Inflammatory bowel disease: The surgical pathology of crohn's disease and ulcerative colitis

Ulcerative colitis and granulomatous colitis are distinct entities, but up to 10 percent of colectoiny specimens remain unclassified. Ulcerative colitis is liriniarily a inucosal disease, and other changes appear to be secondary to this process. By contrast, Crolin's disease, or granulomatous colitis, involves the whole thickness of the bowel wall. About 20 per cent of the cases of Crolin's disease involve the small and large bowel, while another 20 per cent are restricted to the large bowel. Since grantllonlatous colitis is a patchy disease, and many, of the changes are deep within the bowel wall, rectal biopsy may not be as lielpful as in ulcerative colitis. Fully developed granulomas are present in only a small minority of cases, and a diagnostic report of granulomatous colitis may be given in the absence of granulomas. In biopsy material, the differentiation of Inflaninlatory bowel disease from ischenlic colitis and psetidomenlbraliotis colitis may be difficult. In the absence of specific demonstration of an organism it may also be impossible on rectal biopsy to distinguish amebic or bacillary, dysentery from ulcerative colitis. Even by colectomy, 29 of 300 specimens were sufficiently atypical so as not to warrant a label of Crolin's disease or ulcerative colitis. Cancer of the colon, which is comnion in ulcerative colitis, is rare in Crolin's disease, but may also represent a definite complication in the latter. Immunologic studies are still confusing, but it is suggested that patients with ulcerative colitis and Crolin's disease may have a state of altered immunologic reactivity.     

Diagnostic difficulty arising from rectal recovery in ulcerative colitis.

AIMS: To ascertain whether the dogma that a normal rectal biopsy precludes a diagnosis of ulcerative colitis is correct. METHODS: Rectal biopsy specimens from a prospective group of 24 asymptomatic patients, with an established diagnosis of ulcerative colitis, were examined in a blinded study alongside 10 normal rectal biopsy specimens from an age and sex matched patient cohort without ulcerative colitis. Each biopsy specimen was assessed by three pathologists and ascribed to one of four categories: normal; borderline abnormality (one or more minor nonspecific abnormalities which, when combined, did not fulfil the minimal acceptable criteria for a diagnosis of ulcerative colitis); minimal features of chronic ulcerative colitis; and unequivocal ulcerative colitis. RESULTS: Two patients with ulcerative colitis had normal biopsy specimens; nine specimens were categorised as borderline abnormality, one as showing the minimal changes of chronic ulcerative colitis, and 12 as having the typical changes of chronic ulcerative colitis. Thus, 11 (46%) of the 24 patients had a rectal biopsy specimen that was devoid of the acceptable attributes on which a diagnosis is established, despite a confident previous diagnosis. Ten of these 11 cases had disease limited to the rectum. Review of all previous histological biopsy specimens (n = 164) and clinical data, including drug treatment, failed to identify any attributes that might be prognostic markers for future rectal mucosal healing. CONCLUSIONS: A normal rectal biopsy specimen, though uncommon, may occur in longstanding colitis. Moreover, in 46% of these asymptomatic but established cases the degree of healing may preclude a diagnosis of ulcerative colitis without comprehensive clinical and radiological details. Pathologists need to be aware of this minimal end of the spectrum of disease.     

What is colitis? Statistical approach to distinguishing clinically important inflammatory change in rectal biopsy specimens.

Measurements of mucosal dimension, architecture, and cell counts in both lamina propria and epithelium were made on rectal biopsy specimens from 20 patients with irritable bowel syndrome ("normal" controls); 54 patients with ulcerative colitis, Crohn's disease, and non-specific proctitis; eight patients with small bowel Crohn's disease; and 34 in whom the rectal biopsy specimen was not diagnostic. Discriminant analysis was applied to multiple variables based on the measurements, and three variables were identified as of high predictive value. The most powerful discriminant was increased lamina propria cellularity in all forms of chronic colitis. The ratios of surface length to mucosal length and of surface epithelial height to crypt epithelial height also emerged as discriminants. Chronic inflammatory bowel disease was distinguished from normal in 95% of cases with a definite pathological diagnosis, and 85% of borderline cases were correctly classified as either normal or inflammatory when judged by the final diagnosis after follow up. This study provides a basis for automated diagnosis of rectal biopsy specimens and provides objectively validated criteria which can also be applied in routine histological diagnosis.     

