Starting pathology

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Starting Pathology - front page.png
Author: Mikael Häggström, M.D.

  • Conflicts of interest: None. (No financial gain was or is made from this handbook, apart from the academic prestige of being an author.)

Front page images by Mikael Häggström, M.D., except picture of sectioned heart, which is from: Michaud, Katarzyna; Basso, Cristina; d’Amati, Giulia; Giordano, Carla; Kholová, Ivana; Preston, Stephen D.; Rizzo, Stefania; Sabatasso, Sara; et al. (2019). "Diagnosis of myocardial infarction at autopsy: AECVP reappraisal in the light of the current clinical classification ". Virchows Archiv. doi:10.1007/s00428-019-02662-1. ISSN 0945-6317.  This picture is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)

This is a handbook directed at new pathology trainees (mainly residents or trainees with medical doctor degrees or similar). The main goal of this handbook is to provide you with the most pertinent knowledge in order to most efficiently improve the lives of people through better diagnoses and thereby better treatment.

Contents

Copies, prints and reuse

To get a printable version of this handbook (which can also be downloaded for offline use), go to patholines.org, click Starting pathology (handbook), and click Printable version in the left hand menu.[note 1] A normal color printer and normal paper is sufficient, and you can keep the pages together in a binder. If you want even better quality, use color printer paper, or google a "copy shop" for a color print delivery or in-store pickup (possibly as a photo book).

Scary FBI logos like this are often copy-pasted into works, but do not change your copyrights.

This handbook is released under the Creative Commons Attribution 4.0 International (CC-BY 4.0) license, meaning that if you reuse any of its content (such as in scholarly articles or other publications of yours), you need to mention its author (Mikael Häggström, M.D.). Also, many images are Public Domain, that is, without any restrictions. The status of each image, and its creator(s), is seen on its description page (found by clicking the image at Patholines.org). This handbook is published in the United States, and the United States copyright law holds that "In no case does copyright protection for an original work of authorship extend to any idea, procedure, process, system, method of operation, concept, principle, or discovery, regardless of the form in which it is described, explained, illustrated, or embodied in such work.".[1][2] Hence, you can use any texts, tables and graphs herein as Public Domain, and defend such usage by stating that it describes anatomical, physiological and pathological processes and systems. Hence, in practice, the attribution as per above when using texts, tables and graphs from this handbook is a polite request rather than a legal requirement.[3] 

Contact

To contact the page creator/author, write a message to mikaelDot.svghaeggstroemArobaze.svgnuvancehealthDot.svgorg.

Please give feedback on any errors that you encounter in this resource, as well as pertinent omissions that you feel should be there. Preferably, contribute yourself: See the Contribute page at Patholines.org. This is a not-for-profit textbook, so there are no monetary rewards for contributing. Yet, a major co-author or reviewer may be eligible for inclusion on the front page. Contributors will otherwise be mentioned on a second page (with details on what parts were written or reviewed), unless requesting to remain anonymous. Contributors may also mention their efforts on their professional resumes.

Learning pathology

  The goal of this resource is to make a new pathology trainee able to properly handle at least 70% of cases that are expected at an average general pathology department, including the exclusion of the most pertinent differential diagnoses thereof. Its aim is to present you at least one way of doing things that is at least adequate for a particular situation, so that although there may be various routines at various locations, adherence to these methods should not result in a worse reprimand from a senior than "although that was adequate, that is not how we do it here". Still ask for help whenever needed, such as first time you are doing something, or whenever you are not sure about what to do, especially when doing something potentially irreversible.

What a pathologist needs to memorize

The best method for memorization is generally through repeated exposure in everyday practice, and the scope thereof will depend on your eventual location and subspecialty, and you will eventually forget everything else, more or less. Yet, the following things are most important for a pathologist trainee to focus on memorizing:

  • Emergent pathology, mostly relating to intraoperative or frozen section consultations. This includes information that usually cannot be timely looked up on the Internet when needed.
  • Main pitfalls: The most common and dangerous situations where a pathologist may not recognize the need to look something up further or ask a senior colleague, or where a significant risk of diagnosis error remains after doing so.
  • Interpretation of non-written results, including patterns and signs which can be seen grossly or under the microscope. It confers the ability to translate visuals and other more or less non-verbalizable information into words that can be looked up if needed, and conceive the most likely diagnoses based on both describable and more abstract appearances.
  • Proficiency in diagnosing equivocal or borderline cases where readily available sources and evidence usually deal with discrete and specific disease entities and subcategories thereof. Unusual or equivocal presentations of very common diseases and conditions are still generally more common than rare diseases, and constitutes a major workload in everyday pathology practice. However, most textbooks still give disproportionately large room for rare diseases compared to such presentations. Nevertheless, strive to master the common conditions (including the most common pitfalls) before diving into the uncommon. After all, you will get by with effectively handling the regular cases wherever you work, so that you will have time to study or ask others for unfamiliar cases, as long as you know your pitfalls, and have an idea about your unknowns:
  • Having an idea of one’s unknowns; being aware of a lack of knowledge in unfamiliar fields. For example, a pathologist generally does not need in depth knowledge about diseases that are generally sent out to specialized centers (such as pediatric musculoskeletal oncology), but just enough to be able to suspect such diseases. In the same manner, a pathologist needs to have an idea of the optimal limits of practice, between what should optimally be handled personally by the pathologist and what is better handled by others, including senior colleagues, technicians, pathology assistants, junior colleagues and artificial intelligence.
  • Where to find information for various situations. It includes which person or which search engine is most useful for various clinical situations. See the Using resources section below for further information. Similarly, a pathologist often needs to be efficient at finding what is relevant among a large amount of information, and be able to integrate it into a decision or a relatively short report. For questions where a look-up does not readily give the answer, a new trainee usually gets satisfactory replies even from senior trainees, but the more experienced you get, the more you need to establish contacts with particular people, such as certain subspecialties, who are most likely to be able to answer your questions when needed.
This resource aims to cover what you need to memorize as a first year pathology trainee.
  • How to distinguish memorization-worthy versus look-up versus practically useless information. With the ease of access to pathology information on the Internet through smartphones and computers, those studying for the everyday practice as a pathologist should not waste time memorizing what can essentially always be conveniently and timely looked up when needed. This includes most of the content of books and web pages that are sorted by names of diseases and conditions, because if the name of a disease is already known, then it can relatively quickly be looked up when needed in such sources. When finding relevant look-up information on the Internet or local repositories, it is generally enough to remember enough of its related words in order to find it again. After all, other doctors and even laypersons can look up diseases and conditions themselves, without the need for a pathologist consultation, so the expertise of memorizing such readily available information is expendable. Similarly, electronic systems are better suited than the human brain for the storage and rapid retrieval of databases of for example immunohistochemistry and genetics results of various diseases. The topics listed in this section are already immense enough to cover a lifetime of learning. Learning pathology therefore optimally involves the memorization of where and how to find look-up information, rather than directly memorizing such information. Therefore, if you need to choose a textbook to study, then choose one that you will always be able to quickly reach through your smartphone whenever you need its look-up information. Accordingly, the final aim of this resource is to help pathology trainees to give accurate and clinically useful reports to clinicians, in synergy with the resources that are available in everyday pathology practice, and to establish routines to continue such practices. The intended end result is to help clinicians to improve the lives as much as possible to as many people as possible, even if it means forgoing the prestige of becoming a walking encyclopedia. It also means finding high-yield learning sources, for even if they may take longer time to find, you will be better prepared for real life than when you study low-yield knowledge, which includes statistics that is very unlikely to be used diagnostically, mainly because their calculations would be so complex that it is not worth it. For example, in reality you generally have a pattern of signs and other findings and you want to know the likelihood of each differential diagnosis, and for this purpose you only get limited help by knowing the reverse likelihood of what percentage each individual condition is to display the finding, because it would still be necessary to also know for example the epidemiology of each disease to calculate its likelihood. Instead, the optimal studying is generally not of diseases individually, but rather of patterns of signs and other findings and the likelihoods of each differential diagnosis thereof. Arguably the best method of acquiring such knowledge is to be involved in many real cases at a pathology department, making your own diagnostic thinking of them, and correcting your thinking based on how you differed from a senior's report. The next best method is arguably to solve virtual cases such as found in pathology qbanks.
  • How to efficiently study for exams that contain questions that require direct memorization of look-up (or even practically useless) information, as long as such exams are in the way of practicing pathology. The best approach is arguably to spend enough time and effort on memorizing what is memorization-worthy, to the point where you will pass an exam even if you will fail multiple questions that require memorization of look-up or practically useless information. However, when starting pathology training, do not focus on studying for any final exams that are years away, because the content on such exams is systematically very different from what you need to know initially. For instance, you initially need to know how to handle the common types of cases, but exam makers on the other hand, in their effort to distinguish those who have studied more extensively than others, will systematically choose presentations that are not commonly encountered.  Further exam advice is found in the Secrets chapter at patholines.org.
Type of information Examples (usually) Learning approach
Memorization-worthy
  • Emergent matters
  • Pitfalls
  • Interpretation of non-written results
Directly memorizing it.
Look-up
  • Textbooks and websites organized by names of diseases and conditions
  • Immunohistochemistry results
  • Associations between genetic mutations and diseases, and related molecular biology.
  • Classifications such as cancer staging
  • Large tables and diagrams
  • Long lists
Knowing where to find it when needed, and how to use it.
Low-yield
  • Diseases individually
Instead studying patterns of findings and signs, and how they support various differential diagnoses.
Practically useless
  • History
  • Most of scholarly articles
  • Most clinical management
Avoiding, or skipping to potentially useful parts.

Whether any piece of information is useful versus useless depend mainly on:

  • The likelihood of a situation where the information is useful.
  • The benefit versus detriment of having versus not having the information at hand in such a situation.

The clinical management aspects that can be useful for pathologists to learn are the thresholds for pathologic findings that substantially change the clinical management, such as a cancer stage that determines whether clinicians will try to completely remove all tumors versus treat palliatively. With such knowledge, pathologists can put relatively more effort on the cases and parts thereof that make the most difference to the patient. Otherwise, clinical management knowledge is generally useless to a pathologist.

Lectures may be memorization-worthy depending on the content, but a lecture of look-up-information is practically useless unless you maintain a system to quickly retrieve the information when needed. Thus, sometimes, it is better to study something more memorization-worthy while pretending to listen to a lecturer.

Also keep in mind that pathology in our look-up era is mainly a processing work rather than a memorization one, since your most important skills are to interpret findings, and sometimes involve a vast amount of information in order to suggest the most likely diagnoses. Again, arguably the best method fur such purposes is solving real or virtual cases.

Using resources

This resource is written with the intention to teach you what to do in the most common situations you are expected to encounter during your first years of pathology training, at least until the point that you are usually fairly confident about what disease or condition you have at hand, because then you know what words to use to look it up in the vast literature out there. At that point, the fastest way to get more information is generally by Googling the disease or condition name, followed by pathology outlines (which is generally the most likely to quickly give you the information you need), since Internet will always be readily available in pathology.[note 2] The most efficient method of studying to solve a case at hand is to not read articles in their entirety, but to scroll directly to the parts that are most likely to give you the information you need (generally past the first half of Pathology Outlines articles).

Specific search methods for some specific purposes include the following (and the author has no financial or other conflicts of interests in mentioning any of these):

  • Google, and then clicking the Images tab, if you just want to see more micrographs of the disease or condition. Even when you don't have a clue what condition you are looking at, you may find something that looks similar to your case by entering words you would use for the microscopic findings that you see.
  • Adding cancer.net staging in Google searches for definitions of cancer stages, for example Googling prostate cancer cancer.net staging. The first search will then generally be the one from the American Society of Clinical Oncology.
  • Considering a subscription for ImmunoQuery[note 3] (or equivalent database if you find one) in order to generate the most pertinent immunohistochemistry stains when you have two or more differential diagnoses for a case at hand. It is not sufficient to just memorize a few usually positive or negative immunostains for each disease and condition, because what you need in reality is to figure out what immunostains to order so that you can pinpoint one diagnosis among your multiple differentials. To master that, you will need to memorize a vast amount of immunostains and at what percentages they are positive for a vast amount of diseases and conditions, or you can have an online service like ImmunoQuery do that work for you. After all, in pathology there is essentially no immunohistochemistry that is so emergent that you do not have the time to use a computer or smartphone to look it up.
  • ClinVar to look up the pathogenicity of specific genetic variants/mutations.

If the above resources do not provide a sufficient answer:

  • Googling what you are looking for. You may add the word pathology or equivalent if results are too clinical or layman-oriented. Before even reading the title of results, first look at the URL. If it is from a reputable organization then you may proceed to check if the title is pertinent to what you are looking for, but if it is from an unfamiliar site then you should only proceed if you don't find a better source among your search results, and you will need to look for additional proof of reliability such as authorship of the content in order to use it in the diagnostics of any case. You can generally rely on more articles for presumably well-established topics (such as anatomy, and relatively common diseases) than for potentially controversial and experimental topics, in which case you generally need to ask yourself if the author has a conflict of interest.

Ask a colleague at least whenever your own memory or a resource search is not enough, and there is a significant risk that you may do something irreversible that will negatively affect a patient.

Regarding lectures and knowledge your colleagues will tell you, make a judgment for each piece of information if it fits a criterion for memorization, or if it merits being written down somewhere you can find it so that you can look it up when needed.

Wikipedia often shows up among top Google results, and is generally accurate.[4]

Whenever possible, use textbooks and other sources that you can quickly access online, because you will likely always be close to the Internet, but not always close to your collections of physical material. Keep in mind that for the vast majority of content, you only need to have a hunch of where to find it again when needed, or what search terms to use. If something may be difficult to find again, you may add it to a personal digital collection to be readily available in times you need it.

Strive for sources that, taken together, are comprehensive enough for the presentation at hand. For example, if you first look in a resource on only benign conditions that may cause your presentation, you generally need to look for another source that includes malignant conditions as well.

Generally skip any part that tries to explain a microscopic appearance using only words, since a Google image search is generally more useful.

Test question

A 4 year old girl with a renal mass
Histopathology of Wilms' tumor, original.jpg
Histopathology of Wilms' tumor, annotated.jpg

You are a new resident at a community hospital that is closely affiliated with a university hospital. The attending gives you a couple of slides from a case that is not yet signed out to preview and then come back with what you think would be the next steps. You are also told to share them with a med student who rotates at the department. One of the cases is from a kidney of a 4 year old girl. You look up the patient's history and she was admitted for orthopedic care for multiple fractures, and CT incidentally found a kidney tumor where workup was initiated as an inpatient. Microscopy shows the image at right. The med student has a smartphone and by googling "common kidney tumors in children", Wilms' tumor (also known as nephroblastoma) shows up as one of the top choices. You look up the condition on Pathology Outlines and the case seems to fit the microscopic description with its 3 typical components (second image at right).[5] On the same web page you also quickly see the following pieces of look-up information:

  • Risk classification systems, where for example "COG intermediate risk" requires favorable histology and no evidence of anaplasia.
  • That there are no specific/diagnostic laboratory findings.
  • A bunch of associated genetic changes (WT1 (11p13), CTNNB1 (3p22), IGF2 (11p15), TP53 (17p13), MYCN (2p24), and 1q gain).
  • A bunch of associated immunohistochemistry results in the tumor, related non-neoplastic tissue, as well as in notable differential diagnoses (WT1, PAX8, vimentin, CD56, CD57, cytokeratins, EMA, desmin, cyclin D1, BCL2, CD34, myogenin, MyoD1, INI1, Glypican 3, AMACR, CK7, melanocytic markers (MelanA, HMB45), BRAF V600E, TFE3, TFEB, BCOR, and FLI1)

Which of the following would be the best next step if you were to decide yourself?

  1. Diagnosing Wilms' tumor, COG intermediate risk, based on the shown microscopic view alone.
  2. Look at the complete blood count for diagnostic findings.
  3. Order genetic testing for WT1 (11p13), CTNNB1 (3p22), IGF2 (11p15), TP53 (17p13), MYCN (2p24), and 1q gain.
  4. Order immunohistochemistry for WT1, PAX8, vimentin, CD56, CD57, cytokeratins, EMA, desmin, cyclin D1, BCL2, CD34, myogenin, MyoD1, INI1, Glypican 3, AMACR, CK7, MelanA, HMB45, BRAF V600E, TFE3, TFEB, BCOR, and FLI1.
  5. Say "I don't know" and ask for help.
Correct answer
Say I don't know and ask for help.png

A major skill of a pathologist is having an idea of one’s unknowns. Furthermore, pediatric oncology is generally outside the limits of independent practice of any individual pathologist, generally requiring at least consultation with a colleague before diagnosis, classification and decisions about further workup (which in this case may be made at a pediatric oncology center). Thus, even if you though you knew how to proceed on your own, saying "I don't know" and asking for help is still the most correct as a new resident for a case like this.
Incorrect answers

You can skip reading these if you are already agree with the explanation above.

  1. Although the microscopic view that is shown is enough to diagnose Wilms' tumor, it is not enough to classify it as COG intermediate risk without first having looked at the entirety of the microscopy slides to exclude evidence of anaplasia.
  2. There are no specific/diagnostic laboratory findings of Wilms' tumor.
  3. A senior or specialist consultation would be needed in order to find out which genetic tests would actually be worth performing in this case, even after reviewing the history or asking a clinician for any suspected syndrome associated with Wilms' tumor.
  4. The choice of immunohistochemistry panels should be based on which ones most efficiently distinguish the possible differential diagnoses of the case at hand, and not just which ones are associated with the lead diagnosis. As with genetic testing, a senior or specialist consultation would be needed in order to find out which immunohistochemistry tests would actually be worth performing in this case.  


Using this resource

In this resource, it is recommended to read attentively until the end of the emergent pathology section. That part can be regarded as mainly describing concepts, which are relevant to read through and understand or at least consider. The rest will mainly provide guidelines for various situations, such as when you are presented with a biopsy of the gastrointestinal tract. Memorization-worthy information will generally be highlighted by: Memorization-worthy: , otherwise it is recommended to scroll quickly through such situation-based chapters, just to get an idea of what kind of information is available there, and then keeping this resource at a known location for whenever you are in that situation.

  • Memorization-worthy:  This resource is available open-access and ad-free by googling patholines and then Starting pathology (handbook).

This resource is aimed at presenting the most important knowledge that you will need when starting pathology. For further knowledge that you will need as a pathologist and any subspecialization, the best way is to learn from reality, by solving the cases and problems that get presented to you, and thereby look specifically for the information that you will need among the immense literature and other information that is out there.

Also, this resource assumes that you use additional sources when needed (such as The WHO Classification of Tumors or others in the Using resources above). Therefore, it will not simply repeat such information, but may display external links to further information.

This resource also assumes that you will ask a colleague for advise if you see an unfamiliar presentation, and any literature lookup thereof still does not explain it. Therefore, this resource will focus on the most common presentations and the main differential diagnoses thereof, which may include rare conditions if for example the clinical management thereof would be significantly different. On the other hand, most rare conditions that generally have distinct presentations will be omitted. Therefore, keep in mind that there are many such rare conditions that you do not know about, so keep asking colleagues whenever a presentation remains strange to you.

Be tolerant to encountering many repetitions of the same content in related articles, since for example a cervical biopsy and a cervical cone have similar microscopic evaluation.

Using question banks

To test your knowledge on memorization-worthy information, seek questions that present you with a possible real life situation, as well as all pertinent information you can readily look up before needing to answer the question, so to ensure that it tests you on pertinent information as per the items earlier in this chapter. On the other hand, don't waste time on questions whose answer requires memorization of look-up or practically useless information (except if you want to practice looking up the answers online). There are about 5000 questions in PathPrimer, PathDojo and BoardVitals combined, so you can be picky about what questions to focus on.

Consider the usefulness of each question before spending significant time memorizing its answers or explanations, in order to maximize the useful knowledge you will learn overall. Generally, skip questions that test you on look-up information and practically useless information. Whenever you have a question where you can not picture in what real life situation it would be relevant to remember, then you can generally assume that it never will be. For questions that consists of a useful item together with a more useless one, only learn the the useful part and move on. If you can, flag/mark questions on memorization-worthy information that you did not know, and move on fairly quick on those as well, and later revisit those questions specifically if you have the time, as repetition is generally more efficient than lingering.

A common sign that a question will deal with look-up or practically useless information is where it asks which of the alternatives is false or correct for one particular condition, and the alternatives are relatively heterogenous (such as one dealing with diagnosis and another one dealing with prognosis). The high prevalence of such questions is mainly because they are easy and quick create, because the question creator can simply look up a condition, choose some more or less random facts, and then change small details to create alternatives. It requires no real life experience in everyday pathology practice, and learning from such a question is hence generally not useful for that purpose either. The thought processes of real life pathology is generally the opposite of this, because you are generally presented with a specific location, gross appearance and microscopic appearance, and you need to practice on finding the most likely causative condition thereof among many differential diagnoses. Even other kinds of memorization-worthy pieces of information generally have a more limited scope among alternatives (like knowing the optimal staining duration in hematoxylin for a frozen section among alternative durations (see Emergent pathology). Thus, to practice your knowledge in memorization-worthy pathology, it is generally most efficient to skip false-versus-correct questions, in order to spend your limited time on something more worthwhile. Similarly, questions are in general rather low-yield whenever they deviate from the realistic direction.

Other signs of unrealistic and therefore rather low-yield questions include those that mention what kind of test identified the condition, but does not give you the test result (such as a case presentation that includes "Serology identified the organism").

If you have gone through all 5000 questions of the main question banks, and still have plenty of time for a second round, then you may work on lower yield questions as well. For example, you may practice on looking up answers for look-up questions, unless the presentation makes it clear that you cannot timely and conveniently do so (such as being in a rush during a frozen section).

Test question

A question on a question

You want to practice your memorization-worthy knowledge in real life pathology and not for exams ( as per the Secrets chapter at patholines.org.). You find the following multiple choice question: "Which of the following statements for squamous cell carcinoma (SCC) of the skin is false?"

  • For staging of SCC of the of the head and neck, pT1 corresponds to a diameter ≥ 2 cm and < 4 cm (this is the false alternative, as this defines pT2, whereas pT1 is defined as ≤ 2 cm)[6]
  • Most patients have a favorable outcome after surgical resection.
  • It occurs most often in sun exposed areas.
  • It often presents as a hyperkeratotic scaly plaque.
  • Microscopy typically shows carcinoma of keratinocytes that infiltrates the dermis.

What is the most efficient way of dealing with this question for real-life pathology practice?

  1. Choosing an answer, then thoroughly reviewing each alternative, as well as the question explanation.
  2. Like the first alternative, but only if you answered the question wrong.
  3. Only carefully review the single association you need to answer the question correctly (in this case, that for SCC of the skin, pT1 is defined as ≤ 2 cm).
  4. Skip this question and move on.
Correct answer

Skip this question and move on.png
The answer alternatives of this question are all over the place (a mix of prognosis, location, staging, gross description and microscopic description), which usually means that it was created by just looking up the condition in a resource and picking information from there, resulting in a collection of what is usually just look-up information.

Incorrect answers

You can skip reading these if you are already agree with the explanation above.

1 and 2. These are waste of time.
3. If this was a question of memorization-worthy information, or if you were studying for an exam, this would generally be the correct answer. However, staging of cancers can essentially always conveniently and timely be looked up when needed, so this is not memorization-worthy for everyday pathology practice.


 

General advice

Priority

1. More invasive intraoperative consultations
(such as open surgery)
2. Less invasive intraoperative consultations
(such as skins)
3. Fresh lymph nodes
4. Fresh breast tissue (should be in
formalin within an hour from surgery)
5. Other fresh tissue
6. Tissue in formalin

  • When making a mistake, admit that you did it and learn from it so as to focus on not repeating it.
  • Say "I don't know" instead of making up answers for what you do not know.
  • Try to fit findings with the clinical picture so that the report makes sense, but do not make up findings that you do not see, and do not omit relevant features just to fit an expected story.
  • Ask for help whenever needed, such as first time you are doing something, or whenever you are not sure about what to do, especially when doing something potentially irreversible. Also ask for help in moments whenever there is a high risk that you will not achieve what you need to do within a clinically acceptable time. For prioritizing when you have more than one thing ongoing at the same time, the list at right can be used. Still, before asking, try to do as much as you can, as long as you do not do anything potentially irreversible, so that you can evaluate how you did it compared to the standard, and thereby know better how you will do it next time.
  • Do not wait for the whole pile. Whenever you can, do not be idle or do less urgent work while there is a pile of more urgent work gathering for you elsewhere. Instead, be familiar with where such piles are forming, and go there and grab whatever you may start working on right away.
  • For larger specimens that need fixation before final grossing, you can still start writing a report of measurements and other externally visible findings to save time for later.
  • Save your digital reports frequently.

Comprehensiveness

On this handbook, the following formatting is used for comprehensiveness:

  • Minimal depth
  • (Moderate depth)
  • ((Comprehensive))
  • << Decision needed between alternatives separated by / signs >>
  • {{Common findings / In case of findings}}
  • [[Comments]]
  • Link to another page
  • Organs, important regions or other important key words.

Emergent pathology

  Memorization-worthy:  Information relating to emergent pathology is often not conveniently and timely looked up when needed because of the need for a fast report.

 

Frozen sections

Even new pathology trainees may end up being the first responders to frozen sections (as well as intraoperative consultations by gross inspection only).

Preparation

Prepare at least the following:

  • Finding out which senior to call for help if responding to a frozen section. A fairly new pathology trainee should generally not independently make a report to the referring physician without having at least consulted with a senior, and therefore the diagnostics of frozen section slides is not included in this section. In the meantime, ensure that you have the contact information to relevant seniors and/or attendings, and the means to perform micrography and telepathology if that person may not be able to be physically present within an acceptable time.
Main sites of metastases for some common cancer types. Primary cancers are denoted by "...cancer" and their main metastasis sites are denoted by "...metastases".[7]
  • If possible, look up pertinent medical histories of potential cases that may appear as frozen sections or other forms of intraoperative consultations. For example, surgery departments may have schedules of patients for the day that you will cover frozen sections. On such lists, types of surgeries that often come as intraoperative consultations mainly include potentially malignant skin excisions, lung excisions (larger than biopsies), ovarian tumors, and samples from other common metastasis sites (lungs, liver, brain, bone). The most important details to find out are:
  • What you may do yourself if you will be alone when you get the specimen, or if you need to wait for particular seniors before doing potentially irreversible steps such as inking and sectioning.
  • Previous biopsies. For expected excisions from common metastasis sites, look thoroughly for any past cancer diagnoses. Note the pathologic diagnoses of the biopsies((, as well as the collection dates and accession numbers.))
  • Tumor sizes where applicable(, and whether the estimation was from imaging or microscopy).
  • Make sure you have a working microtome. Switch its blade if you are not certain it has had limited use.
  • Prepare at least as many chucks as you think you will need according to any surgery schedule (or at least 3 of preferably various sizes).

(If you don't have a conductor, or if the embedding medium completely hardened before you applied it, perform cryotomy of the embedding medium to get a larger and smoother top.)

  • Inspect the H&E staining containers and refill if necessary.
  • Ensure that you have frozen section medium, as well as cover slips and mounting fluid.

Performing frozen sectioning

  • Inform relevant seniors.
  • Look at any requisition form or otherwise check or confirm what answers the requesting clinician wants. When the histopathologic type of tumor is known from before and its distance to the closest margin is relatively far, a gross intraoperative consultation is generally enough to measure that distance.
  • Measure the size of the specimen.
  • If you are permitted to proceed with the following steps, which are potentially irreversible, still consider whether there are any surprising aspects that requires you to wait until a senior arrives.
  • Ink relevant margins
  • 'Section the specimen so as to be able to see relevant pathologies, and closest distances to relevant margins.
  • Select tissue to be able to answer the clinician's questions.
  • Trim samples to make them equally thick, since you will need to section away more from thick pieces before thinner pieces will appear in cryotomy slices.
Minimal time in solutions for frozen sections.

