GUIDELINES FOR THE INITIAL BIOPSY DIAGNOSIS OF CHRONIC IDIOPATHIC INFLAMMATORY BOWEL DISEASE A STRUCTURED APPROACH TO COLORECTAL BIOPSY ASSESSMENT

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1 Guidelines for the Initial Biopsy Diagnosis of Chronic Idiopathic Inflammatory Bowel Disease 1 GUIDELINES FOR THE INITIAL BIOPSY DIAGNOSIS OF CHRONIC IDIOPATHIC INFLAMMATORY BOWEL DISEASE A STRUCTURED APPROACH TO COLORECTAL BIOPSY ASSESSMENT INTRODUCTION These practical notes supplement the Guidelines for the initial biopsy diagnosis of suspected chronic inflammatory bowel disease. The British Society of Gastroenterology Initiative, published in the Journal of Clinical Pathology and circulated to members of the BSG. They are directed at histopathologists assessing colorectal biopsies for suspected intestinal inflammation, and provide a detailed, structured approach to routine biopsy assessment to extract maximum diagnostic information from biopsies. The colorectal mucosa has a limited repertoire of responses to injury, and the similarity of pathological changes in ulcerative colitis, Crohn s disease and other intestinal inflammation causes considerable diagnostic confusion and uncertainty. Effective management, however, depends on accurate clinicopathological classification, and it is hoped by following the scheme adopted here errors can be minimised. The evidencebase, consensus development, clinical and histological principles have been presented in the Guidelines. This supplement draws heavily on detailed descriptions of CIIBD and its pathological mimics by many authors. Extensive references are included in the Guidelines and are not repeated here. The use of references and updating the structured approach through literature searching and critical review should be part of the routine practice of evidencebased pathology. The structured approach provides five questions to be answered, four biopsy compartments to be examined, detailed checklists for answering the questions, and guides to assessment of the answers. The diagnostic value of the various histopathological features to be assessed follows the grading in the Guidelines(* - ***). A STRUCTURED APPROACH TO BIOPSY ASSESSMENT FIVE DIAGNOSTIC QUESTIONS Biopsy decision making should follow the sequence of questions: 1 Is the mucosa normal or inflamed? 2 Are there features of CIIBD? 3 If the features suggest CIIBD, do they support a diagnosis of ulcerative colitis or Crohn s disease? 4 Are there features suggestive of acute infective-type colitis? 5 Do the features represent another form of inflammation? THE FOUR COMPARTMENTS To answer the five questions, the features of diagnostic importance in the four compartments are: MUCOSAL ARCHITECTURE change of surface topography decreased crypt density crypt architectural abnormality (distortion, branching, shortening) LAMINA PROPRIA CELLULARITY increase and altered distribution of cell types usually present granulomas and giant cells

2 2 Guidelines for the Initial Biopsy Diagnosis of Chronic Idiopathic Inflammatory Bowel Disease NEUTROPHIL POLYMORPH INFILTRATION lamina propria crypt epithelium (cryptitis) crypt lumina (crypt abscess) surface epithelium EPITHELIAL ABNORMALITY mucin depletion surface epithelial damage metaplastic change surface intraepithelial lymphocytes apoptosis subepithelial collagen THE CHECKLIST Using structured assessment the questions can be answered through the following checklists: 1 IS THIS MUCOSA NORMAL? normal crypt density*** (more than 6/mm; closely packed) undistorted crypt architecture*** (no crypt distortion; branched crypts less than 1/mm; no crypt shortening in a well-orientated section) flat mucosal surface*** (almost) normal density, distribution and population of lamina propria cells (upper third; superficial/basal 2:1) without granulomas and giant cells*** no neutrophil polymorph infiltration (no more than 1-2 in an occasional crypt)*** intact, columnar, surface epithelium*** normal mucin content of goblet cells** Special problems in diagnosing normality in the four compartments 1a Mucosal architecture