Mucin depletion in inflammatory bowel disease.

The mucin and gland content of 26 rectal biopsy specimens--five normal specimens, 10 from patients with ulcerative colitis, and 11 from patients with Crohn's disease--were measured using a Quantimet image analyser. There was significantly less mucin in the groups with ulcerative colitis compared with either those with Crohn's disease or the normal controls. The difference in the gland content between the groups with ulcerative colitis and Crohn's disease and between the group with Crohn's disease and the normal controls did not reach significance. The results suggest that it is worth while assessing the mucin content of rectal biopsy specimens from patients with inflammatory bowel disease. In routine practice this assessment can be made by eye using a suitably stained section.     

Intraepithelial and lamina propria leucocyte subsets in inflammatory bowel disease: an immunohistochemical study of colon and rectal biopsy specimens.

AIMS--To gain new insights into the pathogenesis and differential diagnosis of ulcerative colitis and colonic Crohn's disease. METHODS--Immunohistochemistry for different leucocyte subsets was performed in biopsy specimens of the sigmoid colon and rectum from 55 patients with inflammatory bowel disease and 11 healthy controls. RESULTS--Colonic biopsy specimens from patients with active ulcerative colitis had significantly higher numbers of CD45+ and CD3+ leucocytes compared with those from patients with inactive disease, and higher numbers of total leucocytes and macrophages than those from patients with Crohn's disease. Rectal biopsy specimens from patients with Crohn's disease had greater numbers of intraepithelial leucocytes (CD45, CD3 and CD8 cells) than specimens from patients with active or inactive ulcerative colitis, or from healthy controls. CONCLUSIONS--Because of the phenotypic differences in the inflammatory infiltrate in the mucosa from the sigmoid colon and the rectum, the segment of the intestine to be biopsied should be specified. Assessment of the leucocytic component of the intraepithelial infiltrate in rectal biopsy specimens was more useful than examination of colonic biopsy specimens in the differential diagnosis of ulcerative colitis and Crohn's disease.     

Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohn's disease from ulcerative colitis

AIMS: To determine whether the presence and location of giant cells or granulomas in relation to crypts distinguishes between ulcerative colitis and Crohn's disease. METHODS AND RESULTS: Twenty-nine large bowel mucosal biopsy specimens showing giant cells and/or granulomas in a background more typical of ulcerative colitis than Crohn's disease were collected between 1986 and 1996. Each was subject to detailed independent analysis by three histopathologists. Follow-up of the cases was by examination of all previous and subsequent gastrointestinal surgical or biopsy material and by scrutiny of the clinical notes by a gastroenterologist. On the basis of the accumulated histological data 10 of these 29 cases were accorded the diagnosis of ulcerative colitis. In nine of these 10 cases the clinical diagnosis, where known, was in keeping with this and all nine contained only crypt-associated giant cells and/or granulomas. The tenth case contained a solitary free-standing granuloma and clinically the patient had perianal disease, suggesting that the true diagnosis was Crohn's disease. CONCLUSIONS: Isolated giant cells and well-defined epithelioid granulomas distant from crypts do not, as a rule, occur in ulcerative colitis, and hence their presence in a colonoscopic biopsy showing features of chronic inflammatory bowel disease is a strong pointer towards the diagnosis of Crohn's disease. Crypt-associated giant cells and granulomas can occur in ulcerative colitis and in themselves are unreliable features for the discrimination between Crohn's disease and ulcerative colitis.     

Histological discrimination of idiopathic inflammatory bowel disease from other types of colitis.