Test question

Hematoxylin in frozen sectioning

You are put on frozen sectioning duty, and a specimen arrives. You inform the attending over the phone, who will require a moment to reach the room, and therefore tells you to prepare two microscopy slides in the meantime. You make sections, but the note that instructs the number of dips or duration in the hematoxylin solution has become unreadable due to a hematoxylin stain. You don't have any phone signal in the frozen section room, so you don't have time to look it up. To what extent will you put the slide in the hematoxylin solution?

  • A. 1 minute and 30 seconds
  • B. 1 dip
  • C. 10 seconds
  • D. 5 dips
Answer

Time in hematoxylin solution.jpg

Explanation

This is generally the minimal time required for proper hematoxylin staining during frozen sections. Yet, if you know the solution is not expired or diluted, and you are really in a rush, then you can possibly have it acceptably stained in 1 minute in hematoxylin.


Troubleshooting

Problem Cause Solution
Tissue cracks off in cryotomy
  • Block too cold
Repair by warming slightly and adding embedding medium
Thick and thin slices
  • Inconsistent clamping
  • Dull blade
  • Incorrect blade angle
  • Ensure block holder and blade holder are tight
  • Change blade
  • Correct knife angle
Wrinkled, compressed or puckered sections
  • Dirty or dull blade
  • Tissue too warm
  • Clean blade
  • Move or replace blade
  • Cut tissue at colder temperature
Tissue advances but does not cut
  • Inconsistent clamping
  • Ensure blade holder is tight
Sections roll up
  • Anti-roll plate is not adjucted correctly
  • Readjust anti-roll plate
Sections thaw on the blade
  • Blade is too warm
  • Cool the blade
Sections stick to the anti-roll plate or blade
  • Static in the cryostat
  • Apply anti-static spray or anti-static gun
Sections split vertically
  • Dirt or nick on blade
  • Clean, move or replace blade
Sections have fine cracks parallel to the blade edge
  • Too cold temperature
  • Warm the tissue
Sections show signs of vibrations
  • Specimen too loose
  • Incorrect blade angle
  • Tighten chuck to the holder
  • Change the blade angle
Stain is dull and muddy
  • Drying artifact
  • Put sections on glass slides immediately in fixative

Suspected malignant skin excisions

While most frozen sections can be predicted from schedules of the operating room and thereby be looked up beforehand, suspected malignant skin excisions often come from outside the main surgery department, even more indicating memorization of how to handle them.


Tissue selection
Tissue selection from suspected malignant skin lesions, by lesion size:[8][note 5]
<4 mm 4 - 8 mm 9 - 15 mm
Tissue selection from skin excision with less than 4 mm suspected malignant lesion.png Tissue selection from skin excision with 4-8 mm suspected malignant lesion.png Tissue selection from skin excision with 9-15 mm suspected malignant lesion.png

In table above, each top image shows recommended lines for cutting out slices to be submitted for further processing. Bottom image shows which side of the slice that should be put to microtomy. Dashed lines here mean that either side could be used.  

Other frozen sections

Although these are generally given on schedules of the operating room, any pathologist may end up suddenly covering for another one, and subsequently be presented with the frozen section case without having had the time to look it up beforehand.

In malignant or suspected malignant cases, surgical margins are generally more important than main tumor diagnosis.

  • In lung wedge resection and lobectomy, sample the surgical margin that is presumably closest to a tumor for frozen sectioning.  
  • In an intestine with tumor, it is generally enough to open the intestine (avoiding cutting through a tumor unless it is corcumferantial, and grossly measuring the distances to the proximal and distal surgical margins, as well as the distances to the radial or mesenteric surgical margins.  
  • For a donor kidney biopsy, generally evaluate as per local protocol.  

Reporting of intra-operative consults

  • Call the requesting clinician
  • Verify that you are talking to that person, or someone who can immediately convey the diagnosis to that person
  • Tell the patient identity (with at least two different identifiers, such as name and date of birth)
  • (Ask for a readback of your diagnosis)
  • State your diagnosis
  • (Make sure the clinician reads the diagnosis back to you.)

Example:

  • Hello, this is from pathology. I have a frozen section result for Dr. (name of the clinician)
  • This is Dr. ____, and I have a diagnosis on (patient name and date of birth)(, so if you could please read back to me after,) the diagnosis is (diagnosis)

See also

 

Donor kidney biopsy

  Memorization-worthy:  A donor kidney biopsy may come for frozen sectioning.

Gross processing

Prepare a separate slide for right versus left kidney if applicable.

Microscopic evaluation

Generally evaluate as per local protocol, which generally includes the following parameters, given individually for right and left kidney:

 

Fixation

 

Immersion

Adipose tissue with crumpling artifact due to insufficient fixation.

Within an hour after removal from the body,[10] tissue samples should generally be placed in vessels with enough fixative to allow them to lie freely in the solution.[11] The standard fixation fluid is generally 10% neutral buffered formalin, which is roughly equivalent to 4% formaldehyde.[12] The ratio of tissue:formalin should be 1:5[13] to 1:10[14].[14]

Duration

The duration depends on tissue thickness, where formalin will penetrate and fix the tissue at ~1 mm/hour.[15]

When not to use formalin

The main exceptions to using formalin are mainly:

  • A tophus or other specimen suspicious for gout versus pseudogout should be sent in alcohol or dry, since formalin will dissolve the crystals.
  • Lymph nodes (or other lymphoid aggregates) with a suspicion of lymphoma, where samples are generally put in a special solution for flow cytometry.
  • Products of conception with a need to take samples for genetic testing.


Gross processing

  Following are general notes on selection and trimming in pathology.  

Fresh specimens

The initial processing of fresh specimens is also termed triaging.

  • For intraoperative consults including frozen sectioning, see separate article on Emergent pathology.

When triaging a specimen, the measurements are most important as these may change after fixation. Other descriptions can generally be made after the specimen is fixed.

Before cutting

  • Confirm that the patient identity on the specimen container matches the identity that will be applied to the gross description and cassettes. {{If the referral or requisition form is available, confirm the patient identity on that one as well.}}
For unclear or potentially ambiguous handwriting (here "Right" or "Left" renal stone), look at the referral or requisition form ((and the medical record if available)).
  • (Check for any discrepancy between the specimen description on the container and on the referral or requisition form, such as left versus right.)
  • Don't omit any piece in the container, such as ones hidden in wraps.
  • Generally measure in 3 dimensions, or in volume, but the greatest dimension is generally enough for specimens less than 0.4 cm.
  • Generally weigh entire organs, after having any attached tissue trimmed away if feasible.
  • (Note the color of the sample, even when unremarkable, but do not linger on deciding it.)[note 6]
  • Generally, use inking for resection margins where cancer radicality is important.  
  • (On fatty or greasy surfaces, apply vinegar to emulsify and remove the fat, dry the specimen and then ink. Otherwise, vinegar can be used either before or after inking to "dry" it.)
  • (Preferably photograph or make a drawing where slices have been taken.)[16]
  • Remove any surgical stitches from samples before microtomy.
  • (At least for larger samples, consider looking for medical imaging or biopsy reports in order to better guide the process.)[17]
  • Fix bone in formalin prior to decalcification. Use reminders so not to forget bone that is decalcifying.

Cutting

  • When cutting with the longer knives, try to cut in one stroke - do not use like a saw (continuous back and forth)
  • Generally, strive to make slices perpendicular to visible interfaces of relevant tissues.
  • Generelly dissect and inspect the entire specimen, while keeping relevant parts intact enough for presentation to seniors and/or maintaining orientation.
  • Trim tissues for microscopy examination to a thickness of maximum 3-4 mm.[note 7]

Perpendicular versus en face sections

Perpendicular and en face sections

Two major types of sections in gross processing are perpendicular and en face sections:

  • Perpendicular sections allow for measurement of the distance between a lesion and the surgical margin.
  • En face means that the section is tangential to the region of interest (such as a lesion) of a specimen. It does not in itself specify whether subsequent microtomy of the slice should be performed on the peripheral or proximal surface of the slice (the peripheral surface of an en face section is closer to being the true margin, whereas the proximal surface generally displays more area and therefore generally has greater sensitivity in showing pathology, also compared to perpendicular sections).
  • A shaved section is a superficial en face slice that contains the entire surface of the segment.

Tissue selection

When sampling sections to submit for microscopic examination, whenever you sample from something that looks abnormal, generally try to also sample from the same type of tissue that looks normal.[note 8]

Biopsy wraps, bags and sponges

Items used for submitting specimens: (Biopsy) wrap, (biopsy) sponge, (tissue processing) cassette and (biopsy) bag.

Put the following types of specimens in bags:

  • Tiny specimens that need to be poured out from their containers.
  • Bloody specimens such as endometrial curettages or products of conception. For products of conception, chorionic villi may otherwise contaminate other specimens. Bloody specimens may stick to wraps, so generally avoid that situation.
  • Friable tissue such as urinary bladder biopsies.

Put the following types of specimens in bags, wraps or sponges:

  • Other tiny specimens
  • ((Any small piece of tissue where there is no leftover specimen to retake sections, since tissues occasionally get lost from cassettes, and the absence of a wrap, sponge or bag in the cassette of such cases points towards a mistake made at gross processing.))

Specimens must be fixed enough to be put on sponges.

H&E staining urgency

(Even in departments where other staff are primarily responsible for determining the urgency of H&E staining of each specimen, still double-check that it is correct if you can, such as by cassette color.) A major indication for rushing cases through H&E staining is a high risk of cancer, especially where immunohistochemistry staining will likely be performed, and the decision and types of staining will be determined by the standard H&E stain. Tissues that are generally rushed are:

  • Brain biopsy.
  • Lung biopsy.
  • Breast needle biopsy.
  • Biopsy from known tumor tissue.
  • Suspected malignant lymph nodes, including lymphoma. However, these are generally not urgent when submitted together with a tumor, except mainly for the following (which are generally urgent):

In both these cases, the cases are rushed so that immunohistochemistry can be performed if a metastasis is not readily detected on standard H&E slides, so that it is available by the time the rest of the slides are out. Immunohistochemistry in these cases can detect micrometastases that are not readily visible on H&E stain, but are evident on cytokeratin AE1/AE3. However, if the lab stains such cases regardless of whether H&E stain shows a metastasis or not, then they do not need to be rushed.

Marking cassettes

Use only hard pencil (or specially purchased histology markers), as marks made with pens, Sharpie markers, or scientific freezer-safe markers can get dissolved in tissue processing.[18]


Evaluation

 

Microscopy settings

Usual parts of a microscope.

Generally the condenser is placed in its highest position or just slightly lower. At low magnification objectives (mainly 4x and 10x objectives), the opening of the condenser (or iris) diaphragm should be wide open. This corresponds to turning away or "lowering" the condenser on microscopes where the condenser apparatus can be turned to the side (and is shown as "without condenser" in images below). For high-dry (40x) and oil-immersion objectives (100x), the diaphragm should be closed slowly while looking at a sharply focused section until the level of illumination is just slightly reduced, in order to attain optimal contrast and resolution (and corresponds to "with condenser" in images below).[19]

Low magnification has a greater span of focus compared to high magnification, so it is normal to need to focus if you're increasing magnification. If there's a constant visual artifact, even after you've cleaned the eye piece and objective lenses with lens tissue, try raising or lowering the condenser if you can, and the artifact may disappear out of focus.

Main steps

  • Preferably, look up past medical history of the patient, mainly past cancers that could possibly appear in the current specimen.
  • Look at each microscopy slide by plain eye, to plan the microscopy screening so as to not miss peripheral fragments.
  • Have a systematic direction of screening through microscopy slides, such as from top left to bottom right as seen in the microscope. When the microscope makes what you see two-way mirrored, the starting position is with the objective pointing at the bottom right of the glass slide.
  • Look in particular for whatever is requested or suspected on the requisition form or equivalent.

While learning, you will generally focus relatively more on high magnification features with high specificity, but still have a habit of learning how your cases look at low magnification as well. In time, you will increasingly correlate diseases and conditions with their overall low magnification patterns - patterns that may require 1000 words to describe and thus cannot conveniently be part of written criteria, but will nevertheless allow you to make quicker and more accurate diagnoses.

Complete your evaluation even if you encounter a finding, as there may be additional findings as well.

Artifacts

In microscopy, an artifact is an apparent structural detail that is caused by the processing of the specimen and is thus not a legitimate feature of the specimen. Major artifacts to account for include:

Differential diagnoses of artifacts are mainly:

  • Foreign bodies. In contrast to contamination, these conform more naturally to the surrounding tissue.
  • Organisms, to be particularly considered when there are multiple objects of the same size.

Order recuts from the same paraffin-embedded tissue if artifacts significantly impairs your diagnostic evaluation of the glass slide. However, artifacts caused by gross processing may affect recuts as well.

General patterns

Following are major patterns that often help in making a diagnosis.

Architectural patterns

Cellular patterns

Nuclear patterns

When feasible, classify nuclei as follows:

Other patterns

Inflammation

Measuring distances

There are also eye pieces that show a ruler in the field of view, but make sure you match it with the correct objective and other settings to make the measurement valid.

Counts per mm2

There are multiple situations where a finding will be quantified in terms of amount per mm2. To make such calculations, you need to know the size of the area you see in the microscope. It is usually possible to look up what theoretically would be the area, but the most reliable way of knowing is to use a calibration slide to measure the diameter of your view. The area is then calculated as:

  • Area in mm2 ≈ (diameter in mm)2 x 0.79

Sometimes "high power field" (HPF) is used for area, but it has a substantially different area for different microscopes, for example:

Microscope type Area per HPF
  • Olympus BX50, BX40 or BH2 or AO or Nikon with 15x eyepiece
  • Olympus BX43 with 10x eyepiece
0.096 mm2 [21]
AO with 10x eyepiece 0.12 mm2 [21]
Nikon Eclipse E400 with 10x eyepiece and 40x objective 0.25 mm2
Leitz Ortholux 0.27 mm2 [21]
Leitz Diaplan 0.31 mm2 [21]

When your instructions are to count a specific number of HPFs, one HPF can be assumed to be 0.2 mm2.[22] If the view area in your microscope significantly differs from this area, calculate how many views you need to count as:

Views = HPFs required x 0.2
Your microscope area (in mm2)

For example, if your instruction is to count 10 HPFs and each view in your microscope shows 0.096 mm2, you should count in this many views:

10 x 0.2 ≈ 21
0.096

Subsequently, if your microscope area is significantly different from 0.2 mm2 and you need to state your result in terms of count/HPF, use:

Count/HPF = Average count in your view x 0.2
Area of your view in mm2

For example, if you have counted an average of 10 cells (or other object of interest) in each of your views, and the area of your view is 0.096 mm2, then your count/HPF is:

10 x 0.2 ≈ 21
0.096

Micrography and telepathology

Unless you have more specific equipment for taking microscopic images and showing cases to remote colleagues, you can perform these tasks as follows:

  • With a stationary computer, you can connect to a microscopy camera. For telepathology, you can start a videoconferencing session with your senior, then share the screen while showing a micrograph, or the live view so that you can move around.
  • With a mobile phone:
You can send micrographs to your senior, but it is technically difficult to keep the focus while moving the glass slide.

Cytology

In cytology samples, or any sample with scattered cells rather than coherent tissue, also evaluate the following:

  • Adequacy of specimen. There may be too few cells to make a proper diagnosis.
  • Background, mainly if it is clear or dirty
  • Overall cellularity


Evaluation of suspected malignancies

  For evaluation of suspected malignancies such as tumors, the most important aspect is whether it is benign or malignant. If malignant, then staging is necessary.[23] There are generally specific criteria for various forms of tumors, which should be used whenever applicable, but following are some generalizations.

A general approach is to start looking at the slide which seems to contain most tumor (excluding any necrosis), facilitating a diagnosis, and shows what kind of cells to look for in the periphery.

Benign or malignant

Cellular features of malignant cells versus normal cells.
Benign[24] Malignant[24]
Gross examination
  • Well demarcated from surrounding tissue
  • Usually no tumor capsule

Possibly:

  • Necrosis
  • Infiltration or invasion into surrounding tissue
  • Bleeding
Microscopy Almost no irregularities of cellular structures Nuclear atypia:
  • Enlargement
  • Pleomorphism
  • Nuclear polychromasia, which means variability in nuclear chromatin content.
  • Numerous mitotic figures

Overall diagnosis

For specific diagnoses by organ system, see anatomic diagram on Patholines Main page. This resource will give the main steps towards reaching a diagnosis, but before making a tumor diagnosis, always confirm with The WHO Classification of tumors, and generally an experienced pathologist as well until you feel confident.

Visually, tumors and other suspected malignancies can usually be classified into one of the following groups:

Further pinpointing of a specific tumor type is often attained by thinking of one or more possible diagnoses, and looking up their differential diagnoses, followed by comparing their microscopic descriptions and multiple micrographs with the case at hand. When two or more diagnoses seem to fit with the case at hand, consider performing immunohistochemistry. Find relevant target proteins that are expected to stain substantially differently between the possible diagnoses. If it's not evident from initial sources, you may use Immunoquery.com which will generally suggest the most relevant target proteins to distinguish the suspected conditions at hand.

Gland-like tumors

Gland-like tumors are mainly evaluated for cellular atypia, architectural dysplasia and invasion, and thereby classified into the following main categories:

  • Hyperplastic lesions, lacking significant atypia
  • Adenomas, which can range from mild to high-grade dysplastic, yet are generally confined within their anatomic layers, that is, they are not invasive.
  • Adenocarcinomas, with the main criterion being invasiveness. Evaluate specifically by location when possible. Some specific locations included in this resource:

Squamoid tumors

These are more or less looking like a squamous-cell carcinoma:

Differential diagnoses depend on location, such as:

Spindle-cell tumors

For Spindle-cell tumors, the shape of the nuclei is a clue to the diagnosis, with the following tendency:

  • Pointed on both ends: True fibroblastic tumors
  • Pointed on one end and blunted on the other ("bullet-shaped"): Neural
  • Blunted on both ends ("cigar-shaped"): Smooth muscle
  • Triangular: Myofibroblastic

Evaluate specifically by location when possible, such as spindle-cell tumors of the midgut.

Undifferentiated tumor

An initial panel of cytokeratin (CK), S100, vimentin and LCA (CD45) can be used.[26]

No tumor

If a neoplasm has been ruled out for what clinically appeared like a tumor, seek a diagnosis that can be consistent with such a clinical finding. For example, for a breast biopsy of what appeared to look like a mass, and there is no neoplasia, look mainly for dense fibrosis, so that you can report that thereby explain the finding, rather than merely write "benign breast tissue".

Additional levels or slices

Additional material is indicated in the following situations:

  • Re-excision does not identify tumor cells in a clearly non-radical primary excision or biopsy.
  • The most aggressive pattern is seen in the last available section, in which case more sections are indicated (from the same paraffin block if additional tissue is not available).

Depending on availability and greatest suspicion, additional material is either acquired by taking addition step sections of remaining tissue in a paraffin block, or taking additional slices from the original specimen.

Staging

Staging is generally done by TNM classification. Specific TNM systems should be used whenever applicable, mainly the manual by the American Joint Committee on Cancer (AJCC) if you can access it.   Otherwise, a general system may be used:[23]

T: size or direct extent of the primary tumor

    • Tx: tumor cannot be assessed
    • Tis: carcinoma in situ
    • T0: no evidence of tumor
    • T1, T2, T3, T4: size and/or extension of the primary tumor

N: degree of spread to regional lymph nodes

    • Nx: lymph nodes cannot be assessed
    • N0: no regional lymph node metastasis
    • N1: regional lymph node metastasis present; at some sites, tumor spread to closest or small number of regional lymph nodes
    • N2: tumor spread to an extent between N1 and N3 (N2 is not used at all sites)
    • N3: tumor spread to more distant or numerous regional lymph nodes (N3 is not used at all sites)

M: presence of distant metastasis

    • M0: no distant metastasis
    • M1: metastasis to distant organs (beyond regional lymph nodes)

Put your main focus on features that will determine the final stage. For example, if you see a lymph node involved by cancer, the presence or absence of lymphatic invasion is no longer critical, but rather the presence or absence of additional involved nodes or distant metastasis.

Radicality

If tumor is seen at edge of the sample, but it is not inked, consider confirming the finding with adjacent microtomy levels, especially if no ink is seen on an inked surgical margin. In this case, a separation artifact in top image has removed a surgical margin of connective tissue, seen on adjacent microtomy section in bottom image.

Determine if malignant cells are located close to, or even in, any surgical resection margins.

Lymphovascular invasion

Lymphovascular invasion should always be mentioned. When present at margins, it does not count as tumor extension.

Typing and grading

Also note "treatment effect", seen as fibroelastotic tissue, here with scattered remaining tumor cells.

Beyond determining overall malignancy diagnosis (such as adenocarcinoma), probable origin and staging, classification of tumors into a specific histopathologic type or grade is generally of relatively less value. In cases of clearly non-malignant tumors where it is difficult to determine the specific histopathologic type or grade, it is generally acceptable to conclude the evaluation and report it as such, unless the clinician specifically requests otherwise. For potentially malignant or high-risk tumors, typing and grading often still affects the management.

Reporting

For cancers, generally include a synoptic report, such as per College of American Pathologists (CAP) protocols at cap.org/protocols-and-guidelines. If a surgery produces a specimen with cancer, as well as re-excisions from certain directions, you should preferably give the closest distance to margins in each specimen, as well as the closest distance overall in a synoptic, for example:

A. (Specimen with most of the cancer)
  • (...)
  • Invasive carcinoma is present at inked medial margin (see specimen B for final medial margin), and is located 0.3 cm from the lateral margin.

B. (Re-excision in the direction of the medial margin)

  • (...)
  • Invasive carcinoma is located 0.5 cm from the new medial margin.

Synoptic report

  • (...)
  • Distance from invasive carcinoma to closest margin: 0.3 cm
  • Closest margin(s) to invasive carcinoma: Lateral

 


Immunohistochemistry

  When learning pathology, the percentages by which immunohistochemistry results are positive or negative for various diseases are generally easily looked up when needed, so what a pathologist needs to learn is mainly how to select the optimal immunohistochemistry panels in the first place for various presentations where the diagnosis is unknown.

Immunohistochemistry ordering

The main approaches to immunohistochemistry ordering are:

  • Look for a specified panel for the presentation at hand. For example, for an undifferentiated tumor with no clear lineage differentiation, an initial panel of cytokeratin (CK), S100, vimentin and LCA (CD45) can be used.[26]
  • Coming up with the most relevant differential diagnoses for the case at hand, and find the immunohistochemistry stains that best distinguish them. Immunohistochemistry profiles for diseases and conditions, as well as their main differential diagnoses, is generally found at Pathology Outlines, or you can pay for a subscription to ImmunoQuery[note 3]:

Using Immunoquery

The main page of ImmunoQuery gives you the "Diagnoses" option, where you enter up to 3 differential diagnoses to generate the optimal immunohistochemistry panel to differentiate them (you may need to click ∨ Suggested Panel to show it if it is collapsed). It also displays an automatic message when the included antibodies/immunostains are not sufficient for a satisfactory panel, in which case you can:

  • Make a specific search only including the two conditions where suggested immunostains were insufficient, if you had previously compared 3 diagnoses.
  • Consider additional stains from the "Comprehensive panel" displayed below the suggested one.
  • Switch the "Sensitivity" setting (seen at top) from 1 (which means that diffuse, focal as well as not specified staining count as positive) to 3 (which means that only diffuse staining counts as positive whereas both focal and absent staining count as negative, and references without any specified staining pattern are omitted from the analysis). This has less data to support the suggested stains (since many references do not specify whether positivity was diffuse or focal), but can sometimes state a better distinction between conditions. When including a stain based on its distinguishing features on a sensitivity setting of 3, you need to keep the practice of classifying only diffuse staining counts as positive, and focal to absent staining as negative.

Test question

ImmunoQuery for a squamous cell carcinoma
Squamous cell carcinoma, with large cells with abundant eosinophilic cytoplasm and large, often vesicular, nuclei.

The attending gives you a lung biopsy case to preview. You are first uncertain about the type of tumor, so you ask a fellow resident, who finds a diagnostic area of the tumor and tells you that this is a typical squamous cell carcinoma. You also look through the patient's history, and find that the patient has had a squamous cell carcinoma of the anus in the past, and you now want to find out whether the tumor originated in the lung, or if it is a metastasis from the anus, or possibly the skin. You therefore do an ImmunoQuery lookup, with the following results:

Suggested Panel

Insufficient antibodies for a satisfactory panel to differentiate Lung squamous cell carcinoma and Anus squamous cell carcinoma

Antibodies Lung SCC Anus SCC Skin SCC
EpCAM 81% Positive
Membrane, Cytoplasm
75% Positive
Membrane, Cytoplasm
0% Positive
Membrane, Cytoplasm
GATA3 5% Positive
Nucleus
20% Positive
Nucleus
84% Positive
Nucleus
p16 17% Positive
Cytoplasm, Nucleus
87% Positive
Cytoplasm, Nucleus
45% Positive
Cytoplasm, Nucleus

You go talk with the attending, who agrees that EpCAM, GATA3 and p16 should be in the panel, but just as ImmunoQuery also tells, the attending thinks that the panel is not satisfactory to differentiate lung SCC from anus SCC, and wants you to add one more stain to improve the panel. You go back to ImmunoQuery and increase the Sensitivity from 1 to 3 (which means that only diffuse staining counts as positive whereas both focal and absent staining count as negative, and references without any specified staining pattern are omitted from the analysis), and get the following results:

Suggested panel
Antibodies Lung SCC Anus SCC Skin SCC
EpCAM 74% Positive
Membrane, Cytoplasm
50% Positive
Membrane, Cytoplasm
0% Positive
Membrane, Cytoplasm
DLK 28% Positive
Membrane, Cytoplasm
N/A
Membrane, Cytoplasm
100% Positive
Membrane, Cytoplasm

You also perform a repeated search by only entering Lung and Anus SCC, and you get the following results:

Suggested panel
Antibodies Lung SCC Anus SCC
p16 17% Positive
Cytoplasm, Nucleus
87% Positive
Cytoplasm, Nucleus
Comprehensive panel

Top results:

Antibodies Lung SCC Anus SCC
p16
Cytoplasm, Nucleus
17% 87%
GRPR
Cytoplasm
56% 100%

You switch sensitivity from 1 to 3 for this result as well, showing:

Suggested panel

No antibodies to differentiate Lung squamous cell carcinoma and Anus squamous cell carcinoma

Comprehensive panel

Top result:

Antibodies Lung SCC Anus SCC
GRPR
Cytoplasm
46% 91%

You go talk with a technician at the histology lab, and your hospital offers all the stains in the alternatives, at similar costs, so you don't have to think about expenses and logistics of sending the case out to external labs.

In addition to EpCAM, GATA3 and p16, what is the best alternative, given the information you retrieved above, to differentiate lung versus anus squamous cell carcinoma?

  1. Add DLK to the panel, and favor anus origin if having a diffusely membranous staining rather than diffusely cytoplasmic.
  2. Add DLK to the panel, and favor anus origin if having a diffusely cytoplasmic staining rather than diffusely membranous.
  3. Add GRPR to the panel, and favor anus origin if having either a diffuse or focal cytoplasmic staining.
  4. Add GRPR to the panel, and favor anus origin if having a diffuse but not a focal cytoplasmic staining.
  5. The ImmunoQuery results above are not sufficient to suggest an additional stain besides EpCAM, GATA3 and p16.
Correct answer
GRPR answer.jpg

GRPR is the top result when specifically comparing lung versus anus squamous cell carcinoma, both at sensitivity settings 1 and 3, with no major difference between them, and thus anus origin is favored in case of either diffuse or focal cytoplasmic staining. DLK showed as N/A for anus SCC.


Immunohistochemistry evaluation

The main methods for evaluating immunohistochemistry results are:

  • Looking up each differential diagnosis at for example Pathology Outlines and comparing their expected staining to see which entity is most likely.
  • Paying for a subscription to ImmunoQuery,[note 3] where you can enter immunohistochemistry results and generate a list of most likely conditions with that profile.