Architectural abnormality with a normal lamina propria cell population may result from previous inflammatory damage (eg inactive CIIBD) and mucosal prolapse in the distal rectum. Crypt alteration around lymphoid follicles is acceptable for a normal biopsy. (Fig. 1) 1b Lamina propria cellularity In distinguishing between the normal and minor diffuse transmucosal increase attention should be paid to the basal third and especially to the plasma cells and lymphocytes. Their density should be assessed relative to the upper third. A mild diffuse superficial increase should only be diagnosed in the absence of other changes if the pathologist is confident it is not normal. Discontinuous inflammation may only be detected using multiple levels. Differences between synchronous biopsies should be noted. Epithelioid cell granulomas and giant cells should be specifically sought before reporting normality. 1c Neutrophil polymorph infiltration Neutrophil polymorph infiltration above 1-2 in an occasional crypt equates with active inflammation. 1d Epithelial abnormality Mucin depletion and surface epithelial damage are non-specific indicators of epithelial injury. Surface epithelial lymphocytic infiltration, a thickened subepithelial collagen layer and apoptosis should be sought as specific features of rare forms of inflammation. MAKING AN ASSESSMENT OF NORMALITY Knowledge of the range of appearances of the normal colorectal mucosa and effects of biopsy trauma should allow the pathologist to distinguish between normality and important inflammatory change with reasonable accuracy. When there is doubt over mucosal abnormality and CIIBD is suspected clinically, multiple levels of the biopsy should be examined. In patients with Crohn s disease and in inactive

3 Guidelines for the Initial Biopsy Diagnosis of Chronic Idiopathic Inflammatory Bowel Disease 3 Figure 1 Normal colorectal mucosa with an almost flat surface and straight, parallel crypts extending from immediately above the muscularis mucosa to the surface. The majority of lamina propria cells are situated in the upper third. Figure 2 Ulcerative colitis. (a) There is mild architectural distortion, increase of lamina propria cells and mild metaplastic change of surface epithelium. (b) More marked architectural distortion, increase of lamina propria cells and neutrophil polymorph infiltration. (c,d) Severe changes including marked crypt irregularity and prominent lymphoid aggregates (c) or follicles (d). Figure 3 Crohn s disease. (a,b) Both show mild architectural irregularity, and a mild patchy increase of lamina propria cells. (c) More severe architectural irregularity and patchy increase in lamina propria cellularity. Figure 4 A predominantly superficial increase of lamina propria cells and only minimal architectural distortion in a patient with acute onset diarrhoea and presumed infective type colitis. The patient had a subsequent normal biopsy.

4 4 Guidelines for the Initial Biopsy Diagnosis of Chronic Idiopathic Inflammatory Bowel Disease Figure 5 Infective type colitis. Irregularly dilated crypt abscesses are present but otherwise the crypt architecture is normal. There is a transmucosal increase of lamina propria cells. Figure 6 Pseudomembranous colitis. An early mucosal lesion. Figure 7 Mycobacterium avium - intracellulare infection. Pale histiocytes and multinucleate giant cell formation within the lamina propria. Figure 8 Microscopic colitis of lymphocytic type. There is an increase of lymphocytes within surface epithelium (a), crypt epithelium and lamina propria (b). Figure 9 Microscopic colitis of collagenous type. A dense subepithelial collagen band is present. Figure 10 Mucosal prolapse. There is surface and crypt irregularity and extension of smooth muscle fibres from the muscularis mucosae into the lamina propria. Figure 11 Entamoeba histolytica within inflammatory exudate overlying rectal mucosa. (a) H&E, (b) PAS. Figure 12 Acute graft versus host disease. (a) Focal epithelial cell degeneration, crypt dilation and crypt abscess formation. (b) Apoptosis of crypt epithelium.