AIMS--To assess the value of histology in diagnosing inflammatory bowel disease (IBD) in colorectal biopsy specimens. METHODS--Retrospective, double blind evaluation of colorectal biopsy specimens from 41 patients with colitis (28 with ischaemic colitis and 13 with acute self-limited colitis) and 84 patients with IBD (42 with Crohn''s disease and 42 with ulcerative colitis). RESULTS--The features distinguishing IBD from other forms of colitis included distorted architecture, lymphocyte and plasma cell infiltrate, excess of polymorphonuclear leucocytes, polymorphonuclear cryptitis, crypt abscesses, and basal lymphoid aggregates. The features discriminating between Crohn''s disease and ulcerative colitis included an irregular or villous surface, distorted architecture, decrease in mucus content, and polymorphonuclear cryptitis. Using multivariate analysis, 90% of patients with Crohn''s disease and 71% of those with ulcerative colitis were correctly classified, the former being strongly defined by epithelioid granulomas, microgranulomas and isolated giant cells, and the latter best defined by an irregular or villous surface, decrease in mucus content and crypt atrophy. CONCLUSIONS--Examination of colorectal biopsy specimens is a reliable method for diagnosing IBD. In the absence of epithelioid granulomas, microgranulomas and isolated giant cells a diagnosis of Crohn''s disease is based on the absence of histological criteria favouring ulcerative colitis. The histological spectrum of indeterminate colitis remains to be clarified.     

Value of counting colonic mucosal Ig-containing cells in the differential diagnosis of chronic inflammatory bowel disease.

AIMS: To investigate whether counting cells containing immunoglobulin (Ig) subclass in colonic biopsy specimens of patients with chronic inflammatory bowel disease, in addition to conventional histological evaluation, can improve the differentiation of patients with Crohn's disease from those with ulcerative colitis. METHODS: The colonic and rectal biopsy specimens of 40 patients with chronic inflammatory bowel disease, comprising 20 patients with Crohn's disease and 20 with ulcerative colitis, were used and sections were stained specifically for IgA, IgM, and IgG heavy chains using an indirect immune peroxidase method. The immunoglobulin subclass containing cells were counted using an ocular grid counting method in a light microscope. A linear stepwise discriminant analysis was performed on Ig subclass containing cell counts in combination with 16 reproducible histological features. The results of this discriminant analysis were compared with the results of the discriminant analyses in which only the histological features were used. RESULTS: Applying stepwise discriminant analysis, two histological features (an excess of histiocytes in the lamina propria and the villous or irregular aspect of the mucosal surface) in combination with IgMax were selected as the most discriminatory parameters that distinguish Crohn's disease from ulcerative colitis. IgMmax was defined as the maximum value of the mean percentage of IgM containing cells over all the biopsy locations. The use of this combination resulted in a better classification in 20% of the patients with Crohn's disease and in 9% of the patients with ulcerative colitis compared with the use of histological features alone. CONCLUSIONS: Morphometric enumeration of Ig subclass containing cells in colonic mucosal biopsy specimens has diagnostic value as a means of differentiating individual patients with Crohn's disease from those with ulcerative colitis.     

Mucosal capillary thrombi in rectal biopsies

We studied the initial rectal biopsy from 46 patients in whom subsequent follow-up established the diagnosis of either self-limited colitis or inflammatory bowel disease. An additional 12 non-inflamed rectal biopsies were also studied. There was between 2 and 8 years of follow-up in each of these cases. Staining for fibrin (MSB, fibrinogen), platelets (factor XIIIA, Y2/51), and capillary basement membrane (reticulin, collagen 4) was performed to identify thrombotic material within capillaries. Mucosal capillary thrombi were best identified by staining for factor XIIIA; thrombi were observed in 8/13 cases of ulcerative colitis, 4/10 cases of Crohn's disease, 1/3 cases of unspecified inflammatory bowel disease and 5/20 cases of self-limited colitis. The presence of capillary thrombi was not related to the severity of inflammation, but none of the control biopsies showed capillary thrombi. Their presence seems of little diagnostic value in distinguishing inflammatory bowel disease from self-limited colitis. The pathogenetic significance of these mucosal capillary thrombi is uncertain.     