Preferably, immunohistochemistry results will be very specific or sensitive for a suspected condition, thereby confirming it if positive, or excluding it if negative, respectively. Even when that is not the case, immunohistochemistry can at least alter the likelihoods of different differential diagnoses. In practice, clinicians or pathologists do not state exact or even approximate numbers of likelihoods of differential diagnoses ( see the Reporting chapter for phrasing uncertainty), since reality is too complex for that, but to demonstrate the general principle of how immunohistochemistry results can be calculated, the following formula can be used:

  • Gross likelihood of a disease/condition = (Pre-test probability) x (Probability that the condition shows the immunohistochemistry results at hand).

The pre-test probability is a product of for example the incidence of the condition in the patient's epidemiologic type such as age and sex, as well as the probability that the condition would have caused the clinical course, including signs and symptoms, as well as the microscopic impression. For example, if you want to differentiate a pleomorphic liposarcoma from a pleomorphic rhabdomyosarcoma in soft tissue, you may find in ImmunoQuery that the following stains are most efficient in distinguishing the two, with the following percentages of being positive:

Soft tissue pleomorphic liposarcoma Soft tissue pleomorphic rhabdomyosarcoma
Desmin 17% 95%
Actin HHF-35 0% 71%

Let's say for example that your pre-test probability was about 30% for pleomorphic liposarcoma and 70% for pleomorphic rhabdomyosarcoma, that desmin stains positive, and actin HHF-35 stains negative in this case. Assuming that 0% positive rate means that 100% stain negative, the probability that pleomorphic liposarcoma shows these immunohistochemistry results at hand is:

  • 17% x 100% = 17%

The gross likelihood of pleomorphic liposarcoma therefore becomes:

  • 30% x 17% = 5.1%

In the same way, the corresponding gross likelihood of pleomorphic rhabdomyosarcoma is calculated as:

  • 70% x 95% x (100% - 71%) = 19%

As a result in this case, immunohistochemistry resulted in pleomorphic rhabdomyosarcoma going from about twice as likely compared to pleomorphic liposarcoma to about 4 times as likely. Although results like these do not make major differences individually, detailed calculations of results from a large panel of immunohistochemistry stains can have a major impact when taken together, even if each stain has relatively low sensitivity and specificity.[note 9]


Consultation

  Save phone numbers to pertinent seniors so that you can contact them in urgent situations.  

When to ask

For grossing, general factors for asking for assistance include:

  • Unfamiliarity with the specimen type at hand.
  • Malignancy risk of the case.
  • Inability to retake sections in case the first ones are insufficient:
  • A risk of irreversibility of any processing, such as inability to perform special tests by putting it in formalin.
  • Low redundancy of tissue at hand, such as very small pieces of relevant tissue.
  • Low accessibility in obtaining the specimen at hand, such as through deep surgery or imaging-based biopsy.[note 10]

What do ask for

When consulting a senior, generally read up on the medical history and(/or) operative report of the patient. Also, try to diagnose each case as much as possible before asking, so that you will practice your skills and further improve them based on how they differ from what a senior would do. If taking a slide tray with you, don't forget the slide on your microscope.

What you generally want to know are:

  • ((Note if the office door open, and how much, and generally leave it the same way on the way out.))
  • The pathology issues at hand.
  • If you are given information for writing a pathology report, what will you do after writing it in the system? Save, sign or notify them otherwise?

Getting in touch with clinicians

Ask the referring doctor for clarification whenever needed for your diagnosis. In more emergent situations:

  1. Look at the referral for any number to call.
  2. If intraoperative, call the operating room number.
  3. Call the hospital switch to connect you with the referring doctor.

In less emergent situations, you may also try the following:

  • Consider texting the person rather than call (and use case/patient number rather than identifiable information, unless you are using an appropriately encrypted system).
  • For inpatients, find out from for example medical records where the patient is located, call the hospital switch to connect you with that location, even if with a nurse or other caregiver, and ask that person for the phone number to the referring doctor, or other person in charge of the patient.

The optimal time to get in touch with hospitalists is generally around 2pm to 3pm (when they are usually done with the more emergent tasks of the day but haven't yet left for the day).


Reporting

  Following are general notes on reporting in pathology.

  • Save your digital work frequently, and also when you leave a desk, even if you think you'll be back shortly. It doesn't matter how much time and effort you spend on something if you're just going to let it disappear.
  • Double-check your report, especially if you copy-pasted and adapted a previous report rather than using a template with blank fields or making your report from scratch.

Components

Selection and trimming

From the stage of selection and trimming, a histopathology report should preferably include:

  • Case:
  • Patient identification and/or sample number
  • Type of tissue sample as described on container
  • Dimensions of original tissue[27]
  • Directions or other features of any inked surfaces.
  • Generally the weight of larger samples[27]
  • Dimensions of pathologic components[27]
  • Whether the entire specimen or representative sections were submitted.

Microscopic evaluation

  • Specimen chronology, often A, B, C, etc., at least where there are multiple specimens from the same case. With multiple specimens, preferably write out the chronology for all of them first, so that you don't miss reporting any of them later.
  • Specimen type and/or surgery type, such as "appendix, appendectomy", for clarification. This is not necessary at all departments. For the procedure, use the same term as the operating report whenever possible.
  • Microscopic description. This is not always necessary, but should be included if the diagnosis is uncertain. One systematic approach is to describe findings from largest to smallest ones. For example, a description of a tumor can start with the demarcation of the tumor, followed by texture, cell shapes, nucleus shapes and chromatin appearance.
  • Diagnosis or most probable diagnoses.
  • If the diagnosis does not clearly account for all conditions that were requested, suspected or asked to be ruled out by the referring clinician (such as stated on the requisition form), you need to classify the specimen as "positive for" versus "negative for" for each such condition, or give a reason for why an evaluation thereof could not be made.
  • In case of malignancy or suspected malignancy:
  • Depth or most distant invasion of malignant findings.[27] Depending on location, it may need to exclude important pathways, such as vascular, neural and/or through capsules or other layers.
  • Whether the resection is radical or not.

Depth

Factors supporting a relatively more comprehensive report, particularly in the inclusion of negated findings:

  • Lack of explanation from existing evidence. For example, an inflamed appendix that fits the medical history does not need detailed mention of harmless incidental findings.
  • Prospective review: If your report is likely to undergo double-reading by another pathologist before sign-out, it should either be more detailed, because the doctor who will do the double-reading then gets an idea of your thought process, including what you have looked for versus what may still need to be evaluated. If you know who will do the prospective review for a report of yours, you may alternatively convey your thought process by other means such as directly talking to that person.
  • Highly suspected locations, such as given from the referral.
  • Difficulty in obtaining the specimen, such as a CT-guided biopsy versus a skin shave.
  • Defensive precautions, which appears to be more common among doctors in the Unites States compared to for example Europe.[28][29]

Multiple instances of the same type of pathology (such as lung nodules) can often simply be reported as such, at least with a particular mention of the largest or the most severe example thereof.

Uncertainty

Words, from
most likely to
least likely
  • (is)
  • positive for
probably
likely
suggesting
suspicious for
possibly
(benign condition)
cannot be excluded
not likely
(malignant condition)
cannot be excluded
  • negative for
  • effectively ruling out

When something looks very much like a specific entity but you are not sure, preferably use "-like" (or when feasible, "-oid" such as squamoid for squamous-like cells).

When the clinical picture strongly favors a certain condition, and the pathology favors it as well, findings are generally described as "consistent with". Sometimes, "bordering on" can be described when the picture almost fits specified criteria of a specific diagnosis.

It is alright to consider the diagnosis of a pathology report to be a combination of the clinical picture and what can be seen on the specimen. For example, if the microscopy picture is uncertain, you may to a certain degree tend towards the diagnosis that best fits the clinical picture. However, mention differential diagnoses if they are still significantly possible, and would confer a different treatment or another substantially different consequence.

For both findings and diagnoses, is preferable to write "negative for..." rather than "no..." to emphasize the possibility of false negative findings.

Synoptic reports

For cancers, generally include a synoptic report, such as per College of American Pathologists (CAP) protocols at cap.org/protocols-and-guidelines. However, synoptic reports are generally not needed for tumor metastases.

Sizes

Whenever possible, give numerical quantities of sizes, rather than descriptions that are subjective (such as "small" or "large") or variable (such as "apple-sized").

Tailoring

The information contained in the reporting sections in this resource assume that the clinician has requested the exam for the topic at hand, but should still be tailored to any particular questions or requests by the clinician. Any relevant findings beyond the issues or questions raised by the clinician should also be mentioned. The reporting templates in this resource do not cover every recurring situation, so it is often more efficient to create your own repository of report templates that you can copy-paste for various cases. When doing so, however, have marks for relevant items that are frequently changed in the template, which should be readily seen as unfinished in the report if you haven't tailored it to the case at hand (such as "...measuring _____."), so as to avoid omissions or even wrongly entered information from templates.

The most important findings can be moved to near the top of the report if feasible, but doctors performing subsequent double-reading may prefer a consistent anatomic order.

Wording

If a certain grammatical rule has a risk of making the report less clear to the reader, ignore that rule in that situation.

Restrict acronyms/abbreviations to those who are certainly well known among all doctors, such as "cm".[note 11]

Generally describe what can be seen rather than processes (such as preferring "an abundance of" rather than "proliferation of").

If using a dictation device, avoid "no", and instead use "negative for" (and "positive for" in opposite cases), since there's a risk of "no" not being transcribed and thereby creating the opposite meaning.

Skin excisions

In skin cancers, use "peripheral" or "radial" margins (whereas "lateral" margin should be reserved for the margin opposite to the medial margin).[30]

Appendix

 

Gross processing

  • Measure the length of the appendix.[31]
  • ((Note its shape.[31] ))
  • Inspect the serosa (color, congestion, adhesions, hemorrhage, exudate etc)
  • ((Describe and measure the mesoappendix.))
  • Cut off about 1.5 cm from the tip and split it in half long the lumen. Divide the remainder into about 3-5 mm thick transverse slices.[31]
  • ((Note the wall thickness[31]))
  • Look mainly for:[31]
  • Luminal pus or obstruction, including stones.
  • Look for any yellow firm areas at the tip, which may be carcinoids. Carcinoids may hide behind obstructions in the tip. If found grossly, submit entire appendix, and ink the surgical margin and submit separately en face[note 12]
  • Wall defects
  • Exterior coatings. Note if it contains "stones" or fruit kernels.
  • Any tumor. If found:
  • Measure the greatest dimension of the tumor
  • Look for foci of carcinoma or lymph nodes in the mesoappendiceal fat, which may be lymphatic or perineural invasion

Tissue selection

  • At least one half of the tip
  • At least one slice from visually inflamed areas.
  • ((A transverse slice closest to the base, that is, the surgical cut.))
  • ((At least one transverse slice from an intermediate part.))

Particular findings indicating additional sampling include:[31]

  • Wall discoloration
  • External green-gray-yellow coating
  • Suspected wall defects

Submit the entire appendix if:

Gross pathology of mucocele of the appendix.
  • You find a mucocele.
  • The surgical report mentions perforation but none is found grossly.
  • The surgical report mentions appendicitis but no significant inflammation is found grossly.

Gross report

Example:

((Labeled - appendix. The specimen is received in formalin and consists of a resected)) appendix measuring __ cm in length and __ cm in maximum diameter. The serosa is tan-red {{and
  • hyperemic?
  • smooth / ragged / granular?
  • congested?
  • with a patchy purulent exudate?
  • with adhesions?}}

The attached mesoappendix measures __ cm and appears {{

  • unremarkable?
  • hyperemic?
  • (focally) inflamed?}}

On cut sections, the lumen {{is dilated and contains {{

  • (brown) (semisolid) fecal material?
  • purulent (blood-tinged) exudate?
  • a small amount of blood?
  • a fecalith?}}

No perforation is identified. ((Representative sections are submitted for microscopic examination in __ cassette(s).))

 

Microscopic evaluation

Always look for inflammation and malignancy.

Inflammation

Appendix neoplasms by incidence and prognosis.
Main article: Appendicitis

Neutrophilic infiltrates of the wall of the appendix in the correct clinical context confers a diagnosis of appendicitis.

Malignancy

  • Look for cancerous cells (also for specimens with clinical appendicitis).
  • Look in particular for carcinoid tumors of the distal tip.
  • In the presence of mucus, look for any mucinous neoplasm.

Report

  • Description of objective findings.
  • Presence or absence of malignancy.

Example, using image at right:

Histopathology of appendicitis.jpg

Mucosa with ulceration. ((No atypia in residual mucosa.)) Inflammatory cells in the stroma and all muscle layers, as well as on the serosal surface and adherent adipose tissue. No evidence of malignancy. ((Optionally: No perforation))

For cancers, generally include a synoptic report, such as per College of American Pathologists (CAP) protocols at cap.org/protocols-and-guidelines.    

Appendicitis

  Appendicitis may histopathologically be defined as neutrophilic infiltrates of the wall of the appendix in the correct clinical context.

   

Gross processing

Standard sections if the appendix appears inflamed and there are no signs of malignancy. Describe abnormal signs including:

 

Microscopic evaluation

  • Evaluate depth of the inflammation.
  • Look for any perforation of the wall.
  • Look for cancerous cells (which may have caused the appendicitis).  
  • (Attempt to specify the type of appendicitis as either of the following:)

Types

Classification of acute appendicitis based on gross pathology and light microscopy characteristics[34]
Pattern Gross pathology Light microscopy Image Clinical significance
Acute intraluminal inflammation None visible
  • Only neutrophils in lumen
  • No ulceration or transmural inflammation
Histopathology of acute intraluminal inflammation of the appendix.jpg Probably none
Acute mucosal inflammation None visible
  • Neutrophils within mucosa, and possibly in submucosa
  • Mucosal ulceration
May be secondary to enteritis.
Suppurative acute appendicitis May be inapparent.
  • Dull mucosa
  • Congestion of surface vessels
  • Fibropurulent serosal exudate in late cases
  • Dilation of the appendix
  • Neutrophils in mucosa, submucosa and muscularis propria, potentially transmural.
  • Extensive inflammation
  • Commonly intramural abscesses
  • Possibly vascular thrombosis
Acute suppurative appendicitis with perforation.jpg Can be presumed to be primary cause of symptoms
Gangrenous/necrotizing appendicitis
  • Friable wall
  • Purple, green or black color
  • Transmural inflammation, obliterating normal histological structures
  • Necrotic areas
  • Extensive mucosal ulceration
Histopathology of necrotizing appendicitis, high magnification.jpg Will perforate if untreated
Periappendicitis May be inapparent.
  • Serosa may be congested, dull and exudative
  • Serosal and subserosal inflammation, no further than outer muscularis propria to be called isolated.
Histopathology of periappendicitis.jpg If isolated, probably secondary to other disease
Eosinophilic appendicitis None visible
  • >10 eosinophils/mm2 in muscularis propria.
  • No changes conforming to other types of appendicitis
Possibly parasitic, or eosinophilic enteritis.
Chronic appendicitis[35]
  • Fibrosis
  • Predominantly mononuclear infiltrate rather than neutrophilic.
Should preferably correlate with long-term or recurrent symptoms.

Further workup

(In acute suppurative appendicitis, still look for any periappendicitis. Also look by the lumen for parasites.)

Microscopy report

Should include, if detected:

  • Acute or chronic appendicitis
  • Depth of inflammation
  • Any abscess and\or perforation
  • Necrosis and\or ulceration, at least if transmural

(Classification into one or several types as per table above.)

Example
Acute appendicitis and periappendicitis with transmural necrosis

 

Gallbladder

 

Gross processing

Cholecystectomy grossing

  • Describe the serosa (smooth and intact versus disrupted, adhesions, inflammation, tumor implants, necrosis, porcelain).
  • (Inspect the adventitia (the roughened juxtahepatic surface), where disruptions are generally iatrogenic and optional to report.)
  • Cut off the cystic duct margin and submit
  • Look for any cystic duct lymph node, describe and submit if present
  • Open the gallbladder longitudinally on the serosal surface. Do not open along the adventitia.[note 13]
  • (Estimate the amount of bile.)
  • {{Estimate the number and describe gallstones.}}
  • Describe the mucosa (such as velvety, granular, trabeculated, and/or with cholesterol stippling)
  • Look for any gallbladder polyps or tumors. Tumors will usually be hard.
  • Open the spiral neck, and look for lesions and gallstones therein
  • Cut through the wall, and look for any tumors or Rokitansky-Aschoff sinuses
  • Look for gallstones in the container
Gross report
((Labeled - gallbladder. The specimen is received in formalin and consists of a resected)) {{
  • previously opened?
  • focally disrupted (on the juxtahepatic avdentitial surface only)?
  • edematous?}}

gallbladder measuring __ cm in length and __ cm in maximum diameter. The serosa is

  • {{(mottled) tan / pink / red (generally combinations thereof) and}}
  • smooth {{/ with patchy adhesions}}

Upon opening, the lumen contains ((__ [[volume in cc/cm3]]))

  • green {{/ brown / blood-tinged / yellow-white and chalky / clear colorless
  • viscid / sludge-like / thick}}

bile {{and

  • (approximately) __ (number) / multiple
  • black / brown / green / yellow / tan / white (generally combinations thereof)
  • irregular / multifaceted / spiculated / ovoid / mulberry-like / barrel-like

gallstones measuring up to __ cm in greatest dimension.}} The mucosa is

  • green {{/ tan / yellow-red / brown / pink}}
  • and velvety {{/ granular / trabecular
  • with diffuse cholesterol stippling?}}

The spiral neck is patent {{/ obstructed by one additional similar gallstone measuring __ cm}}. The wall measures up to __ cm in thickness. {{ Rokitansky-Aschoff sinuses are present within the fundus. There is a __ (color) cystic duct lymph node present measuring __ cm in greatest dimension. }} ((Representative sections are submitted for microscopic examination in __ cassette(s). ))

Rifts on the adventitial side that are consistent with surgical trauma need mentioning only in tumor cases.

Carcinoma

Pathology trainees that find an unsuspected tumor should generally notify a senior before continuing.

  • State whether the gallbladder is intact when you received it.
  • Ink the surgical margin (adventitial surface).
  • Ink the cystic duct margin (lightly) and put in a separate cassette. Notify the lab to have it submitted en face[note 12]
  • Look for any cystic duct lymph nodes. If found, bisect and submit.
  • Measure the tumor in greatest dimension and thickness and state where in the gallbladder it is located (fundus, body, etc and whether it is on the peritoneal or hepatic side).
  • Measure the margin to the cystic duct resection
  • State all other abnormalities including stones, Rokitansky-Aschoff sinuses etc.

Take sections from:

  • Cystic duct margin, en face
  • Cystic duct lymph node if present
  • Sections of tumor, full thickness
  • Sections of unaffected gallbladder

Autopsy grossing

Gross pathology of gallbladder carcinoma, with a prominent nodule.

The gallbladder and biliary tract may be cut open from either end:

  • Starting from the gallbladder: Cut the gallbladder open and from there dissect the cystic duct and common bile duct through the ampulla of Vater.
  • Starting from the duodenum: Identify the ampulla of Vater, possibly by bile flow when squeezing the gallbladder. Dissect the common bile duct, cystic duct and thereafter the gallbladder. If the cystic duct is difficult to find, transverse cuts may be performed at its presumed location.
  • In the gallbladder, inspect the contents and the appearance of the wall. Look mainly for signs of carcinoma. Optionally, estimate the volume of bile therein.
  • In the biliary tract, look mainly for stones and stenosis.

     

Microscopic evaluation

Look at least at the epithelial lining, for atypia and inflammation (such as edema and inflammatory cells,  ).

Other findings

Report

For cancers, generally include a synoptic report, such as per College of American Pathologists (CAP) protocols at cap.org/protocols-and-guidelines.    

Cholecystitis

  Inflammation of the gallbladder:

Gross processing

As per basic Gallbladder.

Microscopic evaluation

Look for signs of acute or chronic cholecystitis. If you find either, keep looking for the other as well, in case it is both acute and chronic.

Findings in acute cholecystisis

Main initial features are edema and hemorrhage.[37]

  • Initially often also congestion and fibrin deposition in and around the muscular layer.[38]
  • Later often necrosis of the mucosa and and deeper layers, with neutrophils.[38]
  • Variable reactive epithelial changes, which may resemble dysplasia.[38]

There may be fresh thrombi within small veins.[38]

Findings in chronic cholecystitis

Rokitansky-Aschoff sinus.

Typical features are:[40]

  • Smooth muscle hypertrophy in the muscularis
  • Mild inflammatory infiltrates
  • Rokitansky-Aschoff sinuses

Other findings favoring the diagnosis are:[40]

  • Granulomas (from ruptured Rokitansky-Aschoff sinuses) strongly favor the diagnosis.
  • Hyalinized collagen
  • Dystrophic calcification
  • Lymphoid aggregates
  • Atrophic and/or ulcerated mucosa
  • Metaplastic changes, such as gastric or intestinal mucosa

For a general gallbladder screening, see gallbladder.

Lymph nodes

Look for reactive lymphadenopathy or metastasis.  

Microscopy report

Report:

  • Relevant findings from the evaluation.
  • Any cholelithiasis as per the gross report.
Template

 

(Gallbladder, cholecystectomy:)
<<Acute and/or chronic>> cholecystitis.
{{Cholelithiasis.}}

 

Gallbladder polyp

   

Gross processing

Photograph of a 6 mm large hyperplastic polyp of the gallbladder.

As per gallbladder, with addition to submitting the entire polyp unless very large.

Microscopic evaluation

Look for signs of the most common polyp types:

 

Endoscopic gastrointestinal biopsies

 

Gross processing

  • Count the number of fragments. They can be classified as “multiple” at over 5 or 6 specimens. Possibly add “Mixed with luminal material”.
  • Preferably stain with eosin if any fragment is smaller than about 0.3 cm
  • Biopsies that are thicker than about 3-4 mm generally need to be bisected.

Microscopic examination

(Read the endoscopy report before evaluating (except for polyp biopsies, where it can be presumed that the purpose is to look for any malignancy).)

Example normal reports

Further information in main articles of each location.

Esophagus
(Middle third esophagus, biopsy:)
Squamous mucosa without significant histopathologic changes.
(Negative for eosinophilic esophagitis.)
Gastroesophageal junction
(GE junction, biopsy:)
Squamous mucosa without significant histopathologic changes.
(Negative for gastric mucosa or intestinalized (Barrett's) mucosa.)
Stomach
(Gastric, biopsy:)
Gastric mucosa without significant histopathologic changes.
((Negative for Helicobacter pylori organisms on H&E slide.))
Duodenum
(Small bowel, biopsy:)
Duodenal mucosa without significant histopathologic changes.
((Negative for celiac disease.))
Colon
(Colon, biopsy:)
Colonic mucosa without significant histopathologic changes.
((Negative for colitis.))

 

Esophagus

 

Microscopic evaluation

On esophageal biopsies, look at least for esophagitis:

Esophagitis

GE junction with chronic esophagitis, including plasma cells (black arrow), an acute inflammation with neutrophils (white arrow), as well as basal layer hyperplasia (yellow double-headed arrow).

Look for signs of (reflux) esophagitis, mainly:[42]

  • Inflammatory cells, especially when intra-epithelial. Neutrophils confer a diagnosis of acute inflammation, while plasma cells, eosinophils and excess T cells confer a diagnosis of chronic inflammation. In eosinophil-predominant inflammation, also evaluate as suspected eosinophilic esophagitis.
  • Basal cell hyperplasia exceeding 15 - 20% of the epithelial thickness.
  • Stromal papillae reaching upper third of the epithelium.
  • Loss of orientation of superficial epithelial cells.
  • Ballooned squamous cells

Microscopy report

Example normal report for an esophagus biopsy:

(Middle third esophagus, biopsy:)
Squamous mucosa without significant histopathologic changes.
((Negative for eosinophilic esophagitis.))

Example report with signs of reflux:

(Mid esophagus, biopsy:)
Squamous mucosa with reactive changes consistent with reflux.
((Negative for eosinophilic esophagitis.))

 

Eosinophilic esophagitis

 

Microscopic diagnosis

Eosinophilic infiltrate. In this case also intercellular edema giving a spongy appearance.

It is characterized by a prominent eosinophilic infiltrate in the esophagus, with consensus guidelines defining it as over 15 intra-epithelial eosinophils per HPF.[43] [note 14]

Report

  • If positive:
  • Presence of eosinophilic esophagitis
  • Number of eosinophils per HPF

In borderline cases, such as an incidental finding of eosinophils at around 15/HPF, a separate explanatory comment can be made, such as:

(Esophagus, biopsy:)
Squamous mucosa with increased intraepithelial eosinophils of up to 15/HPF. See comment.
...

Comment: There is no evidence of eosinophilic microabscesses. Although this may represent reflux esophagitis, a diagnosis of eosinophilic esophagitis is considered in the correct clinical setting.

 

Gastroesophageal junction

 

 

Microscopic examination

The main findings to look for are:

Barrett's esophagus

The main diagnostic sign of Barrett's esophagus is the presence of goblet cells. A true goblet cell should have rounded shape, clear to bluish cytoplasmic mucin, and be randomly scattered.[44] The mucin usually indents the nucleus.[44]

 

Esophagitis

GE junction with chronic esophagitis, including plasma cells (black arrow), an acute inflammation with neutrophils (white arrow), as well as basal layer hyperplasia (yellow double-headed arrow).

Look for signs of (reflux) esophagitis, mainly:[42]

  • Inflammatory cells, especially when intra-epithelial. Neutrophils confer a diagnosis of acute inflammation, while plasma cells, eosinophils and excess T cells confer a diagnosis of chronic inflammation. In eosinophil-predominant inflammation, also evaluate as suspected eosinophilic esophagitis.
  • Basal cell hyperplasia exceeding 15 - 20% of the epithelial thickness.
  • Stromal papillae reaching upper third of the epithelium.
  • Loss of orientation of superficial epithelial cells.
  • Ballooned squamous cells

Report

(Document the type of mucosa:

  • If both gastric and squamous mucosa is present in the same fragment, report as "Gastroesophageal junctional mucosa with..."
  • If not, report the presence of squamous and/or gastric mucosa.)

Examples:

(GE junction, biopsy:)
Squamous mucosa without significant histopathologic changes.
(Negative for gastric mucosa or intestinalized (Barrett's) mucosa.)
(GE junction, biopsy:)
Gastroesophageal junctional mucosa with chronic inflammation and reactive changes(, non-specific.
Negative for intestinalized (Barrett's) mucosa.)

In case of multiple signs of reflux esophagitis:

(GE junction, biopsy:)
Gastroesophageal junctional mucosa with changes consistent with reflux esophagitis.
(Negative for intestinalized (Barrett's) mucosa.)

 

Barrett's esophagus

 

Microscopic examination

Generally, the main finding to look for in biopsies from the esophagus is intestinalized mucosa (Barret's esophagus), which is defined as the presence of columnar epithelium with goblet cells.[45] A true goblet cell should have rounded shape, clear to bluish cytoplasmic mucin, and be randomly scattered.[46] The mucin usually indents the nucleus.[46]

Further workup of intestinalized mucosa

If intestinalized mucosa (Barret's esophagus) is present, look for dysplasia:

Also perform a screening for esophagitis.  

Microscopy report

Incomplete Barret's esophagus does not need specific mention:

Histopathology of Barrett's esophagus, annotated.jpg
(GE junction, biopsy:)
Gastroesophageal mucosa with chronic inflammation and intestinal metaplasia, consistent with Barrett's esophagus.
Negative for dysplasia.

 

Esophageal adenocarcinoma

  Mainly present in endoscopic biopsy of the gastroesophageal junction or distal esophagus.

Microscopic evaluation

In biopsies, classify as either low, moderately or high differentiated.

Reporting

Esophagus, biopsy:
Recurrent invasive adenocarcinoma, moderately differentiated.

 

Stomach

 

Microscopic evaluation

Generally screen for:

Microscopy report

Example in case of normal findings:

(Gastric, biopsy:) Gastric mucosa without significant histopathologic changes.
((Negative for Helicobacter pylori organisms on H&E slide.))