5 Guidelines for the Initial Biopsy Diagnosis of Chronic Idiopathic Inflammatory Bowel Disease 5 ulcerative colitis, particularly where there is no macroscopic disease, a colorectal biopsy may appear normal or show only slight variation from normality. Otherwise if the colorectal mucosa is macroscopically and microscopically normal in a patient with current symptoms, clinical investigation will usually be directed towards functional diarrhoea and irritable bowel syndrome. Some rare forms of inflammation (question 5) may show only mild mucosal abnormality and should be excluded before a normal report. 2 ARE THERE FEATURES OF CHRONIC IDIOPATHIC INFLAMMATORY BOWEL DISEASE? If the biopsy is inflamed, the next important diagnostic decision is between CIIBD and infective-type colitis. This is based on identifying architectural and cellular changes of CIIBD: (Figs. 2 & 3) crypt architectural abnormality*** (distortion; branching; shortening) decreased crypt density*** (less than 6/mm; wide spacing) irregular surface*** (irregular; pseudovillous) transmucosal or discontinuous increase in lamina propria cells*** (includes more than 1 lymphoid aggregate/mm) epithelioid granulomas*** surface epithelial flattening*** neutrophil polymorph infiltration** SPECIAL PROBLEMS IN DIAGNOSING CIIBD IN THE FOUR COMPARTMENTS 2a Mucosal architecture Surface irregularity, decreased crypt density, and crypt architectural abnormality are features which strongly suggest CIIBD. These changes may be minimal or absent in active Crohn s disease. Crypt architectural abnormality and reduced crypt numbers are usually marked in established ulcerative colitis although occasionally this is not seen in very early (less than one week)or quiescent disease. Thickening of the muscularis mucosae may be seen in ulcerative colitis. Normal architecture is usual in infective-type colitis but mild crypt distortion may be seen. 2b Lamina Propria Cellularity Changes of lamina propria cellularity depend on the timing of the biopsy in relation to the onset of disease activity. A moderate or severe diffuse transmucosal increase of lamina propria cells is a very strong indicator of CIIBD but this may also be seen occasionally in severe infective-type colitis. A discontinuous increase may be seen in Crohn s disease, resolving ulcerative colitis or infective-type colitis. A prominent lamina propria eosinophilia has been reported in CIIBD and may be more frequent in ulcerative colitis. Although only present in a minority of cases, basal lymphoid aggregates are a feature of CIIBD, and are not seen in infective-type colitis. The presence of basal giant cells is a good marker for CIIBD but is not specific for type. True epithelioid cell granulomas are very strongly suggestive of Crohn s disease. 2c Neutrophil polymorph infiltration The severity of polymorph infiltration in intestinal inflammation is influenced by the timing of the biopsy in relation to onset of an infective episode or a relapse of CIIBD. Interpretation of significant active inflammation demands appropriate clinical information. The severity of neutrophil polymorph infiltration is usually greater in active CIIBD than infective-type colitis if a patient with onset of persistent diarrhoea is not referred for sigmoidoscopy and biopsy until 2-3 weeks after onset. Crypt abscesses are predominantly superficial in infective-type colitis and

6 6 Guidelines for the Initial Biopsy Diagnosis of Chronic Idiopathic Inflammatory Bowel Disease smaller than those seen in chronic inflammatory bowel disease. Focal cryptitis may be seen in Crohn s disease. In the presence of a neutrophil polymorph infiltrate superimposed on other features of CIIBD, pathologists often employ the term active. In ulcerative colitis clinical activity is also related to a severe transmucosal increase in lamina propria cellularity. 2d Epithelial Abnormality Severe mucin depletion is a relatively specific diagnostic feature of ulcerative colitis but is occasionally seen in severe infectivetype colitis. Superficial crypt damage may be prominent in acute ischaemic colitis and pseudomembranous colitis and in its presence CIIBD can usually be excluded. Erosions may occur in infective type colitis and in CIIBD. Flattening of surface epithelium as measured by the ratio of surface epithelial cell height to crypt cell height is a strong discriminant feature for CIIBD. MAKING AN ASSESSMENT OF THE PRESENCE OF CIIBD The most important differentiating features are the architectural abnormalities indicative of CIIBD, which are absent in infection and increased lamina propria cellularity, which is much less marked and more superficial in infective-type colitis than in CIIBD. A combination of architectural, inflammatory and epithelial changes can distinguish between CIIBD, an acute infective-type colitis and other causes of colorectal inflammation in the majority of cases. 