriptive analysis. BMC Medical Research Methodology 2011; 11 : 160.

Desroches S, Lapointe A, Ratte S, Gravel K, Legare F, Turcotte S. Interventions to enhance adherence to dietary advice for preventing and managing chronic diseases in adults. Cochrane Database of Systematic Reviews 2013; 2 : CD008722.

Deyo RA, Dworkin SF, Amtmann D, Andersson G, Borenstein D, Carragee E, Carrino J, Chou R, Cook K, DeLitto A, Goertz C, Khalsa P, Loeser J, Mackey S, Panagis J, Rainville J, Tosteson T, Turk D, Von Korff M, Weiner DK. Report of the NIH Task Force on research standards for chronic low back pain. Journal of Pain 2014; 15 : 569–585.

Dodd S, Clarke M, Becker L, Mavergames C, Fish R, Williamson PR. A taxonomy has been developed for outcomes in medical research to help improve knowledge discovery. Journal of Clinical Epidemiology 2018; 96 : 84–92.

Fisher DJ, Carpenter JR, Morris TP, Freeman SC, Tierney JF. Meta-analytical methods to identify who benefits most from treatments: daft, deluded, or deft approach? BMJ 2017; 356 : j573.

Fransen M, McConnell S, Harmer AR, Van der Esch M, Simic M, Bennell KL. Exercise for osteoarthritis of the knee. Cochrane Database of Systematic Reviews 2015; 1 : CD004376.

Guise JM, Chang C, Viswanathan M, Glick S, Treadwell J, Umscheid CA. Systematic reviews of complex multicomponent health care interventions. Report No. 14-EHC003-EF . Rockville, MD: Agency for Healthcare Research and Quality; 2014.

Harrison JK, Noel-Storr AH, Demeyere N, Reynish EL, Quinn TJ. Outcomes measures in a decade of dementia and mild cognitive impairment trials. Alzheimer’s Research and Therapy 2016; 8 : 48.

Hedges LV, Tipton E, Johnson M, C. Robust variance estimation in meta-regression with dependent effect size estimates. Research Synthesis Methods 2010; 1 : 39–65.

Hetrick SE, McKenzie JE, Cox GR, Simmons MB, Merry SN. Newer generation antidepressants for depressive disorders in children and adolescents. Cochrane Database of Systematic Reviews 2012; 11 : CD004851.

Higgins JPT, López-López JA, Becker BJ, Davies SR, Dawson S, Grimshaw JM, McGuinness LA, Moore THM, Rehfuess E, Thomas J, Caldwell DM. Synthesizing quantitative evidence in systematic reviews of complex health interventions. BMJ Global Health 2019; 4 : e000858.

Hoffmann T, Glasziou P, Barbour V, Macdonald H. Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide. BMJ 2014; 1687 : 1-13.

Hollands GJ, Shemilt I, Marteau TM, Jebb SA, Lewis HB, Wei Y, Higgins JPT, Ogilvie D. Portion, package or tableware size for changing selection and consumption of food, alcohol and tobacco. Cochrane Database of Systematic Reviews 2015; 9 : CD011045.

Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, Harbour RT, Caldwell LM, Creed G. Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database of Systematic Reviews 2011; 7 : CD000333.

ICHOM. The International Consortium for Health Outcomes Measurement 2018. http://www.ichom.org/ .

IPDAS. International Patient Decision Aid Standards Collaboration (IPDAS) standards. www.ipdas.ohri.ca .

Ivers N, Jamtvedt G, Flottorp S, Young JM, Odgaard-Jensen J, French SD, O’Brien MA, Johansen M, Grimshaw J, Oxman AD. Audit and feedback: effects on professional practice and healthcare outcomes. Cochrane Database of Systematic Reviews 2012; 6 : CD000259.

Janmaat VT, Steyerberg EW, van der Gaast A, Mathijssen RH, Bruno MJ, Peppelenbosch MP, Kuipers EJ, Spaander MC. Palliative chemotherapy and targeted therapies for esophageal and gastroesophageal junction cancer. Cochrane Database of Systematic Reviews 2017; 11 : CD004063.

Kendrick D, Kumar A, Carpenter H, Zijlstra GAR, Skelton DA, Cook JR, Stevens Z, Belcher CM, Haworth D, Gawler SJ, Gage H, Masud T, Bowling A, Pearl M, Morris RW, Iliffe S, Delbaere K. Exercise for reducing fear of falling in older people living in the community. Cochrane Database of Systematic Reviews 2014; 11 : CD009848.

Kirkham JJ, Gargon E, Clarke M, Williamson PR. Can a core outcome set improve the quality of systematic reviews? A survey of the Co-ordinating Editors of Cochrane Review Groups. Trials 2013; 14 : 21.

Konstantopoulos S. Fixed effects and variance components estimation in three-level meta-analysis. Research Synthesis Methods 2011; 2 : 61–76.

Lamb SE, Becker C, Gillespie LD, Smith JL, Finnegan S, Potter R, Pfeiffer K. Reporting of complex interventions in clinical trials: development of a taxonomy to classify and describe fall-prevention interventions. Trials 2011; 12 : 125.

Lewin S, Hendry M, Chandler J, Oxman AD, Michie S, Shepperd S, Reeves BC, Tugwell P, Hannes K, Rehfuess EA, Welch V, Mckenzie JE, Burford B, Petkovic J, Anderson LM, Harris J, Noyes J. Assessing the complexity of interventions within systematic reviews: development, content and use of a new tool (iCAT_SR). BMC Medical Research Methodology 2017; 17 : 76.

López-López JA, Page MJ, Lipsey MW, Higgins JPT. Dealing with multiplicity of effect sizes in systematic reviews and meta-analyses. Research Synthesis Methods 2018; 9 : 336–351.

Mavridis D, Salanti G. A practical introduction to multivariate meta-analysis. Statistical Methods in Medical Research 2013; 22 : 133–158.

Michie S, van Stralen M, West R. The Behaviour Change Wheel: a new method for characterising and designing behaviour change interventions. Implementation Science 2011; 6 : 42.

Michie S, Richardson M, Johnston M, Abraham C, Francis J, Hardeman W, Eccles MP, Cane J, Wood CE. The behavior change technique taxonomy (v1) of 93 hierarchically clustered techniques: building an international consensus for the reporting of behavior change interventions. Annals of Behavioral Medicine 2013; 46 : 81–95.

Moraes VY, Lenza M, Tamaoki MJ, Faloppa F, Belloti JC. Platelet-rich therapies for musculoskeletal soft tissue injuries. Cochrane Database of Systematic Reviews 2014; 4 : CD010071.

O'Neill J, Tabish H, Welch V, Petticrew M, Pottie K, Clarke M, Evans T, Pardo Pardo J, Waters E, White H, Tugwell P. Applying an equity lens to interventions: using PROGRESS ensures consideration of socially stratifying factors to illuminate inequities in health. Journal of Clinical Epidemiology 2014; 67 : 56–64.

Pompoli A, Furukawa TA, Imai H, Tajika A, Efthimiou O, Salanti G. Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta-analysis. Cochrane Database of Systematic Reviews 2016; 4 : CD011004.

Pompoli A, Furukawa TA, Efthimiou O, Imai H, Tajika A, Salanti G. Dismantling cognitive-behaviour therapy for panic disorder: a systematic review and component network meta-analysis. Psychological Medicine 2018; 48 : 1–9.

Reeves BC, Wells GA, Waddington H. Quasi-experimental study designs series-paper 5: a checklist for classifying studies evaluating the effects on health interventions – a taxonomy without labels. Journal of Clinical Epidemiology 2017; 89 : 30–42.

Regnaux J-P, Lefevre-Colau M-M, Trinquart L, Nguyen C, Boutron I, Brosseau L, Ravaud P. High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis. Cochrane Database of Systematic Reviews 2015; 10 : CD010203.

Richards SH, Anderson L, Jenkinson CE, Whalley B, Rees K, Davies P, Bennett P, Liu Z, West R, Thompson DR, Taylor RS. Psychological interventions for coronary heart disease. Cochrane Database of Systematic Reviews 2017; 4 : CD002902.

Safi S, Korang SK, Nielsen EE, Sethi NJ, Feinberg J, Gluud C, Jakobsen JC. Beta-blockers for heart failure. Cochrane Database of Systematic Reviews 2017; 12 : CD012897.

Santesso N, Carrasco-Labra A, Brignardello-Petersen R. Hip protectors for preventing hip fractures in older people. Cochrane Database of Systematic Reviews 2014; 3 : CD001255.

Shepherd E, Gomersall JC, Tieu J, Han S, Crowther CA, Middleton P. Combined diet and exercise interventions for preventing gestational diabetes mellitus. Cochrane Database of Systematic Reviews 2017; 11 : CD010443.

Squires J, Valentine J, Grimshaw J. Systematic reviews of complex interventions: framing the review question. Journal of Clinical Epidemiology 2013; 66 : 1215–1222.

Stacey D, Légaré F, Lewis K, Barry MJ, Bennett CL, Eden KB, Holmes-Rovner M, Llewellyn-Thomas H, Lyddiatt A, Thomson R, Trevena L. Decision aids for people facing health treatment or screening decisions. Cochrane Database of Systematic Reviews 2017; 4 : CD001431.

Stroke Unit Trialists Collaboration. Organised inpatient (stroke unit) care for stroke. Cochrane Database of Systematic Reviews 2013; 9 : CD000197.

Taylor AJ, Jones LJ, Osborn DA. Zinc supplementation of parenteral nutrition in newborn infants. Cochrane Database of Systematic Reviews 2017; 2 : CD012561.

Valentine JC, Thompson SG. Issues relating to confounding and meta-analysis when including non-randomized studies in systematic reviews on the effects of interventions. Research Synthesis Methods 2013; 4 : 26–35.

Vaona A, Banzi R, Kwag KH, Rigon G, Cereda D, Pecoraro V, Tramacere I, Moja L. E-learning for health professionals. Cochrane Database of Systematic Reviews 2018; 1 : CD011736.

Verheyden GSAF, Weerdesteyn V, Pickering RM, Kunkel D, Lennon S, Geurts ACH, Ashburn A. Interventions for preventing falls in people after stroke. Cochrane Database of Systematic Reviews 2013; 5 : CD008728.

Weisz JR, Kuppens S, Ng MY, Eckshtain D, Ugueto AM, Vaughn-Coaxum R, Jensen-Doss A, Hawley KM, Krumholz Marchette LS, Chu BC, Weersing VR, Fordwood SR. What five decades of research tells us about the effects of youth psychological therapy: a multilevel meta-analysis and implications for science and practice. American Psychologist 2017; 72 : 79–117.

Welch V, Petkovic J, Simeon R, Presseau J, Gagnon D, Hossain A, Pardo Pardo J, Pottie K, Rader T, Sokolovski A, Yoganathan M, Tugwell P, DesMeules M. Interactive social media interventions for health behaviour change, health outcomes, and health equity in the adult population. Cochrane Database of Systematic Reviews 2018; 2 : CD012932.

Welton NJ, Caldwell DM, Adamopoulos E, Vedhara K. Mixed treatment comparison meta-analysis of complex interventions: psychological interventions in coronary heart disease. American Journal of Epidemiology 2009; 169 : 1158–1165.

Williamson PR, Altman DG, Bagley H, Barnes KL, Blazeby JM, Brookes ST, Clarke M, Gargon E, Gorst S, Harman N, Kirkham JJ, McNair A, Prinsen CAC, Schmitt J, Terwee CB, Young B. The COMET Handbook: version 1.0. Trials 2017; 18 : 280.

For permission to re-use material from the Handbook (either academic or commercial), please see here for full details.

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes: A workshop report with focus on novel entities and a literature review including paediatric cases

Affiliations.

  • 1 Clinical Pathology and Cancer Diagnostics, Karolinska University Laboratory, Karolinska Institute, Stockholm, Sweden.
  • 2 Institute of Pathology and Molecular Pathology, Helios University Clinic Wuppertal, University of Witten/Herdecke, Wuppertal, Germany.
  • 3 Department of Pathology, Medical Faculty Hospital, Charles University, Pilsen, Czech Republic.
  • 4 Università degli Studi di Milano, SC Anatomia Patologica, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy.
  • 5 Department of Biotechnology, Institute of Pathology, University of Siena, Siena, Italy.
  • 6 Hospital Clinic Barcelona, Barcelona, Spain.
  • PMID: 37551450
  • DOI: 10.1111/his.15021

Myeloid/lymphoid neoplasms with eosinophilia (M/LN-eo) and tyrosine kinase (TK) gene fusions are a rare group of haematopoietic neoplasms with a broad range of clinical and morphological presentations. Paediatric cases have increasingly been recognised. Importantly, not all appear as a chronic myeloid neoplasm and eosinophilia is not always present. In addition, standard cytogenetic and molecular methods may not be sufficient to diagnose M/LN-eo due to cytogenetically cryptic aberrations. Therefore, additional evaluation with fluorescence in-situ hybridisation and other molecular genetic techniques (array-based comparative genomic hybridisation, RNA sequencing) are recommended for the identification of specific TK gene fusions. M/LN-eo with JAK2 and FLT3-rearrangements and ETV6::ABL1 fusion were recently added as a formal member to this category in the International Consensus Classification (ICC) and the 5th edition of the WHO classification (WHO-HAEM5). In addition, other less common defined genetic alterations involving TK genes have been described. This study is an update on M/LN-eo with TK gene fusions with focus on novel entities, as illustrated by cases submitted to the Bone Marrow Workshop, organised by the European Bone Marrow Working Group (EBMWG) within the frame of the 21st European Association for Haematopathology congress (EAHP-SH) in Florence 2022. A literature review was performed including paediatric cases of M/LN-eo with TK gene fusions.

Keywords: European Bone Marrow Working Group (EBMWG); bone marrow biopsy; myeloid/lymphoid neoplasms with eosinophilia; paediatric; tyrosine kinase gene fusion.

© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.

Publication types

  • Bone Marrow / pathology
  • Eosinophilia* / genetics
  • Eosinophilia* / pathology
  • Hematologic Neoplasms* / pathology
  • Lymphoma* / pathology
  • Myeloproliferative Disorders*
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion
  • Case Report
  • Open access
  • Published: 01 April 2024

Mediastinal Rosai-Dorfman Disease with KRAS mutation case report and literature review

  • Wenyu Zhang 1 ,
  • Linan Fang 1 ,
  • Jing Wang 2 ,
  • Xiaobo Ma 3 ,
  • Xintong Hu 4 &
  • Wei Liu 1  

Journal of Cardiothoracic Surgery volume  19 , Article number:  166 ( 2024 ) Cite this article

Metrics details

Rosai-Dorfman Disease (RDD) is a rare self-limiting histiocytosis, more prevalent in children and young adults. It typically manifests as painless bilateral massive cervical lymphadenopathy but may also extend to extra-nodal sites, with intrathoracic RDD noted in 2% of cases. Distinguishing mediastinal RDD from thymoma on imaging poses challenges, underscoring the reliance on pathological features and immunohistochemical staining for diagnosis.

Case presentation

Patient, male, 33 years old, underwent lung a CT revealing an enlarged round soft tissue shadow in the anterior superior mediastinum, compared to a year ago. Surgical resection removed the entire mass, thymus, and part of the pericardium, confirming RDD on pathology. Genetic testing using second-generation testing technology identified a KRAS gene point mutation.

Conclusions

No established treatment protocol currently exists for this disease. However, as genetic mutation research progresses, a novel therapeutic avenue is emerging: targeted therapy integrated with surgical interventions.

Peer Review reports

Rosai-Dorfman Disease (RDD), also recognized as sinus histiocytosis with massive lymphadenopathy, is a rare and self-limiting histiocytosis initially documented by Juan Rosai and Ronald Dorfman in 1969 [ 1 ]. Predominantly affecting children and young adults, RDD typically manifests as bilateral, massive, painless cervical lymphadenopathy. However, it can also extend to extra-nodal sites such as the skin, soft tissues, bones, upper respiratory tract, and ocular appendages, with only 2% of patients exhibiting intrathoracic RDD [ 2 ]. Notably, genetic test results for patients with mediastinal RDD remain unreported. Consequently, we present a unique case of mediastinal RDD and provide a comprehensive review of the clinical, pathological and genetic mutational characteristics associated with this disease.