Detection of species-specific helicobacter ribosomal DNA in intestinal biopsy samples from a population-based cohort of patients with ulcerative colitis

The inflammatory bowel diseases are considered an abnormal host immune response to an environmental stimulus. Evidence suggests a role for intestinal bacteria in initiating and/or providing an ongoing stimulus for inflammation in inflammatory bowel disease. Helicobacter pylori is the major cause of active chronic gastritis and peptic ulcers in humans and has been linked to gastric carcinoma and lymphoma. Studies in various animal models, particularly mice, have identified enterohepatic Helicobacter species that are capable of causing hepatitis and enterocolitis. We hypothesize that Helicobacter species may have a role in maintaining inflammation in humans with inflammatory bowel disease. In order to investigate this, biopsy specimens were obtained from patients with and without inflammatory bowel disease. DNA was extracted from the tissues and subjected to PCR with primers designed to detect the ribosomal DNA of members of the Helicobacter species. DNA from six biopsy samples from 60 inflammatory bowel disease patients tested positive. This included 5 of 33 ulcerative colitis patients that were positive compared to 0 of 29 age-matched controls (P < 0.04). Sequencing of the bands produced by PCR amplification revealed >or=99% homology with H. pylori. These results indicate that a member of the Helicobacter species may be involved in some cases of ulcerative colitis.     

Overlap in the spectrum of non-specific inflammatory bowel disease--'colitis indeterminate'.

It is stated that 10-20% of cases of non-specific inflammatory bowel disease cannot be classified. Thirty such cases, designated colitis indeterminate at the time of colectomy, were identified from the pathology files of St. Mark's Hospital. The Histopathological features of the surgical specimens and any available biopsy specimens were studied. In nearly all the cases urgent surgery had been required and the features of incipient or established fulminating disease were present. The pathology of these cases of Crohn's disease and ulcerative colitis overlapped, and differentiating features were scant or unreliable. Accepted criteria of Crohn's disease--namely, fissuring ulceration, transmural inflammation, and a maintained goblet-cell population--were found in cases subsequently proved to be ulcerative colitis. Disease activity greatly affected the evaluation of morphological features. Many of the difficulties were resolved when biopsy material obtained during a quiescent phase was examined. The specimens gave a dynamic perspective of the disease process, often more valuable than the static, non-specific picture of acute disease seen in the surgical specimens. Case of colitis indeterminate form a small distinctive group in the spectrum of inflammatory bowel disease which is characterised by a common pattern of pathology that presents a diagnostic dilemma.     

How could pathologists improve the initial diagnosis of colitis? Evidence from an international workshop

BACKGROUND: The taking of multiple colorectal biopsies is in widespread use although there is little research into their benefit for the pathological diagnosis of inflammatory bowel disease. There is also still debate about appropriate morphological criteria for interpreting these biopsies. AIMS: To determine the effect of single versus multiple biopsies on the accuracy of diagnosis and to study the accuracy and reproducibility of the different criteria used in the diagnosis of multiple biopsies by expert and non-expert pathologists. METHOD: Thirteen expert and 12 non-expert international diagnostic histopathologists attended a workshop. Sixty cases with full follow up were viewed, blinded, in two rounds. Diagnoses were made on rectal biopsies and then full colonoscopic series. RESULTS: Experts correctly identified 24% of Crohn's disease cases (non-experts, 12%) from the rectal biopsies. This improved to 64% (non-experts, 60%) with the full series. The accuracy of the diagnosis of ulcerative colitis also improved slightly with the full series from 64% to 74% overall. Experts had a similar (moderate) level of agreement and accuracy to non-experts. For Crohn's disease, the likelihood ratios (LR) for the most important individual features were 12.4 for granulomas and 3.3 for focal or patchy inflammation. Features favouring ulcerative colitis were diffuse crypt architectural irregularity (LR, 3.4), general crypt epithelial polymorphs (LR, 3.7), and reduced crypt numbers (LR, 2.9). CONCLUSIONS: A full colonoscopic series gave more accurate diagnosis than a rectal biopsy. Accurate pathologists used the same evidence based criteria for multiple biopsies as for single biopsies.     