3 IF THE FEATURES SUGGEST CIIBD, DO THEY SUPPORT A DIAGNOSIS OF ULCERATIVE COLITIS OR CROHN S DISEASE? The recommended features for separating ulcerative colitis and Crohn s disease are: ULCERATIVE COLITIS TYPE severe crypt architectural distortion*** severe, widespread, decreased crypt density*** frankly villous surface*** heavy, diffuse transmucosal lamina propria cell increase*** severe mucin depletion** CROHN S DISEASE TYPE epithelioid granulomas*** discontinuous crypt distortion*** discontinuous inflammation** focal cryptitis* Special problems in diagnosing ulcerative colitis or Crohn s disease in the four compartments 3a Mucosal architecture In active ulcerative colitis severe surface irregularity, crypt architectural abnormality and decreased crypt density are typical. Surface irregularity, especially with development of a pseudovillous pattern, may be so marked in ulcerative colitis that the ratio of villus height to crypt depth may exceed 1:5:1. Crypt density may be less than 4-5/mm. At these levels the architectural changes are very specific for ulcerative colitis. In Crohn s disease architectural abnormalities are usually less marked, and may be focal. 3b Lamina propria cellularity In active ulcerative colitis architectural changes are accompanied by diffuse transmucosal increase of lamina propria cells and heavy neutrophil polymorph infiltration. A diffuse transmucosal increase of lamina propria cells may be seen also in Crohn s disease. A discontinuous increase or marked variation of chronic inflammatory cell numbers between biopsies is a feature of Crohn s disease. In the resolving phase of ulcerative

7 Guidelines for the Initial Biopsy Diagnosis of Chronic Idiopathic Inflammatory Bowel Disease 7 colitis the increase in lamina propria cellularity may also be discontinuous. A prominent increase of lymphoid follicles with an especially marked persistent increase of lamina propria cellularity may be seen in ulcerative colitis, particularly in distal colitis. In larger biopsies which include submucosa the presence of disproportionate inflammation, with inflammatory cell infiltrate more prominent in submucosa than mucosa, can be a useful indicator of Crohn s disease. Epithelioid cell granulomas, when precisely defined as discrete collections of at least five epithelioid histiocytes, are an important highly specific feature of Crohn s disease although the sensitivity is low in a single biopsy. Submucosal granulomas are a more significant finding than mucosal lesions for the diagnosis of Crohn s disease. It is important to bear in mind other uncommon causes of granuloma formation. 3c Neutrophil polymorph infiltration Neutrophil polymorph infiltration of crypts and/or lamina propria is a feature of any active CIIBD. Although crypt abscess formation is widely believed to be a feature of ulcerative colitis, it is by no means pathognomonic and occurs with significant frequency in Crohn s disease and in many other forms of mucosal damage including infective-type colitis. Cryptitis is more common in ulcerative colitis but is also seen in Crohn s disease. Isolated foci of cryptitis with some associated chronic inflammation but adjacent normal crypts is suggestive of Crohn s disease while in ulcerative colitis cryptitis is usually more widespread. 3d Epithelial abnormality Most epithelial changes are non-specific but widespread epithelial damage is seen more frequently in ulcerative colitis than Crohn s disease. Some degree of mucin depletion is not unusual in any type of colorectal inflammation but severe (almost total) mucin depletion is a useful feature separating ulcerative colitis from Crohn s disease. Surface erosions are more frequent in ulcerative colitis than Crohn s disease. Biopsies from patients with any form of CIIBD may occasionally yield fragments of inflammatory polyps composed of granulation tissue with an ulcerated or reepithelialized surface but it is unreliable to categorise inflammatory bowel disease on fragments of inflammatory polyps. In longstanding ulcerative colitis the surface epithelium may show change resembling metaplastic polyps. MAKING AN ASSESSMENT OF THE TYPE OF CIIBD Differential diagnosis depends mainly on the assessing