Patient, male, 33 years old, admitted with a mediastinal mass identified during lung computed tomography (CT). Notably, the patient had previously undergone the excision of a right retroperitoneal mass in our hospital a year ago, with postoperative pathology suggesting paraganglioma. The patient’s medical history was otherwise unremarkable. One year before admission, the patient’s lung CT revealed a round-like soft tissue density shadow in the anterior superior mediastinal thymus area, characterized by clear margins and uniform density. At that time, it had a maximum diameter of 2.1*2.7 cm and a CT value of approximately 41 Hounsfield units (HU). The mass was observed to be attached to the pericardium, with limited pericardial thickening evident (Fig.  1 A). However, a subsequent lung CT post-admission revealed a substantial enlargement of the mass, with a maximum diameter measuring 5.3*2.2 cm (Fig.  1 B). The patient reported weakness but denied other symptoms, including fever, night sweats, and weight loss throughout the disease course. Initially diagnosed as thymoma, surgical intervention was performed to remove the entire mass, thymus, and a portion of the pericardium. Subsequent pathological examination of the excised tissue was conducted.

figure 1

A The patient’s chest CT one year before admission, the size of the lesion was about 2.1*2.7 cm; B The patient’s arterial stage of chest enhancement CT on admission, with a lesion size approximately 5.3*2.2 cm; C The patient’s 3-month postoperative chest CT; D The patient’s 9-month postoperative chest CT; E The patient’s 2-year postoperative chest CT

Hematoxylin and eosin (H&E) staining at low magnification exhibited an alternating distribution of bright and dark bands (Fig.  2 A). Upon high magnification, cytoplasm-rich histiocytes with a significant infiltration of lymphocytes and plasma cells at the periphery were evident, along with the characteristic feature of emperipolesis, indicative of RDD (Fig.  2 B). Immunohistochemical analysis revealed positive expression of S-100 and CD68 in the tissue cells, while CD1a was conspicuously absent (Fig.  2 C, D, E). The ultimate pathological diagnosis established RDD. Patients also underwent comprehensive genetic testing, encompassing “tumor targeted drugs + chemotherapy drugs + immunogenetic testing 1021,” utilizing second-generation detection technology. This encompassed the assessment of four mutations within 1,021 genes associated with tumor development, including point mutations, small indels, copy number variations, and known fusion genes. The findings unveiled a point mutation in KRAS , specifically c.437C > T (p.A146V).

figure 2

A Alternating bright and dark bands were seen under low magnification (HE 100x).; B High magnification reveals cytoplasm-rich histiocytes with more lymphocytes and plasma cells infiltrating the periphery; the emperipolesis is visible (HE 400x); C Histocyte S-100 positive with visible emperipolesis (IHC 400x); D CD68 positive (IHC 400x); E CD1a negative (IHC 400x)

Following a 5-day observation period, the patient was discharged without encountering any complications. Subsequent to discharge, we maintained a scheduled follow-up regimen. Over the course of this follow-up, the patient underwent three repeat lung CT examinations, and the results revealed no discernible evidence of recurrence (Fig.  1 C, D, E).

Discussion and literature review

RDD is a rare histiocytosis, previously categorized as a non-Langerhans cell histiocytosis. However, in the latest classification by the Histoplasmosis Society, cutaneous RDD is now designated within the histiocytosis group C, while other forms of RDD are categorized under the R group of histiocytosis [ 3 ].

The prevalence of RDD is notably low, estimated at 1:200,000. Approximately 43% of patients manifest extra-nodal lesions, and intrathoracic involvement is observed in merely about 2% of patients [ 2 ]. Specifically, mediastinal RDD accounts for a strikingly minimal proportion, constituting only 0.5% or less of all mediastinal space-occupying lesion [ 4 ]. Employing the PubMed database and utilizing the search formula “((thoracic) OR (mediastinal)) AND ((Rosai-Dorfman disease) OR (Sinus histiocytosis with massive lymphadenopathy))”, we conducted a comprehensive search without restricting the time frame. This yielded 142 documents, and subsequent scrutiny in accordance with the PRISMA (Preferred Reporting Items for Systematic Evaluation and Meta-Analysis) guidelines revealed a total of 23 case reports [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ], documenting 23 patients diagnosed with mediastinal RDD (Table  1 ).

CT/MRI plain images of RDD-afflicted patients typically reveal well-defined, irregularly shaped lesions characterized by uniform densities/signals and significantly progressive enhancements on multi-contrast enhancement imaging [ 27 ]. All included patients underwent lung CT or enhanced lung CT before biopsy, yielding varying imaging descriptions. Importantly, none received a pre-biopsy RDD diagnosis, and clinicians primarily considered differential diagnoses such as lymphoma, benign and malignant thymic tumors, pulmonary artery embolism, or noninfectious inflammatory disease [ 13 ]. This underscores the challenge in leveraging lung CT results for definitive diagnoses, emphasizing their role more in disease screening and guiding the surgical approaches. PET-CT may offer improved insights into RDD indications. In a study by Jia et al. [ 11 ], a patient with anterior mediastinal RDD exhibited abnormally high FDG uptake (SUVmax 8.96) on PET/CT, surpassing the average metabolic activity of thymic hyperplasia (SUVmax 1.1), thymoma (SUVmax 2.3) and thymic carcinoma (SUVmax 7.0) [ 28 ]. Notably, two reports by Agarwal et al. [ 6 ] and Furia et al. [ 21 ] recorded even higher SUVmax values at 34.0 and 35.0, indicating a potential reference value for PET-CT in RDD diagnosis.

A definitive diagnosis of RDD typically necessitates HE staining and immunohistochemical analysis. Regardless of the location, RDD is pathologically characterized by sinusoidal hyperplasia of large histiocytes, with extra-nodal lesions often exhibiting a more prominent fibrotic component. Furthermore, in late-stage RDD lesions, fibrosis becomes more prevalent, making the identification of residual RDD islands challenging [ 29 ]. While emperipolesis is a crucial indicator suggesting RDD disease, it is not entirely specific, as scattered emperipolesis can be observed in other histiocytic disorders such as Erdheim-Chester disease, yellow granuloma and malignant histiocytosis [ 30 , 31 , 32 ]. Meanwhile, immunohistochemistry plays a pivotal role in further delineating RDD disease. The immunophenotype of RDD cells typically manifests as positive for S-100 and CD68, with the potential for positivity in CD163 and CD14. Notably, CD1a is usually negative, serving as a point of differentiation from Langerhans cell histiocytosis [ 2 ]. Among all the mediastinal RDD cases included in our study, only one case encountered challenges in obtaining a biopsy sample through surgical resection or puncture. However, histiocytes were observed in all completed pathologies, and immunohistochemistry demonstrated positive results for at least one of S-100 or CD68.

The pathogenesis of RDD remains unclear, with some studies suggesting a potential association with viral infections such as herpesvirus, Epstein-Barr virus, cytomegalovirus, and HIV, but a definitive link has yet to be established [ 33 ]. More recently, investigations have revealed mutations in NRAS , KRAS , MAP2K1 , and ARAF in RDD cases [ 34 , 35 , 36 , 37 , 38 ]. Among the mediastinal RDD cases included in our study, one patient’s mediastinal sample underwent whole exome sequencing, identifying a missense variant in the IRF5 gene [ 7 ]. Another patient showed the presence of a KRAS gene mutation, as identified by next-generation sequencing [ 13 ]. Additionally, Lee et al. reported a RDD case with the same KRAS gene mutation (p.A146V), although the lesion’s location in this patient was not explicitly documented [ 37 ]. In our study, patients underwent genetic testing utilizing next-generation sequencing technology, revealing mutations in the KRAS gene [NM_033360.2: c.437C > T (p.A146V)] at a frequency of 2.4%. The detection technology employed encompassed four mutation types, including point mutations, small indels, copy number variations, and known fusion genes. The average effective sequencing depth was 1714, covering 1021 genes associated with tumorigenesis and development. The testing strategy included the examination of all exon regions of 312 genes, introns, promoters, or fusion breakpoint regions of 38 genes, and partial exons of 709 genes for somatic mutations. Additionally, all exons of 39 genes were scrutinized for germline mutations, along with assessments for tumor mutational burden and microsatellite instability. Remarkably, our case represents the second instance of identifying KRAS gene mutations in mediastinal RDD, offering potential new insights into the etiology of this condition.

There are currently no established standard treatment protocols for mediastinal RDD. Given its often self-limiting nature, conservative management is deemed acceptable. However, among our included cases, surgical resection was undertaken in 21 out of 23 patients for symptomatic relief or definitive diagnosis. The beneficial effects of corticosteroid therapy and radiotherapy were also evident, as reported by Furia et al. [ 21 ]. A pivotal study by Garces et al. highlighted that activating mutations in RAS/RAF/MAPK/ERK or related signaling pathways may play a role in RDD development [ 36 ]. This implies that post-operative genomic analysis and targeted therapy administration could potentially improve outcomes for these patients.

We documented a case of mediastinal RDD with KRAS mutations, exhibiting imaging, pathological, and immunohistochemical features consistent with the characteristics observed in extra-nodal lesions of RDD.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Rosai-Dorfman Disease

Preferred Reporting Items for Systematic Evaluation and Meta-Analysis

Standardized uptake value

Scluster of differentiation

Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy. A newly recognized benign clinicopathological entity. Arch Pathol. 1969;87(1):63–70.

CAS   PubMed   Google Scholar  

Abla O, Jacobsen E, Picarsic J, Krenova Z, Jaffe R, Emile JF, et al. Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease. Blood. 2018;131(26):2877–90.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Bruce-Brand C, Schneider JW, Schubert P. Rosai-Dorfman disease: an overview. J Clin Pathol. 2020;73(11):697–705.

Article   CAS   PubMed   Google Scholar  

Shen C, Liao H. An extremely rare case of Rosai-Dorfman disease in the thymus. J Cardiothorac Surg. 2021;16(1):212.

Article   PubMed   PubMed Central   Google Scholar  

Liu Q, Liao F, Liu Y, Cheng Y, Qi C. Primary unifocal thymic Rosai-Dorfman disease: an extremely rare challenge in diagnostic practice. J Cardiothorac Surg. 2023;18(1):284.

Agarwal A, Ravindran A, Donahue J, Eltoum IE, Abozeed M. Extranodal Rosai-Dorfman Disease: a rare presentation involving anterior chest wall in a middle-aged female. Skeletal Radiol. 2024;53(3):589–94.

Article   PubMed   Google Scholar  

Lv C, Zhong L, Wang Z, Zhao L. Whole-exome sequencing identified the mutation of IRF5 in thymic Rosai-Dorfman disease: a case report. Asian J Surg. 2023;S1015–9584(23):00930–2.

Google Scholar  

Dronamraju V, McSurdy K, Graham R, Rali P, Kumaran M, Proca D, et al. A rare case of Rosai-Dorfman disease presenting as a pulmonary artery mass in a 33-year-old female with hypoxia. Pulm Circ. 2023;13(2):e12214.

Wu L, Zhang Y, Guo X, Tang X, Xin K, Yang L, et al. Primary diffuse Rosai-Dorfman disease in central airway: a case report and literature review. BMC Pulm Med. 2023;23:82.

Li L, Wang Z, Liu L, Wu H, Ren Z, Yuan J. Rosai-Dorfman Disease involving the descending aorta. Circ Cardiovasc Imaging. 2023;16(3):e014582.

Jia T, Zhang B, Zhang X, Xu X, Sang S, Deng S. A rare case of thymic Rosai-Dorfman Disease mimicking malignancy on 18F-FDG PET/CT. Tomography. 2022;8(6):2839–43.

Liu S, Tang E, Xu G, Lei J. Rosai-Dorfman disease in the thymus: a case report. Asian J Surg. 2022;S1015–9584(22):01415–24.

Maniar YM, Meyer CF, Sharp M, Zambidis ET, Qaysi NAI, Horne AJ. Rosai-Dorfman Disease presenting as massive mediastinal lymphadenopathy in an elderly man. Ann Intern Med Clin Cases. 2022;1(8):e220539.

Oramas DM, Moran CA. Primary Rosai-Dorfman disease of the thymus and lung: a clinicopathological and immunohistochemical study of three cases. Pathol Res Pract. 2022;234:153917.

Greggianin C, Yasufuku K, Tong LC, Dhillon G, Digby GC. Middle mediastinal mass compressing the pulmonary trunk in a patient with a history of breast cancer. Chest. 2022;161(5):e265-72.

Nakanosono R, Nakayama H, Nagano H, Takumi K, Oose A, Yano E, et al. A rare case report of Rosai-Dorfman Disease manifesting as a mediastinal mass. J Thorac Imaging. 2021;36(6):W105-8.

Liu J, Wan Y, Pu HX, Peng LQ. Extranodal Rosai-Dorfman Disease of anterior mediastinum: a case report. Sichuan Da Xue Xue Bao Yi Xue Ban. 2021;52(6):1044–6.

PubMed   Google Scholar  

Liu L, Liu J, Miao Q. Primary pulmonary artery Rosai-Dorfman Disease treated with surgical resection. Ann Thorac Surg. 2021;111(6):e433-5.

Tsujimura R, Sato D, Obikane H, Kawachi R, Sugitani M, Hao H, et al. Rosai-Dorfman disease of thymus with elevated serum anti-acetylcholine receptor antibody: a case report. Int J Clin Exp Pathol. 2021;14(10):1061–4.

PubMed   PubMed Central   Google Scholar  

Mohammadi O, ZylberglaitLisigurski M, Mehra D, Pishdad R, Gulec S. Rosai-Dorfman Disease and unusual local invasive presentation. Cureus. 2020;12(3):e7328.

Furia S, Nannini N, Pascarella A, Breda C. Mediastinal Rosai-Dorfman Disease with widespread lesions: when surgical biopsy is needed. Ann Thorac Surg. 2020;109(1):e45-7.

Kaseda K, Horio H, Hishima T, Hato T, Harada M. Rosai-Dorfman disease mimicking mediastinal lymphoma. Gen Thorac Cardiovasc Surg. 2011;59(5):385–7.

Brito J, Sousa V, Teixeira L, Carvalho L, Caseiro-Alves F. Rosai-Dorfman disease manifesting as a mediastinal mass with calcifications. J Thorac Imaging. 2010;25(2):W30-32.

Costa ALP, Silva NOE, Motta MP, Athanazio RA, Athanazio DA, Athanazio PRF. Soft tissue Rosai-Dorfman disease of the posterior mediastinum. J Bras Pneumol. 2009;35(7):717–20.

Prendes BL, Brinkman WT, Sengupta AL, Bavaria JE. Atypical presentation of extranodal Rosai-Dorfman disease. Ann Thorac Surg. 2009;87(2):616–8.

Lim R, Wittram C, Ferry JA, Shepard JAO. FDG PET of Rosai-Dorfman disease of the thymus. AJR Am J Roentgenol. 2004;182(2):514.

Li H, Li D, Xia J, Huang H, Jiao N, Zheng Z, et al. Radiological features of Rosai-Dorfman disease: case series and review of the literature. Clin Radiol. 2022;77(11):e799-805.

Covington MF, Koppula BR, Fine GC, Salem AE, Wiggins RH, Hoffman JM, et al. PET-CT in clinical adult oncology: II. Primary thoracic and breast malignancies. Cancers (Basel). 2022;14(11):2689.

Picarsic J, Jaffe R. Nosology and pathology of Langerhans cell histiocytosis. Hematol Oncol Clin North Am. 2015;29(5):799–823.