Patterns of colonic involvement at initial presentation in ulcerative colitis: a retrospective study of 46 newly diagnosed cases

Studies have shown that rectal sparing and patchiness develop in treated and longstanding ulcerative colitis (UC), making the distinction from Crohn colitis increasingly difficult after treatment is initiated. However, no histologic studies of the incidence of rectal sparing in adults at UC onset have been performed. Colectomy specimens from 46 patients with classic UC histologic features and no Crohn disease features were identified. Biopsy specimens obtained before medical therapy were retrieved and examined blindly by 2 pathologists, along with appropriate control samples. Slides were scored for chronicity (crypt branching, subcryptal plasma cells, lamina propria plasma cells) and activity (cryptitis, crypt abscesses, epithelial injury). In 28 cases, only rectal biopsy specimens were taken; for 16, rectal and at least 1 proximal biopsy specimen were taken. All cases showed rectal involvement; none had rectal sparing at initial biopsy. Of 16 cases with rectal and more proximal biopsy specimens, 5 (31%) showed relative rectal sparing (lower scores in rectum than in more proximal sites). In 16 cases with rectal and more proximal biopsy specimens, chronicity and activity scores were higher in the rectum than in more proximal sites (P = .01; chronicity and activity). The mean overall chronicity score decreased in a linear manner from rectum to cecum. The rectum is involved and shows evidence of chronicity and activity at disease onset in UC, using colectomy as the gold standard for diagnosis. Because rectal sparing at UC onset has been reported, a prospective study using uniform biopsy protocols is needed to establish the true incidence of rectal sparing at presentation.     

Expression of catenins and E-cadherin during epithelial restitution in inflammatory bowel disease

Catenins are cytoplasmic proteins associated with E-cadherin, the prime mediator of cell–cell adhesion. Perturbation in any of these molecules results in altered intercellular adhesion, cell differentiation, and increased migration. In this study, the expression and cellular localization of catenins and E-cadherin in inflammatory bowel disease were examined. The expression of E-cadherin; α-, β-, and γ-catenin; and p120 was evaluated immunohistochemically in 31 paraffin-embedded colonic specimens from 21 patients with ulcerative colitis and Crohn's disease. Loss of normal membranous E-cadherin and α-catenin staining was detected at the mucosal edges around epithelial ulcerations in all cases of active ulcerative colitis and in 50 per cent of cases with active Crohn's disease. Reduced expression of p120 protein was also found at the margins of ulcerated mucosa in all cases of active ulcerative colitis and in 75 per cent of those with active Crohn's disease. There was a statistically significant correlation between the expression of E-cadherin, α-catenin and p120 and disease activity. There were no changes in β- and γ-catenin expression in either ulcerative colitis on Crohn's disease. These findings indicate that altered expression of E-cadherin, α-catenin, and p120 occurs during mucosal ulceration in inflammatory bowel disease. These changes may be involved in promoting cell migration during epithelial restitution of the gastrointestinal mucosa. © 1998 John Wiley & Sons, Ltd.     

Lymphoid follicular hyperplasia–a distinctive feature of diversion colitis

Diversion colitis refers to the inflammatory changes that occur in the defunctioned segment of the large intesting following diversion of the faecal stream. We report the histological features in the defunctioned rectums from seven patients: one each with severe constipation and Behcet's disease, two with Crohn's disease with rectal sparing and three with ulcerative colitis. The appearances of diversion colitis in a previously normal rectum are compared with diversion colitis with superimposed inflammatory bowel disease. Lymphoid follicular hyperplasia was found in all cases. This was marked in patients with inflammatory bowel disease. with or without initial rectal involvement. Other changes comprised surface epithelial degeneration and ulceration, mucosal inflammation including crypt abscesses, and crypt branching. Inflammatory and crypt changes were mild, except in ulcerative colitis where changes were marked and resembled those of the proximal colon. Lymphoid hyperplasia is a distinctive feature in diversion colitis. The term follicular proctitis, previously used to indicate chronic ulcerative colitis exclusively, should be re-examined.     

