Reliability of rectal biopsy in distinguishing between chronic inflammatory bowel disease and acute self-limiting colitis

Aims : In order to assess the validity of previously proposed criteria for the differentiation of chronic inflammatory bowel disease (CIBD) from acute self-limiting colitis (ASLC) all rectal biopsies were reported by a single histopathologist with a long-term gastrointestinal interest over a 4.5-year period. Methods and results : The presence or absence of distorted crypt architecture, increased lymphocytes and plasma cells, villous mucosal architecture, granulomata, basal lymphoid aggregates, basal giant cells and Paneth cell metaplasia was noted for each biopsy. The definite presence of any of the above features, with the exception of intramucosal granulomata, was regarded as indicative of CIBD. Eighteen months later all available case notes were examined and the presenting clinical symptoms and working clinical diagnosis extracted. The final diagnosis, histopathological diagnosis and the presence or absence of any of the above histopathological features were correlated and the positive predictive value of each histopathological feature was calculated. A correct diagnosis of either CIBD or ASLC was made in 80 of 84 and 29 of 31 cases, respectively. Conclusions : Villous mucosal architecture and Paneth cell metaplasia were found to be specific features of CIBD. Distorted crypt architecture, basal lymphoid aggregates and plasma cell infiltration of the lamina propria were also useful features but strict definition of these features is required and discussed. Intramucosal epithelioid granulomas were identified in eight cases of CIBD and four cases of ASLC. In association with ruptured crypts intramucosal granulomas are not specific features of Crohn's colitis.     

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.     

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.     

Differential diagnosis of Crohn's disease of the colon from ulcerative colitis: ultrastructure study with the scanning electron microscope

Mucosal biopsies from patients with Crohn's disease and with ulcerative colitis were studied by scanning electron microscopy. Important abnormalities of the mucosal surface were found in both diseases. For Crohn's disease, the characteristic abnormality was loss of the regularity of the polygonal units, but with preservation of the mucosal integrity and of the normal mucosal design. For ulcerative colitis, the abnormalities were disorganization of the cells, signs of sloughing, and superficial erosions. Patients with Crohn's disease always had a significantly increased number of muciparous cells, while those with ulcerative colitis had obvious signs of decreased mucus production. The lesions of ulcerative colitis could be seen under the scanning electron microscope in mucosal areas that appeared normal endoscopically. We feel therefore that scanning electron microscopy of biopsy specimens from patients with inflammatory bowel diseases can be of great help in differential diagnosis.     

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.     

Importance of cryptolytic lesions and pericryptal granulomas in inflammatory bowel disease.

AIMS: To explore the diagnostic importance of pericryptal granulomas associated with epithelial lysis in colorectal biopsy specimens (cryptolytic colitis). METHODS: A series of patients with suspected inflammatory bowel disease and colorectal biopsy specimens showing either isolated pericryptal granulomas (14 cases) or non-granulomatous pericryptal inflammation (eight cases) were followed. A diagnosis of Crohn's disease was established if subsequent biopsy specimens or intestinal resections showed unequivocal non-crypt related granulomas, or if there was evidence of significant small bowel disease. RESULTS: Of the 14 patients with pericryptal granulomas and biopsy specimens, 10 were subsequently found to have Crohn's disease; of the eight patients with pericryptal inflammation only, one developed Crohn's disease. The former group also had a much higher instance of morbidity and required surgical intervention more often. CONCLUSIONS: The presence of cryptolytic granulomas in a colorectal biopsy specimen otherwise showing only non-specific inflammatory changes should always raise suspicion of Crohn's disease, especially if surgery or ileo-anal pouch formation is contemplated.     

Angiotensin-converting enzyme in Crohn's disease and ulcerative colitis

The relationship between serum angiotensin-converting enzyme activity and inflammatory bowel disease was investigated in 37 patients who had Crohn's disease, 31 patients who had ulcerative colitis, and 104 control subjects. The enzyme activity tended to be depressed in Crohn's ileitis (P less than 0.05) and colitis, but not in Crohn's ileocolitis and ulcerative colitis. No increase in enzyme activity was observed in Crohn's disease ileum or colon or in ulcerative colitis colon. The granulomatous inflammation in Crohn's disease differs from that in sarcoidosis, in which striking elevation of angiotensin-converting enzyme is present in granulomatous tissue and frequently in serum.     