Diamond EL, Dagna L, Hyman DM, Cavalli G, Janku F, Estrada-Veras J, et al. Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease. Blood. 2014;124(4):483–92.

Ruby KN, Deng AC, Zhang J, LeBlanc RE, Linos KD, Yan S. Emperipolesis and S100 expression may be seen in cutaneous xanthogranulomas: a multi-institutional observation. J Cutan Pathol. 2018;45(9):667–73.

Rane SR, Parkhi M, Vishwasrao S, Nakate L. Non-Hodgkin’s lymphoma with extensive emperipolesis mimicking Rosai-Dorfman disease: a rare case report. Indian J Pathol Microbiol. 2019;62(2):319–22.

Delacrétaz F, Meugé-Moraw C, Anwar D, Borisch B, Chave JP. Sinus histiocytosis with massive lymphadenopathy (Rosai Dorfman disease) in an HIV-positive patient. Virchows Arch A Pathol Anat Histopathol. 1991;419(3):251–4.

Matter MS, Bihl M, Juskevicius D, Tzankov A. Is Rosai-Dorfman disease a reactve process? Detection of a MAP2K1 L115V mutation in a case of Rosai-Dorfman disease. Virchows Arch. 2017;471(4):545–7.

Diamond EL, Durham BH, Haroche J, Yao Z, Ma J, Parikh SA, et al. Diverse and targetable Kinase alterations drive histiocytic neoplasms. Cancer Discov. 2016;6(2):154–65.

Garces S, Medeiros LJ, Patel KP, Li S, Pina-Oviedo S, Li J, et al. Mutually exclusive recurrent KRAS and MAP2K1 mutations in Rosai-Dorfman disease. Mod Pathol. 2017;30(10):1367–77.

Lee LH, Gasilina A, Roychoudhury J, Clark J, McCormack FX, Pressey J, et al. Real-time genomic profiling of histiocytoses identifies early-kinase domain BRAF alterations while improving treatment outcomes. JCI Insight. 2023;2(3):e89473.

Shanmugam V, Margolskee E, Kluk M, Giorgadze T, Orazi A. Rosai-Dorfman Disease harboring an activating KRAS K117N Missense mutation. Head Neck Pathol. 2016;10(3):394–9.

Download references

Acknowledgements

Not applicable.

This work was supported by the National Natural Science Foundation of China (#82003284 to Linan Fang) and the Scientific Research Foundation of The First Hospital of Jilin University (#JDYY11202015 to Linan Fang).

Author information

Authors and affiliations.

Department of Thoracic Surgery, the First Hospital of Jilin University, Changchun, Jilin, China

Wenyu Zhang, Linan Fang & Wei Liu

Department of Radiology, the First Hospital of Jilin University, Changchun, Jilin, China

Department of Pathology, the First Hospital of Jilin University, Changchun, Jilin, China

Genetic Diagnosis Center, the First Hospital of Jilin University, Changchun, Jilin, China

You can also search for this author in PubMed   Google Scholar

Contributions

Wenyu Zhang collected and analyzed the patient’s medical records and wrote the original manuscript; Linan Fang, Jing Wang, Xiaobo Ma assisted in the analysis of patient records and gave clinical, imaging and pathological guidance; Xintong Hu provided and analyzed the patient’s genetic test report; Wei Liu drafted the manuscript. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Wei Liu .

Ethics declarations

Ethics approval and consent to participate.

The patient gave written informed consent for this case report and published images.

Consent for publication

Competing interests.

The authors declare no competing interests.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Zhang, W., Fang, L., Wang, J. et al. Mediastinal Rosai-Dorfman Disease with KRAS mutation case report and literature review. J Cardiothorac Surg 19 , 166 (2024). https://doi.org/10.1186/s13019-024-02668-0

Download citation

Received : 26 October 2023

Accepted : 20 March 2024

Published : 01 April 2024

DOI : https://doi.org/10.1186/s13019-024-02668-0

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

  • Rosai–Dorfman disease
  • Sinus histiocytosis with massive lymphadenopathy
  • Mediastinal diseases
  • Immunohistochemistry
  • KRAS mutation

Journal of Cardiothoracic Surgery

ISSN: 1749-8090

literature review including cases

9. Literature reports

9. Literature reports

' src=

“Scientific & medical literature is a significant source of information for the monitoring of the safety profile and of the risk benefit balance of medicinal products, particularly in relation to the detection of new safety signals or emerging safety issues.”

Literature report is any adverse drug reactions reported in

1. Published abstracts or

2. Articles in medical/scientific journals

3. Unpublished manuscripts involving case reports

4. Important safety findings or clinical studies including posters, letters to the editors, and associated communication from scientific meetings.

Current regulatory guidance:

  • Per the European Medicines Agency (EMA), MAHs are required to monitor local scientific and medical publications in countries where they have a marketing authorisation, irrespective of commercial status of products.  
  • The US Food and Drug Administration (FDA) requires submission of reports of serious, unexpected adverse drug reactions (ADRs) described in the scientific literature for products with the same active moiety as products marketed in the US, even though excipient, dosage forms, strengths, routes of administration and indications may vary.
  • The “literature” section of the periodic benefit– risk evaluation report (PBRER) requires a summary of new and significant safety findings for approved products, obtained from published peer-reviewed scientific literature or unpublished manuscripts during the reporting interval.
  • EMA guidelines also require inclusion of relevant applicable safety information for other active substances of the same class as the marketed drug. Consequently, any potentially relevant event identified in the literature may be considered an emerging safety issue requiring prompt immediate analysis and, if needed, corrective and preventive action.
  • Marketing authorisation holders are therefore expected to maintain awareness of possible publications through a systematic literature review of widely used reference databases (e.g. Medline, Excerpta Medica or Embase, Eudravigilance) no less frequently than once a week.

Summary of MLM guidelines:

  • MAHs should perform a systematic literature review of widely used reference databases no less frequently than once a week, unless the active substances of their products are present in the list of publications monitored by the European Medicines Agency (EMA) pursuant to Article 27 of Regulation (EC) No 726/2004.  
  • However, the MAHs need to continue to monitor all other medical literature not covered by the literature reference databases applied for the service by the EMA.
  • The MLM services of EMA started on September 1st, 2015. The full monitoring list contains more than 400 active substance groups. The EMA is responsible for monitoring selected medical literature and for entering identified reports of suspected adverse reactions in EudraVigilance.
  • The clock for reporting starts (Day 0) with awareness of a publication containing the minimum information for reporting.  
  • All the suspect adverse reactions found by the EMA in the listed medical literature, both serious (EU and non-EU) and non-serious (EU only), are not transmitted to MAHs, indeed they are transmitted to EudraVigilance and National Competent Authorities (NCAs) and made available to MAHs via EudraVigilance.  
  • The MAHs, however, should download and include these ICSRs in their safety database. They can provide an assessment of the case, describe a disagreement with, and/or alternatives to the diagnoses given by the primary source and/or indicate the degree of suspected relatedness of each medicinal product to the adverse reactions.
  • Where the MAH identifies a literature case entered by EMA to be a duplicate of the company’s individual case, which was previously submitted to EudraVigilance, there is a need to send a follow-up with the world-wide unique case identifier to EudraVigilance.  
  • In addition to the activities above, MAHs should also monitor the scientific and medical publications in local journals in countries where medicinal products have a MA.
  • Reports of suspected adverse reactions from the scientific and medical literature, including relevant published abstracts from meetings and draft manuscripts, should be reviewed and assessed by MAHs to identify and record possible ICSRs.

How the companies search relevant cases in database:

  • It is important that, in addition to searching for adverse events/reactions, the search is constructed to retrieve any special situation reports (e.g. pregnancy and breastfeeding, overdose, abuse, misuse, medication errors, occupational exposure) and, if relevant, use in specific patient populations (e.g. paediatrics).  
  • The search strategy should also be able to retrieve reports of off-label and compassionate use.  
  • As a general rule, searches should be performed using the active substance.  
  • For combination products, all active substances need to be included in the search strategy.  
  • Searches should not be routinely conducted that exclude unbranded products.  
  • It is common for authors of literature articles to refer to a generic medicinal product and the MAH should assume ownership of the product if it can not, with absolute certainty, confirm that the product is not its own.  
  • In addition, where the formulation is not specified, ownership of the product should be assumed.
  • For some regulators, reports should not be excluded based on the formulation.  
  • Articles referring to a class of drugs that describe a class effect, whilst not appropriate for ICSRs may be relevant for inclusion in periodic reports.  

Safety information: Below safety information is collected from literature reports.

  • New, unexpected serious and non-serious ICSR reports with a  reasonable causal association with the product.
  • Pregnancy outcomes (including termination) with no adverse  outcomes
  • Use in paediatric populations
  • Compassionate supply, named patient use
  • Lack of efficacy
  • Asymptomatic overdose, abuse or misuse
  • Medication error where no adverse events occurred
  • Important non-clinical safety results

Processing of Confirmed ICSRs

1. For literature reports of confirmed cases which can generate ICSRs, a full text of the citation is obtained and, if not in English, translated into English though it is not specified how/who does this or how long this takes).

2. The article is reviewed and the number of valid ICSRs is determined and seriousness/non-seriousness is noted.

3. An ICSR is then created along with a case narrative for serious cases. No narrative is prepared for non-serious ICSRs.

4. Causality assessment and relatedness also performed.

A regulatory reporting form with relevant medical information should be provided for each identifiable patient. The regulatory reporting time clock starts as soon as the MAH has knowledge that the case meets minimum criteria for reportability.

Examples of new events identified through literature review:

Nifedipine and Fatal Aplastic Anemia (1998): Article described a case- control study linking six cases of fatal aplastic anemia with nifedipine Report identified a Type B ADR (bizarre or idiosyncratic, dose independent and unpredictable reaction) Reference: Laporte JR, Ibanez L, Ballarin E, Perez E, Vidal X. Fatal Aplastic anemia associated with nifedipine. Lancet. 1998;352: 619-20

Tamsulosin and ‘Floppy Iris Syndrome” (2005): 15 cases were described in the literature in April, 2005 At the time of publication, none had been reported to the Regulatory Authorities! Reference: Chang DF, Campbell JR,. Intraoperative floppy iris syndrome associated with tamsulosin. J Cataract Refract Surg. 2005;3: 664-73

' src=

👍🏼👍🏼 Good information

' src=

Indetailed information about literature cases. Thans for your fabulous work.

' src=

Great information Author. Can you also provide information on how MLM is actually conducted and where companies can go wrong?

' src=

Great Information. It is very informative for all PV profession specifically freshers self understandable. Great efforts. Thank you

Leave a Reply Cancel reply

  • Case Report
  • Open access
  • Published: 02 April 2024

Shifting perspectives in coronary involvement of polyarteritis nodosa: case of 3-vessel occlusion treated with 4-vessel CABG and review of literature

  • Dylan J. Walter 1 , 3 ,
  • Grace E. Bigham 1 , 2 ,
  • Steven Lahti 2 &
  • Syed W. Haider 2  

BMC Cardiovascular Disorders volume  24 , Article number:  190 ( 2024 ) Cite this article

Metrics details

Polyarteritis Nodosa (PAN) is a systemic vasculitis (SV) historically thought to spare the coronary arteries. Coronary angiography and contemporary imaging reveal coronary stenosis and dilation, which are associated with significant morbidity and mortality. Coronary arteries in PAN are burdened with accelerated atherosclerosis from generalized inflammation adding to an inherent arteritic process. Traditional atherosclerotic risk factors fail to approximate risk. Few reports document coronary pathology and optimal therapy has been guarded.

Database publication query of English literature from 1990–2022.

Severity of coronary involvement eludes laboratory monitoring, but coronary disease associates with several clinical symptoms. Framingham risk factors inadequately approximate disease burden. Separating atherosclerosis from arteritis requires advanced angiographic methods. Therapy includes anticoagulation, immunosuppression and revascularization. PCI has been the mainstay, though stenting is confounded by vagarious alteration in luminal diameter and reports of neointimization soon after placement.

Conclusions

When graft selection avoids the vascular territory of SV’s, CABG offers definitive therapy. We have contributed report of a novel CABG configuration in addition to reviewing, updating and discussing the literature. Accumulating evidence suggests discrete clinical symptoms warrant suspicion for coronary involvement.

- Polyarteritis Nodosa causes coronary arteritis, commonly in asymptomatic patients

- Angiography with Optical Coherence Tomography or ultrasound differentiates the disease

- Laboratory monitoring does not correlate with coronary severity

- Coronary involvement is associated with abdominal pain, new hypertension and young age

- Standard atherosclerotic risk factors do not associate with coronary involvement

- PCI is complicated by arterial stenosis adjacent to dilation and rapid neo-intimal expansion

- CABG offers definitive therapy, though selection of graft material is complex

Peer Review reports

Introduction

Coronary artery disease (CAD) is potentiated by systemic inflammation, evidenced by earlier onset and increased incidence among chronic inflammatory and autoimmune conditions, such as rheumatoid arthritis, systemic lupus, and HIV [ 1 ]. CAD in primary systemic vascular diseases (PSV) is well-documented and inherent to both a generalized inflammatory state and the underlying disease mechanism itself [ 2 , 3 ]. Systemic disease may be present in up to 20% of young patients (< 40y) with premature and advanced CAD [ 4 ].

Polyarteritis nodosa (PAN) is a medium vessel necrotizing vasculitis causing intimal proliferation, luminal narrowing and potential for thrombosis, ischemia or infarction. Vessel wall inflammation may contribute to vessel aneurysm, dissection and even rupture [ 2 , 5 , 6 ]. Severe disease entails renal involvement, mononeuritis multiplex, muscle or mesenteric involvement, limb or digit ischemia and coronary involvement [ 7 ]. Individuals with necrotizing arteritis have significantly higher 5-year mortality compared to those without cardiac manifestation [ 8 ]. Yet, few reports have characterized cardiac manifestations of PAN, with most cases being discovered incidentally or during post-mortem analysis [ 5 , 9 , 10 ].

An annual incidence of 0–1.6 cases per million persons, onset predominantly in the 5th or 6th decade and prevalence of ~ 31 cases per million persons in European countries besets characterization of PAN as an orphan disease [ 4 ]. Effects on coronary vasculature are under-represented, though stenosis, ectasia, aneurysm, dissection, rupture, and sudden cardiac death are documented [ 2 , 5 , 6 ]. Historically, coronary disease in PAN was thought rare and less significant compared to the burdens of cutaneous, renal, neurologic, and mesenteric pathology. Recent literature suggests coronary involvement is more common than previously thought. Moreover, retrospective data points to younger age (age < 40), celiac involvement and new-onset hypertension as strong predictors [ 4 ]. Treatment modalities are convoluted owing to reports of neo-intimal growth in implanted stents causing re-stenosis and early post-operative rupture of vasculature in surgical patients [ 11 , 4 ]. Consequently, sparsity in literature documenting successful coronary bypass in this population exists.

Herein, we summarize recent updated literature offering perspective on therapeutic strategy for coronary PAN. Additionally, we present a patient with chronic epigastric pain and new diagnosis of PAN found to have 3-vessel occlusive disease treated successfully with 4-vessel CABG.

PubMEd query filtered for English literature from 1990 – 2022. Query phrases “Polyarteritis Nodosa and Coronary Artery Disease” and “Polyarteritis Nodosa and Coronary Artery Bypass Grafting” resulted in 29 and 8 hits, respectively. Literature hits with primary focus devoted to polyarteritis and coronary artery disease in adults were reviewed. References for each study selected were screened. Additional articles known to the authors relevant to coronary arteritis not contained in key search phrases were included in discussion.