 

Gastric polyp

 

Microscopic evaluation

Relative incidences of gastric polyps. The remaining 4.8% are mainly constituted by lipomas, GIST, xanthomas and inflammatory pseudopolyps.[50]

 

Fundic gland polyp

Microscopic evaluation

Differential diagnosis

Workup

Dysplasia in fundic gland polyp is mainly seen as nuclear enlargement, hyperchromasia, pseudostratification, and loss of cytoplasmic mucin.[54] However, you don't need to spend much effort in the decision, since these patients have an excellent prognosis whether there is dysplasia or not.

Reporting

Generally, keep it short:

(Stomach, excision:)
Fundic gland polyp

 

Gastritis

 

Inflammation of the stomach. If biopsy is at the esophagus, evaluate as gastroesophageal junction.  

Microscopy evaluation

Mucosal plasma cell infiltrate in mild chronic gastritis.

Look for chronic or acute gastritis. If either is present, still look for the other.

Chronic gastritis

  • Chronic gastritis[55]
  • Presence of plasma cells, lymphocytes, and occasionally lymphoid follicles. Scattered single plasma cells and lymphocytes is normal, and the threshold is subjective, but one definition of chronic gastritis is when seeing chronic inflammation at 4x magnification (as increased dots separating glands)[56] Eosinophils and neutrophils may be present.
  • Reduced mucin in the cytoplasm
  • Enlargement of nuclei and nucleoi
  • Subnuclear vacuolation in antral glands or pits (which is PAS negative)
  • Intestinal metaplasia: with partial replacement of the mucosa of the antrum and body with metaplastic goblet cells of intestinal morphology, absorptive cells and Paneth cells.

When gastritis is present, especially if relatively superficial, also evaluate as a stomach biopsy for Helicobacter pylori.

Acute gastritis

Histopathology of mild active gastritis, with intraepithelial neutrophils (white arrows) as well as in lamina propria (black arrows).
  • Mild acute gastritis:[47]
  • Modest edema of lamina propria
  • Vascular congestion
  • Scattered neutrophils
  • Mucosal hemorrhage
  • Intact epithelium
  • Moderate to severe acute gastritis:[47]
  • Loss of superficial epithelium above the muscularis mucosa
  • Hemorrhage
  • Variable infiltrate with neutrophils
  • Fibrinopurulent luminal exudate
  • Nearby epithelium may show regenerative changes

Microscopy report

  • Mild and/or chronic gastritis and severity
  • (If present, state if positive or negative for Helicobacter pylori organisms.)

Chronic gastritis without neutrophils is preferably also termed "non-active".

Example:

(Gastric, biopsy:) Mild chronic non-active gastritis, non-specific. Negative for Helicobacter pylori organisms on H&E slide.

 

Stomach biopsy for Helicobacter pylori

 

Helicobacter pylori on HE stain, being curved bacteria in the lumen of a gastric foveola.

Microscopic evaluation

Another H&E stain.

Look for:

  • Helicobacter pylori-like bacteria in the lumen, as curved, spirochete-like bacteria, generally in the superficial mucus layer and along microvilli of epithelial cells.[58]
  • Associated inflammation, typically a chronic form of gastritis with germinal centers (follicular gastritis), and plasma cells in lamina propria.[58][note 17] There should be at least 3 plasma cells facing each other to make a diagnosis of chronic gastritis.

Perform immunohistochemistry for H. pylori in cases of moderate to severe chronic gastritis, or even just one neutrophil within the epithelium, where H. pylori is not seen on H&E stains.[59]

Example report

Stomach, biopsy:

Chronic active gastritis.
Positive for helicobacter pylori.

Chronic gastritis without H. pylori-like organisms can be described as non-specific:

Mild chronic gastritis, which is non-specific.

Negative for H. pylori-like organisms on H&E stain.

 

Stomach tumor

 

Microscopic evaluation

Stomach cancer types by relative incidence.[60]

In addition to a general screening ( ), look for atypical or expanded areas, and attempt top classify by at least the most common forms.

Reporting

For cancers, generally include a synoptic report, such as per College of American Pathologists (CAP) protocols at cap.org/protocols-and-guidelines.    

Gastric sleeve

   

Gross processing

  • Measure length and maximum diameter, as well as the length of the staple line.
  • Inspect the serosal surface.
  • Open longitudinally
  • Inspect the mucosa.
  • Measure the maximum wall thickness.

Tissue selection

2 representative sections, in addition to any visible lesions.

Gross report

Example:

((A. Labeled - ___. The specimen is received in formalin and consists of)) a segment of pink-tan stomach measuring __ cm in length and __ cm in maximum diameter. A staple line (surgical margin) is present which measures __ cm in length. The serosal surface is pink-tan and {{focally ragged with scattered transmural defects}}. A minimal amount of soft, yellow perigastric fat is present. Upon opening, the gastric lumen contains a small amount of bloody mucoid material. The mucosa is red-tan with normal rugae and no gross lesions. The wall measures up to ___ cm in thickness. (Representative sections are submitted for microscopic examination in __ cassettes.)

Microscopic examination

Usual stomach screening.  

Example report:

Stomach, partial gastrectomy:
Mild chronic gastritis, non specific.
Negative for H. Pylori microorganisms on H&E stained slide.

 

Duodenum

Small intestine in celiac disease

 

Gross processing

As per Small intestine.

Microscopic evaluation

Intraepithelial lymphocytes, in this case still less than <25 IELs/100 enterocytes.

The main histologic feature of celiac disease is increased intraepithelial lymphocytes (IELs), with or without villous atrophy of the duodenal mucosa.[61] The number of intraepithelial lymphocytes are classified as follows in the duodenum:[62][63]

  • < 25 IELs/100 enterocytes: Negative for intraepithelial lymphocytosis.
  • 25 to 29 IELs/100 enterocytes: borderline
  • > 30 IEL/100 enterocytes: Pathological "lymphocytosis"

Alternative proposed methods is the presence of over 6-12 IELs per 20 enterocytes at the tips of duodenal villi.[63] In the jejunum, the cutoff is at over 40 IELs per 100 enterocytes.[63]

Suggestive but not specific findings for enterocytes are: decreased height, intracytoplasmic vacuolation and reduction or absence of the brush border.[62]

Differential diagnoses

If findings are suggestive of celiac disease, look for at least the following differential diagnoses:

Microscopy report

Example in an unremarkable specimen:

Duodenal mucosa, negative for significant histopathologic changes.
Negative for celiac disease.

 

Colorectal polyp

Gross examination

 

Tissue selection and trimming

There is a separate article for the Grossing of minimally invasive colorectal surgery.

Depending on sample format:[31]

  • Biopsies and polyps of <4 mm are embedded in their entirety. Samples less than 0.3 mm should be stained with eosin to avoid getting lost processing.
  • Polyps 4-8 mm with short stem or without stem: Identify the excision surface and divide the polyp longitudinally through the excision surface.
  • Polyps > 8 mm with a stem long enough to make it possible to take a transverse, whole slice from the stem closest to the excision surface: First, take a transverse slice through the peripheral portion of the stem, encompassing the entire circumference. Then take a 3-4 mm thick slice longitudinally through the polyp and the middle of the stem, after which the two remaining parts on either side are cut into equally thick slices, parallel to the previous slice.
  • Polyps >8 mm with short stem or without stem: Identify the excision surface and cut out a 3-4 mm thick disk that extends longitudinally through the center of the excision surface. Then divide the two remaining portions into equally thick slices, parallel to the previous slice.
  • Polyps that come in parts: Pick out the largest pieces, which are cut as similar as possible to above. Small fragments are sieved and embedded in a separate box.

Gross reporting

  • Polyp and/or fragment sizes
  • Presence or absence of stem of polyps

Example, for a gastrointestinal biopsy:

Labeled: "Sigmoid colon biopsy". The specimen is received in formalin and consists of 4 fragments of pink-tan tissue with a vaguely recognizable mucosal surface, mixed with food-like material. The fragments measure 0.2-0.3 cm in greatest dimension. The entire specimen is submitted for microscopic examination in one cassette.

Microscopic evaluation

Major signs

Look particularly for these, to help sorting into proper diagnosis in next section:

Main types

Consider at least the following conditions:

Incidences and malignancy risks of various types of colorectal polyps.[65]
Colorectal polyps
Type Risk of containing malignant cells Histopathology Image
Hyperplastic polyp 0% No dysplasia.[66]
  • Mucin-rich type: Serrated (“saw tooth”, pictured) appearance, containing glands with star-shaped lumina.[67] Crypts that are elongated but straight, narrow and hyperchromatic at the base. All crypts reach to the muscularis mucosae.[67]
  • Goblet cell-rich type: Elongated, fat crypts and little to no serration. Filled with goblet cells, extending to surface, which commonly has a tufted appearance.[67]
Hyperplastic Polyp of the Rectum (14060044206).jpg
Tubular adenoma 2% at 1.5cm[68] Low to high grade dysplasia[69] Over 75% of volume has tubular appearance.[70] Tubular adenoma of the colon.jpg
Tubulovillous adenoma 20% to 25%[71] 25%-75% villous[70] Histopathology of tubulovillous adenoma.jpg
Villous adenoma 15%[72] to 40%[71] Over 75% villous[70] Villous adenoma of the colorectum (high power view).jpg
Sessile serrated adenoma (SSA)[73]
  • Basal dilation of the crypts
  • Basal crypt serration
  • Crypts that run horizontal to the basement membrane (horizontal crypts)
  • Crypt branching.
Sessile Serrated Adenoma, Transverse Colon, 0.4 cm (3632298679).jpg
Traditional serrated adenoma
  • Protuberant villi with slit-like serrations.[74]
  • Pseudostratified epithelial columnar cells shapes.[74]
  • Eosinophilic cytoplasm and dark, pencil-like nuclei.[74]
  • Golblet cells are present.[74]
Traditional Serrated Adenoma of Colon (5203904731).jpg
Colorectal adenocarcinoma 100%
  • In carcinoma in situ (Tis): cancer cells invading into the lamina propria, and may involve but not penetrate the muscularis mucosae. Can be classified as "high-grade dysplasia", because prognosis and management are essentially the same.[66]
  • Invasive adenocarcinoma: Extending through the muscularis mucosae into the submucosa and beyond.[66]
Adenocarcinoma highly differentiated (rectum) H&E magn 400x.jpg

Other benign

Colonic lipoma, a benign polyp, here being submucosal and pedunculated.

If a more specific diagnosis cannot readily be made, clearly non-malignant colorectal polyps may simply be reported as such.

Further information: Evaluation of tumors

Microscopy report

It should include:[75]

  • Size of polyp (from gross examination)
  • Histopathologic type
  • Depth of growth and/or infiltration
  • Whether the resection is radical

Optionally, it can include degree of differentiation and/or dysplasia.

Example:

Micrograph of tubulovillous adenoma.jpg
50 mm large tubulovillous adenoma with up to high grade columnar epithelial dysplasia. No infiltration. Radical excision.

If multiple polyps are submitted in one container, you may count the amount of each polyp type if you can, but if the amount of fragments in microscopy exceeds the amount of fragments purportedly submitted, then you can simply write "fragments of", like the following example:

Fragments of tubular adenoma and hyperplastic polyp.

More details are given in main articles of histopathologic types.    

Hyperplastic polyp

This article is about colorectal hyperplastic polyps. For hyperplastic polyps of the stomach, see Gastric polyp.
 

Mucin-rich type.

Commonly presents as a colorectal polyp.

Gross evaluation

 

Tissue selection and trimming

There is a separate article for the Grossing of minimally invasive colorectal surgery.

Depending on sample format:[31]

  • Biopsies and polyps of <4 mm are embedded in their entirety. Samples less than 0.3 mm should be stained with eosin to avoid getting lost processing.
  • Polyps 4-8 mm with short stem or without stem: Identify the excision surface and divide the polyp longitudinally through the excision surface.
  • Polyps > 8 mm with a stem long enough to make it possible to take a transverse, whole slice from the stem closest to the excision surface: First, take a transverse slice through the peripheral portion of the stem, encompassing the entire circumference. Then take a 3-4 mm thick slice longitudinally through the polyp and the middle of the stem, after which the two remaining parts on either side are cut into equally thick slices, parallel to the previous slice.
  • Polyps >8 mm with short stem or without stem: Identify the excision surface and cut out a 3-4 mm thick disk that extends longitudinally through the center of the excision surface. Then divide the two remaining portions into equally thick slices, parallel to the previous slice.
  • Polyps that come in parts: Pick out the largest pieces, which are cut as similar as possible to above. Small fragments are sieved and embedded in a separate box.

Gross reporting

  • Polyp and/or fragment sizes
  • Presence or absence of stem of polyps

Example, for a gastrointestinal biopsy:

Labeled: "Sigmoid colon biopsy". The specimen is received in formalin and consists of 4 fragments of pink-tan tissue with a vaguely recognizable mucosal surface, mixed with food-like material. The fragments measure 0.2-0.3 cm in greatest dimension. The entire specimen is submitted for microscopic examination in one cassette.

Microscopic evaluation

There are two main types of hyperplastic polyps, which have genetic differences, as well as different histologic structure, but no significant differences clinically:[76]

  • A microvesicular mucin-rich type
  • A goblet cell-rich type

There is also a mucin-poor type with eosinophilic cytoplasm, which is rare.[76]

Mucin-rich type

Mucin-rich hyperplastic polyp.

Characteristics:[76]

  • Serrations (“saw tooth appearance”) of the luminal portion.
  • Star-shaped lumina.
  • Crypt elongation but they are straight, narrow and hyperchromatic at the base. All crypts reach to the muscularis mucosae.[76]

The basement membrane is frequently thickened.[76]

Histologic structure in goblet cell-rich type

Elongated, fat crypts and little to no serration. Therefore, they may not be obvious without comparing to adjacent normal intestinal wall.[76]

They are filled with goblet cells, extending to surface, which commonly has a tufted appearance.[76]

Epithelial misplacement

Infrequently, the epithelium is misplacement into the submucosa. Such polyps have been termed "inverted hyperplastic polyps". They appear to be restricted to the sigmoid colon and rectum. The misplaced epithelium is mucin-depleted , similar to the basal 1/3 of the polyp. The misplacement is accompanied by the lamina propria, and is continuous with overlying polyp through a gap in the muscularis mucosae. It may require slices at multiple levels to demonstrate microscopically.[76]

In such cases adjacent hemorrhage and hemosiderin deposition is common. Collagen type IV stain will have a strong continuous staining around nests.[76]

Cellular structure

Nuclei are small, regular, round and basal in the luminal half of the crypts, most reliably evaluated near the luminal surface.[76]

There are proliferative changes at the base of crypts, where nuclei are enlarged, the nucleus/cytoplasm ratio is elevated.[76]

Differential diagnoses

The main differential diagnosis for a hyperplastic polyp is adenoma, which generally display:[76]

  • Nuclear stratification
  • Loss of polarity
  • Dysplasia

However, the deep proliferative zones and reactive processes closely mimic changes seen in colorectal adenomas.[76]

Sessile serrated adenoma with minimal deviation dysplasia, wherein architectural changes are subtle, with mild crowding of crypts separated by less lamina propria and showing some degree of disorganization.[77]
Sessile serrated adenoma
  • Size ≥0.5 cm
  • Location in right colon

If both latter findings are present, it is almost always a SSA. Other features causing a suspicion for sessile serrated adenoma are:[76]

  • Dilation of crypts
  • Branching of crypts
  • Horizontal glands at the base
  • Mature mucinous cells at the base of crypts
  • Location in the proximal colon (cecum, ascending, and transverse colon),[78] whereas hyperplastic polyps are most common in the sigmoid colon and rectum. However, both may occur throughout the colon.[79]
Tubular colorectal adenoma
Hyperplastic polyp[80] Tubular adenoma[80]
Nu dysplasia Dysplasia
Proliferative epithelium restricted to base Proliferative epithelium present at the surface
Gland lining cells mature at the surface No surface maturation
Further information: Evaluation of tumors and Tubular colorectal adenoma

Microscopic report

Usually as follows:

(<Sigmoid / Ascending / etc.> colon polyp, polypectomy:) Hyperplastic polyp.

Generally don't report hyperplastic polyp elements of polyps with potential malignant progression (such as tubular and ⁄or villous adenomas), because the patient's clinical management will be based on the more concerning elements.  

Tubular and ⁄or villous adenoma

 

Gross evaluation

 

Tissue selection and trimming

There is a separate article for the Grossing of minimally invasive colorectal surgery.

Depending on sample format:[31]

  • Biopsies and polyps of <4 mm are embedded in their entirety. Samples less than 0.3 mm should be stained with eosin to avoid getting lost processing.
  • Polyps 4-8 mm with short stem or without stem: Identify the excision surface and divide the polyp longitudinally through the excision surface.
  • Polyps > 8 mm with a stem long enough to make it possible to take a transverse, whole slice from the stem closest to the excision surface: First, take a transverse slice through the peripheral portion of the stem, encompassing the entire circumference. Then take a 3-4 mm thick slice longitudinally through the polyp and the middle of the stem, after which the two remaining parts on either side are cut into equally thick slices, parallel to the previous slice.
  • Polyps >8 mm with short stem or without stem: Identify the excision surface and cut out a 3-4 mm thick disk that extends longitudinally through the center of the excision surface. Then divide the two remaining portions into equally thick slices, parallel to the previous slice.
  • Polyps that come in parts: Pick out the largest pieces, which are cut as similar as possible to above. Small fragments are sieved and embedded in a separate box.

Gross reporting

  • Polyp and/or fragment sizes
  • Presence or absence of stem of polyps

Example, for a gastrointestinal biopsy:

Labeled: "Sigmoid colon biopsy". The specimen is received in formalin and consists of 4 fragments of pink-tan tissue with a vaguely recognizable mucosal surface, mixed with food-like material. The fragments measure 0.2-0.3 cm in greatest dimension. The entire specimen is submitted for microscopic examination in one cassette.

Microscopic evaluation

Criteria

Tubular adenoma with low-grade dysplasia.

Dysplastic changes should involve at least the upper half of the crypts and the luminal surface.[81]

  • Nuclear dysplasia is mandatory to diagnose adenoma. It involves:
  • Nuclear atypia: Enlarged hyperchromatic nuclei (that is, dark purple) that are oval or frequently elongated, and with high nucleus to cytoplasm ratio.[81][82]
  • Other cellular atypia: Often nuclear stratification, nuclear crowding (that is, nuclei are bunched-up) and loss of polarity[81]
  • Always changes in gland architecture, such as:[81]
  • Enlarged crypts
  • Gland budding, or otherwise irregular glands[81]
  • Mucin depletion is often seen, but is not required[81]
  • Goblet cell reduction.

Differential diagnoses

Hyperplastic polyp
Hyperplastic polyp[80] Tubular adenoma[80]
Nu dysplasia Dysplasia
Proliferative epithelium restricted to base Proliferative epithelium present at the surface
Gland lining cells mature at the surface No surface maturation
Colorectal carcinoma
Colorectal adenocarcinoma (in this case, not otherwise specified).

edit
Colorectal carcinoma (mainly adenocarcinoma) is distinguished from an adenoma (mainly tubular and ⁄or villous adenomas) mainly by invasion through the muscularis mucosae.[83]

In carcinoma in situ (Tis), cancer cells invade into the lamina propria, and may involve but not penetrating the muscularis mucosae. This can be classified as an adenoma with "high-grade dysplasia", because prognosis and management are essentially the same.[66]

Also, carcinoma also commonly displays:[84]

  • Varying degrees of gland formation with tall columnar cells
  • Frequenty desmoplasia
  • Dirty necrosis, consisting of extensive central necrosis with granular eosinophilic karyorrhectic debris. Garland of cribriform glands are frequently found in their vicinity.

Low or high grade

In low-grade lesions, the crypts should maintain a resemblance to normal colon.[85]

High-grade dysplasia:
-Substantial stratification
-Nuclear pleomorphism
-Atypical mitoses
-Increased nucleus to cytoplasm ratio
-Prominent nucleoli
Typical findings in low-grade versus high-grade tubular and ⁄or villous adenoma
Low-grade[85] High grade[85]
Crowding Pseudo-stratification to early stratification More substantial stratification
Nuclear pleomorphism and atypical mitoses Absent or minimally present Present
Loss of cell polarity Minimal More significant
Crowding, cribriform, or complex architecture No significant Present

High grade lesions also typically have:

  • Cribriform architecture, consisting of juxtaposed gland lumens without stroma in between, with loss of cell polarity. Rarely, they have foci of squamous differentiation (morules). This should be distinguished from cases where piles of well-differentiated mucin-producing cells appear cribriform. In such piles, nuclei show regular polarity with apical mucin, and their nuclei are not markedly enlarged.
  • Increased nucleus to cytoplasm ratio.[85]
  • More "open" appearing nuclei with increasingly prominent nucleoli[85]
  • Back-to-back glands[85]

Tubular or villous

Colorectal adenoma
Type Histopathology Image
Tubular adenoma Over 75% of volume has tubular appearance.[86] Tubular adenoma of the colon.jpg
Tubulovillous adenoma 25%-75% villous[86] Histopathology of tubulovillous adenoma.jpg
Villous adenoma Over 75% villous[86] Villous adenoma of the colorectum (high power view).jpg

Length of villi must be at least twice the depth of the normal mucosal thickness.[81]

Further information: Evaluation of tumors

Further workup

Look for and evaluate any lymph nodes in the tissue specimen, for possible malignancy.

Dissecting pools of mucin at the base of any adenoma should be evaluated for the possibility of mucinous carcinoma.[81]

Report

  • Tubular, tubulovillous or villous adenoma.
  • Any high-grade component (whereas low-grade does not need to be stated in the report as it is presumed otherwise).
  • ((Adenoma size))
  • ((Whether it is radically resected.))

If any lymph nodes are found in the tissue sample, report the presence or absence of malignancy in any of them.

Example:

Sigmoid colon polyp x2, polypectomies:
One tubular adenoma and one tubulovillous adenoma.

   

Sessile serrated adenoma

 


Microscopic examination

The characteristics of sessile serrated adenoma are:[87]

  • Sawtooth serrations of the epithelium
  • Abundant mucin, similar to hyperplastic polyps
  • Basal crypt dilation, with mucous retention, and lateral spread of the crypt bases, commonly described as boot shaped or anchor shaped crypts.

Variations

On low magnification, a sessile serrated adenoma may be flat (left) or protuberant (right):[77]

Variations on higher magnification:

Microscopic report

A brief report is sufficient:

Cecum polyp, polypectomy:
Sessile serrated adenoma.

Differential diagnoses

Regarding location, the diagnosis of a sessile serrated adenoma is supported by a location within the proximal colon (cecum, ascending, and transverse colon), while hyperplastic polyps are most common in the sigmoid colon and rectum. However, both may occur throughout the colon.[89][90]  

Traditional serrated adenoma

 

Traditional Serrated Adenoma of Colon (5203904731).jpg

Presentations

Microscopic evaluation

This case lacks the typical eosinophilic cytoplasm, but otherwise typical with protuberant villiform growth pattern with slit-like serrations and presence of goblet cells.
  • Protuberant villi with slit-like serrations.[74]
  • Pseudostratified epithelial columnar cells shapes.[74]
  • Eosinophilic cytoplasm and dark, pencil-like nuclei.[74]
  • Golblet cells are present.[74]

Differential diagnosis

 

Intestine with tumor and colorectal carcinoma are given later in this handbook. If you suspect a colorectal carcinoma at this time, and you are not familiar with the condition, refer the case to a senior.

Breast biopsy or excision

 

  Fresh breast specimens should be put in formalin within one hour.[note 18] Breast specimens should be immersed in formalin for 6-72 hours.[91]

 

Gross processing

Selection and trimming

For excision (also called lumpectomy):

  • Determine total specimen size. ((Weight the specimen[16]))
  • Ink margins. If sample orientations are marked, use different colors for different directions.[16]
  • Palpate the specimen for masses. If felt, estimate the greatest dimension.[note 19] Compare with radiography if available.[16] Confirm the presence of any known biopsy clips, either visibly or by post-operative radiography (in order to confirm that the specimen includes the region of interest).
Cut a lumpectomy in the direction that gives the shortest distance from margin to margin. If a lumpectomy is uneven as shown, cut so that the first and last slice become wedge shaped (because these will later be cut further, perpendicularly to the margin), avoiding a wedge-shape for remaining slices.
  • Serially section the specimen.
  • When performing triage of fresh lumpectomies, generally make slices 1.1 to 1.5 cm thick. When laid down and flattened, this is generally thin enough to allow for fixation over at least 6 hours, and thick enough to be further cut into 2 or 3 slices after fixation; Note the direction of up/down on each such thick slice so that the relative orientation of the thinner slices thereof is maintained. Slices with solid tumors are cut somewhat thinner since they won't flatten as much when laid down.
  • When selecting tissue for submission after fixation, make 3-4 mm thick slices.[16]
  • Inspect for any grossly visible lesions. If found, measure at least the greatest dimension of the lesion on the slice where it appears largest. (Also compare the greatest gross measurement (including any palpated one) with the greatest measurement at previous imaging, and note if it confers a staging discrepancy between imaging and gross dimensions, with cutoffs at 0.1 cm, 0.5 cm, 1.0 cm, 2.0 cm, and 5 cm.)
Re-excisions

Tissue selection

Further serially section each of the two end sections into perpendicular sections, so that the distance between the surgical margin and any tumor involvement can be measured. If they are visibly involved as pictured, sections can be selectively taken from there. If end sections are not grossly involved, submit one perpendicular section, (every other perpendicular section), ((or the entire end sections)).
  • For lumpectomies, submit:[16]
  • Entire specimen if it can fit in 3-5 slices.
  • If larger:
  • For relatively well demarcated tumors: 1 slice per cm of tumor (minimum of 3 slices of tumor), including both center and periphery of tumor, including closest distance to the surgical margin if possible.
  • For diffuse or even invisible tumors such as often is the case for DCIS and ILC, either still submit whole, or use X-ray to guide what tissue to submit.
  • Additional suspicious areas, including those indicated by radiography.
  • ((Representative sections of margins in each direction.))

Breast specimens where breast cancer is possible should generally not be decalcified even when containing small calcifications, to preserve the ability to perform immunohistochemistry.

 

Gross report

  • Size of original tissue sample, preferably in 3 dimensions.
  • Description of inking
  • Tumor properties, at least:
  • Size in 3 dimensions.[16]
  • Distance from margins[16]
  • Consistency[16]
  • (Description of sectioning and submissions.)
  • ((Time of procurement and time of placement in formalin.[note 18]))

Example:

(The specimen is received fresh and consists of) an irregular fragment of yellow tan fibrofatty tissue measuring 4.0 x 2.8 x 2.0 cm. (The specimen is oriented with two sutures and) the surgical margins are inked as follows: superior-blue, inferior-green, medial-red, lateral-yellow, anterior-orange, and posterior-black. {{A radioactive seed is embedded in the tissue.}} The tissue is serially sectioned {{to reveal a tan-gray, spiculated, indurated mass measuring _cm in greatest dimension. The mass is located _cm from the nearest (<<superior, inferior etc>>) margin. (The specimen is entirely submitted in sequential sections from medial to lateral in 10 cassettes. The medial and lateral margins are submitted as perpendicular sections.) The specimen was procured at _AM/PM on _/_/2020. The specimen was placed in formalin at _AM/PM on _/_/2020.

Lymph nodes

When lymph nodes are submitted together with a biopsy or excision of a suspected or previously confirmed invasive lobular carcinoma (but not necessarily invasive carcinoma with lobular features), generally put the lymph node specimen through H&E processing at a relative rush. If you don't see any involvement on the H&E stain, order immunostain for CK AE1/AE3 in order to visualize otherwise occult lymph node involvement. The rushing of the lymph node samples allows you to have the immunostained slides by a similar time as the rest of the case.[92]  

Staining

Usually H&E staining.