Indeterminate colitis: definition, diagnosis, implications and a plea for nosological sanity

In 1978, Price introduced the concept of indeterminate colitis to describe cases in which colonic resections had been undertaken for chronic inflammatory bowel disease (CIBD), but a definitive diagnosis of either of the classical types of CIBD, ulcerative colitis and Crohn's disease, was not possible. This was especially apposite in cases of acute fulminant disease of the colorectum. More recently, the term indeterminate colitis has been applied to biopsy material, when it has not been possible to differentiate between ulcerative colitis and Crohn's disease. In our opinion, and in those of other workers in this field, the term should be restricted to that originally suggested by Price. This then provides a relatively well-defined group of patients in whom the implications and management of the disease are becoming much clearer. Cases where there are only biopsies with CIBD, but equivocal features for ulcerative colitis and Crohn's disease, should be termed 'CIBD, unclassified', 'equivocal/non-specific CIBD' or IBD unclassified (IBDU), in line with recent recommendations. When the diagnosis is correctly restricted to colectomy specimens, there is now good evidence that the majority of cases will behave like ulcerative colitis. Furthermore, the diagnosis should not be a contraindication to subsequent pouch surgery. When the latter is undertaken, surgeons and patients can expect an increased complication rate, compared with classical ulcerative colitis, especially of pelvic sepsis, but most patients fare well. Only very occasional patients, around 10%, will eventually be shown to have Crohn's disease. This review describes the pathology of cases appropriately classified as indeterminate colitis and the implications of that diagnosis. It also highlights recent advances in its pathological features, clinical management and its immunological and genetic associations.     

Intramucosal ganglion cells are common in diverticular disease

AIMS: Ganglion cells were thought not to occur within the mucosa of the normal colon and found only in the setting of inflammatory bowel disease and neuronal intestinal dysplasia. The aim of this study was to firmly establish the incidence of intramucosal ganglion cells in diverticular disease, normal mucosa and in a spectrum of gastrointestinal diseases. METHODS: We retrospectively reviewed 50 resection specimens from cases of symptomatic diverticular disease and biopsies and/or resection specimens for several neoplastic and non-neoplastic gastrointestinal diseases (50 normal and 120 cases for a variety of gastrointestinal diseases). Normal cases were constituted by biopsies with no clinical history of large bowel disease and no pathology detected microscopically. RESULTS: All 50 cases of diverticular disease contained intramucosal ganglion cells, located within the muscularis mucosae (49/50 cases) as well as within the lamina propria in nine cases. Intramucosal ganglion cells occurred throughout the colorectum within the muscularis mucosae or lamina propria in normal mucosa in 11 cases and in a further 26 colorectal specimens with Crohn's disease (11/20), ulcerative colitis (11/20), adenocarcinoma (1/20), tubular adenoma (2/20), and mucosal prolapse (1/20). None of the 20 hyperplastic polyps contained intramucosal ganglion cells. CONCLUSIONS: We have firmly established the existence of the intramucosal ganglion cells in normal and diseased colorectum, especially in the mucosa of cases of diverticular disease (100% of cases), Crohn's disease and ulcerative colitis. These three conditions are linked by motility abnormalities which may underlie the reason for the presence of intramucosal ganglion cells.     