A 53-year-old African American male with history of hypertension, hyperlipidemia, former tobacco use (20-pack year history), asthma, and obesity presented to the internal medicine clinic with sharp chest pain for 6 months. The pain “came and went" without relationship to exertion but worsened at night and was triggered by eating. Associated shortness of breath, with no response to albuterol inhaler was noted. He was prescribed proton pump inhibitor with isosorbide mononitrate and scheduled for an outpatient stress test. That week, he developed unrelenting epigastric and left upper quadrant abdominal pain and presented to the emergency department where abdominal CT without contrast revealed splenic infarction (Fig.  1 ). EKG showed sinus rhythm without segment or ST abnormalities. Laboratory workup was remarkable for elevated inflammatory markers: ESR 33 and hsCRP 14 mg/L. His troponin level, urinalysis and infectious work-up, including hepatitis panel and hepatitis B serology were unremarkable.

figure 1

CT Abdomen – splenic infarction, hypoechoic lesion measured at 4.2 cm in length

He was admitted for evaluation and had a negative hypercoagulability and polycythemia workup including D-dimer, Ferritin, APLS, Factor V Leiden assay, Prothrombin gene mutation, antithrombin III activity, homocysteine, protein C and S, ANA, JAK2, EPO, Hepatitis and HIV testing. However, episodic bouts of retrosternal chest pain unresponsive to nitroglycerin continued. Serial EKGs were negative for ischemic changes. The surgical team pursued contrast CT for operative planning which uncovered luminal narrowing of the celiac axis and its major branches (proximal hepatic and splenic arteries) (Figs.  2 and  3 a). CT also revealed a 3.3 cm saccular aneurysm of the abdominal aorta above the bifurcation with additional aneurysmal abnormalities of the right (measuring 1.8 cm) and left Iliac artery (measuring 2 cm diameter) (Fig.  3 ). Rheumatology evaluated for vasculitis; but felt the distribution of vascular lesions were inconsistent with typical PAN referencing limited celiac involvement with only initial segments of the splenic and hepatic arteries being affected. He underwent trans-thoracic echocardiography (TTE) which demonstrated a hyperdynamic left ventricle with an estimated ejection fraction of 65–70% and mild hypokinesis of inferior and infero-septal basal segments. Further testing for ANA, MPO, PR-3 and RF was negative but C3 and C4 levels were elevated. A joint radiology-rheumatology conference to decide further management steps, sent the patient for MRI/MRA which revealed persistent narrowing and inflammation of the celiac, splenic and common hepatic artery with pre-contrast T1 hyperintensity and post-contrast enhancement in the arterial wall. IV methylprednisolone was subsequentially initiated.

figure 2

CT Angiography – Narrowing and Dilation of the celiac axis and proximal branches

figure 3

a CT Angiography – Abdominal Aortic Aneurysm, Celiac Trunk and Proximal branch narrowing ( b ) MRA – Abdominal Aortic Aneurysm and bilateral Femoral Artery Aneurysm

Episodic bouts of chest pain persisted without EKG change; repeated troponins remained negative. Formal cardiac evaluation for inferior wall motion abnormalities (WMA) was pursued. Cardiac MRI showed LV concentric hypertrophy with normal function, no wall motion abnormalities and absence of late gadolinium enhancement or other signs of infiltrative disease, ischemia or fibrosis. He completed a 4-day course of methylprednisolone (60 mg IV) and was discharged on oral prednisone (60 mg PO) with an unconfirmed diagnosis of PAN.

In the outpatient setting, he underwent PET scan, notably unremarkable. Repeat CTA confirmed luminal narrowing of the common hepatic and proximal splenic arteries, however, now with new radiologic evidence of a beading appearance in the SMA and celiac trunk. With the combination of laboratory and imaging findings, PAN was determined to be the unifying clinical diagnosis. Mesenteric involvement raised concerns for advanced disease and motivated the decision to proceed with cyclophosphamide (Cyc) infusion therapy.

Prior to Cyc initiation, unrelenting epigastric and left upper quadrant abdominal pain prompted presentation. Again, EKG and troponin levels were negative. Most features of the pain episodes aligned with prior, including intermittent nature, association with food consumption, and absent response to nitroglycerin. However, he now had new onset bilateral numbness in his hands and feet. Inflammatory markers showed CRP 5 (4 at discharge) and ESR 49 (8 at discharge). Esophageal x-ray was negative for abnormality; upper endoscopy for mucosal ulceration was unrevealing. Coronary CT was pursued and showed severe coronary calcification with Agatston score of 981 (99th percentile), preventing analysis of stenosis. Left heart catheterization (LHC) revealed 3-vessel disease, with 90% stenosis of the LAD, 70% of the 2nd diagonal, 100% of the obtuse marginal 1, 70% of the circumflex and 90% RCA occlusion (Fig.  4 ). He was discharged on antianginals with referral for CABG.

figure 4

Coronary Angiography – ( a ) RCA, ( b ) LAD and ( c ) LCx – Each coronary artery showed evidence of diffuse, alternating stenosis and dilatation

Five days post-discharge, successful 4-vessel CABG with skeletonized LIMA technique ( LIMA-LAD and SVG-OM-LPDA-RPDA) was completed under 89 min of bypass time; the 2nd diagonal was small rendering inability to bypass. Preoperatively, LIMA flow was excellent; Intraoperatively, 100 mg hydrocortisone was given for his subacute history of prednisone therapy. His Postoperative surgical graft flow was excellent with easy separation from bypass and and echocardiogram following the procedure showed LVEF 60%. Discharge was post-operative day 7, with medications including aspirin, clopidogrel, metoprolol, rosuvastatin, olmesartan and referral for cardiac rehabilitation. Medical management of PAN included daily prednisone and follow-up with rheumatology to determine optimal timing for initiation of cyclophosphamide while recovering.

Since the inauguration of literature covering PAN coronary arteritis, report of CABG has been rare and successful surgical revascularization in patients with diffuse 3-vessel arteritis is limited to 3 cases (Table  4 ) [ 7 ]. PCI presently encompasses the mainstay of treatment but low case numbers, difficulty in stent placement related to erratic luminal diameter and report of neo-intimal media expansion into apposed stents leave unsettled the optimal revascularization strategy [ 4 , 7 , 11 , 12 ]. A minimally invasive strategy is reasonable in patients with 1 or 2-vessel disease but owing to the mechanism of PAN as a PSV, surgical revascularization, when composed of graft material having less propensity for the systemic pathophysiology of PAN than the coronary arteries, offers a definitive strategy to patients with diffuse 3-vessel disease. In the first case of a 4-vessel CABG configured LIMA-LAD and SVG-OM-LPDA-RPDA, we report excellent post-operative patency and flow.

More broadly, PSVs are categorized by the distribution of vasculature affected (i.e., small, medium, and large). Historically, PSVs are thought to spare the coronary arteries, though recent contributions report 10–50%, 10–45% and 25–30% rates of coronary involvement with PAN, Takayasu and Kawasaki’s vasculitis, respectively [ 13 ]. PAN, first described in 1866, is a PSV causing inflammation in medium-sized vessels, with infrequent small vessel involvement [ 14 ]. Literature first discusses known PAN coronary arteritis in 1948 [ 15 ]. Associations of congestive heart failure, hypertension, pericarditis, and arrhythmia are well documented; yet the bulk of literature and teaching suggest severe coronary disease is rare. Recent case reports and the first retrospective cohort study now argue this point. Furthermore, with modern interventional therapies, a summation of outcomes is long due.

Following histopathologic and clinical associations between PAN and coronary disease, several sought to characterize coronary pathology. Post-mortem analysis of 66 PAN cases by Holsinger and colleagues revealed arteritis in 41 patients (62%); among which presenting symptoms are displayed in Table  1 [ 9 ]. Overall, 89% of hearts with MI pathology also had arteritis [ 9 ]. A separate team conducted necropsy of 36 patients with PAN reporting 18 (50%) had histological evidence of coronary involvement [ 10 ]. (Cassling et al.) tabulated cumulative autopsy confirmed coronary diseased PAN cases in 1985, leading those after him to posit typical coronary syndrome symptoms were rare opposite of systemic hypertension, heart failure, and renal failure, the most common presenting symptoms (Table  1 ) [ 16 ]. Cumulatively, the mean survival in untreated individuals with coronary involvement was 8 months contrasting 5 years in treated individuals [ 16 ].

The pathologic mechanism of coronary arteritis is characterized by three phases (acute, healing, healed), based on histological change. The acute phase is marked by fibrinoid necrosis of the vessel wall and an associated mixed inflammatory infiltrate causing disruption of the media and internal elastic lamina. As vessel wall necrosis and inflammation progresses, perivascular structures are affected. partitioning of inflammatory infiltrates allows fibroblast intrusion, marking the onset of healing. These cells’ products culminate in healed lesions, evidenced by fibrosis, calcium deposition and narrowing of the vessel lumen [ 16 , 17 ]. Medial invasion and disruption are culprits for vascular aneurysm and thrombosis (acute) while fibroblast proliferation generates luminal stenosis. High degrees of vasculitic stenosis present risk of diagnostic mistake for atherosclerosis, differentiation is a challenge [ 11 ].

The acute pathology of coronary PAN (myocardial infarction, dissection, rupture) has been demonstrated in case reports of living patients. Most reports align with our understanding of disease progression as described above. Though limited reports have called into question the mechanisms underlying symptom development, such as (Rajini et al.’s) case of a patient suffering massive anterior wall myocardial infarction (MI) despite angiographically clean vessels and myocardial biopsy without signs of myocarditis. Ultimately, concluding with the postulation that coronary vasospasm underlies some cardiac manifestations of PAN [ 18 ]. (Harada et al.) similarly offers a case of MI with non-obstructed coronary arteries (MINOCA) by angiography causing sudden cardiac death, after which autopsy confirmed absence of coronary disease [ 19 ]. Across the general population, MINOCA rates reach 25% in persons under 35 and decrease with age. Since true incidence of coronary PAN is unclear, these reports may indicate coronary PAN can cause MI even when stenosis, aneurysm, dissection, and thrombus are absent.

More recently, (Huang et al.) reviewed 34 cases mentioning cardiac involvement in PAN and reported the symptoms at presentation (Table  1 ) [ 12 ]. Additional points contesting the 1985 report, along with coronary event rates are summarized in (Table  1 ) [ 7 , 12 , 16 ]. Lesion characterization by angiography was available for 23 patients while 14 had autopsy. Table 1 shows the incidence of stenosis, aneurysm & dissection. Seventy-nine percent (79%, 27) of the patients had coronary stenosis, with single vessel disease being most common (11/27, 40%) (RCA 15%, LAD 12%) and diffuse 3-vessel disease least common (7/27, 25.9%). Significance of vessel distribution remains vague when comparing a recent retrospective study that identified 19 patients with coronary lesions [ 4 ]. Among these, 1 and 3-vessel disease were most frequent (8/19, 42% & 8/19, 42% respectively) followed by 2-vessel disease (3/19, 16%) [ 4 ]. 15 (79%), 14 (74%) and 9 (47%) cases involved the LAD, RCA and LCX, respectively.. The severity of coronary PAN was reflected by 50% (15/30) mortality in a mean 8-month follow-up; speaking to unmet needs for additional work discernably impacting patient outcomes [ 12 ].

Our patient had atypical anginal, epigastric and dyspneic symptoms, aligning with frequent symptomatology cited by prior reports (Table  1 ). His CAG showed 3-vessel disease of the LAD, Circumflex and RCA, again consistent with prior work and harmonious with the fact that PAN is a systemic disease affecting vascular territories globally.

Complicating screening and disease recognition, coronary PAN appears to establish and progress in patients who are either undiagnosed or lacking “classic” systemic manifestations of PSV’s. (Huang et al.) calculated only 26.5% of patients were diagnosed or known to have PAN when presenting with cardiac symptoms [ 12 ]. Others highlighted a patient developing new coronary lesions within a 5-day period [ 5 ]. Our patient was asymptomatic for several years, developed insidious anginal and abdominal pain for 6 months, and subsequently suffered acute symptom exacerbation as acute splenic infarction, culminating in his diagnosis. Less than 2 months passed between diagnosis and onset of dyspnea, his cardiac investigations and intervention. Further entangling recognition, patients with otherwise “stable,” non-cardiac PAN have developed coronary arteritis in the absence of symptoms or elevated inflammatory markers (CRP, ESR) preventing intervention and risk reduction therapies [ 12 , 20 , 21 , 22 ]. Retrospective study revealed that only ~ 52% of patients with coronary PAN had elevated ESR and/or CRP [ 4 ]. Likewise, other works showed clinical and laboratory methods are often unsuccessful in predicting new findings/positive imaging across visceral organ systems, a theme seemingly reflected in coronary PAN [ 23 ]. Incongruence relating to cardiac disease burden and clinical indicators underscores calls for increased surveillance among at risk patients, though the question of whom to screen is one we are only beginning to unravel [ 4 , 12 , 24 , 25 ].

The American College of Rheumatology (ACR) guidelines define the diagnosis of PAN by presence of (at least) 3 diagnostic criteria (Table  2 ) [ 26 ]. No routine surveillance or imaging is recommended during clinically quiescent disease (Table  3 ) [ 7 ]. In lieu of standardized screening, the first retrospective study of risk factors was conducted [ 4 ]. In the cohort of 145 PAN patients, 19 had coronary involvement. Remarkable findings between patients with and without coronary disease included the absence of significant difference in standard atherosclerosis risk factors (smoking, hypertension, diabetes, hyperlipidemia),. while multi-variate analysis revealed new-onset hypertension (OR 6.668, 95% CI, P  = 0.003) and celiac artery involvement (OR 3.722, 95% CI, P  = 0.003) carry significant risk for coronary involvement. Both features (Figs.  2 and 3 a) were prominent in our case. Contrarily, weight loss was a protective factor for coronary disease while coronary disease itself increased risk of cranial, carotid, renal, celiac and lower extremity disease [ 4 ]. Despite sample size, (Lai et al.’s) study is the first to ascribe significance to risk factors. Knowledge of risk factors and discrepancies between symptoms and/or lab markers with development and progression of coronary arteritis should encourage physicians to consider screening with imaging in defined populations.

Identification of coronary lesions in PAN is challenging. Computed tomography angiography (CTA) and coronary angiography (CAG) risk lesion identification without ability to define etiology (i.e., arteritis/inflammation vs. atherosclerosis). CAG with optical coherence (OC) is one method of differentiating arteritis opposed to atheroma but mandates invasive study [ 11 ]. CAG with intravascular ultrasound (IVUS) and cardiac magnetic resonance (CMR) are invasive and non-invasive methods of visualizing the vessel lumen. IVUS offers practical benefits during placement of interventional devices in a mixed stenotic-aneurysmal patterned vessel. Fluorodeoxyglucose-positron emission tomography (FDG-PET) reportedly approaches 92% and 100% sensitivity and specificity for large vessel vasculitis [ 28 ]. Less evidence supports FDG-PET in medium PSV’s making it unsurprising that FDG-PET scanning was negative in our patient. Nonetheless, detecting metabolic uptake as a marker of inflammatory change that precedes anatomic or functional disturbance captured in CAG, CT and MRI could potentiate medical interventions.

Subsidiary the uncommon nature of coronary PAN, comment on treatment and therapy remains guarded [ 29 ]. Strategies include immunosuppressive therapy (ISx) alone and ISx with re-vascularization. These recommendations, not specific to coronary involvement, are provided by the ACR and include glucocorticoids (GC) with Cyclophosphamide (Cyc) as first line, with substitution of (Cyc) for non-GC ISx agents (I.e., Azathioprine, Methotrexate) in non-severe disease [ 7 ] (Table  3 ). Therapy duration was studied by (Guillevin and colleagues) who noted 12 doses of monthly Cyc along with GC is superior to a 6-month strategy, indicated by higher survival (HR 0.44, p 0.02) and sustained remission (HR 0.34, p 0.02) at 32-month follow-up [ 30 ].

Important to coronary PAN, therapeutic consideration includes thrombosis risk. Aside from the risk associated with generalized vascular inflammation, other works show patients with coronary PAN circulate anti-cardiolipin antibodies in greater frequency (~ twofold) than patients without coronary lesions [ 4 ]. Further, the historic necropsy studies revealed cases of thrombus within aneurysmal arterial segments [ 9 , 10 ]. Mechanistically, acute myocardial infarction (AMI) in PAN may occur by atherosclerotic deposition resulting in acute plaque rupture similarly to AMI in the general population, but complete thrombotic occlusion in the absence of atherosclerotic pathology has also occurred [ 31 ]. Preventative therapy should be provided for all patients not having excessive risk of rupture.