Lymphoid follicular hyperplasia--a distinctive feature of diversion colitis

Diversion colitis refers to the inflammatory changes that occur in the defunctioned segment of the large intestine following diversion of the faecal stream. We report the histological features in the defunctioned rectums from seven patients: one each with severe constipation and Beh?et's disease, two with Crohn's disease with rectal sparing and three with ulcerative colitis. The appearances of diversion colitis in a previously normal rectum are compared with diversion colitis with superimposed inflammatory bowel disease. Lymphoid follicular hyperplasia was found in all cases. This was marked in patients with inflammatory bowel disease, with or without initial rectal involvement. Other changes comprised surface epithelial degeneration and ulceration, mucosal inflammation including crypt abscesses, and crypt branching. Inflammatory and crypt changes were mild, except in ulcerative colitis where changes were marked and resembled those of the proximal colon. Lymphoid hyperplasia is a distinctive feature in diversion colitis. The term follicular proctitis, previously used to indicate chronic ulcerative colitis exclusively, should be re-examined.     

Amebic colitis can mimic tuberculosis and inflammatory bowel disease on endoscopy and biopsy

Biopsies of 11 patients with histopathologically diagnosed amebic colitis was evaluated; endoscopically, they were suspected to have tuberculosis or inflammatory bowel disease. Amebiasis was suggested in the differential diagnosis in only 3 cases. Three patients had purely rectal or sigmoid involvement, whereas the others had ileocecal, cecal, ascending, or transverse colon disease. The biopsies showed cryptitis and depletion of mucin but no crypt branching. Crypt abscesses were seen in one biopsy. Trophozoites of Entamoeba histolytica were seen in the exudate in all cases. The trophozoites were round to oval, approximately 25 to 40 microm in diameter and had a single, round nucleus and periodic acid-Schiff-positive cytoplasm. Phagocytosed erythrocytes were present in the trophozoites. Some features of ulcerative colitis and infectious colitis, such as cryptitis and crypt abscesses, are also seen in amebic colitis. Amebic colitis must be included in the differential diagnosis of all patients with suspected inflammatory bowel disease and tuberculosis.     

Clostridium difficile: clinical disease and diagnosis.

Clostridium difficile is an opportunistic pathogen that causes a spectrum of disease ranging from antibiotic-associated diarrhea to pseudomembranous colitis. Although the disease was first described in 1893, the etiologic agent was not isolated and identified until 1978. Since clinical and pathological features of C. difficile-associated disease are not easily distinguished from those of other gastrointestinal diseases, including ulcerative colitis, chronic inflammatory bowel disease, and Crohn's disease, diagnostic methods have relied on either isolation and identification of the microorganism or direct detection of bacterial antigens or toxins in stool specimens. The current review focuses on the sensitivity, specificity, and practical use of several diagnostic tests, including methods for culture of the etiologic agent, cellular cytotoxicity assays, latex agglutination tests, enzyme immunoassay systems, counterimmunoelectrophoresis, fluorescent-antibody assays, and polymerase chain reactions.     

Human gut mucosal mast cells: ultrastructural observations and anatomic variation in mast cell-nerve associations in vivo.

One hundred and seventeen coded intestinal biopsy specimens were examined by electron microscopy. All surgical biopsies were obtained from uninvolved sites of patients with two inflammatory bowel diseases (ulcerative colitis or Crohn's disease) and from patients with preneoplastic and neoplastic diseases (adenocarcinoma, rectal polyp, familial polyposis). Biopsy sites included normal ileum, colon, and rectum as well as conventional ileostomies and continent pouches constructed from the ileum. The data reported here describe the ultrastructural anatomy of human gastrointestinal tract mucosal mast cells in vivo and their anatomic associations with enteric nerves.