Mucin profiles in ulcerative colitis with dysplasia and carcinoma

Mucin secretion was assessed in Crohn's colitis, in ulcerative colitis with regeneration, dysplasia and carcinoma and in non-colitic adenocarcinoma. The high iron diaminealcian blue (HID–AB) and periodate borohydride–saponification periodic acid Schiff (PB–KOH–PAS) techniques were used to demonstrate sulphomucins and sialomucins, and O-acylated sialomucins respectively. There was mucosal hyperplasia and increased sialomucin secretion in Crohn's disease, quiescent and active ulcerative colitis. In colitis with carcinoma inflamed mucosa away from the tumour had increased sialomucins as had colitis with dysplasia. They did not differ statistically from each other or from colitic controls without cancer. Dysplastic crypts frequently secreted sulphomucins and the increased sialomucins were in transitional-like glands in the surface fronds or adjacent to the dysplasia. A comparative study of the HID–AB technique gave total correct qualitative allocation of individual quantitatively assessed crypts. Routine HID–AB staining did not aid the recognition of dysplasia in ulcerative colitis. With the PB–KOH–PAS technique colorectal adenocarcinoma showed a significant diminution in O-acylated sialomucins compared with its adjacent mucosa. Mucosal dysplasia in ulcerative colitis displayed a similar trend in O-acylated sialic acid variants, differing with respect to age- and sex-matched colitic controls. The PB–KOH–PAS technique may be of help in assessing mucin secretion in ulcerative colitis as a guide to the evolution of malignancy.     

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.     

Detection of herpesvirus DNA in the large intestine of patients with ulcerative colitis and Crohn's disease using the nested polymerase chain reaction.

The prevalence of herpesvirus DNA was examined in inflammatory bowel disease tissue. DNA was extracted from resection and biopsy specimens of the large intestine from patients with ulcerative colitis (n = 21), patients with Crohn's disease (n = 29), and patients with noninflammatory bowel disease (controls) (n = 21). The nested polymerase chain reaction was used to detect viral DNA using primer pairs specific for either cytomegalovirus (CMV), herpes simplex virus 1 (HSV1), human herpesvirus 6 (HHV6), varicella zoster virus (VZV), or Epstein Barr virus (EBV). HSV1 and VZV DNA were not detected in any of tissue samples. There was a high prevalence of CMV (81%), HHV6 (76%), and EBV (76%) DNA in ulcerative colitis tissue compared to Crohn's disease tissues (CMV 66%, HHV6 45%, EBV 55%). Control tissue had a relatively low frequency of CMV (29%) and EBV (19%) DNA but a prevalence of HHV6 DNA similar to that of ulcerative colitis (86%). However, the simultaneous presence of HHV6 and CMV and/or EBV DNA in ulcerative colitis tissue (76%) was much greater than in either Crohn's disease tissues (38%) or control tissue (29%) (P < 0.05). There was a low prevalence of CMV, HHV6, and EBV DNA in peripheral blood mononuclear cells from all patient groups. CMV and EBV are capable of reactivating HHV6: the high prevalence of coexistent HHV6 infection with either or both of these two viruses in ulcerative colitis tissue suggests that they may play a synergistic role in the pathogenesis of this disease.     

Absence of Escherichia coli, Listeria monocytogenes, and Klebsiella pneumoniae antigens within inflammatory bowel disease tissues.

BACKGROUND: Escherichia coli, listeria, and streptococcal antigens have been found in Crohn's disease tissues. Antibodies to Klebsiella pneumoniae have been found in patients with inflammatory bowel disease and ankylosing spondylitis. The presence of these bacterial antigens in Crohn's granulomas would be of aetiological interest, while their presence in ulcers alone would be more likely to indicate secondary infection. AIM: To investigate inflammatory bowel disease tissues for the presence of these bacteria. METHODS: Formalin fixed, paraffin processed sections from 53 patients (19 ulcerative colitis, 23 Crohn's disease; 11 normal tissues from cancer resections) were studied by immunohistochemistry. Control tissue consisted of normal human small bowel injected submucosally with either E coli, Listeria monocytogenes, Proteus mirabilis, or Klebsiella pneumoniae serotypes K2, 3, 17, 21, 26, 36, and 50, and colonic biopsies from a child with E coli 0114 infection. Tissues were stained by Gram-Twort, and with specific antibodies for E coli (Dako B357), L monocytogenes (Difco 2302-50), and K pneumoniae (Biogenesis 5580-5208) using an immunoperoxidase technique. RESULTS: Positive staining for E coli was observed on the luminal surface epithelium and in ulcers in 35% of Crohn's disease patients, 26% of ulcerative colitis patients, and no normal controls. Superficial staining for L monocytogenes was observed in one case of ulcerative colitis only. Staining for K pneumoniae was observed in one case of ulcerative colitis and one of Crohn's disease. No granulomas, giant cells, or germinal centres stained positively for any of the three bacterial antigens. CONCLUSIONS: These data do not support a primary role for E coli, L monocytogenes, and K pneumoniae in inflammatory bowel disease. The presence of E coli antigens in ulcers suggests secondary infection in these lesions.     