Revascularization may be indicated when patients' symptoms or acuity are incompatible with timelines of medical therapy. (Table  4 ) highlights the literature's prior revascularization cases and outcomes; clearly, there remains paucity in both quantity and longitudinal follow-up regarding outcomes. Importantly, the safety of CAG in actively inflamed vessels is proven, dating back to 1981 and should not steer physicians away from meaningful interventional opportunities [ 17 ].

Of the 19 patients studied by (Lai et al.), 3 received intervention (2 DES and 1 CABG). At 1 year follow-up, 1 patient with DES had in-stent restenosis while the other retained stent patency [ 4 ] (Table  4 ). (Huang et al.) contributed the case of a 22-year-old male with 3-vessel stenosis presenting with AMI, receiving stent placement to the OM1 [ 12 ]. Four additional stent placements were detailed in the literature. PCI intervention has ranged from 1 to 3-vessel disease requiring multi-stage angioplasty (Table  4 ). Generally, PCI achieves revascularization and resolution of symptoms, albeit limited longitudinal follow-up. Confounding the good outcomes are single case incidents of in-stent restenosis at 1 year and rapid neo-endothelization within 2 previously placed DES’s [ 4 , 11 ]. In review, both authors raise the issue of placement technique and stent apposition difficulties as possible culprits to such outcomes. Adequacy of concomitant immunosuppressive regimen is another consideration. The role of which may be illuminated by the absent neo-endothelization after placement of a second set of stents with more intensive adjunct medical therapy [ 11 ].

Treatment of non-occlusive lesions (aneurysm, dissection) is equally imperative owing to risk of rupture, fistula, thromboembolism and angina [ 29 , 35 ]. Medical therapy reduced aneurysm size in non-coronary lesions. Additionally, follow-up study of 4 prospective trials showed GC & Isx therapy prolong survival in patients with Five Factor Scores (FFS) > 2 [ 36 ]. PCI with stent placement is the mainstay of aneurysm therapy but stent apposition in vessels with multiple points of aneurysm and stenosis is technically challenging and not well studied, disturbing current interventional knowledge. Endovascular coiling is another modality, and there is reported success in alleviating anginal symptoms in a patient with a large LAD CAA [ 29 ]. Techniques such as these may offer additional benefits as cases accumulate.

The surgical approach to therapy has generated mixed results and raises concern over graft vessel candidate(s) [ 2 , 6 , 22 ]. For instance, in Kawasaki disease, left internal mammary artery (LIMA) graft during coronary artery bypass graft (CABG) procedures performed in adults demonstrate 15-year patency at rates as high as 91% [ 37 ]. As such, consensus among surgeons has been preference for LIMA over other vessels. Sparse literature and absent longitudinal study prevent such insight for PAN. Takayasu arteritis (TA) offers another example. Here, IMA’s are avoided in favor of saphenous vein grafts (SVG) because subclavian stenosis, has been associated with TA and would compromise flow through a LIMA. In PAN, one case has documented distal aneurysm and occlusion in the axillary and brachial arteries of a patient with coronary PAN, but no report of subclavian disease exists [ 38 ]. Others described IMA disease in females, introducing concern for graft failure in IMA anastomosis [ 39 ]. Further confounding graft selection is report of an IMA graft artery without significant stenosis on CTA discovered to be markedly stenotic intraoperatively, culminating in abortion of vessel harvest [ 6 , 22 ].

Both the pathology and anatomic location of PAN tempt comment regarding preference for utilization of venous grafts which might avoid direct insult by arteritis. Optimism for this strategy is offset by bypass surgery where 1 patient died after IVC rupture on post-operative day #2 despite laboratory values lacking inflammation [ 4 ]. This event reinforces the diffuse and systemic nature of such inflammatory states. In the past, successful grafts used the LIMA and SVG [ 2 , 24 ] and SVG alone [ 22 , 32 , 33 ]. In each surgical revascularization, preoperative inflammation level was normal, assessed by CRP and ESR. Making the prudent point that those treated with revascularization should also receive medical therapy to reduce inflammatory burden and perhaps breeding the question of whether recent updates in CAD therapies to include colchicine may have synergistic utility in the PAN population. Failure of suppression may increase risk of graft failure or delay healing.

The first case to utilize bilateral IMA’s as graft material was recently reported [ 6 ]. A 21-year-old female diagnosed with PAN 1 after an event of intestinal ischemia was clinically asymptomatic from a cardiac perspective, but coronary CT revealed 3-vessel aneurysm, stenosis and intramural thrombus. Decision for CABG was complicated by positive Allen’s test and anatomic length preventing graft of the radial artery and gastroepiploic artery, respectively. Yet, the patients' age was felt to necessitate use of arterial material. LIMA-LAD with T-composite anastomosis to RIMA-OM1-PDA was successful.

Polyarteritis Nodosa is a rare SVD predominantly affecting medium arteries. Previous teaching and intervention focused on renal, neurological, gastrointestinal and cutaneous involvements, while coronary involvement was considered rare. Accumulating evidence suggests coronary arteritis confers significant morbidity and mortality to these patients. CAG remains the standard diagnostic tool, while new modalities such as OC may be required to differentiate inflammatory change from atherosclerotic process. Identifying risk for coronary involvement (new hypertension, celiac involvement) assists physicians in screening appropriate populations. Standard atherosclerotic risk factors do not approximate risk for coronary disease. PCI with stenting is preferred therapy for occlusive and aneurysmal disease. CABG is another option, especially in 3-vessel disease, but limited case numbers portend careful graft selection. Optimal interventional strategy includes preoperative reduction of inflammatory burden followed by post-operative ISx in conjunction with anti-coagulation.

Herein, we report a case of 3-vessel occlusive disease culminating in a 4-vessel CABG schema not available in prior literature. Though recent works carried our knowledge forward, significant opportunities to advance clinical practice in population screening, interventional materials and optimization of medical management abound.

Availability of data and materials

All data generated or analysed during this study are included in this published article.

Abbreviations

Acute myocardial infarction

Azathioprine

Bare metal stent

Coronary artery bypass graft

  • Coronary artery disease

Computed tomography angiography

Cyclophosphamide

Drug-eluting stent

Fluorodeoxyglucose-positron emission tomography

Five factor score

Glucocorticoids

Internal mammary artery

Immunosuppression

Intravascular ultrasound

Not Reported

Left anterior descending

Left circumflex

Left heart catheterization

Left internal mammary artery

Left main coronary

Left posterior descending artery

Myocardial Infarction with non-obstructed coronary arteries

Methotrexate

Optical coherence

Obtuse marginal

Percutaneous coronary intervention

Posterior descending

Posterolateral

Primary systemic vascular disease

Right coronary artery

Right posterior descending artery

Systemic vasculitide

Systemic vascular disease

Saphenous vein graft

Takayasu's arteritis

Transthoracic echocardiogram

Wall motion abnormalities

Blaum C, Brunner FJ, Kroger F, Braetz J, Lorenz T, Gossling A, et al. Modifiable lifestyle risk factors and C-reactive protein in patients with coronary artery disease: Implications for an anti-inflammatory treatment target population. Eur J Prev Cardiol. 2021;28(2):152–8.

Article   PubMed   Google Scholar  

Yanagawa B, Kumar P, Tsuneyoshi H, Kachel E, Massad E, Moussa F, et al. Coronary artery bypass in the context of polyarteritis nodosa. Ann Thorac Surg. 2010;89(2):623–5.

Owlia MB, Mostafavi Pour Manshadi SM, Naderi N. Cardiac manifestations of rheumatological conditions: a narrative review. ISRN Rheumatol. 2012;2012:463620.

Lai J, Zhao L, Zhong H, Zhou J, Guo X, Xu D, et al. Characteristics and outcomes of coronary artery involvement in polyarteritis Nodosa. Can J Cardiol. 2021;37(6):895–903.

Chu KH, Menapace FJ, Blankenship JC, Hausch R, Harrington T. Polyarteritis nodosa presenting as acute myocardial infarction with coronary dissection. Cathet Cardiovasc Diagn. 1998;44(3):320–4.

Article   CAS   PubMed   Google Scholar  

Shiozaki Y, Morita K, Sawa S, Saito S, Niinami H. Coronary artery bypass using bilateral internal thoracic artery grafts in polyarteritis nodosa. J Card Surg. 2021;36(8):2979–81.

Chung SA, Gorelik M, Langford CA, Maz M, Abril A, Guyatt G, et al. 2021 American College of Rheumatology/Vasculitis foundation guideline for the management of polyarteritis nodosa. Arthritis & Rheumatology. 2021;73(8):1384–93.

Article   Google Scholar  

Guillevin L, Pagnoux C, Seror R, Mahr A, Mouthon L, Toumelin PL, et al. The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine (Baltimore). 2011;90(1):19–27.

Holsinger DR, Osmundson PJ, Edwards JE. The heart in periarteritis nodosa. Circulation. 1962;25:610–8.

Schrader ML, Hochman JS, Bulkley BH. The heart in polyarteritis nodosa: a clinicopathologic study. Am Heart J. 1985;109(6):1353–9.

Lewandowski M, Goracy J, Kossuth I, Peregud-Pogorzelska M. Vasculitis or coronary atherosclerosis? Optical coherence tomography images in polyarteritis nodosa. Kardiol Pol. 2018;76(4):813.

Huang H, Gong Y, Guo L, Zhang Z. Insidious coronary artery disease ina young patient with polyarteritisnodosa: a case report and literature review. BMC Cardiovasc Disord. 2021;21(1):115.

Article   PubMed   PubMed Central   Google Scholar  

Gori T. Coronary Vasculitis. Biomedicines. 2021;9(6):2–16.

Stanton M, Tiwari V. Polyarteritis Nodosa. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2022, StatPearls Publishing LLC.; 2022.

Daniels AC, Watson GA. Polyarteritis nodosa involving coronary arteries, pancreas, ileum kidneys and meninges. Calif Med. 1948;68(5):394–6.

CAS   PubMed   Google Scholar  

Cassling RS, Lortz JB, Olson DR, Hubbard TF, McManus BM. Fatal vasculitis (periarteritis nodosa) of the coronary arteries: angiographic ambiguities and absence of aneurysms at autopsy. J Am Coll Cardiol. 1985;6(3):707–14.

Przybojewski J. Polyarteritis nodosa in the adult-report of a case with repeated myocardial infarction and a review of cardiac involvement. S Afr Med J. 1981;60(13):512–8.

Rajani RM, Dalvi BV, D’Silva SA, Lokhandwala YY, Kale PA. Acute myocardial infarction with normal coronary arteries in a case of polyarteritis nodosa: possible role of coronary artery spasm. Postgrad Med J. 1991;67(783):78–80.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Harada Y, Suzuki T, Shinagawa T, Yoshimoto T. Cardiac arrest in a patient with polyarteritis nodosa. Intern Med. 2013;52(24):2759–63.

Canpolat U, Dural M, Atalar E. Acute inferior myocardial infarction in a young female patient with polyarteritis nodosa. Herz. 2012;37(4):461–3.

Kastner D, Gaffney M, Tak T. Polyarteritis nodosa and myocardial infarction. Can J Cardiol. 2000;16(4):515–8.

Yamamoto Y, Iino K, Ueda H, No H, Nishida Y, Takago S, et al. Coronary artery bypass grafting in a patient with polyarteritis nodosa. Ann Thorac Surg. 2017;103(5):e431–3.

Mandell BF. Angiography and polyarteritis nodosa. West J Med. 1988;149(3):344–5.

CAS   PubMed   PubMed Central   Google Scholar  

Kawajiri H, Koh E, Masuda N, Kira H, Yamasaki T. Coronary artery bypass grafting in a patient with polyarteritis nodosa presenting with acute myocardial infarction and multiple coronary aneurysms. Ann Thorac Cardiovasc Surg. 2014;20(Suppl):769–72.

Xie Y, Seidman MA. Inflammatory comments in coronary artery disease: when to suspect polyarteritis nodosa or other primary systemic vasculitis. Can J Cardiol. 2021;37(6):830–2.

Lightfoot RW Jr, Michel BA, Bloch DA, Hunder GG, Zvaifler NJ, McShane DJ, et al. The American college of rheumatology 1990 criteria for the classification of polyarteritis nodosa. Arthritis Rheum. 1990;33(8):1088–93.

Chung SA, Gorelik M, Langford CA, Maz M, Abril A, Guyatt G, et al. 2021 American college of Rheumatology/Vasculitis foundation guideline for the management of polyarteritis nodosa. Arthritis Rheumatol. 2021;73(8):1384–93.

Khanna S, Garikapati K, Goh DSL, Cho K, Lo P, Bhojaraja MV, et al. Coronary artery vasculitis: a review of current literature. BMC Cardiovasc Disord. 2021;21(1):7.

Bayturan Ö, Tarhan S, Çöpkıran Ö, Düzgün F, Tezcan UK. Endovascular coil treatment of a coronary artery aneurysm related to polyarteritis nodosa. Anatol J Cardiol. 2017;18(5):370–2.

PubMed   PubMed Central   Google Scholar  

Guillevin L, Cohen P, Mahr A, Arène JP, Mouthon L, Puéchal X, et al. Treatment of polyarteritis nodosa and microscopic polyangiitis with poor prognosis factors: a prospective trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in sixty-five patients. Arthritis Rheum. 2003;49(1):93–100.

Reindl M, Reinstadler SJ, Feistritzer HJ, Mayr A, Klug G, Marschang P, et al. Acute myocardial infarction as a manifestation of systemic vasculitis. Wien Klin Wochenschr. 2016;128(21–22):841–3.

Ucar HI, Oc M, Tok M, Ozyuksel A, Oc B, Farsak B. Coronary artery bypass with saphenous vein graft in a middle-aged patient with polyarteritis nodosa. Anadolu Kardiyol Derg. 2007;7(2):231–2.

PubMed   Google Scholar  

Ebersberger U, Rieber J, Wellmann P, Goebel C, Gansera B. Polyarteritis nodosa causing a vast coronary artery aneurysm. J Am Coll Cardiol. 2015;65(5):e1-2.

Wagner AD, Feist T, Prondzinsky R, Fleig WE, Keysser G. Joint and muscle pain with mononeuritis multiplex, tetraparesis, and myocardial infarction in a previously healthy adult. Ann Rheum Dis. 2001;60(11):1003–6.

Iakovou I, Colombo A. Treatment of a coronary aneurysm involving bifurcation with the use of a custom-made polytetrafluoroethylene-covered bifurcation stent system. Catheter Cardiovasc Interv. 2005;64(2):169–72.

Gayraud M, Guillevin L, le Toumelin P, Cohen P, Lhote F, Casassus P, et al. Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: analysis of four prospective trials including 278 patients. Arthritis Rheum. 2001;44(3):666–75.

Tsuda E, Kitamura S, Cooperative Study Group of J. National survey of coronary artery bypass grafting for coronary stenosis caused by Kawasaki disease in Japan. Circulation. 2004;110(11 Suppl 1):II61–6.

Chung DC, Choi JE, Song YK, Lim AL, Park KH, Choi YJ. Polyarteritis nodosa complicated by chronic total occlusion accompanying aneurysms on all coronary arteries. Korean Circ J. 2012;42(8):568–70.

Trueb RM, Scheidegger EP, Pericin M, Singh A, Hoffmann U, Sauvant G, et al. Periarteritis nodosa presenting as a breast lesion: report of a case and review of the literature. Br J Dermatol. 1999;141(6):1117–21.

Download references

Acknowledgements

There are no further acknowledgements.

Disclosures

None, the authors have no financial or other disclosure.

The present report was generated without funding.

