Abstract
Gastrointestinal biopsies comprise a substantial minority of the workload of most histopathology departments. Assessment of IBD, whether new or longstanding, is among the more challenging tasks that face pathologists. Good quality histopathology reports enhance patient management by refining the diagnosis and classification of IBD and by documenting clearly the extent of disease, the degree of activity, the degree of dysplasia, and any complications such as CMV. In order to produce a good quality report, the pathologist should adopt both a systematic approach to assessment and a well-defined structure for the body and conclusion of the report. Adherence to a similar approach and structure by histopathologists working in different centres could help to improve consistency of reporting and allow better comparison between reports issued at different times and/or in different centres. The use of datasets and a simple proforma for IBD pathology reporting should also increase the degree of conformity between centres.
Introduction
Gastrointestinal (GI) biopsies comprise a substantial minority of the workload of most histopathology departments. Assessment and description of inflammatory bowel disease (IBD) biopsies can be challenging. In addition, the IBD pathology workload in many parts of the world is increasing, for several reasons:
There has been a rise in the prevalence of IBD over several decades in Western countries, although the rate of rise is slowing. A steady increase continues in Eastern Europe, Asia, Africa, and South America.1, 2
Histology plays an ever more important role in diagnosis, classification, and management of IBD.
There is a general move towards specialisation in GI pathology and other areas, together with an improvement in our understanding of IBD and of its histological features. As a result, there may be more focus by specialist pathologists on accurate reporting of IBD and on interacting with clinicians. In turn, these changes may encourage clinicians to expect more from the pathologist than in the past.
High-quality pathology reports enhance patient management by refining the diagnosis and classification of IBD and documenting the extent of disease, degree of activity, grade of dysplasia, and other complications such as cytomegalovirus (CMV) infection. Additional newer roles of histopathology include prediction of the response to therapy, assessment of response to therapy, prediction of outcome, and estimation of the risk of future dysplasia. The ideal report comprises a comprehensive and accurate description of the features and a clear interpretation of the biopsy findings in the light of the clinical picture. Adoption of a systematic approach to biopsy assessment and the use of consistent structures for the body and the conclusion of the IBD report should help to simplify the task and to optimise the value of the exercise.
Guidelines and Proformas
Guidelines for IBD reporting are available, but proformas and datasets are sparse. Compliance with reporting guidelines by all pathologists could help to improve consistency of reporting between centres and should facilitate comparison between reports on the same patient produced at different times and/or by different pathologists. Datasets and simple proformas for IBD pathology reporting could also help increase the degree of conformity between pathologists as regards terminology, report structure, interpretation, and style.
Biopsy Requirements and Clinicopathological Correlation
Biopsy Requirements (Practice Points 24.1)
Biopsy samples should have a label that states clearly the anatomical site of origin. Endoscopists should avoid placing all biopsies from various sites in the same specimen container without identifying information. This is especially important at initial diagnosis of IBD, when the assessment of distribution can be crucial for subclassification as ulcerative colitis (UC) or Crohn’s disease.
Precise descriptions of the anatomical site are advisable. Specifically, endoscopists should avoid the ambiguous term ‘rectosigmoid’, which can mean rectosigmoid junction, rectum + sigmoid, or an area somewhere near the rectosigmoid junction. This is particularly important when classification depends partly on the presence or absence of rectal sparing, e.g. UC versus diverticular colitis or UC versus Crohn’s disease (see Chapters 21 and 22).
Correct orientation and adequate size and depth of biopsies are important for accurate diagnosis, because architectural changes and basal plasmacytosis are discriminant between IBD and non-IBD and between UC and Crohn’s disease. Poorly orientated or superficial biopsies may not allow accurate assessment of these features. Laboratory staff should attempt to orientate biopsies correctly, although this is sometimes difficult. Orientation by endoscopists prior to submission may also be helpful, but its effectiveness depends on the skill of the operators and various other factors. Deeper levels from the sections often improve orientation and/or biopsy depth and may provide other useful additional information.
Clinicopathological Correlation
Before assessing GI mucosal biopsies, histopathologists should ensure that they are familiar with the reasons for each type of procedure. Nevertheless, the clinician is ultimately responsible for stating the indication and for including the relevant history. When necessary, the pathologist should not be afraid to report that the clinical details are insufficient for meaningful interpretation. Depending on the local infrastructure, an electronic patient record may help supply missing clinical information and may be worth consulting despite the need for additional time to do so.