Microscopic evaluation

If tumor is found, determine:

  • Tumor size
  • Malignancy
  • Distance from excision margin

Malignancy

The most important is to classify a sample as either of the following:

  • Benign
  • Carcinoma in situ
  • Invasive cancer

Most common types

Women seeking evaluation of a breast lump[93]
Finding Relative
incidence
Histopathology Image
Fibrocystic breast changes 40% Sclerosing adenosis (pictured), with an increase in glandular elements in addition to stromal proliferation that distorts and compresses glands.[94] Histopathology of sclerosing adenosis of the breast.jpg
Radial scar, seen as a fibroelastic stroma and entrapped glands radiating outward. Measure the size of these.[note 20] Histopathology of a radial scar of the breast.jpg
Usual ductal hyperplasia: Cohesive proliferation with haphazard, jumbled cell arrangement or streaming growth pattern. Cells have mild variation in cellular and nuclear size and shape.[95] Histopathology of usual ductal hyperplasia.jpg
No disease 30%
Fibroepithelial tumor 7% Proliferation of both stromal and epithelial components.[note 21] The tumor group mainly includes fibroadenoma and phyllodes tumor. Micrograph of a fibroadenoma.jpg
Atypical ductal hyperplasia 7%[96] Epithelial proliferations which are not qualitatively or quantitatively abnormal enough to be classified as ductal carcinoma in situ.[96] Micrograph of atypical ductal hyperplasia.jpg
Other benign mammary dysplasias and neoplasms 5% Including:
  • Flat epithelial atypia: variably dilated acini lined by one to several layers of epithelial cells with low-grade cytologic atypia, usually columnar.[97]
  • Columnar cell change: Terminal duct lobular unit with epithelium exhibiting tall cells with oval or elongated nuclei orientated perpendicularly to the basement membrane.[98]
Histopathology of flat epithelial atypia and columnar cell change.jpg
Intraductal papilloma: unremarkable epithelial cells lining fibrovascular cores. Histopathology of intraductal papilloma.jpg
Pseudoangiomatous stromal hyperplasia (PASH): Complex interanastomosing vessel-like spaces in dense collagenous, keloid-like stroma. Histopathology of pseudoangiomatous stromal hyperplasia (PASH).jpg
Breast cancer (in situ or invasive) 10% See next section.

Breast cancer types

Breast cancer types, with relative incidences and prognoses.
Cancer type Histopathology Image
Invasive ductal carcinoma (IDC) Carcinomatous cells are seen below the basement membrane of lactiferous ducts. Otherwise, there are no specific histologic characteristics, essentially making it a diagnosis of exclusion.[99] Invasive ductal carcinoma, with occasional entrapped normal ducts.jpg
Ductal carcinoma in situ (DCIS) Malignant epithelial cells confined to the ductal system of the breast, without invasion through the basement membrane.[100] DCIS - Intraductal carcinoma of the breast.jpg
Invasive lobular carcinoma (ILC) The "classic" pattern is round or ovoid cells with little cytoplasm in a single-file infiltrating pattern, sometimes concentrically giving a targetoid pattern. Classic Invasive Lobular Carcinoma of the Breast (6813147194).jpg
Lobular carcinoma in situ (LCIS)
  • Monomorphic, loosely cohesive, slightly enlarged and evenly spaced cells that fill acini.[101]

Cells have indistinct cell borders, pale cytoplasm, and uniform small nuclei with evenly distributed chromatin and inconspicuous nucleoli.[101]

Histopathology of lobular carcinoma in situ.jpg
Mucinous carcinoma Extracellular mucin areas around tumor cells. Histopathology of mucinous invasive ductal carcinoma of the breast.jpg
Medullary carcinoma Seemingly fused tumor cells (syncytial pattern), and a prominent lymphoid infiltrate. Histopathology of medullary breast carcinoma.jpg
Further information: Evaluation of tumors

Previous biopsy site

(For excisions or larger, look up past biopsies, and if in the same area, look for biopsy sites in order to confirm that the previous biopsy represents the same pathologies.)

If tumor is not found

Check the imaging indication, and look for abnormalities that may explain the diagnostic findings:

  • Dense stromal fibrosis for radiodense areas.
  • Calcifications if found on X-ray.

If still not found, note their absence, since it indicates that the biopsy may have missed the target of interest.

Microscopy report

A normal biopsy may be reported as follows

(Fibrofatty tissue with benign ducts and lobules.) Negative for (atypia and) malignancy.

More detailed reports are given at the disease-related articles.    

Fibrocystic breast changes

Microscopic examination

Types:

Differential diagnosis

Sclerosing adenosis may look similar to invasive ductal carcinoma (IDC), but IDC will:[103]

  • Not be lobular at low power
  • Have marked cellular atypia
  • Have no myoepithelial cells surrounding ducts.

When unsure, perform immunohistochemistry for myoepithelial markers (preferably p63 and calponin in breast lesions):

Immunostain with a myoepithelial marker (calponin) in sclerosing adenosis, showing myoepithelial cells surrounding the ducts, thereby excluding invasive carcinoma.

 

Fibroepithelial tumor

 

Gross examination

As per:

or mastectomy.

Microscopic evaluation

Fibroadenoma

Characteristics of fibroepithelial tumor

Biplastic, having proliferation of both stromal and epithelial components,[note 22] arranged into either a pericanalicular pattern (stromal proliferation around epithelial structures), or an intracanalicular pattern (stromal proliferation compressing the epithelial structures into clefts).

Characteristics of fibroadenoma

Fibroadenomas characteristically display hypovascular stroma compared to malignant tumors.[104][105][106] Furthermore, the epithelial proliferation appears in a single terminal ductal unit and has duct-like spaces surrounded by a fibroblastic stroma. The basement membrane is intact.[107]

Characteristics of phyllodes tumor

Benign phyllodes tumor

In contrast to fibroadenomas, phyllodes tumors display a leaf-like architecture, and an increased stromal cellularity.[108] In needle biopsy specimens, phyllodes tumors can be diagnosed in a fibroepithelial tumor if there is prominent mitotic activity of ≥3 per 10 high power fields, or the finding of 3 or more of the following characteristic histologic features:[108]

  • Stromal overgrowth
  • Fat infiltration
  • Stromal fragmentation
  • Subepithelial stromal condensation
  • Stromal nuclear pleomorphism

Further workup

After diagnosing a fibroepithelial tumor, still exclude another type of breast cancer, which may arise within it:[109]

Breast cancer types

Breast cancer types, with relative incidences and prognoses.
Cancer type Histopathology Image
Invasive ductal carcinoma (IDC) Carcinomatous cells are seen below the basement membrane of lactiferous ducts. Otherwise, there are no specific histologic characteristics, essentially making it a diagnosis of exclusion.[110] Invasive ductal carcinoma, with occasional entrapped normal ducts.jpg
Ductal carcinoma in situ (DCIS) Malignant epithelial cells confined to the ductal system of the breast, without invasion through the basement membrane.[100] DCIS - Intraductal carcinoma of the breast.jpg
Invasive lobular carcinoma (ILC) The "classic" pattern is round or ovoid cells with little cytoplasm in a single-file infiltrating pattern, sometimes concentrically giving a targetoid pattern. Classic Invasive Lobular Carcinoma of the Breast (6813147194).jpg
Lobular carcinoma in situ (LCIS)
  • Monomorphic, loosely cohesive, slightly enlarged and evenly spaced cells that fill acini.[101]

Cells have indistinct cell borders, pale cytoplasm, and uniform small nuclei with evenly distributed chromatin and inconspicuous nucleoli.[101]

Histopathology of lobular carcinoma in situ.jpg
Mucinous carcinoma Extracellular mucin areas around tumor cells. Histopathology of mucinous invasive ductal carcinoma of the breast.jpg
Medullary carcinoma Seemingly fused tumor cells (syncytial pattern), and a prominent lymphoid infiltrate. Histopathology of medullary breast carcinoma.jpg

Microscopic report

If, even after consultation, it is not clear whether a tumor is a fibroadenoma or phyllodes tumor, then it can be reported as a cellular fibroepithelial lesion or a fibroepithelial neoplasm.

A phyllodes tumor warrants a comment whether margins are positive or negative for tumor, whereas fibroadenoma does not need such comment.

Example report of fibroadenoma:

Right breast, lumpectomy:

Fibroadenoma.
Negative for atypia or malignancy.

 

Atypical ductal hyperplasia

 

Gross examination

As per:

or mastectomy.

Microscopic evaluation

Histological appearance of atypical ductal hyperplasia (ADH) and immunohistochemical phenotype:[111]
- A - One focus (< 2 mm) of two architecturally disarranged cross sections of tubuli showing a monotonous intraductal proliferation with secondary intraluminal architecture.
- B - One area of an ADH with associated intraluminal calcifications.
- C - Higher magnification of ADH shows low-grade nuclear atypia and monotonous cell proliferation along with secondary intraluminal architecture.
- D - Strong and uniform expression of estrogen receptors (ER). ER immunohistochemistry.
- E - Lack of basal cytokeratins (CK5/6). CK5/6 immunohistochemistry.

Atypical ductal hyperplasia shows epithelial proliferations which are not qualitatively or quantitatively abnormal enough to be classified as ductal carcinoma in situ.[96]

Differential diagnoses

Ductal carcinoma in situ

There is no single definite cutoff that separates atypical ductal hyperplasia from ductal carcinoma in situ, but the following are important distinctive features of atypical ductal hyperplasia, with suggested cutoffs:[112]

  • Size less than 2 mm.
  • Not involving more than one duct.
  • The atypical epithelial proliferation is admixed with a second population of proliferative cells without atypia.
  • The proliferation completely involves the terminal ductal lobular unit(s), to a limited extent.

Also, ADH tends to have rounded lacunae between cells, in contrast to more crescent-shaped (compressed) lucunae in DCIS.

Usual ductal hyperplasia (UDH)

edit
In contrast to usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH) displays:[95]

  • Increased amounts of pale eosinophilic to amphophilic cytoplasm with conspicuous cell borders
  • Atypical architectural patterns, including cribriform spaces, Roman arches, trabecular bars and micropapillae

If uncertain, immunohistochemistry can be performed:[95]

Usual ductal hyperplasia (UDH) Atypical ductal hyperplasia (ADH)
High molecular weight keratins Mosaic to occasionally diffuse Negative
Estrogen receptor Heterogenous staining Diffusely positive

 

Invasive ductal carcinoma

  Ductal carcinoma in situ (DCIS):  

Gross examination

As per:

or mastectomy.

Microscopic evaluation

DCIS.

Malignant epithelial cells confined to the ductal system of the breast.[100] The cells are cohesive and have high grade atypia.[113]

Differential diagnoses

Invasive ductal carcinoma
Has invasion through the basement membrane.[100] In uncertain cases, use immunohistochemistry stain for calponin (has the highest sensitivity) and p63 (has the highest specificity).
Atypical ductal hyperplasia

There is no single definite cutoff, but the following are suggested cutoffs defining a ductal carcinoma in situ:[112]

  • Size over 2 mm.
  • Involving more than one duct.
Lobular carcinoma in situ (LCIS)

When unsure, perform immunohistochemistry for E-cadherin and p120. Both E-cadherin (left image below) and p120 (right) have a membranous staining pattern in ductal carcinoma in situ:

In contrast:

Grading

At least a low/intermediate/high grading (by Van Nuys criteria) as follows:[115]

Low grade DCIS
  • Nuclei 10-15 microns (2-3 times the size of a red blood cell)
  • Nuclei oval, round, regular, evenly dispersed chromatin up to mildly irregular and minimally pleomorphic
  • Nucleoi, if present, are small and indistinct
Intermediate grade DCIS
  • Same nuclear features as low grade
  • Substantial tumor cell (comedo) necrosis is present
High grade DCIS
  • Nuclei >15 microns (over 3 times the size of a red blood cell)
  • Nuclei are pleomorphic with clumped chromatin
  • Nucleoli are prominent, enlarged
  • Necrosis is almost universal and lumenal

(Numerical grading

Use the low/intermediate/high grade to give a numerical grading as follows:[116]

Feature Points
1 2 3
Nuclear grade Low Intermediate High
Glands/papillae >75% 10% - 75% <10%
Mitotic rate (per 10 HPF) <1 1 - 2 >2
Central necrosis <10% 10% - 50% >50%

The points for each feature are added together, giving the following result:[116]

  • 4 - 7 points: Grade 1
  • 8 - 9 points: Grade 2
  • 10 - 12 points: Grade 3

)

Estrogen and progesterone receptors

In DCIS with necrosis, only use the areas of viable DCIS for the calculation of hormone receptors on immunohistochemistry.

Generally perform immunohistochemistry for estrogen and progesterone receptors and calculate the percentage of positive tumor cells.

Reporting

Example:

Left breast mass, 2:00, 1 cm from nipple, ultrasound-guided vacuum assisted core needle biopsy:
Ductal carcinoma in situ.
Negative for invasive carcinoma.

For cancers, generally include a synoptic report, such as per College of American Pathologists (CAP) protocols at cap.org/protocols-and-guidelines.    

Invasive lobular carcinoma

  Invasive lobular carcinoma (ILC):

Gross examination

As per:

or mastectomy.

Microscopic evaluation

Invasive lobular carcinoma.

Characteristics

The "classic" pattern is round or ovoid cells with little cytoplasm in a single-file infiltrating pattern, sometimes concentrically giving a targetoid pattern.

Subtyping

The histologic patterns mainly include:[117][118][119]

Type Prevalence Description Image
Classical 40% Round or ovoid cells with little cytoplasm in a single-file infiltrating pattern, sometimes concentrically giving a targetoid pattern Classic Invasive Lobular Carcinoma of the Breast (6813147194).jpg
Mixed 40% No dominant pattern
Solid 10% Sheets of classical-appearing cells with little intervening stroma.
Alveolar 5% Aggregates of classical-appearing cells
Tubulolobular 5% Cells form microtubules in >90% of tumor (smaller than in tubular carcinoma)
Pleomorphic Classical-appearing but with pleomorphic cells. It may include signet-ring cells, or plasmacytoid cells (pictured) which have abundant cytoplasm and eccentric nuclei.
Histopathology of pleomorphic lobular carcinoma with plasmacytoid cells.jpg

Differential diagnosis

  • In invasive lobular carcinoma, malignant cells have penetrated the basement membrane, in contrast to lobular carcinoma in situ.
  • Invasive ductal carcinoma typically has duct-forming tumor cells rather than single files of tumor cells. In uncertain cases, stain for E-cadherin and p120:

Staging

Stage by the TNM system as follows in sections below.

Also, look for any angiolymphatic invasion. If present, check whether it reaches outside the tumor, and if so, how far.[120] Give greatest dimension (,or 3 dimensions, generally by adding up the estimated thicknesses of involved slices)).[120]

Primary Tumor (T)

Tumor – Depends on the tumor at the primary site of origin, as follows:[121]

Measurements can be made by marking the tumor on microscopy, and then measuring between the markings, which may overlap between multiple slides as shown.
  • T1: Less than 2 cm
  • T1a: 0.1 to 0.5 cm
  • T1b: 0.5 to 1.0 cm
  • T1c: 1.0 to 2.0 cm
  • T2: 2 to 5 cm
  • T3: Larger than 5 cm
  • T4
  • T4a: Chest wall involvement
  • T4b: Skin involvement
  • T4c: Both 4a and 4b
  • T4d: Inflammatory breast cancer, a clinical circumstance where typical skin changes involve at least a third of the breast.

Regional Lymph Nodes (N)

Lymph Node: The lymph node values depend on the number, size and location of breast cancer cell deposits in various regional lymph nodes, such as the armpit (axillary lymph nodes), the collar area (supraclavicular lymph nodes), and inside the chest (internal mammary lymph nodes.)[122][123] Each stage is as follows:[121]

  • N0: There is some nuance to the official definitions for N0 disease, which includes:
  • N0(i+) : Isolated Tumor Cell clusters (ITC),[120] which are small clusters of cells not greater than 0.2 mm, or single tumor cells, or a cluster of fewer than 200 cells in a single histologic cross-section, whether detected by routine histology or immunohistochemistry;
  • N0(mol-): regional lymph nodes have no metastases histologically, but have positive molecular findings (RT-PCR).
  • N1: Mobile ipsilateral axillary nodes. Lymph node clusters 0.2 - 2.0 mm can be called "micrometastasis". At least one carcinoma focus over 2.0 mm is called "Lymph node metastasis". If one node qualifies as metastasis, count all other nodes even with smaller foci as metastases as well.[120]

Critical numbers of involved nodes: 1-3, 4-9, and 10 and over. Note any extranodal extension.[120]

  • N2: Fixed/matted ipsilateral axillary nodes.
  • N3
  • N3a – Ipsilateral infraclavicular nodes
  • N3b – Ipsilateral internal mammary nodes
  • N3c – Ipsilateral supraclavicular nodes

Distant Metastases (M)

  • M0: No clinical or radiographic evidence of distant metastases
  • M0(i+): Molecularly or microscopically detected tumor cells in circulating blood, bone marrow or non-regional nodal tissue, no larger than 0.2 mm, and without clinical or radiographic evidence or symptoms or signs of metastases, and which, perhaps counter-intuitively, does not change the stage grouping, as staging for in M0(i+) is done according to the T and N values
  • M1: Distant detectable metastases as determined by classic clinical and radiographic means, and/or metastasis that are histologically larger than 0.2 mm.

Overall stage

A combination of T, N and M, as follows:[121]

  • Stage 0: Tis
  • Stage I: T1N0
  • Stage II: T2N0, T3N0 T0N1, T1N1, or T2N1
  • Stage III: Invasion into skin and/or ribs, matted lymph nodes, T3N1, T0N2, T1N2, T2N2, T3N2, AnyT N3, T4 any N, locally advanced breast cancer
  • Stage IV: M1, advanced breast cancer
Further information: Evaluation of tumors

Grading

The Nottingham system[124] is recommended for breast cancer grading.[125] The Nottingham system is also called the Bloom–Richardson–Elston system (BRE)[126], or the Elston-Ellis modification[127] of the Scarff-Bloom-Richardson grading system.[128][129] It grades breast carcinomas by adding up scores for tubule formation, nuclear pleomorphism, and mitotic count, each of which is given 1 to 3 points. The scores for each of these three criteria are then added together to give an overall final score and corresponding grade as follows.

Tubule formation

By definition, tubule formation in classic invasive lobular carcinoma is scored as 3.[130]

Nuclear pleomorphism

Such as nuclei being larger, darker, or irregular/pleomorphic. Note: The cancer areas having cells with the greatest atypia should be evaluated.

  • 1 point: nuclei with minimal or mild variation in size and shape
  • 2 points: nuclei with moderate variation in size and shape
  • 3 points: nuclei with marked variation in size and shape

Mitotic count

Mitosis appearances in breast cancer

Mitotic figures are counted only at the periphery of the tumor, and counting should begin in the most mitotically active areas.

  • 1 point: Between 0-5 and 0-11 mitotic counts per 10 high-power fields (HPFs), depending on type of microscope used.[note 24]
  • 2 points: Between 6-10 and 12-22 mitotic counts per 10 HPFs.[note 24]
  • 3 points: Over 10 to 22 mitotic counts per 10 HPFs.[note 24]

Overall grade

The scores for each of these three criteria are added together to give a final overall score and a corresponding grade as follows:

  • 3-5 Grade 1 tumor (well-differentiated). Best prognosis.
  • 6-7 Grade 2 tumor (moderately differentiated). Medium prognosis.
  • 8-9 Grade 3 tumor (poorly differentiated). Worst prognosis.

Immunohistochemistry

Ki-67 index

Ki-67 in an invasive breast cancer: cancer nuclei are stained (brown). There is tumor cell positivity in 70% of the cells (Ki-67 labelling index = 70%).
To count as positive, a nucleus should:
- Not be located in stroma.
- Be at least half within the field of view.
- Be large enough.
Otherwise, even weakly positive nuclei count as positive.

Ki-67 index is mainly relevant in those with stage T1-T2, N0-N1, to determine if chemotherapy is needed (if Ki67 is >30% rather than <5%).[131]

Ki-67 index is most feasibly quantified by a hot spot method,[note 25] Hot spots are areas in which Ki-67 staining is particularly higher relative to the adjacent tumor areas.[132] Usually, the invasive edge of a tumor is a hot spot.[132] When a tumor had several hot spots, the “hottest” spot is selected.[132] Aim to count at least 500 cells in each case, but this is not always possible in cases with low tumor cell density and small tumor size.[132] Also aim to include at least three high-power (×40 objective) fields. Count a nucleus as “positive” if there is any definite brown staining in the nucleus of an invasive breast cancer cell, above the surrounding background in the cytoplasm and extracellular matrix.[133] If a comparisons must be made between core biopsies and sections from an excision, evaluation of the latter should be across the whole tumor.[131] Only nuclear staining counts. Staining intensity of a positive nucleus is not relevant.[131]

HER2

Score[134] Status[134]
0 to 1+ HER2 negative
(not present)
2+ Borderline
3+ HER2 positive

Biomarker retesting

((If the previous biopsy was negative for ER and PR receptors, and the patient has undergone neoadjuvant chemotherapy before excision, then retest ER/PR on the excision.))[note 26]

In breast cancer metastases, retest estrogen and progesterone receptors, and HER2 in the following circumstances:[135]

  • If the status of the primary tumor is unknown or negative for ER/PR and/or HER2
  • If the primary tumor is heterogeneous for ER/PR expression
  • If the metastatic progression is unusual for the tumor characteristics
  • If the relapse is unexpectedly early or late
  • If unusual metastasis location
  • If the initial test was performed more than 10 years ago
  • If the testing turnaround time are relatively short (to reduce potential delays in patient management by retesting)

Estrogen and progesterone receptors

Generally perform immunohistochemistry for estrogen and progesterone receptors and calculate the percentage of positive tumor cells.

Neoadjuvant cases

edit
In neoadjuvant cases (patient has received chemotherapy, endocrine therapy and/or radiotherapy before the excision), perform:

  • Measurement of the tumor bed which generally manifests as a fibroelastic area.
  • Classification of residual cancer, for which there are multiple systems, mainly Residual Cancer Burden (RCB)[note 27] and the American Joint Committee on Cancer post-neoadjuvant therapy staging system (yAJCC).[136]
Further information: Evaluation of tumors

Report

Breast excision

  • Tumor size, if not already given from gross report.[120] Give 3 dimensions or greatest dimension.[120]
  • Histopathologic subtype if apparent, but "invasive carcinoma" is acceptable.
  • Stage[120]
  • Grade, preferably by overall BRE grade. Optionally, give scores for the components thereof.[120]
  • Extent of any angiolymphatic invasion.[120]
  • Margins of resection,[120] either as minimal distance to margin, or as radical vs. not radical excision.
  • Results of any immunohistochemistry and other tests[120]
  • HER2 as a score or status.
  • Ki-67, preferably as labeling index

Example:

Breast excision with 70 x 55 x 18 mm ductal invasive breast cancer. Nottingham grade II. Estrogen receptor positive, progesterone receptor negative, HER2 receptor score 0, Ki-67 index 17%, T1b. Radically removed.

Needle or core biopsy

  • Histopathologic subtype if apparent, but "invasive carcinoma" is acceptable.
  • Results of any immunohistochemistry and other tests, as per excision[120]
  • Presence of absence of angiolymphatic invasion[120]
  • Optionally: Provisional grading. Grading can alternatively be deferred to excision.[120]
  • State if studies are deferred for a later excision sample[120]

For cancers, generally include a synoptic report, such as per College of American Pathologists (CAP) protocols at cap.org/protocols-and-guidelines.

synoptic report example
Tumor type:  invasive ductal carcinoma with micropapillary pattern
Tumor size:  greatest microscopic measurement of invasive carcinoma in positive core(s)):  0.7 cm
In-situ component: no
Microscopic grading (Nottingham modification of the Bloom-Richardson system):
  • Only applies to infiltrating ductal and lobular carcinoma:  
Tubule formation: Little or none (score =3)
Nuclear pleomorphism: Marked variation in size, nucleoli, chromatin clumping, etc. (score =3)
Mitotic count : Less than 6 mitoses per 10 hpf (score =1)
Composite score: 7 points  (applies to infiltrating ductal and lobular carcinoma only)
Histologic grade: Grade II: 6-7  points
Nuclear grade: grade 3
Microcalcifications of non-neoplastic breast glands.
Microcalcifications: Present in non-neoplastic tissue
Lymphocytic host response: absent
Necrosis:  absent
Blood vessel invasion: absent
Lymphatic permeation: indeterminate
Skin involvement: not applicable
Results of immunohistochemical stains for prognostic markers (as per original report):
Estrogen Receptor (ER) Status:  Positive (greater than 10% of cells demonstrate nuclear positivity)
Percentage of Cells with Nuclear Positivity:  91-100%
Average Intensity of Staining:  Strong
Progesterone Receptor (PgR) Status:  Positive
Percentage of Cells with Nuclear Positivity:  51-60%
Average Intensity of Staining:  Strong, moderate and weak
HER-2 by IHC:  2+ / Equivocal
REFLEX HER-2 FISH TEST:  Nonamplificed (ratio 1.5;  3.5 Her-2 signals/cell)
Ki-67:
Percentage of Cells with Nuclear Positivity: 43%
Primary Antibody: MIB1
Cold Ischemia and Fixation Times: 3 minutes
Fixation Time (hours): 14 hours and 33 minutes
Fixative:  formalin

 

Lobular carcinoma in situ

   

Histopathology of lobular carcinoma in situ.jpg

Presentations

Microscopic evaluation

Lobular carcinoma in situ (LCIS) typically display monomorphic, loosely cohesive, slightly enlarged and evenly spaced cells that fill acini.[101] Cells have indistinct cell borders, pale cytoplasm, and uniform small nuclei with evenly distributed chromatin and inconspicuous nucleoli.[101]

Differential diagnosis

The main differential diagnosis is ductal carcinoma in situ (DCIS).

When unsure, perform immunohistochemistry for E-cadherin and p120:

In contrast, both E-cadherin (left image below) and p120 (right) have a membranous staining pattern in ductal carcinoma in situ (DCIS).

Biomarkers

Generally perform immunohistochemistry for estrogen and progesterone receptors and calculate the percentage of positive tumor cells.

Microscopic report

It should contain:[138]

  • Type of resection or biopsy, and location
  • Results of any supplementary studies performed
  • Extent

However, grading and staging is not applicable. (Margins of excision are not relevant)

   

Autopsy

  The extremely minimal autopsy checklist:

  • Check the autopsy referral
  • Cut open and inspect the usually clearly visible organs, as well as the thyroid, pancreas and adrenals.
  • Weigh relevant organs
  • Sample tissues for microscopy and/or microbiology when needed
  • Report at least relevant findings


Checklist for non-forensic autopsy

There are many variants, with the following being a suggestion:

Preparations

  • Confirm that there is a consent from the next of kin to perform the autopsy, and whether it includes any restrictions (such as only examining the thorax).
  • Read the autopsy referral (if separate from the consent form)( and talk with the referring person and/or family why they want the autopsy and what they want to be investigated in particular, if not already evident from the referral. Surprisingly often, the main reason for performing an autopsy is not the cause of death in itself, but for some other question by the clinician or relative, such as a cause of a dementia. This information helps you focus on the most pertinent locations and possible findings to answer the question.)
  • Confirm with any supervisor what you may do independently, and at what stages the supervisor will want to inspect the body and/or organs (for example before evisceration and/or after all pertinent organs have been opened).[note 28]
  • (Go through the patient's medical records, at least if necessary aspects are not included in the referral. The most important aspects are:
  • Time of death
  • Surgical history
  • Current diseases
  • Latest hospital and/or primary care notes)
  • ((History of smoking
  • Medications, especially anticoagulant ones.
  • Family history))

In the autopsy room, before starting examination:

  • Charge and bring a camera to document relevant findings.
  • Use protective wear, generally according to local practice. Tie any knots before putting on gloves for better dexterity.
  • Confirm the identity of the body, generally from attached identity tag.