Author information

Authors and affiliations.

Department of Internal Medicine, MedStar Georgetown University Hospital, Washington DC, 20007, USA

Dylan J. Walter & Grace E. Bigham

Cardiovascular Diseases, MedStar Washington Hospital Center, Washington DC, 20010, USA

Grace E. Bigham, Steven Lahti & Syed W. Haider

Division of Cardiovascular Sciences, , USF Morsani College of Medicine, 2 Tampa General, Circle, STC 5Th Floor, Tampa, Fl, 33606, USA

Dylan J. Walter

You can also search for this author in PubMed   Google Scholar

Contributions

D.W. and G.B. jointly co-authored the article. D.W., G.B., S.L. and S.H. independently analyzed, contributed and crosschecked the findings of the cited literature reviews.

Corresponding author

Correspondence to Dylan J. Walter .

Ethics declarations

Ethics approval and consent to participate.

This article complies with Georgetown University Ethical Code of Conduct and appropriate steps for identity protection have been taken per guidelines of the office of Regulatory Affairs.

Consent for publication

Written, informed consent for publication of laboratory findings and diagnostic imaging, along with all clinical documents related to and communicated in the present case was obtained directly from the subject involved.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Walter, D.J., Bigham, G.E., Lahti, S. et al. Shifting perspectives in coronary involvement of polyarteritis nodosa: case of 3-vessel occlusion treated with 4-vessel CABG and review of literature. BMC Cardiovasc Disord 24 , 190 (2024). https://doi.org/10.1186/s12872-024-03841-y

Download citation

Received : 28 March 2023

Accepted : 12 March 2024

Published : 02 April 2024

DOI : https://doi.org/10.1186/s12872-024-03841-y

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

  • Polyarteritis nodosa
  • PCI in coronary arteritis
  • CABG in coronary arteritis
  • Systemic vasculitis and coronary artery disease

BMC Cardiovascular Disorders

ISSN: 1471-2261

literature review including cases

  • Case Report
  • Open access
  • Published: 01 April 2024

Cytomegalovirus colitis as intestinal obstruction in an immunocompetent adolescent: a case report and literature review

  • Jiongshan Ge 1   na1 ,
  • Yan Li 1   na1 ,
  • Jiaxin Wei 1 ,
  • Jing Wang 2 &
  • Jihai Liu 1  

BMC Infectious Diseases volume  24 , Article number:  365 ( 2024 ) Cite this article

Metrics details

Cytomegalovirus infection manifests varying clinical characteristics and severity in diverse populations with different immune statuses. The signs and symptoms of gastrointestinal involvement are nonspecific. Here, we present a case of cytomegalovirus colitis in an immunocompetent adolescent, which manifested as intestinal pseud-obstruction.

Case presentation

A 15-year-old man who had contracted novel coronavirus infection one month earlier was admitted to our hospital with fever, abdominal pain, and hematochezia. His abdomen was distended, and laboratory evaluation revealed a decrease in the blood count, an increase in inflammatory indicators and hepatic impairment. Imaging shows bowel wall thickening and dilatation of the colon. A diagnosis of intestinal infection combined with acute intestinal pseud-obstruction was made. Diarrhea persisted despite conservative treatment with empirical antibiotics. A colonoscopy was performed. Pathology confirmed cytomegalovirus infection. Ganciclovir therapy was initiated, and subsequent review showed a good recovery.

Conclusions

The case was diagnosed as cytomegalovirus colitis. We reviewed the reports of 9 cases of bowel obstruction, including our own, and found that the majority of the adult patients were elderly with underlying disease. Clinical and endoscopic manifestations are typically nonspecific, and imaging shows typical signs of intestinal obstruction. The final diagnosis was confirmed by pathology. Most of them have a good prognosis. We suggest that cytomegalovirus colitis can also lead to intestinal obstruction and that viral reactivation in immunocompetent individuals may be associated with inflammatory conditions and viral coinfection, particularly with the novel coronavirus.

Peer Review reports

Cytomegalovirus (CMV) infection is common, with approximately 83% of the global population testing seropositive [ 1 ]. People with normal immune function usually have no symptoms, or they may experience fever, mononucleosis, or hepatitis. Immunodeficient individuals are susceptible to viral reactivation, which can affect end organs, such as the lungs, central nervous system, and digestive tract. Recently, there has been a notable increase in CMV colitis among immunocompetent patients, which has garnered significant attention. In healthy individuals, the most affected part of the digestive tract is the colon, exhibiting symptoms like hemorrhage, abdominal pain, and diarrhea [ 2 ]. CMV colitis with intestinal obstruction as the primary manifestation has rarely been reported before.

A 15-year-old male was admitted to the emergency room after presenting a high fever for 10 days, abdominal colic, and mucous bloody stool for 4 days. He had severe abdominal distension and a cessation of passing gas. A month ago, he was suspected of being infected with the novel coronavirus (SARS-CoV-2) due to fever and a sore throat. He took ibuprofen to defervesce. Afterward, jaundice developed. Laboratory tests in other hospitals found that transaminase levels increased, and liver injury caused by acute infection was considered, but no additional pathogenic tests were conducted. Silybin and other hepatoprotective drugs were administered. One week later, symptoms were relieved, and transaminase levels decreased. In addition, he had no other notable medical or family history.

His complete blood count showed a white blood cell count of 0.36 × 10 9 /L (Normal range(NR): 3.50–9.50 × 10 9 /L), with neutrophils accounting for 45.8% (NR: 50%-75%), lymphocytes accounting for 42.0% (NR: 20%-40%), hemoglobin 57 g/L (NR: 120-160 g/L), and platelet count of 59 × 10 9 /L (NR: 100–350 × 10 9 /L); his C-reactive protein was 267 mg/L (NR: < 8.0 mg/L). There was also hepatic impairment, with ALT was 72U/L (NR: 9-50U/L) and AST was 54U/L (NR: 15-40U/L). The stool sample showed an elevated level of white blood cells (20–30/HPF, NR: 0–1) and red blood cells (2–3/HPF, NR: 0). Abdominal computed tomography (CT) showed thickening of the rectal and sigmoid bowel wall with dilation of the proximal colon (Supplementary Fig.  1 ).

We diagnosed as probable intestinal infection and acute intestinal pseud-obstruction. Colonoscopy is considered risky at this time. We promptly inserted an ileus catheter and initiated empirical therapy with meropenem, vancomycin, and human immunoglobulin. His abdominal pain resolved, and his blood count and liver function gradually normalized, but diarrhea continued.

The persistence of the symptoms compelled us to continue the search for the cause. Plasma metagenomic next-generation sequencing (mNGS) showed 50 Epstein‒Barr viruses; serum polymerase chain reaction showed that CMV copy was negative, and plasma CMV-IgG/IgM were also negative. Plasma SARS-CoV-2 IgG was positive, confirming a recent case of novel coronavirus disease (COVID-19). The test for Clostridium difficile, fungi, Mycobacterium tuberculosis, Salmonella, Shiga, rotavirus, and parasites in feces was negative. Other tests, such as antinuclear antibody, antiphospholipid antibody, and HIV tests, were negative. Seventeen days later, he was scheduled for a colonoscopy. Sigmoid colonic and rectal ulcers were observed (Supplementary Fig.  2 A, B). Hematoxylin–eosin (HE) staining revealed CMV inclusion bodies, and immunohistochemical (IHC) staining demonstrated positive CMV antigen (Fig.  1 ), confirming colitis caused by CMV infection.

figure 1

Histopathological examination of the patient. a HE staining, × 10 magnification. Multiple cytomegalic inclusions are present. b IHC staining, × 10 magnification. A positive area of CMV antigen stained brown is visible

We started intravenous ganciclovir at a dosage of 500 mg/daily for 21 days. Meanwhile, due to the destruction of the superficial intestinal mucosa and persistent diarrhea, considering that inflammatory bowel disease cannot be definitely ruled out, he was also given oral mesalazine and prednisone (starting at 70 mg/daily) to repair the intestinal mucosa and reduce inflammatory reactions after consulting with the Department of Gastroenterology. During a follow-up examination three months later, his blood count and biochemical indicators were normal. Endoscopic findings revealed stenosis of colon lumen and histological signs of chronic inflammation (Supplementary Fig.  2 C, D). CMV was negative for the IHC test, and his stool gradually returned to normal.

This is a case of CMV colitis with acute intestinal pseud-obstruction. After the catheter was inserted, the obstructive symptoms were quickly relieved. Although there was no direct serological evidence, CMV infection was subsequently confirmed through pathological examination. However, this case occurred in an immunocompetent adolescent who was infected with the novel coronavirus one month ago. Liver injury before onset is considered most probably as one of the manifestations of CMV reactivation. After extensive evaluation, no evidence of existing immunodeficiency leading to CMV disease was found.

A total of 9 cases [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ], including our case, were identified by searching PubMed using the keywords "cytomegalovirus" and "colitis" and reviewing relevant literature citations to retrieve previously reported cases of CMV colitis with intestinal obstruction. Patients with inflammatory bowel disease, AIDS, organ transplantation, and treatment with steroids or immunosuppressive agents were excluded (Supplementary Table  1 ). Of these, 6 (66.7%) were male. The average age was 61 years (range: 15–91), and 66.7% of the participants were over 60 years old. 6 (66.7%) of them had multiple co-morbidities, including chronic constipation, diabetes, chronic obstructive pulmonary disease, and other complications. Most of the cases were diagnosed through pathology. 7 of them were treated with ganciclovir, and a total of 2 (22.2%) people died.

The retrospective analysis also revealed that the most common symptoms were fever, abdominal pain, and diarrhea. The endoscopic examination revealed mostly ulceration, while imaging findings showed dilated intestines. M. Paparoupa et al. [ 10 ] and Dinesh et al. [ 5 ] reported cases of mechanical obstruction caused by fibrotic stenosis, thickening and edema of the bowel wall. In the present case and in the remaining cases, the location of the obstructive lesion was not identified, and paralytic ileus caused by toxic megacolon or Ogilvie syndrome was considered. The most common sites involved are the sigmoid colon and rectum. Based on the results of our study, we believe that CMV colitis should increase the rare clinical presentation of intestinal obstruction, even in a population with normal immunity. For patients diagnosed as CMV colitis with normal immunity, clinicians should observe abdominal symptoms and signs in clinical practice, and be alert for acute intestinal obstruction. Similarly, the presence of CMV should be reasonably suspected in patients with intestinal obstruction. Analysis showed that conservative treatments, such as ganciclovir and placement of obstruction catheters, were usually effective for CMV colitis presenting with intestinal obstruction, without the need for surgery.

It is believed that CMV latent infection exists in early myeloid cells, particularly CD34 + hematopoietic stem cells, which can be reactivated to infect parenchymal cells of various organs [ 11 ]. Viremia is crucial for pathogenesis, and there is a threshold relationship between the viral load controlled by the body's immunity and the occurrence of end-organ invasion [ 12 ]. Therefore, virus reactivation and corresponding diseases can easily occur when immunity is inhibited or damaged. However, immunocompetent people are not always unaffected. A retrospective analysis conducted by Yoon et al. [ 2 ] revealed that the majority of immunocompetent patients diagnosed with CMV gastroenteritis were elderly (74.4%) and had underlying chronic conditions (79.1%), which is consistent with our study. Immunity is affected by both aging and the basal state, so it is reasonable to assume that CMV disease may be rare in truly immunocompetent young patients. The patient's infection occurred after COVID-19, prompting us to further explore the interaction between these two viruses. An increased incidence of herpes virus reactivation has been observed in patients with COVID-19 [ 13 ]. In addition to being associated with inflammatory responses and steroid use, SARS-CoV-2 infection results in a reduction in lymphocytes and upregulation of T-cell apoptotic processes [ 14 , 15 ]. The ACE-2 receptor of SARS-CoV-2 entering cells is highly expressed in gastrointestinal epithelial cells. The immune regulation of the lung-gut axis indirectly affects gastrointestinal endothelial cells through pulmonary infection and is susceptible to CMV [ 16 ]. These are all proposed as possible mechanisms of CMV reactivation after SARS-CoV-2 infection. The specific mechanisms of virus-immune system interactions require further investigation and validation in large cohorts.

Cytomegalovirus disease involving the digestive tract can occur in immunocompetent hosts. Aside from abdominal pain, it can also manifest as intestinal obstruction, and generally, conservative treatment is effective. Early recognition of CMV colitis presenting with intestinal obstruction helps to avoid unnecessary disease prolongation and improves prognosis. The reactivation of cytomegalovirus is associated with inflammation in healthy individuals, and novel coronavirus coinfection is considered to be one of the potential contributing factors.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Abbreviations

  • Cytomegalovirus

Computed tomography

Metagenomic next-generation sequencing

Hematoxylin–eosin

Immunohistochemical

Normal range

Zuhair M, et al. Estimation of the worldwide seroprevalence of cytomegalovirus: a systematic review and meta-analysis. Rev Med Virol. 2019;29(3):e2034. https://doi.org/10.1002/rmv.2034 .

Article   PubMed   Google Scholar  

Yoon J, et al. Endoscopic features and clinical outcomes of cytomegalovirus gastroenterocolitis in immunocompetent patients. Sci Rep. 2021;11(1):6284. https://doi.org/10.1038/s41598-021-85845-8 .

Article   CAS   PubMed   PubMed Central   Google Scholar  

Machens A, Bloechle C, Achilles EG, Bause HW, Izbicki JR. Toxic megacolon caused by cytomegalovirus colitis in a multiply injured patient. J Trauma Acute Care Surg. 1996;40(4):644.

Article   CAS   Google Scholar  

Lin Y-H, Yeh C-J, Chen Y-J, Chang M-C, Su I-H, Cheng H-T. Recurrent cytomegalovirus colitis with megacolon in an immunocompetent elderly man. J Med Virol. 2010;82(4):638–41. https://doi.org/10.1002/jmv.21712 .

Dinesh BV, Selvaraju K, Kumar S, Thota S. Cytomegalovirus-induced colonic stricture presenting as acute intestinal obstruction in an immunocompetent adult. BMJ Case Rep. 2013;2013:bcr2013200944. https://doi.org/10.1136/bcr-2013-200944

Article   PubMed   PubMed Central   Google Scholar  

Cho JH, Choi JH. Cytomegalovirus ileo-pancolitis presenting as toxic megacolon in an immunocompetent patient: a case report. World J Clin Cases. 2020;8(3):552–9. https://doi.org/10.12998/wjcc.v8.i3.552 .

Charatcharoenwitthaya P, Pausawasdi N, Pongpaibul A. Education and imaging: gastrointestinal: Ogilvie’s syndrome: a rare complication of cytomegalovirus infection in an immunocompetent patient. J Gastroenterol Hepatol. 2014;29(10):1752. https://doi.org/10.1111/jgh.12760 .

Article   CAS   PubMed   Google Scholar  

Kim BS, et al. Cytomegalovirus colitis induced segmental colonic hypoganglionosis in an immunocompetent patient: a case report. World J Clin Cases. 2021;9(20):5631–6. https://doi.org/10.12998/wjcc.v9.i20.5631 .

Lagarto M, Santos A, Freitas BD, Anastácio M, Jesus S. The overlooked agent: cytomegalovirus colitis in an immunocompetent patient. Cureus. 2023;15(3):e36926. https://doi.org/10.7759/cureus.36926 .

Paparoupa M, Schmidt V, Weckauf H, Ho H, Schuppert F. CMV colitis in immunocompetent patients: 2 cases of a diagnostic challenge. Case Rep Gastrointest Med. 2016;2016:e4035637. https://doi.org/10.1155/2016/4035637 .

Article   Google Scholar  

Human Cytomegalovirus | SpringerLink. Available: https://link.springer.com/book/10.1007/978-3-540-77349-8 . Accessed 29 Jul 2023.

Griffiths P, Baraniak I, Reeves M. The pathogenesis of human cytomegalovirus. J Pathol. 2015;235(2):288–97. https://doi.org/10.1002/path.4437 .