The endoscopy report can act as a request form.3 It usually provides comprehensive information about the macroscopic findings, and often includes the endoscopist’s interpretation. Indeed, some guidelines strongly recommend its use as the request form. Depending on the format, the endoscopy report may also list the indication(s) for the procedure and may state whether the patient has suspected new IBD or longstanding/treated IBD. If these important details are absent, the clinician should submit them as additional information. Unfortunately, some endoscopy reporting software has serious deficiencies. For example, at least one endoscopy reporting system offers the incorrect option of ‘indeterminate colitis’, and gastroenterologists sometimes use it to describe the macroscopic appearances, even though it is a label that is not applicable to endoscopy.4, 5
Biopsies from a sufficient number of sites
Ileum
At least four additional sites in the large bowel
Especially important for new disease
Adequate number of biopsy fragments from each site
At least two from each site, and preferably more
Site of origin of each biopsy should be clear
Avoid the imprecise label ‘rectosigmoid’
Biopsy quality
Full mucosal thickness, including muscularis mucosae
Correct orientation
Deeper levels may improve orientation and/or depth and are often useful
Good clinical details
Endoscopy form is useful, but sometimes omits details
Electronic patient record may help
If the details are inadequate, the pathologist should state this
Necessary Clinical Information
Several items are necessary or important for interpretation. Table 24.1 lists a selection.
| Detail | Circumstances | Importance | |
|---|---|---|---|
| New IBD | Treated IBD | ||
| New or treated disease | Essential | ||
| Indications for the procedure |
|
| Important |
| Established IBD history | N/A |
| Essential |
| Medications |
|
| Important |
| Symptom duration | Days/weeks/months | N/A | Important in new disease |
| Smoking/family history | N/A | May be useful | |
| Tests for infection | Stool culture | CMV tests | Important |
| Symptoms | Diarrhoea / rectal bleeding / abdominal pain / perianal lesions | Important, especially in new disease | |
| Medical history | Surgery to bowel / other surgery / diverticula / radiotherapy | Essential | |
| Endoscopic appearances |
| Essential | |
| Imaging findings | Small bowel disease, e.g. strictures | Essential | |
CMV, cytomegalovirus; IBD, inflammatory bowel disease; NSAID, non-steroidal anti-inflammatory drug; UC, ulcerative colitis.
Disease duration is a vital item of information. The pathologist needs to know if the patient is presenting for the first time or has established IBD, for two reasons in particular.
1. Chronicity and/or treatment may have a profound effect on the histology and distribution of IBD, and particularly on the distribution of UC between and within anatomical sites. Therefore, the distribution of changes is less useful in treated than in new IBD for the discrimination between UC and Crohn’s disease.
2. The reasons for biopsy are not identical. In new disease, the priorities are the diagnosis and subclassification of IBD. In established IBD the detection or exclusion of dysplasia and of other complications such as CMV infection are higher priorities than they are in new disease. Confirmation or modification of any previous diagnosis is also useful but is often a lower priority than at initial presentation.
In new disease, the duration of symptoms is an important item of information because very early IBD (i.e. in patients with symptoms for <6 weeks) may not show the typical microscopic changes. Architectural changes typically take many weeks or even several months to develop (see Chapter 21).
In treated, longstanding IBD, several items of clinical information are important, including previous diagnosis, the extent of disease at previous presentations, and the duration of disease. Extent and duration have an association with the risk of dysplasia.
Endoscopic findings should always be available to the pathologist examining IBD biopsies. The details should include distribution of disease, endoscopic grading of activity, evidence of previous surgery, the presence and extent of diverticula, the nature and site of any other focal lesions, and the endoscopist’s interpretation of the findings. The exact site of each biopsy often appears on the endoscopy form. This may be useful when comparing histology with macroscopic findings, e.g. when polyps or other focal lesions are present, and may be helpful if the labelling of biopsy containers is not clear.
Several conditions can mimic new or established IBD. These include diverticular disease, diversion proctocolitis, and radiation colitis (see Chapter 22). If clinical information is absent or incomplete, there is a higher risk of misdiagnosis of these entities as IBD. Pathologists should always consider the possibility of an alternative diagnosis, especially if clinical details are scanty. Of course, endoscopists do not always know the full clinical picture. For example, they may not notice subtle diverticula or they (or even the patient) may be unaware of relevant information such as previous radiation therapy or undiagnosed HIV infection.
Assessment of Biopsies
Initially, a checklist of features is worth considering. Table 24.2 is a suggestion.