Comparative mapping of the local distribution of immunoglobulin-containing cells in ulcerative colitis and Crohn's disease of the colon.

The local response pattern of immunoglobulin-containing cells was compared in Crohn's disease and ulcerative colitis by paired immunohistochemistry on specimens of the large bowel wall. In the "Crohn mucosa" with persisting glands the total cell count was on the average raised more than three times compared with controls. The numbers of IgA, IgM and IgG immunocytes were increased 2.0, 4.8 and 28.6 times, respectively. Only 0-2 IgD- and IgE-containing cells were generally found per section. No consistent differences in the mucosal response pattern were revealed when Crohn's disease was compared with ulcerative colitis. The deeper layers of the bowel wall were in both diseases more or less densely infiltrated by immunocytes-IgG cells compromising about 80%. Immunoglobulin-containing cells in the muscularis propria and subserosa were characteristically found in Crohn's disease. There was no indication of a primary defect in the secretory immunoglobulin system which appeared to be normal in areas with intact glands. The pronounced local humoral immune response, particularly that involving IgG, might be of pathogenetic importance by aggravating and perpetuating in the inflammatory bowel disease.     

Circulating antibodies to heat-shock protein 60 in Crohn''s disease and ulcerative colitis.

Heat-shock proteins (HSPs) are highly conserved immunogenic intracellular molecules that are induced by inflammatory mediators and may induce autoimmune phenomena in vivo. We have recently demonstrated the increased expression of HSP-60 in the colonocytes of patients with ulcerative colitis. To study further the role of HSP-60 in inflammatory bowel disease, we have now measured antibodies to recombinant mycobacterial HSP-65 (a member of the HSP-60 family) in patients with Crohn's disease, ulcerative colitis, healthy volunteers and, as disease controls, patients with confirmed bacterial diarrhoea. In comparison with healthy controls (n = 20; median level of 89 ELISA units; range 24-292), serum IgA HSP-60 antibodies were elevated in Crohn's disease (n = 21; 157; 57-364; P < 0.05) and active ulcerative colitis (n = 16; 188; 58-373; P < 0.01) but not bacterial diarrhoea (n = 10; 106; 51-285). Increased IgA HSP-60 antibody levels in patients with inflammatory bowel disease may occur as the result of HSP release from injured gut epithelium; alternatively, increased intestinal permeability could facilitate mucosal access of luminal antigens and the generation of cross-reactive anti-bacterial HSP antibodies.     

Differences between tissue-associated intestinal microfloras of patients with Crohn's disease and ulcerative colitis

A leading hypothesis for the role of bacteria in inflammatory bowel diseases is that an imbalance in normal gut flora is a prerequisite for inflammation. Testing this hypothesis requires comparisons between the microbiota compositions of ulcerative colitis and Crohn's disease patients and those of healthy individuals. In this study, we obtained biopsy samples from patients with Crohn's disease and ulcerative colitis and from healthy controls. Bacterial DNA was extracted from the tissue samples, amplified using universal bacterial 16S rRNA gene primers, and cloned into a plasmid vector. Insert-containing colonies were picked for high-throughput sequencing, and sequence data were analyzed, yielding species-level phylogenetic data. The clone libraries yielded 3,305 sequenced clones, representing 151 operational taxonomical units. There was no significant difference between floras from inflamed and healthy tissues from within the same individual. Proteobacteria were significantly (P = 0.0007) increased in Crohn's disease patients, as were Bacteroidetes (P < 0.0001), while Clostridia were decreased in that group (P < 0.0001) in comparison with the healthy and ulcerative colitis groups, which displayed no significant differences. Thus, the bacterial flora composition of Crohn's patients appears to be significantly altered from that of healthy controls, unlike that of ulcerative colitis patients. Imbalance in flora in Crohn's disease is probably not sufficient to cause inflammation, since microbiotas from inflamed and noninflamed tissues were of similar compositions within the same individual.     