Shafiee A, et al. Reactivation of herpesviruses during COVID-19: a systematic review and meta-analysis. Rev Med Virol. 2023;33(3):e2437. https://doi.org/10.1002/rmv.2437 .

Amanati A, et al. Severe acute respiratory syndrome coronavirus-2 Alpha variant (B.1.1.7), original wild-type severe acute respiratory syndrome coronavirus 2, and cytomegalovirus co-infection in a young adult with acute lymphoblastic leukemia, case report, and review of the possible cytomegalovirus reactivation mechanisms. J Med Case Reports. 2023;17(1):66. https://doi.org/10.1186/s13256-022-03750-8 .

Jeannet R, Daix T, Formento R, Feuillard J, François B. Severe COVID-19 is associated with deep and sustained multifaceted cellular immunosuppression. Intensive Care Med. 2020;46(9):1769–71. https://doi.org/10.1007/s00134-020-06127-x .

Carll WC, Rady MY, Salomao MA, Patel B, Singh VP, Sen A. Cytomegalovirus haemorrhagic enterocolitis associated with severe infection with COVID-19. BMJ Open Gastroenterol. 2021;8(1):e000556. https://doi.org/10.1136/bmjgast-2020-000556 .

Download references

Acknowledgements

The authors thank the patient for his consent to publish this report. We thank the reviewers for their helpful comments on this paper.

This work was supported by the National High Level Hospital Clinical Research Funding (serial number 2022-PUMCH-B-109).

Author information

Jiongshan Ge and Yan Li contributed equally to this work.

Authors and Affiliations

Emergency Department, The State Key Laboratory for Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China

Jiongshan Ge, Yan Li, Di Shi, Jiaxin Wei & Jihai Liu

Pathology Department, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No.1 Shuaifuyuan Wangfujing Dongcheng Districtg, Beijing, 100730, China

You can also search for this author in PubMed   Google Scholar

Contributions

JS. G. drafted the manuscript, Y.L. collected the patient’s information, JH. L., D. S., and JX. W. edited the manuscript, and J. W. provided pathological pictures. All the authors have read and approved the final manuscript.

Corresponding author

Correspondence to Jihai Liu .

Ethics declarations

Ethics approval and consent to participate.

Not applicable.

Consent for publication

Written Informed consent was obtained from the patient and his legal guardians for publication.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: supplementary figure 1..

(A, B): Abdominal computed tomography. (A) The distended transverse colon. (B) Thickening of the rectal and sigmoid colon wall with peripheral inflammatory exudation.

Additional file 2: Supplementary Figure 2.

(A, B, C, D): The first colonoscopy and three months later, sigmoid colon and rectum. (A, B) 17 days after being hospitalized. Thickening and edema of the intestinal wall, a smaller intestinal cavity, and deep ulcers were observed. (C, D) 3 months after discharge. A narrow intestinal cavity and inflammatory polyps are visible, but the ulcer has improved.

Additional file 3: Supplementary Table 1.

Clinical characteristics of 9 cases of CMV enteritis with intestinal obstruction.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Ge, J., Li, Y., Shi, D. et al. Cytomegalovirus colitis as intestinal obstruction in an immunocompetent adolescent: a case report and literature review. BMC Infect Dis 24 , 365 (2024). https://doi.org/10.1186/s12879-024-09255-7

Download citation

Received : 10 September 2023

Accepted : 26 March 2024

Published : 01 April 2024

DOI : https://doi.org/10.1186/s12879-024-09255-7

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

  • Intestinal obstruction

BMC Infectious Diseases

ISSN: 1471-2334

literature review including cases

U.S. flag

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

  • Publications
  • Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

  • Advanced Search
  • Journal List
  • J Orthop Case Rep
  • v.6(3); Jul-Aug 2016

How much Literature Review is enough for a Case Report?

Ashok shyam.

1 Indian Orthopaedic Research Group, Thane, India

Literature review is an essential part of any scientific document. It’s the foundation on which the premise of scientific research is built. Every scientific study has to be seen in context of the existing knowledge and literature. However literature is growing at exponential rate today and especially with so many online journals today it’s really difficult to review all literature. This poses unique challenge to authors who wish to submit a case report for Journal of Orthopaedic Case Reports.

First issue is how much important is literature review for a case report. From early days of case reports, literature review is been the most important cornerstone of a case report. Especially since earlier only rare cases were considered as case reports [ 1 ]. So to establish the rarity of the case it was important to thoroughly review the literature. For us at Journal of Orthopaedic Case Report, literature review is one of the most significant part of the case report. Most of the times it is the section which decides on acceptance or rejection of borderline cases. For cases that are rare we recommend our authors to do a thorough review of literature and also prepare a table of literature review which should be added to the manuscript. For cases where is the focus is on a specific clinical learning point, the literature review needs to be more exhaustive. When a clinical point has to be made, the literature review should cover all the alternative plans that are already described in literature or at least similar cases that have used a different plan. Many cases that are published in Journal of Orthopaedic Case Reports are more on clinical strategies that are improvised and applied to clinical cases. In these scenario we wish our authors to provide rationale for their choices with back up from literature. Also a thorough review of all exiting strategies should be added to the review. The intention is to make the reader aware of all existing management options and then understand why particular option was chosen in the particular patient. This will also help effective communication between the authors and reviewers and ultimately the readers.

The second issue is how much literature to review. With so much literature available at times literature review may miss important article which is relevant to the case. At times it happens that too much literature is added to the article making it bulky and in need for repeated editing. To resolve these issues we would recommend authors to do a thorough PubMed and google Scholar review which will include most important of the articles. If the number of articles relevant to your search are exceeding thirty you may apply filters like selecting articles published in last 5 years or selecting articles only from PubMed. Selecting article only on PubMed will help get the most relevant articles in your review but an additional scrutiny of google result will help you not miss out on important articles. Google will most of the times provide a very comprehensive list of articles and it may need some effort on part of authors to find the relevant articles. But combining both search strategies will definitely make the review more complete and relevant. The number of references should be limited to maximum of 30 for journal of orthopaedic case reports. This will again require authors to review select the most relevant articles from the literature search. Try and include the most recent articles and also from the most relevant authors and medical centres. In case a particular authors has written multiple articles on similar topic, one of his most relevant can be included while others can be left. Articles that are most close to your clinical scenario should be preferred over other articles. Also articles that have chosen strategies similar to yours should be preferred. If the number of articles is still much more, try to limit the references in terms of geography and include articles that are relevant in your country or geographical location to make is more comparable. Also patient profiles can be matched in terms of age and gender to provide for a better comparison between your case and the case from literature. As far as possible provide a literature review table with list of articles, authors names, number of patients, interventions, results and complications to provide a complete perspective to reader. Review of complications needs a special mention and it should be a part of every surgical case that is reported.

In the end try and weave a continuous narrative including parts from your case and reference to context from literature and make an interesting story for readers and editors. We all love a good story which is told in a well woven text and has relevant learning points underlined.

Editor-Journal of Orthopaedic Case Reports

Conflict of Interest: Nil

Source of Support: None

  • Case report
  • Open access
  • Published: 31 March 2024

Atypical lipoma of the right piriformis muscle: a case report and review of the literature

  • Xiao Qiu 1 ,
  • Xiaoyong Luo 1 &
  • Renmei Wu 1  

Journal of Medical Case Reports volume  18 , Article number:  189 ( 2024 ) Cite this article

32 Accesses

1 Altmetric

Metrics details

Piriformis muscle mass is rare, which is particular for intrapiriformis lipoma. Thus far, only 11 cases of piriformis muscle mass have been reported in the English literature. Herein, we encountered one patient with intrapiriformis lipoma who was initially misdiagnosed.

Case presentation

The patient is a 50-year-old Chinese man. He complained of osphyalgia, right buttock pain, and radiating pain from the right buttock to the back of the right leg. Both ultrasound and magnetic resonance imaging demonstrated a cyst-like mass in the right piriformis muscle. Ultrasonography-guided aspiration was performed on this patient first, but failed. He was then recommended to undergo mass resection and neurolysis of sciatic nerve. Surprisingly, final histology revealed the diagnosis of intrapiriformis lipoma. The patient exhibited significant relief of symptoms 3 days post-surgery.

Diagnosis and differential diagnosis of radicular pain are potentially challenging but necessary. Atypical lipoma is prone to be misdiagnosed, especially in rare sites. It is notable for clinicians to be aware of the presence of intrapiriformis lipoma to avoid misdiagnosis and inappropriate treatment.

Peer Review reports

Piriformis syndrome (PS), also known as sciatic nerve outlet syndrome, caused by compression of the sciatic nerve by the piriformis muscle, is characterized by occasional sciatic-type pain, tingling, and numbness in the buttock along the sciatic nerve pathway down to the lower thigh and the calf [ 1 ]. The causes of PS are diversified, including inflammatory, traumatic, tumoral, and malformative factors [ 2 , 3 ]. PS triggered by space-occupying lesions of the piriformis muscle is very rare. Up to date, only 11 cases of piriformis muscle mass have been reported in the English literature [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ].

Lipomas are one of the most common mesenchymal neoplasms and can occur in any region of the body that contains fat component, including the subcutaneous soft tissues, mediastinum, retroperitoneum, bones, or along the gastrointestinal tract [ 11 ]. Intrapiriformis lipoma is rare and the diagnosis might be intractable when presenting atypical. In addition, misdiagnosis can lead to inappropriate treatment, which causes unsatisfactory outcomes. Here, we present a case of a large intrapiriformis lipoma that was initially misdiagnosed, highlighting that clinicians should be aware that intrapiriformis lipoma might harbor atypical manifestations upon examination.

A 50-year-old Chinese man presented to the orthopedics department with chief complaints of osphyalgia, right buttock pain, and radiating pain from the right buttock to the back of the right leg. The right buttock pain was the most prominent symptom. The pain was accelerated by movement and relieved by lying supine, which induced abnormal walk in the patient. No previous relevant treatment or surgery was reported. Additionally, there was no significant relevant family or social history.

Lasegue’s sign and its strengthening test were positive. Physical examination also demonstrated the positive findings of right femoral nerve traction test and Faber test, and the limitation of right hip abduction was observed. Neurological examination of the lower limb did not demonstrate any loss of sensation or reduced muscle power in any of the nerve root distributions. Non-remarkable finding was revealed after the abdominal examination.

As no apparent abnormalities were indicated upon the plain radiograph imaging of his lumbar spine, magnetic resonance imaging (MRI) scan of the lumbar/sacral area of the spine was then suggested, showing lumbar disc herniation (LDH), which did not account for the patient’s predominant right buttock pain. Thus, the musculoskeletal ultrasound (MSK-US) for the sciatic nerve scanning was performed, implying that the right sciatic nerve was pushed by an anechoic mass within the right piriformis muscle measuring 6 cm mediolateral, 2.3 cm anteroposterior, and 2.6 cm craniocaudal. The lobulated mass was cystic-like with regular margins and no posterior wall enhancement (Fig.  1 ). Subsequently, further MRI of the pelvis and ipsilateral hip indicated a cystic-like lesion in piriformis muscle region with low T1 signal and high T2 signal, and the maximum measurement was about 3.1 cm mediolateral and 2.2 cm anteroposterior (Fig.  2 ). Considering these results, a piriformis ganglion was suspected, and the differential diagnoses included hematoma, metastatic tumor, and so forth.

figure 1

Sonographic examination showing a separate anechoic mass (white arrows) above the outlet of the right piriformis muscle pushing the right sciatic nerve (blue arrows). A Sagittal view(low- frequency probe); B Transverse view (high-frequency probe)

figure 2

MRI demonstrating multiple cysts (arrows) in piriformis muscle region with long T1 ( A ) and long T2 ( B ) signals

Aiming to achieve the final diagnosis, the ultrasonography-guided aspiration was conducted, but failed due to unextracted cystic fluid. In addition, significant resistance was encountered when injecting with physiological saline. As for the undefined nature of the mass and the associated serious symptoms, malignancy could not be excluded; the patient was suggested to undergo piriformis muscle mass resection and neurolysis of sciatic nerve. Operative finding showed the compression of right sciatic nerve by a fat-like mass at the lower margin of piriformis muscle measuring 5 cm mediolateral, 2 cm anteroposterior, and 2 cm craniocaudal. Final histology revealed that the lesion was fibrous adipose tissue, which was consistent with diagnosis of lipoma (Fig.  3 ). The patient exhibited significant relief of symptoms 3 days post-surgery. No recurrence of relevant symptoms was observed during 24-month follow-up period.

figure 3

Under microscope inspection, removed specimen revealed fibrous adipose tissue within the lesion, consistent with lipoma

Lower back pain can present with radicular pain caused by lumbosacral nerve root pathology. As a major cause of lower back pain, sciatica, and radicular leg pain, LDH is usually the first considered diagnosis. Similarly, in our case LDH was initially considered according to the MRI of the lumbar/sacral spine. However, the primary pain in the right buttock of this patient was unexplained on the diagnosis of LDH.

PS, also known as sciatic nerve outlet syndrome, is a type of sciatic neuralgia caused by compression of the piriformis muscle on the sciatic nerve. Typical manifestations include buttock pain and radiating pain in the innervated area of the sciatic nerve. In general, etiologies are composed of traumatic bleeding, adhesions, scars, anatomical variations, and so forth [ 2 ]. Of note, intrapiriformis lesion enlarging the muscle may be the common cause of sciatic nerve compression-induced secondary PS, whereas PS triggered by space-occupying lesions of the piriformis muscle is very rare. To the best of our knowledge, only 11 cases have been reported in the literature thus far; these patients and our present case are summarized in Table  1 [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ], among which only 1 case of intramuscular lipomas occurring within the piriformis muscle leading to secondary PS have been previously reported in the literature [ 6 ].

Lipomas can be classified into superficial and deep lesions according to the location. Deep-seated lipomas are less common than superficial lipomas, which may be located under the muscle (submuscular), within the muscle (intramuscular), between the muscles (intermuscular), or on top of the muscle (supramuscular) [ 11 ]. Clinically, lipomas often present as asymptomatic slow-growing mass or swelling with no palpable mass. The application of ultrasound (US) in the examination of lipomas is very frequent. Usually, superficial lipomas might manifest as a hyperechoic solid mass without posterior acoustic enhancement or show as a isoechoic mass on gray-scale US. Compared with superficial lipomas, the deep-seated type can present as various US characteristics. In addition, few reports in the literature show the hypoechoic, isoechoic, or anechoic properties of deep ones [ 12 , 13 , 14 ]. However, the intrapiriformis lipoma in our case was featured as an anechoic lesion, usually indicated as cystic lesions. The MRI of the pelvis and ipsilateral hip showed the same signal characteristics as those of water on all sequences. Therefore, the lesion within piriformis muscle region was then misdiagnosed as ganglion and distinguished from neuschwannoma, liposarcoma, hematoma, lymphoma, metastatic tumor, and so on. Therefore, ultrasonography-guided aspiration was performed while noncystic fluid was extracted.

The echogenicity of lipomas may range from hyperechoic to anechoic, depending on the component percentage of connective tissue and other reflective interfaces presented within a lipoma [ 15 ]. It has been postulated that US and MRI appearance of lipomas are largely dependent on the internal cellularity, specifically on the proportion of fat and water within the lesion [ 16 ]. When the proportion of water in the lipoma is high, it may present the same imaging characteristics as this case.

Generally, intrapiriformis lipoma does not require treatment in the absence of symptoms, while for our case, considering the serious symptoms of this patient and undefined nature, even including malignancy, after series of examinations, surgical treatment was recommended. Fortunately, the patient showed significant relief of symptoms 3 days after surgery. No recurrence of associated symptoms was observed during 24-month follow-up period.