the severity of architectural abnormality, the density and distribution of lamina propria cellularity and epithelial abnormality. The most marked changes are usually seen in ulcerative colitis. A single biopsy is not sufficient to predict accurately the final definitive diagnosis in up to 30% of cases of ulcerative colitis and up to 60% of cases of Crohn s disease. Final diagnosis depends on an accumulation of clinical, radiological and endoscopic features and examination of sequential biopsies and biopsies from multiple sites. Correlation of biopsy appearances with the clinical duration and activity of disease is essential. A terminal ileal biopsy may be useful if Crohn s disease is suspected. 4 ARE THERE FEATURES SUGGESTIVE OF ACUTE INFECTIVE-TYPE COLITIS? If inflammation is present which is not diagnostic of CIIBD then acute infectivetype colitis and other causes of inflammation have to be considered. Biopsy is important as in up to 60% of cases a causative organism is not identified. The infective types of colitis a pathologist is most likely to encounter are those associ-

8 8 Guidelines for the Initial Biopsy Diagnosis of Chronic Idiopathic Inflammatory Bowel Disease ated with organisms such as Salmonella, Campylobacter, Shigella and certain types of E. coli. However rarer infective causes of inflammation such as those seen in association with immunodeficiency should be considered. Many features classically associated with infective-type colitis are only seen in the early acute phase (within 2 weeks of onset). (Figs. 4 & 5) Some patients may only be investigated after several weeks or months of symptoms. Many of these will show only a slight increase in lamina propria cellularity. The features which should lead to suspicion of an infectivetype colitis are: retention of normal architecture*** superficial increase in lamina propria cellularity*** neutrophil infiltration in early phase** mucin depletion** discontinuous inflammation and focal cryptitis* Special problems in diagnosing infectivetype colitis in the four compartments 4a Mucosal architecture Mucosal architecture is usually normal in acute infective-type colitis although mild crypt dilatation and occasional branched crypts may be seen. Superficial dilated crypts, lined by flattened epithelium, may show a string of pearls appearance when adjacent cystic crypt abscesses are lined up within the same crypt or tend to melt away towards the mucosal surface. Architectural distortion may be seen in some cases of chronic shigellosis. 4b Lamina propria cellularity The lamina propria is oedematous and shows a mixed increase of mononuclear cells which is mainly superficial. In the later stage of resolving infection only a mild superficial increase of plasma cells, lymphocytes and histiocytes may be seen, giving the appearance often called a non-specific proctitis, although this term is unhelpful and should be avoided. 4c Neutrophil polymorph infiltration Foci of neutrophil polymorphs are seen around crypts with associated capillary dilatation and neutrophil polymorph margination in early lesions. Cryptitis and poorly developed crypt abscesses are present, mainly superficially and may be dilated as described above. The crypt abscesses often contain less neutrophil polymorphs than those seen in active CIIBD and the cells may appear to be caught up within thin streams of mucus. 4d Epithelial abnormality Campylobacter colitis and verotoxin producing E. coli colitis may show superficial haemorrhagic necrosis superimposed on diffuse acute inflammation. Superficial mucosal and crypt damage may be marked in pseudomembranous colitis associated with Clostridium difficile infection. In the early stage of pseudomembranous colitis typical volcano-like lesions may be seen. Later, superficial necrosis involving upper crypt epithelium leads to a characteristic appearance of crypt withering with overlying inflammatory slough which may be difficult to distinguish from ischaemic colitis. In some cases however the histological features of Clostridium difficile associated colitis are less marked and may be difficult to distinguish from the more usual infective-type colitis described above. (Fig. 6) MAKING AN ASSESSMENT OF INFECTIVE-TYPE COLITIS Diagnosis of infective-type colitis relies heavily on the absence of features usually seen in CIIBD, especially architectural distortion and prominent increase of cellularity of the lamina propria. However in the first attack of CIIBD it may be difficult to distinguish between in-