External inspection

  • Measure the size of <<clinically significant / ( all)>> scars, marks, bruises or wounds. Estimate the depth of wounds, either by number or presumed anatomic layer.
  • Note any therapeutic tubes or lines
  • Inspect the lower legs for swelling (and compare their circumferences taken 10 cm above the ankle. If swelling is suspected, later press the legs while observing the femoral veins emptying into the pelvic cavity to discern if there is free flow.
  • Discern the race, gender, nutritional status, and apparent versus stated age
  • Inspect the external ears, eyes, nostrils and mouth.)

In situ inspection

  • Note any atypical organ arrangement
  • Estimate (or measure) excessive amount of fluid in body cavities.
  • (Measure the thickness of subcutaneous fat at the thorax and abdomen.)

Evisceration

Y-incision
  • The standard Y-incision is from each acromion process to the xyphoid process. For larger breasted patients, the incision is done under the breast, making it easier to manage later.
  • From here the incision extends down the central abdomen, to the patient’s left of the umbilicus, ending at the pubis. Care is taken not to cut too deeply into the abdomen, to avoid puncturing the peritoneal cavity and/or bowel.
  • The skin is reflected back over the face and along the sides. Always cut perpendicular to bone.
  • Take measurement of the chest and abdominal pannus at this time.
Chest plate
  • Using rib cutters or Stryker saw, cut laterally along the ribs, ending at the sterno-clavicular junction.
  • Remove chest plate by detaching it from the diaphragm and pulling upward toward the head.
  • Inspect the ribs for fractures
  • Also, squeeze out bone marrow on a piece of wrapping tissue and submit.
  • Perform in situ examination as per checklist.
Peritoneal loose bodies may be found in the peritoneal cavity, and are generally caused by torsion and autoamputation of an epiploic appendage, which eventually becomes embedded in a fibrous capsule.
Bowel removal
  • Pull up stomach and find the ligament of Treitz (pictured).
  • At the ligament of Treitz, place two hemostats & cut through the bowel between the clamps.
  • Cut the mesenteric adipose close to the bowel, without perforating it.
  • When you reach the rectum, place two hemostats and cut through the bowel between the clamps as before.
Supra-pelvic organ blocks
  • Cut the diaphragm free from the body wall on both sides extending down to the spinal column.
  • From here pull all the organs to the left and make an incision along the right side of the spinal column to free the organs
  • Do the same along the left side.
  • Tease the soft tissue of the neck to expose the carotid arteries.
  • Tie off both sides leaving long stumps, which are marked with strings for embalming purposes.
  • Dissect the tissue of the neck to expose the thyroid cartilage.
  • Transect immediately above the thyroid cartilage, freeing the trachea and esophagus.
  • Start to dissect away the tissue around and behind the thyroid cartilage & esophagus.
  • Continue this dissection down, following the spinal column to the bifurcation of the abdominal aorta.
  • At this point, remove the organ block from the body.
Pelvic organs
  • Bluntly dissect the urinary bladder away from the wall of the true pelvis
  • Continue this blunt dissection down into the pelvis to include the vagina (if female) & rectum
  • Pull directly anterior to free these structures
  • You will hear a loud suction noise when done correctly
  • At this point, cut straight down to remove the pelvic organs
  • If male, insert the scissors into the pelvis toward the feet as far as possible & then down to include the prostate
  • To remove the testis, bluntly dissect along the inguinal canal, exposing the spermatic cord
  • Pull up on the cord until the testis pulls through the canal & out of the scrotum
  • Transect the spermatic cord.

Skull cap
  • Separate the hair of the scalp, cut from ear to ear (just behind each ear) over the posterior crown of the head.
  • Reflect the skin forward over the face & back to the neck, exposing the skull cap (use a towel for better grip).
  • Using a scalpel, outline the cut on the anterior & posterior skull cap cutting away the temporalis muscles. The outline should make ~45 degree angle located at the level of the ear.
  • Use the Stryker saw to cut along the outline. Be sure to cut through the skull bone but not into the brain tissue.
  • Make a V-shaped notch in the anterior midline to help the skull cap stay in place following autopsy
  • Pull skull cap off
Brain
  • Do an in situ examination before removing.
  • Gently insert fingers over frontal lobes and pull backwards.
  • Using scalpel/scissors, cut away the exposed cranial nerves.
  • Cut away the tentorium, keeping the scalpel close to the bone.
  • Free the cerebellum.
  • Insert scalpel/scissors as deep as possible to cut the brain stem.
  • Pull brain out gently.
  • Place a wedge at level of sella turcica and hit it with a hammer to expose pituitary gland.
  • Remove the gland gently.
  • Weigh the brain.

Organ packages

Organs are generally initially separated into the following packages:

  • Thorax
  • Gastrointestinal, including liver, spleen and pancreas.
  • Pelvic, including urinary bladder and uterus/prostate.

The kidneys and adrenals may be included in either the gastrointestinal or pelvic package.

To separate the thoracic from the abdominal package:

  • Turn the packages with the dorsal side up.
  • Optionally: Cut the aorta just distally to the exit of the left subclavian vein, and separate the descending thoracic aorta from the rest of the thorax.
  • Optionally: Cut the esophagus at its superior attachment to the trachea, and separate it from the thorax.
  • Free the basilar aspects of the lungs from the diaphragm.
  • Identify the inferior vena cava (IVC) and transect it as close to the diaphragm as possible.
  • Detach the pericardium from the diaphragm as close to the line of attachment as possible.

Heart

edit

  • Remove the parietal pericardium
  • Separate the heart from the from lungs by cutting through the major vessels. The pulmonary artery should be cut first and the lumen inspected for any pulmonary embolism.
  • Weigh the heart.
  • Dissect the coronary vessels.    
  • On the right side of the heart, dissect in the direction of blood flow: Superior vena cava > right atrium > tricuspid valve > right ventricle. Look for thromboses or patent foramen ovale.[note 29]
  • Dissect the atrial appendages, to exclude thromboses.
  • Dissect the left ventricle, such as into circumferential slices from the apex to the base.[note 30] Inspect (and measure) the left ventricular wall thickness.
Valve circumferences are measured at the basal ring (bottom in image).
  • (Measure the circumferences of the four valves. Cutoffs for valve dilatation:[139]
  • Mitral valve: circumference greater than 9.9 cm in males and 9.1 cm in females
  • Aortic valve: circumference greater than 8.5 cm in males and 7.9 cm in females
  • Tricuspid valve: circumference greater than 11.8 cm in males and 11.1 cm in females
  • Pulmonic valve: circumference greater than 7.5 cm in males and 7.4 cm in females)

Look for signs of myocardial infarction. Further information: Heart autopsy and Autopsy of myocardial infarction

Other thorax

  • Dissect the aorta, with an anterior dissection of the aortic arch and major branches, and posterior dissection of the descending thoracic aorta. Check for thrombosis and degree of atherosclerosis. Then separate the descending thoracic aorta from the esophagus.
Relations of the aorta, trachea, esophagus and other heart structures
  • Dissect the pulmonary arterial system, from the pulmonary trunk and including at least segmental arteries. To avoid cutting through the left main bronchus (passing anteriorly to the left main pulmonary artery), the initial dissection of the left main pulmonary artery may begin from an anterior perspective but keeping the cuts along the posterior wall, until the dissection can be seen and be continued from a posterior approach. Check the pulmonary arteries for blood clots.
Blood clots[140]
Pre-mortem Post-mortem
Tumor embolus in the main pulmonary artery.jpg Gross pathology of a postmortem blood clot.jpg
Texture Dull Shiny
Wall adherence Yes No
Color Grey. Possibly zebraic appearance by lines of Zahn, with mixed red and grey/yellow Dark-red ("currant jelly") to tan-pink ("chicken-fat")
Pressurized Yes, can eject from lumen No, needs to be pulled-out
Consistency Firm and brittle Elastic, jellylike
  • Esophagus: Separate it from the trachea and dissect it.
  • Dissect the trachea and the bronchial tree, at least to segmental bronchi. Check for obstructions.
  • Make some additional sections through the lung parenchyma. Squeeze at each side to detect any pus and edema.[141]  
  • Cut each thyroid lobe in horizontal slices and inspect the parenchyma.  
  • ((Look for parathyroid glands, and if found, inspect for nodules or hypertrophy.  ))
  • Look for enlarged lymph nodes in the hilar and paratracheal area.

Retroperitoneal

For orientation, the coeliac trunk and mesenteric arteries exit the aorta from the anterior side.

  • Dissect the descending abdominal aorta. Cut external iliac artery from a dorsal approach, or after freeing ureters.[note 31]
  • Inspect the renal arteries for patency. ((Dissect them until entry into kidneys.))
  • Make a couple of cuts through the adrenal glands, such as transversal ones, and look mainly for tumors.  
  • Cut the kidneys in the coronal planes.  
  • Dissect the ureters to the bladder. Look for any increased caliber or abnormal contents.
  • Dissect the prostate in males, and the urinary bladder, by an anterior approach. Dissect the ureteropelvic junctions. Inspect the bladder content and the urothelial surface.
  • Dissect the rectum.
  • In females, bivalve the uterus by cutting along right and left lateral aspects. Measure the ovaries.

Peritoneal

  • Remove the diaphragm and excess omentum
Wischnewski spots of the stomach are associated with hypothermia.[142]
  • Dissect the stomach along the greater curvature, as well as the duodenum and the esophageal entry into the stomach.
  • Dissect the extrahepatic biliary tract and gallbladder.[note 32] 
  • Make consecutive liver slices, such as in the sagittal or coronal plane.  
"Long" and "short" axis.[143]

Note its shape, color and consistency.

  • Inspect the pancreas regarding color and consistency. ((Separate it and measure its dimensions.)) Cut it in consecutive short axis slices. Note the appearance of the parenchyma (and the size of the duct).  
  • Separate the spleen and make consecutive short axis slices through it. Note its shape, color, texture and consistency.
  • Separate the intestines until the rectum, and dissect them by a longitudinal section, looking for focal and diffuse lesions. Note the presence or absence of the appendix.

For the liver, pancreas and spleen, sectioning preferably goes almost but not fully through each organ, so as to keep the slices together.

Brain

edit

  • Weight the brain. Overall normal range (95% prediction interval) is 1100 to 1700 g,[144] +60g for males and -60g for females.[145]
  • Inspect: Grooves indicating herniation? Hemorrhages?
  • Dissect the basilar artery and circle of Willis, either before or after separation from the brain. [[If there is likely a need to demonstrate the case to an additional person later, the arteries of the skull base are preferably dissected after first separating them from the brain.]] Look mainly for thromboses.
  • Separate the brainstem, cerebellum and cerebrum, which may be done by first separating the former two together from the cerebrum.
Normal brain versus in Alzheimer's disease.
  • Slice each part, looking for hemorrhages and/or infarcts.
  • For the cerebrum, cut it into slices about 1 cm thick. It can be done from frontal to occipital, or by starting coronally into two halves at the level of the mammillary bodies and continuing in each direction from there.
  • At least in people aged over 65-75 years of age {{or with suggestive history}}, look for signs of Alzhemier's disease (see picture).

 

Demonstration

Consider summoning involved clinicians for a demonstration of any findings.

Weighing

Separate and weigh these organs, either before or after cutting into them, but before tissue sampling.

Tissue sampling

Sample tissues for microscopy from wherever histopathology may aid in establishing the cause of death. Following are routine samples:

In addition, generally sample all gross lesions, except uterine fibroids, diverticula and multiple intestinal polyps. One sample is sufficient in case of multiple metastases. Lesion samples should include adjacent normal tissue.

Furthermore, generally save a piece of tissue in formalin from at least all sampled locations, in case the sample gets lost or gets processed incorrectly.  

Microbiology

Indications

Cultures for microbiology are indicated in the following cases, if less than 24 hours have passed since the time of death:[note 33]

  • Fever of unknown origin
  • At request of the requesting physician
  • (Drug addicts
  • Patients from nursing homes)
Sites
  • Blood cultures from the right ventricle/atrium
  • Any exudates or pus collections
  • (Any organ suspected to have inflammation)
  • {{Cerebrospinal fluid if meningitis is suspected}}
  • {{Body fluids, by individual indication}}

Toxicology

  • {{Toxicology is taken if highly suspected from the history. Up to 2.5 ml can be obtained from each eye, using a red top tube.}}

Reporting of non-forensic autopsy

The order of the sections may vary.[146]

((Where findings are made, still negate additional findings in the region, such as: "There is a 18.0 cm curvilinear well-healed thin scar in the left thorax. Otherwise, there are no puncture marks or healed surgical scars on the torso."))

Data

  • Autopsy No.: ________
  • (Hospital No.:000046)
  • Patient name: Bloggs, Joe
  • (Patient No.:)
  • (Ward :_______)
  • Age [[or birthdate]]: _____
  • (Sex: ______)
  • (Race: ______)
  • (Permission: From [[usually close relative of the deceased.]])

((The medical records of the <<patient/deceased>> [[Either denomination works]] were reviewed prior to the commencement of the autopsy.))

  • Date (and time) of death: ______
  • Date (and time) of autopsy: ______
  • (Date of report: _________)
  • Attending physician: _______
  • (Prosector:__________)
  • {{Limitation of the autopsy}} [[such as restriction to thorax only]].

Final autopsy diagnosis / Preliminary diagnoses

[[May be preliminary if histopathology samples are taken.]]

  • [[First, generally the final cause of death, such as:]]
  • {{Acute circulatory failure with pulmonary edema and congestion of abdominal organs.}}
  • [[Other diagnoses that may have caused the death is listed in causative order:]]
  • {{Acute myocardial infarction.}}
  • {{Severe arteriosclerosis.}}
  • [[Other autopsy diagnoses, including presumably incidental ones:]]
  • {{Hepatic steatosis.}}
  • [[Clinically known diagnoses may be marked as such:]]
  • {{Type 2 diabetes (clinical diagnosis).}}
(Clinical history

_________)

(Laboratory data

_________)

External inspection

((The autopsy is performed approximately __ hours after death.)) The body is a ((well developed,)) << ((well nourished)) / {{underweight / overweight}}>> (__ year old) [[if not already given in data]]) << woman / man >>. ((The body appears as stated age.)) (Lengths is __ cm and weight is __ kg..)

Usual signs of death. (Rigor mortis is << well marked / broken >>. Lividity is seen on the << front / back and/or side >>.)

(On the torso there are no puncture marks or healed surgical scars.)

((The skin is <<pale / icteric / cyanotic>>. The body hair shows a normal <<male / female>> distribution. There is no peripheral edema. The head is not deformed. It is covered by <<scanty / moderate / abundant>> amount of [[color:]] ____ hair. The irides are [[color:]] ___. The pupils are round, regular and equal, measuring _cm in diameter. The corneae and lenses are transparent. The sclerae are clear. The conjunctivae are <<pink / pale>>. The nose and external ears are unremarkable and their passages are clear. The lips and gums show no lesions. {{The lips are pale/cyanotic.}} The mouth is not remarkable {{/edentulous /contains a frothy fluid}}. The neck structures are symmetrical, and there are no unusual masses. {{There is jugular venous distention}}. The thorax has normal contour and symmetry. [[In females:]] breasts and nipples are unremarkable. The abdomen is flat {{/protuberant}}. External abdominal palpation detects no abnormal masses or fluid waves. The extremities show no scars or deformities. The nails are normal {{/cyanotic/clubbed}}. No palpable inguinal masses.))

Internal examination

((Standard thoracic incisions are employed.))
{{Overall severe autolysis, making pathologic assessment difficult.}}
((The subcutaneous fat measures ___ in thickness over the thorax and _cm over the abdomen. The skeletal muscles are red-brown, normally firm and of normal bulk. There is no subcutaneous emphysema. The abdominal organs are in their usual anatomic positions. The diaphragmatic domes reach the <<sixth / seventh>> intercostal space, bilaterally.))

Serous cavities
No increased amount of fluid in the pericardial, pleural or abdominal cavities. Serous surfaces are smooth and lustrous.(No signs of inflammation. No adhesions.) [[These are preferably located by the corresponding system of each cavity:]]
  • ((The pleural surfaces are smooth and the cavities are dry. {{The <<right / left>> pleural cavity contains _cc/ml of <<clear / bloody / straw-colored>> fluid and show <<soft / hard>> adhesions.}}
  • The pericardial cavity contains _cc/ml of straw-colored fluid and shows no adhesions.
  • The peritoneal cavity contains _cc/ml of straw-colored fluid. ))
Circulatory system

edit
The heart << has normal weight / is enlarged [[ > 399 g in women and> 449 g in men]] >>, weighing ___ g. ((The epicardium is transparent. There is a moderate amount of subepicardial fat.

Normal configuration (No atrial or ventricular dilation. No ventricular wall thickening) / {{The left ventricle has {{concentric}} hypertrophy, with a wall thickness of ___ mm.}} ((No atrial or ventricular dilation. The right and left auricular appendage is unremarkable. The left ventricular wall thickness is __ cm and the right is ___. The trabeculae carneae are normal ({[Finding-begin}}/ prominent /flattened}}.))
[[A comprehensive report may describe each atrium, valve and ventricle etc. in order of blood flow.]]

(Foramen ovale is closed.) ((The ductus arteriosus is obliterated))
The coronary arteries ((arise in normal position. The coronary ostia are << patent {{partially occluded by arteriosclerotic calcification}}>>. They)) have << no / mild / moderate / severe >> {{and partially calcified}}
arteriosclerosis. They are traced, ((throughout their length by transverse sections)) {{after fixation and decalcification}} <<without significant constrictions.{{ / The lumina of the left anterior descending, right coronary, and left circumflex coronary arteries are _%, _%, and _% narrowed, respectively.}} [[If the degree of stenosis on microscopy sections of coronary arteries only differ slightly from the gross description, preferably write "mild/moderate/severe atherosclerosis consistent with the gross inspection."]] (Gross measurement of coronary artery stenosis is generally more accurate than microscopic measurement, so the former generally has precedence.)

No thrombi in the cardiac atria (including auricles), chambers or coronary arteries.

Chordae tendineae, the endocardium and heart valves are unremarkable. (The endocardium is smooth and shiny. Chordae tendineae are unremarkable. The valves are normal in number, and are thin and fine at the openings.) ((The endocardium is smooth, transparent and free of mural thrombi. The valve leaflets and chordae tendinae are overall delicate, pliable and free of lesion or calcification. <<Its leaflets are thin and pliable / No signs of inflammation>>.
  • The tricuspid valve <is / is not> dilated, measuring _cm in circumference.
  • The pulmonic valve <is / is not> dilated, measuring _cm in circumference. It is composed of <<two / three>> cusps which are discrete and pliable.
  • The mitral valve <is / is not> dilated, measuring _cm in circumference. Its leaflets are thin and pliable {{/ redundant / adherent to each other}}.
  • The aortic valve <is / is not> dilated, measuring _ cm in circumference. It is composed of <<two / three>> cusps which are thin and pliable.

{{The cusps are calcified at the bases / adherent to each other.}} {{The valve displays mild / moderate / severe myxomatous degeneration.}} The epicardium and subepicardium are unremarkable. The papillary muscles are normal {{ / hypertrophied}}))

The myocardium has ((a homogeneous reddish brown color, and)) no signs of <<fresh lesion / ((areas of necrosis or hemorrhage))>> (or scar){{/ streaks of white scar tissue}}. In the aorta (and its major branches) there is {{widespread}} << no / mild / moderate / severe >> arteriosclerosis. No aneurysm. (Renal arteries ((are patent and)) have no significant stenosis.) No thrombus in (vena cava, ) the pulmonary arteries ((or the pulmonary veins)){{The <<right / left>> <<proximal and/or distal pulmonary arteries contain coiled, red-purple thromboemboli with(out) attachment to the intima.}} ((The portal system appears unremarkable. The vena cavae are also unremarkable. There is a free flow of blood from the veins of the lower extremities.))

Respiratory system
The larynx, trachea and bronchi are normally configured, with non-irritated lining. ((Larynx has normal configuration. The vocal cords are smooth and symmetrical. The trachea and the larger bronchi have non-irritated lining. No ulceration. Lumina are patent.)) {{The bronchial lumina contain small amounts of frothy mucoid material.}}

No foreign content((, dilatation or mucosal change)). ((Normal lobar structure. No tumor. No visible signs of inflammation.))
The lungs ((have the usual shape and lobar divisions, are expanded and)) have << normal / increased >> weight, of __ g on the right and ___ g on the left. (The consistency is normal) {{/ abnormally firm. There is <<minimal / moderate / extensive subpleural anthracotic pigment present.}}Cut Surfaces[note 34] are unremarkably dark red, with no definable tumors( or bleeding).
{{There are firm with patchy areas of tan-grey consolidation of location. Watery and frothy liquid is pressed from the parenchyma, indicating pulmonary edema.}}
(The rib cage is intact) / {{Multiple rib fractures, consistent with CPR.}} ((There are no masses in the mediastinum.))

Digestive system

((The tongue has no bleeding.))

The esophagus, stomach and intestines are ordinarily configured, without tumors or blood in the lumen. ((The esophagus is lined by a smooth, tan-white non-irritated epithelium, and the mucosa has normal thickness. No diverticula, varices, mucosal tears or ulcerations.
The ventricle is of normal size, with normal wall-thickness. There is unremarkable <<partially digested food / fluid in the lumen>>, with no suspicion of blood content. The mucosa has well-formed rugae and shows <<no signs of lesions / {{mild / moderate erosions, but no ulceration}}. The gastric serosal surface is smooth.))

((The duodenum, jejunum and ileum and colon are ordinarily configured with non-irritated lining. Content is normal. The mucosa is intact throughout. No visible tumor. The ileocecal valve is competent.))

(The appendix is non-irritated and of normal size.)[note 32] {{There are scattered <<colonic / sigmoid>> diverticula without inflammation or perforation.}}

Minimal More comprehensive Normal ranges
The liver weighs ___g. The liver is << of normal size / {{enlarged}}, at ___g. [[Men: 970-1860 g.[147] Women 600-1770g.[148].]]

The liver surface is <<smooth ((and glistening)) {{/deformed by small and large nodules}}((, and is <<light tan / dark brown>> in color)). << Normal/ {{/ firm}} consistency. Cut surface[note 34] is normal / << (shows normal homogeneous brown parenchyma) / {{Yellowish color, indicating steatosis}} / {{dark nutmeg similar paths, indicating congestion}}. (No focal changes.)((The liver edge is _cm below the right costal margin.)) The gallbladder has (regular size,) thin walls ((lined by a velvety green mucosa)). It contains {{__ number of gallstones measuring up to __ mm. Otherwise}} normal bile ((of about ___ ml [[or cc]]. No tumor or gallstones.)) {{Mild / Moderate / Severe cholesterolosis.}} ((The gallbladder serosa is smooth.))   The (extrahepatic) bile ducts are open(, ordinary and without gallstones in the lumen).
The pancreas has normal size (and shape, measuring __ )[[dimensions or weight]]. Cut surfaces[note 34] are normal((ly tan and lobulated, without bleeding or definable focal changes. The main pancreatic duct is patent.)).

Lymphoid and endocrine organs

The spleen is of << normal size {{ / Enlarged [[> 230g]]}}>>, at ___ g. Normal consistency / {{ Firm consistency indicating of chronic venous stasis}}. Cut surfaces[note 34] have normal appearance / ( normal bluish-red color, with no definable focal changes). ((The splenic artery and vein are normal.))

The thyroid and adrenal glands are normal bilaterally / (are ordinarily configured and with no definable focal changes on cut surfaces[note 34]). [[These are preferably located by the corresponding system of each cavity:]]((
  • The thyroid weighs _ grams [[Up to 30 g versus over 30 g grams is an accepted cutoff between normal and increased weight of the thyroid gland[149]]] and is symmetrical. Its consistency is soft {{/firm}}. Its external surface is brown and smooth {{/nodular / wrinkled}}. On sectioning it presents a homogeneous dark red appearance {{/contains several small nodules / contains a cyst}}. <<One/Two/Three/Four>> parathyroids are identified and appear normal.  
  • The adrenals are normal in size, shape and consistency. The cortices are orange with <<normal / increased / decreased>> thickness. The medullas are grey (autolyzed).

))

No abnormal lymph nodes. ( Lymph nodes in para-tracheal, para-aortic and abdominal regions are of normal size, texture and color.)
((No definable focal changes on cut surfaces[note 34].))
Urogenital

edit The kidneys are equally sized / (of normal size, with a total weight of ___ g)((a weight of ___ g on the right side and ___ g on the right)).

Sex Weight, reference range[note 35]
Right kidney Left kidney Total
Men[150] 80–160 g (2.8–5.6 oz) 80–175 g (2.8–6.2 oz) 160-335g (5.6-12.8 oz)
Women[151] 40–175 g (1.4–6.2 oz) 35–190 g (1.2–6.7 oz) 75-365g (2.6-12.9 oz)


(No abnormal adhesions between the kidneys and surrounding fibrous capsules.)
The kidneys have smooth surfaces/ {{<<Finely / Coarsely>> granular brown surface, possibly indicating benign nephrosclerosis. There are a few cysts on the surface containing clear fluid}}. Cut surfaces have well-defined medulla, cortex, and papillae. {{The cortices and/or medullas are narrowed and congested. The papillary portions are intact.}}
The renal pelvis and ureters are unremarkable /( Renal pelvis and ureters have normal calibers, with non-irritated mucosal surfaces and open lumens).
The urinary bladder ((lies below the symphysis pubis and)) is unremarkable / ( is of normal size, with normal mucosa, and no tumor.)(( The urinary bladder contains __cc/ml of <<clear {{/ turbid}} urine. The wall is not thickened. The ureteral orifices are patent. The serosal surfaces are smooth and glistening {{and show <<soft / hard>> fibrous adhesions}})).
[[Either:]]

  • [[Male]]: The prostate is of <<normal size (( measures _x _ x _ cm>> and has normal color. The consistency is <<normal elastic)){{/ firm / nodular}}. (No definable focal changes on cut surfaces[note 34]). The testes are ((descended {{, atrophic}} and)) without abnormal masses.(( The penis and scrotum are unremarkable.))
  • [[Female]]:
Uterus and adnexa are unremarkable.[note 32] ((The uterus is normal. It measures __ x __ x __cm and weighs __ grams. Its serosal surface is <<smooth {{/ deformed by multiple nodules ranging between __ and _ cm}}>>. The cervix is unremarkable. The endometrial cavity is lined by a smooth atrophic velvety, tan membrane. The ovaries and fallopian tubes are normal.))
Central nervous system

edit

The meninges and venous sinuses are unremarkable. ((The skull is unremarkable. The calvarium is opened in the usual manner. The scalp and overlying fascia are not remarkable. The skull is <<normal in thickness {{/ somewhat thickened in the frontal areas}}. The cerebrospinal fluid is clear. The dura and venous sinuses are unremarkable. The leptomeninges are thin, shiny and non-irritated, with no visible bleeding. The superficial blood vessels are not congested. The sulci and gyri are <<normal {{/ flattened}}.

(No visible thrombi. No epidural, subdural or subarachnoid hematoma.)

The brain is symmetrical and weighs ___g. ( The cerebral and cerebellar hemispheres are of equal size, and have a normal weight of ___g. [[Men: 1.180 to 1.620 g. Women: 1.030 to 1.400 g]][152][153]
No signs of herniation (No grooves on the bases of the cerebrum or cerebellum.)

((The cerebral ventricles are of normal size, with normal linings.)) Cut surfaces ((after fixation)) of the cerebrum, cerebellum and brainstem show (normal gray and white parenchyma, and) no ((encephalomalacia, ))(hemorrhages, tumors or other) focal abnormalities. ((The gyral pattern is preserved.))
The basal cerebral arteries << are ordinary / {{have mild / moderate / severe atherosclerosis}}>> without aneurysms or occlusions.

Skeleton

Scalp and base of skull are ordinary / (without visible lesions or injuries).
((The vertebral column is unremarkable. The musculature is fairly well developed. There are no deformities of the musculoskeletal system. The bone marrow appears red and cellular.))