Table 24.2 Checklist of main histological features in a colorectal biopsy for inflammatory bowel disease
| Category | Subcategory | Feature | Comments |
|---|---|---|---|
| Quality of biopsy | Adequacy |
| Need at least two from each site |
| Orientation and depth | Full mucosal thickness with surface epithelium and muscularis mucosae | Twists or bends can distort architecture | |
| Lumen | Microorganisms | Parasites, e.g. amoebae | In differential diagnosis of IBD |
| Exudate | Pseudomembrane | ||
| Architecture | Crypts | Crypt distortion | Branching, loss of parallelism, dilatation, angulation |
| Crypt atrophy | Shortening and wider spacing | ||
| Mucosal surface | Smooth or villiform | ||
| Lamina propria | Chronic inflammation | Plasma cells |
|
| Lymphocytes | Dense lymphocytic/lymphoplasmacytic infiltrate | ||
| Lymphoid aggregates | Increased number/size (subjective) | ||
| Granulomas |
| ||
| Acute inflammation | Does not necessarily equate with activity | ||
| Subepithelial collagen | Increased thickness | >20 μm for collagenous colitis | |
| Fibrosis | Note the intra-biopsy distribution if present | ||
| Smooth muscle fibres | |||
| Blood vessels | Amyloid/vasculitis | Congo red to confirm amyloid | |
| Microorganisms | CMV inclusions |
| |
| Epithelium | Acute inflammation |
| These features represent activity if superimposed on chronic changes |
| Paneth cells | Paneth cell metaplasia/increase in number of Paneth cells | May occur in normal, especially if proximal to splenic flexure | |
| Mucin | Mucin depletion | None/mild/moderate/severe | |
| Apoptosis | No. of crypt epithelial apoptoses | ||
| Nuclear features | Dysplasia | Grade as low grade or high grade | |
| Regenerative/reactive atypia | ‘Indefinite for dysplasia’ if atypia is unclassifiable | ||
| Distribution | Architectural changes | Within and between sites | |
| Chronic inflammation | Within and between sites | ||
| Acute inflammation | Severity at each site |
IBD, inflammatory bowel disease.
A systematic approach to the microscopic assessment of biopsies is advisable. Table 24.3 is a suggestion. In addition, the pathologist can pose a series of questions. Figure 24.1 shows an example as a flow chart. In practice, this stepwise process is not always possible or appropriate. However, it represents a starting point or a foundation and, together with a checklist of features, it can assist with the production of an accurate and useful report.
Table 24.3 ‘PAID’ scheme for summarising inflammatory bowel disease biopsy histology
PATTERN Recorded as text; no code
| ACTIVITY | ||
|---|---|---|
| Grade (at each site) | Criteriaa | Code |
| None | No intraepithelial neutrophils, erosions, or ulcers | A0 |
| Mild | Cryptitis in up to 25% of crypts / | A1 |
| crypt abscesses in up to 10% of crypts / both | ||
| Moderate | Cryptitis in>25% of crypts / | A2 |
| crypt abscesses in>10% of crypts / | ||
| sparse small foci of surface erosion / combinations | ||
| Severe | Ulceration or multiple foci of erosion | A3 |
| INTERPRETATION | ||
| IBD – probabilityb | Comment | Code |
| IBD definite / very likely | Histology is of IBD or is highly suggestive/supportive of IBD Subcategorise as below | IBD-DVL |
| IBD more likely than other causes | Histology is more likely to be IBD than other causes but is not convincing Subcategorisation may be inappropriate | IBD-F |
| No definite evidence of IBD | IBD-0 | |
| Subcategory of IBDb | ||
| UC definite / very likely | Histology is of UC, or strongly favours UC over CD | UC-DVL |
| UC more likely than CD | Histology does not distinguish, but favours UC over CD | UC-F |
| IBD unclassified | Histology does not discriminate between UC and CD | IBDU |
| CD more likely than UC | Histology does not distinguish, but favours CD over UC | CD-F |
| CD definite / very likely | Histology is of CD, or strongly favours CD over UC | CD-DVL |
| DYSPLASIA | ||
| Grade | Comment | Code |
| No dysplasia | D0 | |
| Low-grade dysplasia | Specify site(s), and number of biopsies involved | DL |
| High-grade dysplasia | Specify site(s), and number of biopsies involved | DH |
| Indefinite for dysplasia | Unclassifiable atypia | DI |
CD, Crohn’s disease; DVL, definite or very likely; F, favoured; UC, ulcerative colitis.
Modified from Feakins RM and BSG. J Clin Pathol. 2013;66:1005–26.4