9 Guidelines for the Initial Biopsy Diagnosis of Chronic Idiopathic Inflammatory Bowel Disease 9 fective-type colitis and CIIBD, either ulcerative colitis or Crohn s disease. Chronic shigellosis in particular may mimic CIIBD and the granulomatous inflammation of schistosomiasis may be confused with Crohn s disease if characteristic ova are not identified. If there is any doubt over the diagnosis, cases should be followed up. CIIBD may on occasion be triggered by an infective episode. 5 DO THE FEATURES REPRESENT ANOTHER FORM OF INFLAMMATION? The search for rarer types of inflammation may be indicated by a clinical history of: immunosuppression, bone-marrow transplantation, HIV infection, anal-receptive sexual intercourse, diversion of the faecal stream, irradiation and drugs, particularly NSAIDs, gold, penicillamine, cytotoxic drugs and antibiotics. AIDS or other forms of immunosuppression should provoke particularly careful search for features of infection by Mycobacterium aviumintracellulare (Fig. 7), CMV, Herpes simplex virus, Cryptosporidia Treponema pallidum, Chlamydia trachomatis and Entamoeba, amongst others. The various subtypes of microscopic colitis should be considered in a biopsy showing mild inflammatory changes (Figs. 8 & 9). SPECIAL PROBLEMS IN DIAGNOSING OTHER INFLAMMATION IN THE FOUR COMPARTMENTS 5a Mucosal architecture Architectural change is generally less important than other changes in the diagnosis of rarer types of colitis. Diversion colitis may show crypt architectural distortion, decreased crypt density and even severe mucosal atrophy. Crypt architectural change accompanied by varying degrees of inflammatory infiltrate may be seen in colitis associated with diverticular disease and may mimic Crohn s disease or ulcerative colitis. Crypt architectural distortion is seen in mucosal prolapse, accompanied by extension of smooth muscle from the muscularis mucosae into the lamina propria and variable inflammatory cell infiltration (Fig. 10). 5b Lamina propria cellularity Although increased eosinophil numbers in the lamina propria may be seen in CIIBD and parasitic infection, if eosinophils represent the major increased population and there is an appropriate clinical history then the possibility of eosinophilic gastroenteritis should be considered. An increase of lamina propria cellularity, particularly of lymphocytes, may be seen with non-steroidal anti-inflammatory drug (NSAID) use. Diversion colitis may be associated with changes similar to CIIBD, including dense lymphocytic infiltration and lymphoid follicle and granuloma formation(fig. 11). If diversion of the faecal stream has been undertaken in the setting of CIIBD, it may be particularly difficult to determine to what extent the changes are due to diversion or to the CIIBD. Causes of granuloma formation, other than Crohn s disease, include infections such as tuberculosis, atypical mycobacterial infection, Chlamydia, Yersinia, schistosomiasis and fungi as well as foreign bodies. Extremely rare granulomas due to colonic sarcoidosis have been described. Inflammatory processes other than Crohn s disease where cryptolysis occurs may show pericryptal histiocytic reaction mimicking granuloma formation; this feature should be interpreted with caution and isolated discrete granulomas should be sought. Fibrosis of the lamina propria and/or haemosiderin deposition may be seen in chronic ischaemic colitis and may be accompanied by crypt distortion in areas of regeneration. Fibrosis of the lamina propria and fea-

10 10 Guidelines for the Initial Biopsy Diagnosis of Chronic Idiopathic Inflammatory Bowel Disease tures resembling mucosal prolapse may be seen in diverticular colitis. 5c Neutrophil polymorph infiltration Neutrophil polymorph infiltration of lamina propria and crypts may accompany the changes of diversion colitis and diverticular colitis. Polymorphs may accompany rarer types of infection such as those seen in association with anal-receptive sexual intercourse and in patients with HIV or AIDS. The histological features of amoebic colitis may show a close similarity to CIIBD, in particular, the acute phase of ulcerative colitis. A search for amoebae should be made wherever surface purulent material is seen. Amoebae are not difficult to find once the possibility has been entertained in an ulcerated biopsy. They may be confused with macrophages, especially those containing red blood cells, but critical assessment of morphology and comparison with a section of a known case is helpful for confirmation. PAS staining is also helpful for identification of amoebae (Fig. 12). 