Despite the potentially significant challenges for the diagnosis and differential diagnosis of radicular pain, it is highly necessary and essential. It is notable that medical practitioners should be aware of this condition and exclude space-occupying lesions of piriformis muscles when encountering patients presenting with radicular pain. Our case highlighted the atypical manifestations of lipomas in rare areas such as piriformis muscles, for which condition-adequate examinations should be performed and surgery might be finally suggested to reach the final diagnosis, thus avoiding misdiagnosis and inappropriate treatment and increasing the life quality of these patients.

Availability of data and materials

The authors of this manuscript are willing to provide additional information regarding the case report.

Abbreviations

Musculoskeletal ultrasound

Magnetic resonance imaging

Piriformis syndrome

Lumbar disc herniation

Hopayian K, Song F, Riera R, Sambandan S. The clinical features of the piriformis syndrome: a systematic review. Eur Spine J. 2010;19:2095–109.

Article   PubMed   PubMed Central   Google Scholar  

Kirschner JS, Foye PM, Cole JL. Piriformis syndrome, diagnosis and treatment. Muscle Nerve. 2009;40(1):10–8.

Article   PubMed   Google Scholar  

Byrd JWT. Piriformis syndrome. Oper Tech Sports Med. 2005;13(1):71–9.

Article   Google Scholar  

Salar O, Flockton H, Singh R, Reynolds J. Piriformis muscle metastasis from a rectal polyp. Case Rep. 2012. https://doi.org/10.1136/bcr-2012-007208 .

Domínguez-Páez M, De Miguel-Pueyo LS, Medina-Imbroda JM, González-García L, Moreno-Ramírez V, Martín-Gallego A, et al . Sciatica secondary to extrapelvic endometriosis affecting the piriformis muscle. Case report. Neurocirugia (Astur). 2012;23(4):170–4.

Drampalos E, Sadiq M, Thompson T, Lomax A, Paul A. Intrapiriformis lipoma: an unusual cause of piriformis syndrome. Eur Spine J. 2015;24:551–4.

Park JH, Jeong HJ, Shin HK, Park SJ, Lee JH, Kim E. Piriformis ganglion: an uncommon cause of sciatica. Orthop Traumatol Surg Res. 2016;102(2):257–60.

Article   CAS   PubMed   Google Scholar  

Lodin J, Brušáková Š, Kachlík D, Sameš M, Humhej I. Acute piriformis syndrome mimicking cauda equina syndrome: illustrative case. J Neurosurg Case Lessons. 2021;2(17): CASE21252.

Sanuki N, Kodama S, Seta H, Sakai M, Watanabe H. Radiation therapy for malignant lumbosacral plexopathy: a case series. Cureus. 2022;14(1): e20939.

PubMed   PubMed Central   Google Scholar  

Ward TRW, Garala K, Dos Remedios I, Lim J. Piriformis syndrome as a result of intramuscular haematoma mimicking cauda equina effectively treated with piriformis tendon release. BMJ Case Reports CP. 2022;15(3): e247988.

Paunipagar BK, Griffith J, Rasalkar DD, Chow LTC, Kumta SM, Ahuja A. Ultrasound features of deep-seated lipomas. Insights Imaging. 2010;1(3):149–53.

Goldberg BB. Ultrasonic evaluation of superficial masses. J Clin Ultrasound. 1975;3(2):91–4.

Rahmani G, McCarthy P, Bergin D. The diagnostic accuracy of ultrasonography for soft tissue lipomas: a systematic review. Acta radiologica open. 2017;6(6):2058460117716704.

Fujioka K. A comparison between superficial and deep-seated lipomas on high-resolution ultrasonography: with RTE and MRI appearances. Biomed J Sci Tech Res. 2019;19:14220–4.

Google Scholar  

Behan M, Kazam E. The echographic characteristics of fatty tissues and tumors. Radiology. 1978;129(1):143–51.

Inampudi P, Jacobson JA, Fessell DP, Carlos RC, Patel SV, Delaney-Sathy LO, et al . Soft-tissue lipomas: accuracy of sonography in diagnosis with pathologic correlation. Radiology. 2004;233(3):763–7.

Download references

Acknowledgements

The author(s) gratefully acknowledge the useful suggestions given by Dr Ji-Bin Liu of Thomas Jefferson University, and the author(s) thank Xiaobo Luo for providing language assistance during article writing.

Not applicable.

Author information

Authors and affiliations.

Department of Ultrasound, Suining Central Hospital, 127 Desheng West Road, Suining, Sichuan, China

Xiao Qiu, Xiaoyong Luo & Renmei Wu

You can also search for this author in PubMed   Google Scholar

Contributions

Renmei Wu contributed to the collection of the medical history data. Xiao Qiu contributed to the manuscript preparation of this case report. Xiaoyong Luo supervised the case report.

Corresponding author

Correspondence to Renmei Wu .

Ethics declarations

Ethics approval and consent to participate.

The study protocol was approved by the ethics review board of Suining Central Hospital (no. LLSLH20220011).

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The author(s) declared no potential conflicts of interest regarding the publication of this manuscript.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Qiu, X., Luo, X. & Wu, R. Atypical lipoma of the right piriformis muscle: a case report and review of the literature. J Med Case Reports 18 , 189 (2024). https://doi.org/10.1186/s13256-024-04507-1

Download citation

Received : 04 April 2022

Accepted : 13 March 2024

Published : 31 March 2024

DOI : https://doi.org/10.1186/s13256-024-04507-1

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

  • Piriformis muscle

Journal of Medical Case Reports

ISSN: 1752-1947

  • Submission enquiries: Access here and click Contact Us
  • General enquiries: [email protected]

literature review including cases

IMAGES

  1. 50 Smart Literature Review Templates (APA) ᐅ TemplateLab

    literature review including cases

  2. The Importance of Literature Review in Scientific Research Writing by

    literature review including cases

  3. How To Write A Literature Review

    literature review including cases

  4. Literature review sample UK. Not sure about the format of literature

    literature review including cases

  5. FREE 8+ Sample Literature Review Templates in PDF

    literature review including cases

  6. literature review article examples Sample of research literature review

    literature review including cases

VIDEO

  1. 3_session2 Importance of literature review, types of literature review, Reference management tool

  2. Chapter two

  3. Part 03: Literature Review (Research Methods and Methodology) By Dr. Walter

  4. Research Methods

  5. Approaches , Analysis And Sources Of Literature Review ( RESEARCH METHODOLOGY AND IPR)

  6. Sources And Importance Of Literature Review(ENGLISH FOR RESEARCH PAPER WRITING)

COMMENTS

  1. How to Write a Literature Review

    Examples of literature reviews. Step 1 - Search for relevant literature. Step 2 - Evaluate and select sources. Step 3 - Identify themes, debates, and gaps. Step 4 - Outline your literature review's structure. Step 5 - Write your literature review.

  2. Writing a Literature Review

    A literature review is a document or section of a document that collects key sources on a topic and discusses those sources in conversation with each other (also called synthesis ). The lit review is an important genre in many disciplines, not just literature (i.e., the study of works of literature such as novels and plays).

  3. Ten Simple Rules for Writing a Literature Review

    Literature reviews are in great demand in most scientific fields. Their need stems from the ever-increasing output of scientific publications .For example, compared to 1991, in 2008 three, eight, and forty times more papers were indexed in Web of Science on malaria, obesity, and biodiversity, respectively .Given such mountains of papers, scientists cannot be expected to examine in detail every ...

  4. How To Write A Literature Review (+ Free Template)

    Okay - with the why out the way, let's move on to the how. As mentioned above, writing your literature review is a process, which I'll break down into three steps: Finding the most suitable literature. Understanding, distilling and organising the literature. Planning and writing up your literature review chapter.

  5. Writing a literature review

    Writing a literature review requires a range of skills to gather, sort, evaluate and summarise peer-reviewed published data into a relevant and informative unbiased narrative. Digital access to research papers, academic texts, review articles, reference databases and public data sets are all sources of information that are available to enrich ...

  6. What is a Literature Review?

    A literature review is a survey of scholarly sources on a specific topic. It provides an overview of current knowledge, allowing you to identify relevant theories, methods, and gaps in the existing research. There are five key steps to writing a literature review: Search for relevant literature. Evaluate sources. Identify themes, debates and gaps.

  7. 5. The Literature Review

    A literature review may consist of simply a summary of key sources, but in the social sciences, a literature review usually has an organizational pattern and combines both summary and synthesis, often within specific conceptual categories.A summary is a recap of the important information of the source, but a synthesis is a re-organization, or a reshuffling, of that information in a way that ...

  8. Guidance on Conducting a Systematic Literature Review

    Literature reviews establish the foundation of academic inquires. However, in the planning field, we lack rigorous systematic reviews. In this article, through a systematic search on the methodology of literature review, we categorize a typology of literature reviews, discuss steps in conducting a systematic literature review, and provide suggestions on how to enhance rigor in literature ...

  9. PDF CHAPTER 3 Conducting a Literature Review

    3.1 Summarize what a literature review is, what it tells the reader, and why it is ... chapter then offers concrete steps taken to construct a literature review including identifying what sources are needed, how ... in some cases, published. The peer-review process, while imperfect, seeks to ...

  10. Steps in Conducting a Literature Review

    A literature review is an integrated analysis-- not just a summary-- of scholarly writings and other relevant evidence related directly to your research question.That is, it represents a synthesis of the evidence that provides background information on your topic and shows a association between the evidence and your research question.

  11. Chapter 9 Methods for Literature Reviews

    9.3. Types of Review Articles and Brief Illustrations. EHealth researchers have at their disposal a number of approaches and methods for making sense out of existing literature, all with the purpose of casting current research findings into historical contexts or explaining contradictions that might exist among a set of primary research studies conducted on a particular topic.

  12. Research Guides: Literature Review: Getting Started

    Chapter 3: Writing the Review of Literature for Your Study by Steven R. Terrell This user-friendly guide helps students get started on--and complete--a successful doctoral dissertation proposal by accessibly explaining the process and breaking it down into manageable steps. Steven R. Terrell demonstrates how to write each chapter of the proposal, including the problem statement, purpose ...

  13. Literature Reviews, Theoretical Frameworks, and Conceptual Frameworks

    A literature review should connect to the study question, guide the study methodology, and be central in the discussion by indicating how the analyzed data advances what is known in the field. ... A researcher drawing upon this framework holds the assumption that learning is a dynamic social process involving questions and explanations among ...

  14. Literature review as a research methodology: An ...

    As mentioned previously, there are a number of existing guidelines for literature reviews. Depending on the methodology needed to achieve the purpose of the review, all types can be helpful and appropriate to reach a specific goal (for examples, please see Table 1).These approaches can be qualitative, quantitative, or have a mixed design depending on the phase of the review.

  15. Systematic, Scoping, and Other Literature Reviews: Overview

    Systematic Review. These types of studies employ a systematic method to analyze and synthesize the results of numerous studies. "Systematic" in this case means following a strict set of steps - as outlined by entities like PRISMA and the Institute of Medicine - so as to make the review more reproducible and less biased.

  16. Structure of a report (Case study, Literature review or Survey

    Literature review Explore the literature/news/internet sources to know the topic in depth; Give a description of how you selected the literature for your project; Compare the studies, and highlight the findings, gaps or limitations. Case study An in-depth, detailed examination of specific cases within a real-world context.

  17. Chapter 3: Defining the criteria for including studies and ...

    Unless the study reports separate data from the eligible section of the population (in which case data from the eligible participants can be included in the review), review authors will need a strategy for dealing with these studies (see MECIR Box 3.2.a). This will involve balancing concerns about reduced applicability by including participants ...

  18. Pure mucinous adenocarcinoma of the breast with the rare

    Pure mucinous adenocarcinoma of the breast with the rare lymphoplasmacytic infiltration: A case report with review of literature. Yash Hasmukhbhai Prajapati, Yash Hasmukhbhai Prajapati. ... Mucinous carcinoma of the breast is a unique entity with specific histological features including the presence of extracellular mucin pools ...

  19. Subcutaneous tissue involvement in idiopathic inflammatory ...

    Subcutaneous tissue involvement in idiopathic inflammatory myopathies: Systematic literature review including three new cases and hypothetical mechanisms Autoimmun Rev . 2023 Feb 1;22(4):103284. doi: 10.1016/j.autrev.2023.103284.

  20. Myeloid/lymphoid neoplasms with eosinophilia and tyrosine ...

    A literature review was performed including paediatric cases of M/LN-eo with TK gene fusions. Keywords: European Bone Marrow Working Group (EBMWG); bone marrow biopsy; myeloid/lymphoid neoplasms with eosinophilia; paediatric; tyrosine kinase gene fusion.

  21. Mediastinal Rosai-Dorfman Disease with KRAS mutation case report and

    Background Rosai-Dorfman Disease (RDD) is a rare self-limiting histiocytosis, more prevalent in children and young adults. It typically manifests as painless bilateral massive cervical lymphadenopathy but may also extend to extra-nodal sites, with intrathoracic RDD noted in 2% of cases. Distinguishing mediastinal RDD from thymoma on imaging poses challenges, underscoring the reliance on ...

  22. The Literature Review: A Foundation for High-Quality Medical Education

    Such work is outside the scope of this article, which focuses on literature reviews to inform reports of original medical education research. We define such a literature review as a synthetic review and summary of what is known and unknown regarding the topic of a scholarly body of work, including the current work's place within the existing knowledge.

  23. 9. Literature reports

    Literature report is any adverse drug reactions reported in. 1. Published abstracts or. 2. Articles in medical/scientific journals. 3. Unpublished manuscripts involving case reports. 4. Important safety findings or clinical studies including posters, letters to the editors, and associated communication from scientific meetings.

  24. Shifting perspectives in coronary involvement of polyarteritis nodosa

    Literature first discusses known PAN coronary arteritis in 1948 . Associations of congestive heart failure, hypertension, pericarditis, and arrhythmia are well documented; yet the bulk of literature and teaching suggest severe coronary disease is rare. Recent case reports and the first retrospective cohort study now argue this point.

  25. Cytomegalovirus colitis as intestinal obstruction in an immunocompetent

    Pathology confirmed cytomegalovirus infection. Ganciclovir therapy was initiated, and subsequent review showed a good recovery. The case was diagnosed as cytomegalovirus colitis. We reviewed the reports of 9 cases of bowel obstruction, including our own, and found that the majority of the adult patients were elderly with underlying disease.

  26. Septoplasty in neonate using balloon dilation: Case report and

    However, in cases of patients with an uncorrected deviated nasal septum, it can have physiological, anatomical, cosmetic, and psychological impacts. Many studies have reported different approaches to correct neonatal deviated nasal septum, including observation, stenting, close reduction, and septoplasty.

  27. How much Literature Review is enough for a Case Report?

    For us at Journal of Orthopaedic Case Report, literature review is one of the most significant part of the case report. Most of the times it is the section which decides on acceptance or rejection of borderline cases. ... In the end try and weave a continuous narrative including parts from your case and reference to context from literature and ...

  28. Pancreaticopleural fistula causing pleural effusion: a case report and

    Pancreaticopleural fistula is a rare complication of pancreatitis and poses diagnostic and therapeutic challenges. This case report sheds light on the unique challenges posed by pancreaticopleural fistula as a rare complication of pancreatitis. The aim is to contribute valuable insights to the scientific literature by presenting a case involving a middle-aged man with acute necrotizing ...

  29. Atypical lipoma of the right piriformis muscle: a case report and

    Up to date, only 11 cases of piriformis muscle mass have been reported in the English literature [4,5,6,7,8,9,10]. Lipomas are one of the most common mesenchymal neoplasms and can occur in any region of the body that contains fat component, including the subcutaneous soft tissues, mediastinum, retroperitoneum, bones, or along the ...

  30. Paternally Inherited Noonan Syndrome Caused by a

    Background: Noonan syndrome (NS)/Noonan syndrome with multiple lentigines (NSML) is commonly characterized by distinct facial features, a short stature, cardiac problems, and a developmental delay of variable degrees. However, as many as 50% of individuals diagnosed with NS/NSML have a mildly affected parent or relative due to variable expressivity and possibly incomplete penetrance of the ...