{{Other organs

if evaluated.}}

Histopathology

No samples taken / {{Tissue samples have been taken from the << heart, lungs, liver and/or kidneys >> for supplementary microscopic and/or bacteriological examination.}}

((Clinicopathologic correlation))

[[Discussion of how findings relate to the probable clinical course.]]

Microscopy report

{{Overall <<moderate / severe>> post-mortem autolysis((, making interpretations on cellular level <<difficult / unfeasible>>)).}} [[The degree of autolysis may be specified for each site individually.]]

(After the location identifier, each list item can generally begin as "This section/These sections[note 36] << shows / reveals >>...)

  • Breast: ((Section(s) show(s))) no focal changes. {{Non-proliferative fibrocystic changes and microcalcifications.}}
  • Bone marrow from <<rib / __ [[other location]] >>: Section shows trilineage hematopoiesis. There is no evidence of malignancy.  
  • Lymph nodes at __ [[ location]]: ((Section(s) show(s)))__ [[number of]] benign{{, reactive lymph node(s) with anthracotic pigment deposition}}.
  • Heart: Sections of ___ [[location]] show no evidence of infarction.  
  • Coronary arteries: Sections of the three main coronary arteries reveal << mild / moderate / severe>> atherosclerosis, with approximately __%, __% and __% stenosis of the left anterior descending, left circumflex coronary artery and right coronary artery, respectively.  
Thyroid parenchyma with autolytic changes, with thyroid follicular cells sloughing off into the follicles. It does not need mentioning in the report (unless severe enough that further evaluation impossible).
  • Thyroid gland: ((Section(s) show(s))) normal follicles with no focal changes.
  • Parathyroid: <<1, 2, 3, 4>> parathyroid gland(s) examined; ((Section(s) show(s))) no focal changes or signs of hyperplasia.  
  • Pituitary gland: ((Section(s) show(s))) adenohypophysis and neurohypophysis with no focal changes.  
  • Liver: ((Section(s) show(s))) {{congested}} hepatic parenchyma with no focal changes.  
  • Adrenal glands: ((Section(s) show(s))) right and left adrenal glands with no focal changes. (The cortices and medullae are unremarkable.)
  • Spleen: ((Section(s) show(s))) normal distribution and architecture of the red and white pulp.
  • Kidneys: ((Section(s) show(s))) both kidneys with {{<<mild / moderate / severe >> <<generalized / focal / nodular>> glomerular sclerosis, and <<mild / moderate / severe >> arteriosclerosis.}} There are no focal changes.  
Gastroesophageal junction with autolytically denuded gastric mucosa (no further comment needed as metaplasia or dysplasia cannot be negated).
  • Gastroesophageal junction: ((Section(s) show(s))) squamo-epithelial junction with no metaplasia or dysplasia.  
  • Pancreas: ((Section(s) show(s))) {{autolytic}} (pancreatic parenchyma with) no focal changes.  
  • Lungs: {{Sections of all lobes of the lung}} show vascular congestion. (There is no evidence of edema, acute bronchopneumonia, malignancy or thromboemboli.)  
  • Urinary bladder: ((Section(s) show(s))) <<normal {{/ autolytically denuded}}>> urothelium.
  • Brain: ((Standard sections of the cerebral cortex, basal ganglia, hippocampus, thalamus/substantia nigra, medulla oblongata and cerebellum show)) intact cytoarchitecture. There is no evidence of hemorrhage, tumor, metastatic disease or vasculitis.  

Males:

  • Testis: ((Section(s) show(s))) no focal changes. (There <<are no / are few / is a normal amount of>> visible mature spermatozoa.)
  • Prostate: ((Section(s) show(s))) no focal changes {{/nodular prostatic hyperplasia. There is no evidence of malignancy}}.

Females:

  • Uterus: ((Section(s) show(s))) no focal changes.
  • Ovary: ((Section(s) show(s))) no focal changes bilaterally.

 

External applications

  The standard reference range reference is duplicated because of technical reasons by being included in Patholines:Templates.

Heart autopsy

Autopsy cutting checklist

edit

  • Remove the parietal pericardium
  • Separate the heart from the from lungs by cutting through the major vessels. The pulmonary artery should be cut first and the lumen inspected for any pulmonary embolism.
  • Weigh the heart.
  • Dissect the coronary vessels. More details in section below.  
  • On the right side of the heart, dissect in the direction of blood flow: Superior vena cava > right atrium > tricuspid valve > right ventricle. Look for thromboses or patent foramen ovale.[note 37]
  • Dissect the atrial appendages, to exclude thromboses.
  • Dissect the left ventricle, such as into circumferential slices from the apex to the base.[note 38] Inspect (and measure) the left ventricular wall thickness.
Valve circumferences are measured at the basal ring (bottom in image).
  • (Measure the circumferences of the four valves. Cutoffs for valve dilatation:[154]
  • Mitral valve: circumference greater than 9.9 cm in males and 9.1 cm in females
  • Aortic valve: circumference greater than 8.5 cm in males and 7.9 cm in females
  • Tricuspid valve: circumference greater than 11.8 cm in males and 11.1 cm in females
  • Pulmonic valve: circumference greater than 7.5 cm in males and 7.4 cm in females)

In case of suspected infarction, see autopsy of myocardial infarction.

For left and right wall thickness, uppr limits of 1.5 cm and 0.5 cm, respectively, are generally used to distinguish wall thickening on autopsy.[155][note 39]

Gross examination of coronary arteries

Coronary vessels, with annotated arteries.svg

To find the right and left coronary arteries, look distally to each corresponding aortic valve cusp.

Make longitudinal ((or transverse cuts at 3 mm intervals[156]) through:

  • The right coronary artery.
  • ((The right marginal artery))
  • The left coronary and circumflex artery.
  • The left anterior descending artery.
  • ((The left marginal artery))
  • ((The left diagonal branch))
  • {{Any vessel grafts to the heart}}

Examine for atherosclerosis, stenosis and thrombi

(If the coronary arteries are calcified, sharply dissect them from the heart, without cutting too deeply into the muscle. Fix them in formalin, decalcify them and then cut them at 3 mm intervals.)

Estimate the percentage of any significant stenosis or occlusion.  

The presence of a totally occlusive thrombotic mass confers a diagnosis of likely sudden cardiac death death even in the absence of microscopically visible necrosis.[156]

Weight

Cardiomegaly can be defined as a weight exceeding the 95th percentile of normal individuals, preferably adjusted for weight, size, age and gender.[157][note 40]

Weight of heart versus body.[158][note 40]

Microscopic examination

Myocardium

Look for:

  • Signs of myocardial infarction

If one or more is present, see Autopsy of myocardial infarction

  • (Optionally, also look for:)

Reporting

This is en example report: edit
The heart << has normal weight / is enlarged [[ > 399 g in women and> 449 g in men]] >>, weighing ___ g. ((The epicardium is transparent. There is a moderate amount of subepicardial fat.

Normal configuration (No atrial or ventricular dilation. No ventricular wall thickening) / {{The left ventricle has {{concentric}} hypertrophy, with a wall thickness of ___ mm.}} ((No atrial or ventricular dilation. The right and left auricular appendage is unremarkable. The left ventricular wall thickness is __ cm and the right is ___. The trabeculae carneae are normal ({[Finding-begin}}/ prominent /flattened}}.))
[[A comprehensive report may describe each atrium, valve and ventricle etc. in order of blood flow.]]

(Foramen ovale is closed.) ((The ductus arteriosus is obliterated))
The coronary arteries ((arise in normal position. The coronary ostia are << patent {{partially occluded by arteriosclerotic calcification}}>>. They)) have << no / mild / moderate / severe >> {{and partially calcified}}
arteriosclerosis. They are traced, ((throughout their length by transverse sections)) {{after fixation and decalcification}} <<without significant constrictions.{{ / The lumina of the left anterior descending, right coronary, and left circumflex coronary arteries are _%, _%, and _% narrowed, respectively.}} [[If the degree of stenosis on microscopy sections of coronary arteries only differ slightly from the gross description, preferably write "mild/moderate/severe atherosclerosis consistent with the gross inspection."]] (Gross measurement of coronary artery stenosis is generally more accurate than microscopic measurement, so the former generally has precedence.)

No thrombi in the cardiac atria (including auricles), chambers or coronary arteries.

Chordae tendineae, the endocardium and heart valves are unremarkable. (The endocardium is smooth and shiny. Chordae tendineae are unremarkable. The valves are normal in number, and are thin and fine at the openings.) ((The endocardium is smooth, transparent and free of mural thrombi. The valve leaflets and chordae tendinae are overall delicate, pliable and free of lesion or calcification. <<Its leaflets are thin and pliable / No signs of inflammation>>.
  • The tricuspid valve <is / is not> dilated, measuring _cm in circumference.
  • The pulmonic valve <is / is not> dilated, measuring _cm in circumference. It is composed of <<two / three>> cusps which are discrete and pliable.
  • The mitral valve <is / is not> dilated, measuring _cm in circumference. Its leaflets are thin and pliable {{/ redundant / adherent to each other}}.
  • The aortic valve <is / is not> dilated, measuring _ cm in circumference. It is composed of <<two / three>> cusps which are thin and pliable.

{{The cusps are calcified at the bases / adherent to each other.}} {{The valve displays mild / moderate / severe myxomatous degeneration.}} The epicardium and subepicardium are unremarkable. The papillary muscles are normal {{ / hypertrophied}}))

The myocardium has ((a homogeneous reddish brown color, and)) no signs of <<fresh lesion / ((areas of necrosis or hemorrhage))>> (or scar){{/ streaks of white scar tissue}}.    

Autopsy of myocardial infarction

Autopsy cutting checklist

edit

  • Remove the parietal pericardium
  • Separate the heart from the from lungs by cutting through the major vessels. The pulmonary artery should be cut first and the lumen inspected for any pulmonary embolism.
  • Weigh the heart.
  • Dissect the coronary vessels. More details in section below.  
  • On the right side of the heart, dissect in the direction of blood flow: Superior vena cava > right atrium > tricuspid valve > right ventricle. Look for thromboses or patent foramen ovale.[note 41]
  • Dissect the atrial appendages, to exclude thromboses.
  • Dissect the left ventricle, such as into circumferential slices from the apex to the base.[note 42] Inspect (and measure) the left ventricular wall thickness.
Valve circumferences are measured at the basal ring (bottom in image).
  • (Measure the circumferences of the four valves. Cutoffs for valve dilatation:[159]
  • Mitral valve: circumference greater than 9.9 cm in males and 9.1 cm in females
  • Aortic valve: circumference greater than 8.5 cm in males and 7.9 cm in females
  • Tricuspid valve: circumference greater than 11.8 cm in males and 11.1 cm in females
  • Pulmonic valve: circumference greater than 7.5 cm in males and 7.4 cm in females)

Look for areas of fibrosis ( ) or hemorrhage. Sample tissue from suspected areas, at least in cases where a diagnosis cannot be made from gross examination alone.

Gross processing of coronary arteries

Coronary vessels, with annotated arteries.svg

Make longitudinal (or transverse cuts at 3 mm intervals[156]) through:

  • The right coronary artery.
  • (The right marginal artery)
  • The left coronary and circumflex artery.
  • The left anterior descending artery.
  • (The left marginal artery)
  • (The left diagonal branch)
  • {{Any vessel grafts to the heart}}

Estimate the percentage of any significant stenosis or occlusion.  

The presence of a totally occlusive thrombotic mass confers a diagnosis of likely sudden cardiac death death even in the absence of microscopically visible necrosis.[156]

Microscopy of the myocardium

By individual parameters

Myocardial histologic parameters (HE staining)[156][160] Earliest manifestation[156] Full development[156] Decrease/disappearance[156] Image
Streched/wavy fibres 0.5–4 h[160] Histopathology of myofiber waviness in myocardial infarction.jpg
Coagulative necrosis: cytoplasmic hypereosinophilia 1–3 h 1–3 days; cytoplasmic hypereosinophilia and loss of striations > 3 days: disintegration Histopathology of coagulative necrosis of cardiomyocytes.jpg
Interstitial edema 4–12 h Histopathology of interstitial edema in myocardial infarction.jpg
Coagulative necrosis: ‘nuclear changes’ 12–24 (pyknosis, karyorrhexis) 1–3 days (loss of nuclei) Depends on size of infarction Histopathology of myocardial infarction with loss of nuclei.jpg
Neutrophil infiltration 12–24 h 1–3 days 5–7 days Histopathology of neutrophil infiltration in myocardial infarction.jpg
Neutrophil karyorrhexis 1.5–2 days 3–5 days Histopathology of myocardial infarction with karyorrhexis and few lymphocytes.jpg
Macrophages and lymphocytes 3–5 days 5–10 days (including ‘siderophages’) 10 days to 2 months Histopathology of macrophages and lymphocyte infiltration with early removal of necrotic debris in myocardial infarction.jpg
Vessel/endothelial sprouts* 5–10 days 10 days–4 weeks 4 weeks: disappearance of capillaries; some large dilated vessels persist Histopathology of granulation tissue with formation of microvessels in myocardial infarction.jpg
Fibroblast and young collagen* 5–10 days 2–4 weeks After 4 weeks; depends on size of infarction; Histopathology of fibroblast proliferation and early collagen deposition in myocardial infarction.jpg
Dense fibrosis
Further information: Myocardial fibrosis
4 weeks 2–3 months No Histopathology of dense fibrous scar replacing myocyte loss in myocardial infarction.jpg
  • Some authors summarize the vascular and early fibrotic changes as ‘granulation tissue’, which is maximal at 2–3 weeks

Chronological

Time Gross examination Histopathology
(light microscopy)
0 - 0.5 hours None[note 43] None[note 43]
0.5 – 4 hours None[note 44]
  • Glycogen Depletion, as seen with a PAS Stain
  • Possibly waviness of fibers at border
4 – 12 hours
  • Sometimes dark mottling
  • Initiation of coagulation necrosis
  • Edema
  • Hemorrhage
12 – 24 hours
  • Dark mottling
  • Ongoing coagulation necrosis
  • Karyopyknosis
  • Hypereosinophilia of myocytes
  • Contraction band necrosis in margins
  • Beginning of neutrophil infiltration
1 – 3 days
  • Infarct center becomes yellow-tan
  • Continued coagulation necrosis
  • Loss of nuclei and striations
  • Increased infiltration of neutrophils to interstitium
3 – 7 days
  • Hyperemia at border
  • Softening yellow-tan center
  • Beginning of disintegration of dead muscle fibers
  • Apoptosis of neutrophils
  • Beginning of macrophage removal of dead cells at border
7 – 10 days
  • Maximally soft and yellow-tan
  • Red-tan margins
  • Increased phagocytosis of dead cells at border
  • Beginning of granulation tissue formation at margins
10 – 14 days
  • Red-gray and depressed borders
  • Mature granulation tissue with type I collagen[161]
2 – 8 weeks
  • Gray-white granulation tissue
  • Increased collagen deposition
  • Decreased cellularity
More than 2 months Completed scarring[note 45] Dense collagenous scar formed[note 45]
If not else specified in boxes, then reference is nr [162]

Topography

Classify the topographic distribution of any myocardial infarction, if possible:

Reporting

Example of a normal report:

  • In the myocardium, there is no evidence of fresh lesion. (The myocardium has normal texture and a homogeneous reddish brown color. No inflammation or scarring.)

   

Ruptured intercalated discs

 

Ruptured intercalated discs, in this case regarded as a visual artifact, and was not reported.

Ruptured intercalated discs of myocytes of the heart have two main causes:

  • Microtome processing, thereby being a visual artifact,[163] not needing reporting.
  • Forceful myocardial contraction, at least in case of heart autopsy. This is mainly caused by ventricular fibrillation[164] or electric shock,[165]

If a lab often cause it as a visual artifact, it may be ignored in the report.[notes 1] If not, look for signs indicating forceful myocardial contraction, and thereby the mentioning of the findings in the report. Such signs are:[164][165]

  • Alternating bundles of hypercontracted myocytes with hyperdistended ones.
  • Square-shaped myocardiocyte nuclei.
  • Hyperdistended myocardiocytes with detached sarcomeres, and in proximity of hypercontracted myocardiocytes.

 

Lung autopsy

  Autopsy of the lungs, not including larger pulmonary vessels (instead summarized at Autopsy - Other thorax).

Basic autopsy cutting

In non-forensic Autopsy:

The lungs may be cut after removing the heart through cutting through the major vessels close to it, or by removing each lung by cuts by each lung hilum.
  • Dissect the pulmonary arterial system, from the pulmonary trunk and including at least segmental arteries.
  • Dissect the bronchial tree, at least to segmental bronchi. Check for obstructions.
  • Weigh each lung (possibly first if having cut each lung at the hilus).
  • Make some additional sections through the lung parenchyma. Squeeze at each side to detect any pus and edema.[166]
For context, see Autopsy

Gross evaluation

Gross pathology of miliary "millet seed-like" tuberculosis.
  • A spongy consistency, and watery and frothy liquid being pressed from the parenchyma, indicates simple edema.[167]
  • A spongy consistency and reddish (blood-stained) fluid being pressed from the parenchyma, indicates acute congestion.[167]
  • A brownish or dark reddish color of the fluid pressed from the parenchyma indicates chronic congestion, and may not have a spongy consistency.[167]

Normal weight:

Left Right
Men[147] 112-675g 155-720g
Women[148] 105-515g 101-589g

   

Microscopic evaluation

Look for the most common pathologic lung findings:[168][169]

  • Alveolar fluid.  
  • Vascular congestion, which can usually be seen easiest in the alveolar walls. It indicates left sided heart failure, especially when seen together with alveolar fluid.  
  • Inflammatory cells, where a mild to moderate lymphocytic infiltrate is consistent with with heart failure, while neutrophils indicate pneumonia. pigmented macrophages of the lung may indicate chronic heart failure.
  • Mycobacteria in regions of the world with substantial prevalence
  • Carcinoma  
  • Aspiration: Other foreign contents in airways.  
  • Embolism of pulmonary arteries.

Main diagnoses

  • Left sided heart failure:
If respiratory epithelial shedding is seen, look for vascular leakage, mucus hypersecretion and/or widespread airway narrowing, together indicating asthma death.[171] Otherwise, it is a frequent postmortem change.

Additional potential findings are mentioned in the general Lungs article.

Reporting

Report findings and if they are consistent with already known diagnoses.

Example:

Histopathology of pulmonary congestion and siderophages.jpg
Presence of sideophages indicating chronic heart failure. Prominent vessels, including alveolar capillaries, and a moderate lymphocytic infiltrate, consistent with chronic heart failure or acute decompensation.

   

Kidney autopsy

   

Autopsy cutting

A fine granular surface can be reported as nephrosclerosis, and is associated with arteriosclerosis and glomerulosclerosis.[172]

In non-forensic autopsy, on each side:

  • After evaluating the adrenal gland, dissect the renal fascia and perirenal fat laterally, and make an incision in the renal capsule. The renal capsule can then generally be loosened by hand. Note the surface texture. (Determine the color and consistency of the kidney.)
  • Dissect the kidney in the coronal plane, towards the hilum. Inspect the cut surfaces.

Gross report

edit The kidneys are equally sized / (of normal size, with a total weight of ___ g)((a weight of ___ g on the right side and ___ g on the right)).

Sex Weight, reference range[note 46]
Right kidney Left kidney Total
Men[173] 80–160 g (2.8–5.6 oz) 80–175 g (2.8–6.2 oz) 160-335g (5.6-12.8 oz)
Women[174] 40–175 g (1.4–6.2 oz) 35–190 g (1.2–6.7 oz) 75-365g (2.6-12.9 oz)


(No abnormal adhesions between the kidneys and surrounding fibrous capsules.)
The kidneys have smooth surfaces/ {{<<Finely / Coarsely>> granular brown surface, possibly indicating benign nephrosclerosis. There are a few cysts on the surface containing clear fluid}}. Cut surfaces have well-defined medulla, cortex, and papillae. {{The cortices and/or medullas are narrowed and congested. The papillary portions are intact.}}
The renal pelvis and ureters are unremarkable /( Renal pelvis and ureters have normal calibers, with non-irritated mucosal surfaces and open lumens).    

Microscopic evaluation

Kidney with substantial autolysis, but otherwise being unremarkable.
The lining of a simple cyst, with inconspicuous nuclei. They usually have a single layer of cuboidal, flattened or atrophic epithelium,[175] but this case has a somewhat thicker fibrous layer.

Findings

The main findings to look for:[176]

Glomerular findings

  • Diffuse and/or nodular mesangial deposits:
  • Thrombi

Tubulointerstitial findings

  • Interstitial inflammation
  • Cytologic atypia in the tubular epithelial cells
  • Crystals
  • Atypical or pigmented casts

Vascular findings

  • Thrombi
  • Mural deposition of amorphous material
  • Vasculitis
  • Congestion

Diagnoses

If indicated by findings above:

Diabetic nephropathy

Nodular acellular light purple glomerular matrix deposits, typical of diabetic nephropathy.

For alterations in glomerular matrix and/or cellularity, the most common cause is diabetic nephropathy, and typically presents as glomerular enlargement, mesangial sclerosis, basement membrane thickening and and arteriolar hyalinosis.[176]

Hypertensive nephropathy

Hypertensive nephropathy has two types:

  • Benign hypertensive nephrosclerosis: Characterized by arterial or arteriolar hyalinosis, intimal fibrosis, or medial hypertrophy.[178]
  • Malignant hypertensive nephrosclerosis: Characterized by fibrinoid necrosis (acute stage) or myointimal cell proliferation, usually with an “onion-skinning” appearance (chronic stage).[178]
Hypertensive nephropathy, showing fibrous intimal thickening (arrow), interstitial fibrosis, tubular atrophy with thickened tubular basement membranes.

Report

  • Findings and if they are consistent with already known diagnoses.

   

Brain autopsy

Gross processing

Steps

Sample from the pituitary if it protrudes above the sella turcica.   Brain: edit

  • Weight the brain. Overall normal range (95% prediction interval) is 1100 to 1700 g,[144] +60g for males and -60g for females.[179]
  • Inspect: Grooves indicating herniation? Hemorrhages?
  • Dissect the basilar artery and circle of Willis, either before or after separation from the brain. [[If there is likely a need to demonstrate the case to an additional person later, the arteries of the skull base are preferably dissected after first separating them from the brain.]] Look mainly for thromboses.
  • Separate the brainstem, cerebellum and cerebrum, which may be done by first separating the former two together from the cerebrum.
Normal brain versus in Alzheimer's disease.
  • Slice each part, looking for hemorrhages and/or infarcts.
  • For the cerebrum, cut it into slices about 1 cm thick. It can be done from frontal to occipital, or by starting coronally into two halves at the level of the mammillary bodies and continuing in each direction from there.
  • At least in people aged over 65-75 years of age {{or with suggestive history}}, look for signs of Alzhemier's disease (see picture).
Brain with bacterial meningitis: The dura is retracted to show leptomeninges with edema and multiple small hemorrhagic foci.

Report

edit

The meninges and venous sinuses are unremarkable. ((The skull is unremarkable. The calvarium is opened in the usual manner. The scalp and overlying fascia are not remarkable. The skull is <<normal in thickness {{/ somewhat thickened in the frontal areas}}. The cerebrospinal fluid is clear. The dura and venous sinuses are unremarkable. The leptomeninges are thin, shiny and non-irritated, with no visible bleeding. The superficial blood vessels are not congested. The sulci and gyri are <<normal {{/ flattened}}.

(No visible thrombi. No epidural, subdural or subarachnoid hematoma.)

The brain is symmetrical and weighs ___g. ( The cerebral and cerebellar hemispheres are of equal size, and have a normal weight of ___g. [[Men: 1.180 to 1.620 g. Women: 1.030 to 1.400 g]][180][181]
No signs of herniation (No grooves on the bases of the cerebrum or cerebellum.)

((The cerebral ventricles are of normal size, with normal linings.)) Cut surfaces ((after fixation)) of the cerebrum, cerebellum and brainstem show (normal gray and white parenchyma, and) no ((encephalomalacia, ))(hemorrhages, tumors or other) focal abnormalities. ((The gyral pattern is preserved.))
The basal cerebral arteries << are ordinary / {{have mild / moderate / severe atherosclerosis}}>> without aneurysms or occlusions.  

Microscopy

Tissue selection

Gross pathology of a brain after sectioning, showing a normal brain with the cerebrum cut in coronal sections, and the cerebellum, pons and medulla cut in horizontal sections. Standard sections for microscopic examination are annotated.

(Take samples for microscopy from:

  • Cerebrum:
  • Frontal lobe
  • Hippocampus
  • Thalamus and substantia nigra
  • Cerebellum, including dentate nucleus
  • Basal ganglia
  • Medulla oblongata)

Look for any hemorrhage, tumor, metastatic disease, vasculitis or infarction.

Substantia nigra

Substantia nigra in Parkinson's disease: A. Pars compacta neuron with a Lewy body, extracellular neuromelanin and pigment-laden macrophages. B. Alpha-synuclein-positive Lewy neurit.

In people over about 60 years of age, or in a history of suspected Parkinson's disease, look at the pars compacta for Lewy bodies and any alpha-synuclein-positive neurites, indicating Parkinson's disease.

Hippocampus

In people over about 60 years of age, or in a history of suspected Alzheimer's disease, look for its main signs in the hippocampus:

 

Basal ganglia

A lacunar infarct in the thalamus.

Look for lacunar infarcts, which are most common in the deep nuclei of the brain.[183]

Infarction

Attempt to estimate the age of any infarct. Also look at blood vessels for thrombus or stenosis.

Chronology at early infarction:

  • At first, injured neurons shrink and become eosinophilic, with condensed nuclei. Astrocytes swell (Alzheimer type II cells).[184]
  • After 6 to 8 hours, neutrophils have surrounded cerebral vessels and begin to infiltrate.[185]

A more detailed chronology is as follows:[186]

Finding Appearance
Eosinophilic (red) neurons 6 hours[187] -35 days
Polymorphonuclear leukocytes 1-37 days
Other acute neuronal injuries 1-60 days
Coagulative necrosis 1 day - 5 years
Spongiosis of surrounding tissue 1 day and older
Astrogliosis (gemistocytes) 2 days and older
Neo-vascularization 3 days and older
Hemosiderin pigment 3 days and older
Mononuclear inflammatory cells 3 days–50 years
Macrophages 3 days–50 years
Cavitation 12 days or older

Common normal findings

{{further|

Microscopy report

Example in normal findings:

((Standard sections of the cerebral cortex, basal ganglia, hippocampus, thalamus/substantia nigra, medulla oblongata and cerebellum show)) intact cytoarchitecture. There is no evidence of hemorrhage, tumor, metastatic disease or vasculitis.

 

External link

Female reproductive system:

Cervical biopsy

  This article includes endocervical curettage (ECC).      

Gross processing

Example report:

(Optionally: A. Container is labeled - __. The specimen is received in formalin and consists of ) 1 fragment(s) of pink-tan tissue with a vaguely recognizable mucosal surface. The tissue measures __ cm. (The surgical margin is inked black. The specimen is bisected and entirely submitted for microscopic examination in one cassette.)

Microscopic evaluation

Anatomic/Histologic location

Describe mucosa as squamous (or ectocervical), endocervical (generally mucinous and glandular) or transformation zone mucosa.

Pathologies

edit
Look for cervical dysplasia. It is mainly seen as nuclei with hyperchromasia, coarse chromatin and irregular contours.[190]

 

edit
Other common findings:

Example report

Endocervix, curettings:
Fragments of squamous and endocervical glandular epithelium without significant histopathologic changes.
Negative for dysplasia.

 

Cervical cone

  Unless otherwise specified, the primary focus is any cervical neoplasia.