5d Epithelial abnormality Some mucin depletion is seen in all forms of CIIBD and in resolving infection, HIV enteropathy and ischaemia. Lymphocytic colitis is part of the spectrum of microscopic colitis in which there is a marked increase of intraepithelial lymphocytes. This can usually be appreciated without direct counting and is often associated with epithelial flattening and a normal mucosal architecture. Involvement of the large bowel in the field of therapeutic irradiation may result in cytological atypia of crypt epithelium. Apoptosis of crypt epithelium together with increased cellularity, particularly increased lymphocytes in lamina propria and epithelium, is seen in NSAID use. Apoptosis may also be seen with cytotoxic drugs and laxatives as well as in HIV, AIDS and graft-versus-host disease (Fig. 13). The subepithelial changes of collagenous colitis may be more pronounced in the proximal colon and diagnosis may not be made in biopsies from the distal colon or rectum. In acute ischaemic colitis there is epithelial necrosis which predominantly involves surface epithelium and the superficial aspect of the mucosa but in severe cases there may be full thickness mucosal necrosis. The necrosis is of coagulative type with marked destruction but the outline of crypts may still be visible. The presence of necrotic mucosa together with acute inflammatory exudate and bacteria may give rise to pseudomembrane formation, mimicking the appearance of Clostridium difficile associated pseudomembranous colitis. MAKING AN ASSESSMENT Inflammation which is inconsistent with CIIBD or typical infective-type colitis should lead to consideration of other causes. Detailed clinical information and histological assessment are necessary to identify these. In all biopsies, particularly where histopathological changes are not in keeping with the clinical features, a particularly careful search should be made for granulomas, excess eosinophils, lamina propria fibrosis, amoebae, intraepithelial lymphocytes, apoptosis and excess subepithelial collagen. REACHING AN OPINION ON DIAGNOSIS AND WRITING A REPORT The use of the reporting proforma may assist in ensuring that the pathologist collects all relevant information, and provides an alternative to the free descriptive part of a report. The pathologist should then be armed with enough information to place the biopsy in a clinically useful diagnostic category. Although even minor changes may be significant, it is important to be aware of minor changes acceptable for normality and biopsies that are normal should be reported as such. If a biopsy is abnormal, exact classification of the disease process should not be made without full clinical information.

11 Guidelines for the Initial Biopsy Diagnosis of Chronic Idiopathic Inflammatory Bowel Disease 11 Terms such as non-specific proctitis/ colitis mild proctitis or non-specific inflammation are confusing in relation to clinical decisions and have been used inappropriately to hide the pathologistis inability to assess the diagnostic probability or judge the limits of the normal range. The categories in the recommended reporting system relate to clinically important diagnostic groups. The recommended categories are: NORMAL: directs investigation to functional causes of diarrhoea, but Crohn s disease is not excluded. INFLAMMATION UNCLASSIFIED: definite inflammation but insufficient features to categorise. CHRONIC IDIOPATHIC INFLAMMATORY BOWEL DISEASE: ULCERATIVE COLITIS TYPE CROHN S DISEASE TYPE INDETERMINATE (not possible to make a distinction) INFECTIVE-TYPE COLITIS OTHER COLITIS (specified) A probability assessment should be given using the standard terms: suggestive: pathologist favours the diagnosis but is not certain highly suggestive: pathologist has a definite opinion but full clinical follow-up and/ or correlation not available. Regular clinicopathological discussion of cases of suspected CIIBD is to be encouraged and a final diagnosis should not be made without the necessary supplementary information. AUTHORSHIP These guidelines were prepared by members of the British Society of Gastroenterology and are a working summary based on the Guidelines published in J Clin Pathol 1997;50: The authors wish to thank Anne Kane and David Hughes for photographic assistance. We plan that this guideline will be revised from time to time. Comments or suggestions should be sent to: Clinical Services and Standards Committee, British Society of Gastroenterology, 3 St Andrews Place, Regent s Park, London NW1 4LB.