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.     

Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn's disease.

The perpetuation of inflammation in ulcerative colitis and Crohn's disease may be regulated in part by an increased secretion of proinflammatory cytokines due to either an appropriate response to initial stimulating agents, and/or due to an impaired down-regulation of cytokine secretion. The aim of this study was to determine the secretion patterns of the proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-1 beta, from isolated lamina propria mononuclear cells (LPMNC) isolated from colonic biopsies from patients with untreated ulcerative colitis or Crohn's disease. LPMNC isolated from involved inflammatory bowel disease (IBD) mucosa spontaneously produced increased amounts of TNF-alpha, and IL-6, and IL-1 beta. The TNF-alpha secretion from IBD LPMNC could be further enhanced by pokeweed mitogen stimulation. The secretion patterns of TNF-alpha and IL-1 beta by LPMNC from patients with either ulcerative colitis or Crohn's disease demonstrated a close correlation with the degree of tissue involvement and mucosal inflammation. LPMNC from non-involved ulcerative colitis mucosa secreted markedly increased levels of IL-6 compared with non-involved Crohn's disease mucosa or control mucosa. The heightened IL-6 secretion from LPMNC from non-involved ulcerative colitis mucosa without visible or microscopic signs of inflammation indicates that the pathophysiologic mechanisms involved in the initiation of inflammation may differ between ulcerative colitis and Crohn's disease. The determination of proinflammatory cytokine secretion by isolated LPMNC from colonoscopic biopsies may be a sensitive method for monitoring the severity of mucosal inflammation in IBD patients.     

Diagnostic difficulties in inflammatory bowel disease pathology

This review summarizes some of the common diagnostic problems encountered by pathologists when evaluating patients with chronic colitis and in whom inflammatory bowel disease (IBD) is either suspected or within the differential diagnosis. Both ulcerative colitis (UC) and Crohn's disease (CD) show characteristic, but non-specific, pathological features that may overlap and result in a diagnosis of 'indeterminate colitis' (IC). However, other reasons why pathologists may entertain a diagnosis of IC include failure to recognize or accept certain 'hardcore' histological features as indicative of CD, an attempt to classify cases of chronic colitis based on mucosal biopsy material or in the absence of adequate clinical and radiographic information, and the presence of other disease processes that mask, or mimic, IBD. In addition, some cases of UC may show unusual CD-like features, such as discontinuous or patchy disease, ileal inflammation, extracolonic inflammation, granulomatous inflammation in response to ruptured crypts, aphthous ulcers, or transmural inflammation. Furthermore, other forms of colitis, such as microscopic colitis, diverticulitis and diversion colitis may, on occasion, also show IBD-like changes. The clinical and pathological features that aid in the distinction between these entities, and others, are covered in detail in this review.     

Decreased expression of protectin (CD59) in gut epithelium in ulcerative colitis and Crohn's disease

Without adequate protection, the cells of the human body would be susceptible to destruction by the complement system. The main defense against complement lysis is a molecule called protectin (CD59) that is widely distributed in human tissues. Because the complement system has been suggested to be involved in the pathogenesis of inflammatory bowel diseases, we examined the expression of protectin in the colonic epithelium of patients with ulcerative colitis or Crohn's disease and controls. Colorectal specimens from 6 patients with ulcerative colitis, 8 patients with Crohn's disease, and 4 controls were obtained from surgical resections. Frozen sections of the specimens were immunostained for protectin using the Bric 229 monoclonal antibody. The expression of protectin was found to be decreased in the epithelium of patients with ulcerative colitis. In patients with Crohn's disease, the epithelial expression of protectin was decreased in diseased areas of gut while the expression did not significantly differ from that in controls in macroscopically normal areas. There was no difference in the expression of protectin on vascular endothelium, mononuclear cells, or smooth muscle. The reduction in epithelial expression of protectin in patients with ulcerative colitis or Crohn's disease may render epithelial cells vulnerable to complement lysis and lead to the destruction of gut epithelium as seen typically in these diseases.