   

Gross processing

  • Measure length, as well as the transverse and sagittal diameter of the ectocervical surface.[75]
  • Optionally, weight the sample.[75]
  • Note the symmetry of the sample, and the position of the cervical canal.[75]
  • Note whether the circumference is complete. If not, and the directions are indicated on the cone, determine the approximate position of the defect.[75]
  • Cones excised by knife should be inked on the excision surfaces. Those excised by laser do not need inking.[75]

Selection and trimming

Gross preparation of cervical cone.svg
  • If the cone is more than 1 cm long, take transverse slices from the top of the cone and towards the ectocervix, and stop when approximately 1 cm of the ectocervical portion of the cone remains.
  • Cut the portion into radial or sagittal slices. Sagittal slices are made perpendicularly to the portion surface, and should be divided into at least the four quadrants.[note 47][75]

In cases where the cone is small and fragmented, try to orient the preparations and divide them if possible to obtain sagittal slices.[75]   

Microscopic evaluation

Anatomic/Histologic location

Describe mucosa as squamous (or ectocervical), endocervical (generally mucinous and glandular) and/or transformation zone mucosa.

Cervical dysplasia

edit
Look for cervical dysplasia. It is mainly seen as nuclei with hyperchromasia, coarse chromatin and irregular contours.[194]

 


Radicality

Locations of non-radicality should be reported in relation to tissue markings (such as needles), or in terms of quadrants or corresponding to a clock face, based on the patient being in supine position.

Look whether there is normal epithelium on each side of all slices where neoplasia is seen, and when the epithelium is missing in any direction, consider ordering additional serial sections or step sections.

HPV changes

Also look koilocytic changes of human papillomavirus (HPV), with such cells typically displaying:

  • Nuclear enlargement (two to three times normal size).
  • Irregularity of the nuclear membrane contour, creating a wrinkled or raisinoid appearance.
  • A darker than normal staining pattern in the nucleus, known as hyperchromasia.
  • Perinuclear cytoplasmic vacuolization ("nuclear halo").

Other findings

edit
Other common findings:

Microscopy report

If a neoplasia is found, the report should include:[75]

  • The histolopathological type and degree of differentiation
  • Location and extent
  • Radicality
Histopathology of CIN 3.jpg

High-grade squamous intraepithelial lesion (CIN-2), present at 3:00 to 12:00.
All margins of excision are negative for CIN-2.

Example report in a normal case:

Cervix at transformation zone without significant histopathologic changes.
Negative for neoplasia/carcinoma.

   

Endometrial polyp

       

Microscopic evaluation

The main objectives are:

  • Making a diagnosis of endometrioid polyp. An endometrial polyp may be diagnosed in the presence of 2 of the following 3:
  • Thick-walled vessels
  • Collagenous stroma
  • Epithelium on at least 3 sides
  • Look for signs of atypia or malignancy.

Reporting

Most importantly:

  • Benign versus malignant (or presence or absence of atypia.)
  • ((The size of the polyp.))
  • ((The type of epithelium at both the surface and gland coverings.))

Example of a minimal report:

Benign endometrial polyp.

   

Endometrial curettings

   

Gross processing

  • Generally submit all tissue for microscopy, even larger volumes.
  • Look for products of conception if indicated from referral and/or history

Microscopic evaluation

Describe the anatomic/histologic type of epithelium.

Look mainly for:

Anatomic/histologic epithelium type

(Determine the type or phase of the endometrium:) edit

In contrast, endocervical mucosa typically consists of mucinous columnar epithelium and mucinous glands. Evaluate this like a cervical biopsy or cervical cone.

The phases of endometrium through the menstrual cycle:

If you want to specify the phase by day, then it's more accurate to state it as days past ovulation where applicable, since the follicular phase may vary substantially.

Hyperplasia, atypa and/or malignancy

  • Look for signs of atypia or malignancy:

edit

Microscopy report

Example in a normal case:

(Benign endometrium and endocervical mucosa without significant histopathologic changes.) Negative for neoplasia ((or viral cytopathic changes)).

 

Endometrial thickening

     

Hysterectomy sampling

A regular hysterectomy grossing is performed, but with the following sampling:[205]

  • 2 longitudinal sections through ecto/endocervix (1 anterior and 1 posterior)
  • 2 longitudinal sections through upper endocervix/lower uterine segment (1 anterior and 1 posterior), immediately adjacent to the sections taken from the cervix
  • 4 full-thickness representative sections of endomyometrium (2 anterior and 2 posterior)
  • Transversely section the remaining anterior and posterior endomyometrium (~1 cm thick). Submit the entire endometrium from the lower uterine segment to the fundus, maintaining orientation.
  • Submit entire fimbriae (longitudinally sectioned) and 2 representative cross-sections on each side.

Microscopic evaluation

  • Look for signs of atypia or malignancy:

edit

Reporting

Most importantly:

  • Presence or absence of atypia.

   

Hysterectomy

    For a freshly received uterus, generally gross it fresh to include either opening it up (small specimen, no suspected malignancy seen) and/or serial sectioning, in order to let the formalin penetrate it properly. Ensure the endometrium is immersed in the formalin (such as having the serosa oriented upwards).    

Gross processing

Gross examination

For orientation:

  • The round ligament lies anterior to the tubes and ovaries.[208]
  • The peritoneum extends further down along the cervix posteriorly than anteriorly.[209] Its ends bluntly posteriorly and sharply anteriorly.[209]

When received the same day as the surgery, perform the following steps at least to serial sectioning before putting (back) in formalin, preferably with paper towels between slices, so that it fixes properly:[208]

  • (Remove the adnexa.[208] Weigh the uterus without the adnexa.)
  • Perform a general inspection
  • Measure the 3 dimensions, including the cervix. (Also measure the length of the cervix, the maximum diameter of the cervix, and the width of the cervical os.)
  • (Ink the surgical margin of the cervix for orientation, such as black on the posterior side.)
  • Open the uterus by transmural radial cuts on both sides of the uterine cavity.[note 48] The cavity is sometimes be squeezed or rolled around a leiomyoma, and you'll you have to improvise and perhaps go around the leiomyoma to open the cavity properly.
  • Inspect the mucosa. If any polyps:  
    If more extensive tumor, gross as per endometrial cancer
  • Serially section through almost the entire depth of the myometrium at approximately 1 cm intervals, still keeping the specimen together.
  • Measure the thickness of the mucosa and myometrium
  • Inspect the myometrium. If any tumor:  

Gross report

Applicable in bleeding disorders, pain, leiomyoma and endometrial hyperplasia:[208]

Components:[208]

  • (Shape of uterus and adnex)
  • Measurements
  • Mucosa, such as smooth or irregular.
  • (Even the absence of) any polyps.  
  • Mucosal and endometrial thickness.  
  • (Even the absence of) any smooth muscle tumor.  
Example
(A. Labeled - __. The specimen is received in formalin and consists of a resected) uterus with cervix [and bilateral fallopian tubes and ovaries]. The uterus and cervix measure __ ((cm superior to inferior)) x __ ((cm cornu to cornu)) x __ cm ((anterior to posterior,)) and weighs ___ grams. The serosa is [tan-pink and smooth]. The cervix measures ___ cm in diameter and ___ cm in length. The ectocervical mucosa is [tan-pink and smooth] and the cervical os[ is patent] and measures ___ cm in diameter. The specimen is bisected in the coronal plane. The endocervical canal is [patent and displays a tan-pink smooth mucosa]. The endometrial cavity is [triangular] and is lined by[ smooth] endometrium measuring [0.1] cm in average thickness. The myometrium measures up to ___ cm in thickness.[

- It displays __ intramural leiomyomata measuring up to __ cm in greatest diameter.

] The right ovary measures ___ cm and has a [tan-pink and smooth] capsule. Cut sections show [no gross lesions]. The right fallopian tube measures ___ cm in length and ___ cm in average diameter. The serosa [is tan-pink and smooth]. Cut sections reveal a small patent lumen and no gross lesions. The left ovary measures ___ cm and has a [tan-pink and smooth] capsule. Cut sections show [no gross lesions].The left fallopian tube measures ___ cm in length and ___ cm in average diameter. The serosa [is tan-pink and smooth]. Cut sections reveal a small patent lumen and no gross lesions. Representative sections are submitted for microscopic examination in ___ cassettes.

Slices for microscopy

Applicable in bleeding disorders, pain, leiomyoma and endometrial hyperplasia:[208]

Submit:[208][210]

  • One, (two - at 6 and 12 o'clock), ((or four)) cross-sections from any accompanying ectocervix/endocervix (aiming to include the transformation zone). In subtotal extirpation, a cross-section is taken from the lower resection border.
  • ((A transverse slice through the endocervix, possibly divided into two.))
  • Endometrium and myometrium, by one slice from the front and one from the back wall of the corpus.
  • {{Any mucosal parts with macroscopically abnormal appearance, including polyps.}}
  • {{For any area suspicious for malignancy, submit a full cross-section of the uterine wall that includes the serosa. Use multiple contiguous cassettes if needed.}}
  • {{Samples from all smooth muscle tumors >5 cm in diameter.}}  

A specific sampling scheme is used in: Endometrial thickening

See also:

Microscopic evaluation

Look for signs of malignancy:

  • Myometrium tumors:  
  • Polyps:  
  • Endometrial thickening:  

Cervix

edit
Look for cervical dysplasia. It is mainly seen as nuclei with hyperchromasia, coarse chromatin and irregular contours.[211]

 

edit
Other common findings:

Uterine body

(Determine the type or phase of the endometrium:) edit

In contrast, endocervical mucosa typically consists of mucinous columnar epithelium and mucinous glands. Evaluate this like a cervical biopsy or cervical cone.

The phases of endometrium through the menstrual cycle:

If you want to specify the phase by day, then it's more accurate to state it as days past ovulation where applicable, since the follicular phase may vary substantially.

Main pathologic findings

edit

Microscopy report

Examples of reports:

Normal cases
[note 49]
Uterus, cervix, bilateral tubes and ovaries, abdominal hysterectomy and bilateral salpingo-oophorectomy:
  • Benign cervix.
  • Benign atrophic endometrium.
  • Benign ovaries.
  • Benign fallopian tubes.
  • Negative for malignancy.
Microscopy of hysterectomy shows ecto and endocervix without atypia. The glands have columnar epithelium without atypia.

In the uterine cavity, there is endometrial mucosa with ordinary thickness and regularly arranged endometrial glands. (Optionally: Description of likely menstrual phase.) Sharp delimitation between endometrium and myometrium. The myometrium contains no focal changes. No evidence of malignancy.

Endometrial intraepithelial neoplasia
Uterus, cervix, bilateral tubes and ovaries, hysterectomy and bilateral salpingo-oophorectomy:
  • Endometrial intraepithelial neoplasia; entire endometrial/myometrial junction submitted for microscopic exam.
  • Benign lower uterine segment.
  • Benign bilateral tubes and ovaries.

 

Smooth muscle tumor

 

Smooth muscle tumor (in this case leiomyoma).

 

Gross processing

Gross examination

Fibroid locations.

Examine and describe:[208]

  • Location. If in the uterus:
  • Intramural/submucosal/subserosal (see image)
  • (Posterior/anterior/right or left lateral.)
  • Number of tumors, if multiple
  • Size
  • (Presence or absence of any hemorrhage or necrosis.)
  • ((Demarcation))

Selection

In case of hysterectomy, submit pieces from all smooth muscle tumors >5 cm in diameter.[208]

Submit any macroscopically abnormal parts of the tumors (hemorrhagic, necrotic, brittle or softening areas, and areas with blurry delimitation).[208]

Microscopic examination

Distinguish leiomyoma (benign) from leiomyosarcoma (malignant) by looking at the latter's criteria:[216]

  • Marked cellular atypia
  • Mitoses: > 10 mitoses/10 high power fields
  • Necrosis

Diagnosis of conventional leiomyosarcoma requires 2 of these 3 histologic features.[216]

 

Microscopic report

Report:

  • Microscopic findings, including any visible linings
  • Diagnosis or most probable one
  • Any linings or borders.

Example, for a cervical polyp:

Polyp lined by a single layer of columnar epithelium consistent with endometrium. The interior consists of smooth muscles in a whorled pattern. No atypia. The finding is consistent with a pedunculated submucosal leiomyoma.

   

Intrauterine device

 

Gross processing

These are generally just visually described, with no samples for microscopic examination. Example report:

Copper IUD.jpg
T-shaped item with metal-coated arms and stem (Optionally: consistent with an intrauterine device with copper), with attached threads measuring 6.5 cm each.

 

Products of conception

 

 

Gross processing

Look up the gestational age of the pregnancy.

  • Look for fetal tissue (fetus, fetal membranes or chorionic villi). If chorionic villi are found, no lengthy search is needed for other kinds of fetal tissue, just a quick look for obvious ones. Membranous material is less reliable, and may still indicate further sampling. Inspect any found fetal tissue for gross anomalies. If found, submit one piece of the fetus and one piece of the placenta.[219]
  • If fetal parts are not visually found, search for diagnostic placental tissue, which is soft and shaggy or spongy (as opposed to membranous, which is likely to be decidua or blood clots).[219]
  • If no fetal or placental tissue is found, all presented tissue generally needs to be submitted.

Gross report

(Labeled - products of conception.) The specimen (is received <<fresh / in formalin>>) and consists of multiple fragments of soft tan-pink decidua, blood clots and amniotic sac measuring about 5 cc in aggregate. The intact amniotic sac measures 2.3 cm in greatest dimension. Fetal tissue is identified within the amniotic sac, measuring 1.0 cm in crown-rump length. Representative sections are submitted for microscopic examination (in 1 cassette).

Microscopy

The most important is to detect the presence of chorionic villi.

In the absence of chorionic villi, look for implantation site intermediate trophoblasts (ISITs):

  • In the absence of both chorionic villi and ISITs, preferably perform cytokeratin immunostaining of each tissue sample, such as CAM5.2.[220]
  • In the absence of chorionic villi and ISITs even after staining, call the clinician, since there may be an ectopic pregnancy.

Microscopy report

Examples:

Histopathology of chorionic villi at gestational age of 9 weeks.jpg

((Products of conception/fetal tissue:)) Products of conception, including immature chorionic villi, and fetal tissue corresponding to first trimester pregnancy. ((Spontaneous abortion, clinically.))

Histology of implantation site intermediate trophoblasts.jpg

((Products of conception/fetal tissue:)) Fragments of focally necrotic decidua and implantation site, consistent with intrauterine products of conception. Negative for chorionic villi.

 

Fallopian tube

Gross processing

Paratubal cysts can be ignored if incidentally found.

(Look in the history for any intra-fallopian coils (Essure devices).)[note 50]

For sterilization
  • Measure length and average diameter of each tube
  • Serially section at 3-4 mm intervals,[221] or 2-3 mm if suspected malignant (including BRCA mutation).[222] Submit
  • Submit 1 (or 3) circumferential transverse sections. If the specimen is only a segment of the tube of less than <5mm((, ink the surgical cut surfaces and)) submit all tissue.[221]

Example gross report:

(A. Labeled - __. The specimen is received in formalin and consists of) two fimbriated segments of fallopian tube measuring __ cm in length and __ cm in average diameter. On sectioning, each displays a patent lumen. No gross abnormalities are identified. The tubes are unoriented. The specimen is serially cross-sectioned and representative sections are submitted for microscopic examination in two cassettes.

Microscopic examination

Fallopian tubes may be substantially edematous and congested, which can generally be attributed to surgery, in which case it does not need mention in the report.
  • Ensure there is at least one full cross-section from each tube, and take further samples otherwise.
  • Check for patency of the lumen.

Tumor

The most common tumor of the fallopian tubes is adenomatoid tumor:[223]

Reporting

Example of a normal report in sterilization:

(Right and left fallopian tubes, laparoscopic bilateral salpingectomy:)
Complete cross-sections of histologically unremarkable fallopian tubes.

When included in a uterus specimen, normal tubes and ovaries may simply be mentioned as:

Bilateral fallopian tubes and ovaries, unremarkable.
Histopathology of an ectopic pregnancy in a fallopian tube, with chorionic villi and implantation site changes  .

When done for ectopic pregnancy, report any rupture, either from the gross report or from microscopy, for example:

Benign ruptured fallopian tube with ectopic products of conception, including degenerated immature chorionic villi and implantation site with fresh hemorrhage.

   

Ovary

Gross processing

"Long" and "short" axis.[224]

The ovary is cut in the longitudinal plane (through the "long axis").

Ovaries, including those with cysts, are almost never inked.

Gross report

Template:

(A. Labeled - __. The specimen is received in formalin and consists of) an ovary measuring ___. The ovarian capsule is tan-pink and smooth. Cut sections reveal solid, white and whorled parenchyma, and no gross lesions. Representative sections are submitted for microscopic examination in __ cassettes.

Microscopic examination

Signet ring cell carcinoma metastasis to the ovary, also called Krukenberg tumor: Gross pathology (top, cross-section at right) and histopathology at low and high magnification.[225]

Generally look for signet ring cells, which is a major feature of metastatic tumors to the ovary.


Placenta

   

Gross processing

  • Determine the shape of the placenta
  • Look for any accessory lobes
  • Determine the completeness of placental membranes, opacity, color and consistency (slimy/slippery?)
  • Determine the point of rupture from nearest margin
  • Note where the membranes are inserted
  • Examine the umbilical cord
  • Measure the distance between the insertion point and the nearest placental margin
  • Measure the cord length and give proximal and distal diameter. In placental pathology, the proximal umbilical cord refers to the segment closest to the placenta, and distal is the segment closest to the fetus.[note 51]
  • Count the number of vessels away from the insertion
  • Weigh the trimmed disk, after having trimmed away the cord and membranes, and after having removed excess amounts of loose retroplacental blood clots over the maternal surface.
  • Examine the fetal surface (chorionic plate):
  • Note its color
  • Look for any pathologies including granular excrescences, subchorionic fibrin or subamniotic hemorrhage
  • Look at the integrity and extent of the vasculature, including any traumatic damage. Also palpate the vasculature for any thrombosis. If a thrombus is grossly found for a live birth, the baby may have thrombosis, so the finding must immediately be reported to the clinician in care of the baby.
  • Examine the maternal surface (basal plate) for completeness, adherent blood clots, depressions, calcifications and fibrin
  • Take a membrane roll and cord sections, before sectioning the placenta
  • With the fetal surface down on the cutting board, cut the placenta at 1cm intervals so that it can be reconstructed.
  • Palpate the parencyhmal sections for areas of induration.
  • Note the color of the parenchyma and describe any pale areas, cysts, thrombi, increased fibrin, calcifications and infarcts. For possible infarcts, estimate the total amount of infarcted tissue as a percentage of the placental volume. Infarction is clinically significant if it involves at least 5-10% of the placental volume.
Gross pathology of placental disorders.[226]

Tissue selection

  • Distal (toward fetus) membrane roll and cross section of distal cord. It should include the area of rupture.
  • Proximal (toward placenta) membrane roll and cross section of proximal cord ( 2-3 cm from insertion). They should include membranes up to the chorionic plate.

A membrane roll is created by cutting a strip, about 3 cm wide, of membrane, from the rupture site to the placental insertion. Hold the edge with forceps and roll it around the forceps, and then cut a transverse section of the roll.
Cord sections should be no thicker than 4mm.

  • Placental section including fetal surface ( full thickness if possible)
  • Placental section including maternal surface (full thickness if possible)
  • Any lesions or abnormalities

Avoid taking placental sections near the margin

Gross report

Placenta weight by gestational age.

Example in a normal case:

(A. Labeled with patient's name and medical record number. The specimen is received fresh and consists of a) placenta with attached membranes and umbilical cord. The membranes are tan-red( with a marginal insertion. The site of rupture is __ cm from the nearest placental margin. There is no accessory lobe.) The trimmed placental weight is __ gramsTemplate:Comprehensive-begin-Corresponding to the __th percentile for the gestational age)). The placental disc measures __ cm and varies in thickness from __ to __ cm. The umbilical cord is tan-pink and eccentrically inserted(, __ cm from the nearest placental margin, and measures __ cm in length, __ cm in proximal diameter and __ cm in distal diameter.) Cut sections of the cord reveal three blood vessels. The fetal surface is blue-pink, smooth with normal vasculature and << minimal / moderate / major>> subchorionic fibrin deposition. The maternal surface is complete with <<minimal / moderate / major>> physiologic calcifications. Sectioning reveals a red, spongy, homogenous parenchyma without gross lesions. (Representative sections are submitted for microscopic examination in 4 cassettes.)

KEY OF SECTIONS (example):

  • 1- distal membranes and umbilical cord
  • 2- proximal membranes and umbilical cord
  • 3- placental section including fetal surface
  • 4- placental section including maternal surface

Microscopic examination

  • Look for inflammation, especially by the fetal surface in the intervillous spaces and around the fetal blood vessels.[note 52]
  • At least if there is a suspicion of meconium in the amniotic fluid (from clinical history and/or the gross exam), look for the following histopathologic signs of it:[228]

Other relatively common findings

Microscopy report

Generally, also include major gross findings, such as an area of placental abruption.

Example of normal report:

(Placenta, <<vaginal/Caesarean>> delivery:)
Third trimester placenta with term villous histology. Placental weight (__ gm), at __th percentile for gestational age. Membranes without significant histopathologic changes((, negative for chorioamnionitis)). Trivascular umbilical cord, with no significant histopathologic changes((, negative for funisitis)).

 

Vulva

 

Gross processing

Generally as per skin.

Microscopic examination

Histopathology of high-grade squamous intraepithelial lesion (HSIL) of vulva (left in image) with full thickness dysplasia, compared to normal epithelium at right.

Mainly look for squamous vulvar intraepithelial lesions:

  • Low-grade squamous intraepithelial lesion (LSIL):[230]
  • Acanthosis, papillomatosis, and/or atypical koilocytosis in upper layers
  • Usually mild atypia and mitoses, limited to the lower third of stratum spinosum and basale
  • Binucleated epithelial cells
  • High-grade squamous intraepithelial lesion (HSIL):[230]
  • Enlarged atypical nuclei and mitoses involving middle and upper third of the epithelium.
  • Also telling are atypical mitoses and/or extension in hair follicles and skin appendages.

Staging of vulvar cancer

Tumors of the vulva are staged as per the AJCC, 8th Ed:[231]

Primary tumor (T)
TNM FIGO Criteria
TX Primary tumor cannot be assessed
T0 No evidence of a primary tumor
Tisa Carcinoma in situ (preinvasive)
T1a IA Lesions ≤2 cm, confined to the vulva or perineum and with stromal invasion ≤1 mmb
T1b IB Lesions >2 cm or any size with stromal invasion >1 mm, confined to the vulva or perineum
T2 II Tumor of any size with extension to adjacent perineal structures (distal third of the urethra, distal third of the vagina, anal involvement)
T3 IVA Tumor of any size with extension to any of the following proximal two thirds of the urethra, proximal two thirds of the vagina, bladder mucosa, or rectal mucosa or fixed to pelvic bone
Regional lymph nodes (N)
TNM FIGO Criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 1 or 2 regional (inguinofemoral) lymph nodes with the following features (see N1a, N1b)
N1a IIIA 1 or 2 lymph node metastases, each < 5 mm
N1b IIIA 1 regional lymph node metastasis ≥5 mm
N2 Regional (inguinofemoral) lymph nodes with the following features (see N2a, N2b, N2c)
N2a IIIB 3 or more lymph node metastases, each < 5 mm
N2b IIIB 2 or more regional lymph node metastases ≥5 mm
N2c IIIC Regional lymph node metastasis with extracapsular spread
N3 IVA Fixed or ulcerated regional lymph node metastasis
Distant metastasis (M)
TNM FIGO Criteria
M0 No distant metastasis
M1 IVB Distant metastasis (including to pelvic lymph nodes)

 

Male reproductive system

Phimosis

     

Gross processing

Generally sample one or two representative sections in a cassette, in addition to sections of any grossly visible lesions.  

Microscopic evaluation

Look for:

Optionally, note any sclerosis and/or fibrosis.

Reporting

  • Description of objective findings, and any suspected underlying disease.
  • Presence or absence of dysplasia.

   

Vas deferens

 

Gross processing in sterilization

In sterilization:[234]

  • Measure length and diameter.
  • Serially section
  • Submit 2 cross sections measuring 5 mm in length.

Communicate to the histology lab to section the specimen as tubular structures, in order to get proper cross-sections.

Microscopic examination in sterilization

Confirm that there is a complete cross-section from each side. Example images of normal vas deferens:

Report

Example report:

Right and left vas deferens segments, excisions:
Complete cross-sections of vasa deferentia without significant histopathologic changes.

 

Skin

Suspected malignant skin excisions

  Suspected malignant skin excisions:    

Common targets

If directly suspected from the referral, see:

  • Melanoma

Gross processing

Gross examination

Note:

  • Color
  • Well-defined or diffuse border
  • Size
  • Any elevation
Tissue selection
Tissue selection from suspected malignant skin lesions, by lesion size:[8][note 53]
<4 mm 4 - 8 mm 9 - 15 mm
Tissue selection from skin excision with less than 4 mm suspected malignant lesion.png Tissue selection from skin excision with 4-8 mm suspected malignant lesion.png Tissue selection from skin excision with 9-15 mm suspected malignant lesion.png

In table above, each top image shows recommended lines for cutting out slices to be submitted for further processing. Bottom image shows which side of the slice that should be put to microtomy. Dashed lines here mean that either side could be used.  

Microscopic evaluation

If the lesion was pigmented on gross examination, evaluate as a dark skin focality. If not:

Look for atypical cells, possibly by scrolling through the epidermis at intermediate magnification and then through the dermis at a lower magnification. If atypical cells are found, look for:

  • Similarity to squamous cells: See below:

Squamous cell-like skin proliferations: Differential diagnosis

Main differential diagnoses and their characteristics:[236]

General benign imitators of skin malignancy

Further workup of malignant findings

In case of skin cancer, determine whether the peripheral/radial and deep margins are clear, close or continuous.[237][note 56] A close margin has various definitions for different malignancies, but for basal-cell carcinoma and cutaneous squamous cell carcinoma it is defined as being closer than 1 mm from the edge (but yet non-continuous with it),[237][238] but 2-3 mm for melanoma.[239]

Previous biopsy

(At least if there is a known previous biopsy, look for changes that are consistent with a biopsy site, to confirm that it was taken from the excised area.) Such changes in the skin include:

  • Granulation tissue in more fresh biopsies
  • Dense collagen
  • Fibrosis with vertical blood vessels
  • Fibrosis that replaces solar elastosis

Reporting

Preferably see specific article on the condition at hand, if available.

  • Optionally, the presence of a keratinized squamous epithelium.
  • Any abnormalities, generally preceded by location in terms of epidermal, dermal or more specific layers thereof.
  • If malignant:
  • Degree of differentiation
  • Radicality, mainly into either of the following: edit
  • >___ mm (Definitions vary for the distance as per Further workup of malignant findings above): "Clear margins" (or: "Clear margins at over __ mm")((or the exact distance thereof)).))
  • <___ mm but not continuous with edge: "Close margins at __ mm at (location). [[Locations are mainly the deep edge, or the (superior/inferior/medial/lateral) radial edge.]]." Numbers are generally given at an exactness of 0.1 mm.[237]
  • Continuous with margin: "Not radically excised at (location)."
  • Perineural or vascular invasion if present.

 

Basal-cell carcinoma

 

Nodular basal-cell carcinoma.

Basal-cell carcinoma (BCC):    

Gross processing

Gross examination

Note:

  • Color
  • Well-defined or diffuse border
  • Size
  • Any elevation
Tissue selection
Tissue selection from suspected malignant skin lesions, by lesion size:[8][note 57]
<4 mm 4 - 8 mm 9 - 15 mm
Tissue selection from skin excision with less than 4 mm suspected malignant lesion.png Tissue selection from skin excision with 4-8 mm suspected malignant lesion.png Tissue selection from skin excision with 9-15 mm suspected malignant lesion.png

In table above, each top image shows recommended lines for cutting out slices to be submitted for further processing. Bottom image shows which side of the slice that should be put to microtomy. Dashed lines here mean that either side could be used.  

Microscopic evaluation

Broadly consists of determining the following:

  • Whether it is basal-cell carcinoma or a differential diagnosis.
  • Aggressiveness pattern
  • Radicality

Optionally, further subtyping of basal-cell carcinoma can be made.

Characteristics