INFLAMMATORY BOWEL DISEASE - PART 10 doc

332 Hart Fig. 4. Ulcerative colitis. (A) Low-power view demonstrating mild crypt architectural distortion, basal lymphoplasmacytic infiltrates, and diffuse neutrophilic infiltrates. (B) (Opposite page) High-power of the same biopsy revealing a granuloma adjacent to a ruptured crypt. Transmural disease is another characteristic feature of Crohn’s disease, but of course this feature cannot be assessed in endoscopic biopsy specimens. Inflammation can extend into the submucosa (or even deeper) in active ulcerative colitis, so the presence of inflammatory cells in the superficial portion of submucosa sometimes included in a biopsy specimen cannot automatically be assumed to be diagnostic of Crohn’s disease. However, in ulcerative colitis, the inflammation of the overlying mucosa is always more severe than that of the submucosa. There- fore, a biopsy that exhibits marked inflammation of the superficial submucosa, with relatively little active inflammation in the overlying mucosa, would suggest a diagnosis of Crohn’s colitis. There are additional histologic features which, while not diagnostic, can be helpful in favoring a diagnosis of either ulcerative colitis or Crohn’s colitis. For instance, the degree of crypt architectural distortion tends to be greater in ulcerative colitis. Thus, biopsies from ulcerative colitis patients often reveal significant mucosal atrophy with numerous branched crypts and marked alteration of the normal parallel arrange- ment of the crypts. Biopsies from patients with Crohn’s colitis, in con- trast, may exhibit only mild crypt architectural distortion with relatively Chapter 17 / Pathologic Features of IBD 333 334 Hart Fig. 5. Early Crohn’s colitis. (A) Low-power view showing a lymphoid follicle. (B) High-power of the same biopsy reveals an early aphthous erosion, with focal neutrophilic infiltrate directly over the lymphoid follicle. Chapter 17 / Pathologic Features of IBD 335 little atrophy. Moreover, biopsies from patents with active ulcerative colitis usually exhibit significant depletion of the normal mucin content of the crypt epithelial cells, while the mucin is often relatively preserved in active Crohn’s disease (7). Unfortunately there is considerable overlap in these features in biopsies from ulcerative colitis and Crohn’s colitis patients, and their assessment is also subjective. One can also take advantage of the fact that Crohn’s disease can affect any portion of the gastrointestinal tract, while ulcerative colitis is essentially limited to the colon. Biopsies of the terminal ileum may reveal significant ileitis in some patients with Crohn’s disease. The histologic features of Crohn’s ileitis are essentially identical to those evident in colonic biopsies (Fig. 6). Although some ulcerative colitis patients with pancolitis may exhibit so-called “backwash ileitis,” histologic assessment usually can allow distinction from Crohn’s ileitis. Backwash ileitis generally consists only of scattered neutrophils in the lamina propria and surface epithelium, with relative preservation of the mucosal architecture. In Crohn’s ileitis there is usually marked distortion of normal villous architecture at least focally, and the degree of active inflammation is often greater as well. Of course biopsies of the upper gastrointestinal tract may also be quite helpful in making a diagnosis of Crohn’s disease if involvement can be documented. Even biopsies of endoscopically normal mucosa can reveal evidence of Crohn’s disease (e.g., granu- lomas and focal inflammatory cell infiltrates). Histologic Distinction Between IBD and Other Forms of Colitis The histologic features of a number of other forms of colitis can overlap with those described previously for IBD. Definitive distinction usually requires correlation with the clinical history, laboratory test results and colonoscopic features. Depending on the amount of this clinical data made available to the pathologist, a firm histologic diagnosis of IBD may be possible in some cases, while in others only a differential diagnosis can be given. The histologic appearance of each form of colitis is discussed in the following, emphasizing features most useful in differentiating from IBD. I NFECTIOUS COLITIS Most enteric bacteria (e.g., Escherichia coli, Salmonella, Shigella, Yersinia, and Campylobacter) produce a nonspecific form of colitis, which in the past has been termed “acute self-limited colitis.” Histologi- cally there are neutrophilic infiltrates in the lamina propria, and in more severe cases, there may be foci of cryptitis and crypt abscesses. These 336 Hart Fig. 6. Crohn’s ileitis. There is prominent distortion of normal villous architecture. features are quite similar to those of IBD, although in infectious colitis the neutrophilic infiltrates tend to be more superficial (Fig. 7). The key features in terms of distinction from IBD are the maintenance of normal crypt architecture and the lack of a basal lymphoplasmacytic infiltrate (6,8,9). However, these two histologic findings are difficult to assess in poorly oriented biopsies. The inflammatory changes in infectious colitis may be patchy or diffuse, so this diagnosis must be considered in the differential with both ulcerative colitis and Crohn’s colitis. Gram stains performed on biopsy specimens are not useful since luminal bacteria are abundant in health. Instead, confirmation of the diagnosis requires a positive stool culture, which is obtained in only a minority of cases. Without a positive stool culture, presumptive diagnosis rests on the self- limited clinical course or the resolution of symptoms with antibiotic therapy. Colitis owing to E. coli O:157H7 infection is histologically more distinctive, most often being right-sided and prominently hemorrhagic. Severe cases may be transmural and can be clinically confused with Crohn’s disease. Stool cultures must be specifically sent for E. coli O:157H7 and may be negative unless obtained soon after the onset of symptoms (10,11). Colitis owing to Entamoeba histolytica infection is often segmental and may be transmural, closely simulating Crohn’s disease clinically (12). Stool ova and pararsites (O & P) examination Chapter 17 / Pathologic Features of IBD 337 is usually diagnostic, although multiple specimens may need to be examined. If colon biopsies are obtained from the edge of an ulcer, the trophozoites can be seen within acute inflammatory cell exudate or necrotic debris, and highlighted with a PAS stain. Clinical suspicion of E. histolytica infection should be reported to the surgical pathologist so that a special effort is made to find the organism, which may be sparse. I SCHEMIC COLITIS While histologically distinctive, acute ischemic colitis may clinically and colonoscopically be confused with IBD. When patchy, particularly if focal ulceration develops, ischemic colitis can resemble Crohn’s colitis. Segmental left-sided ischemic colitis has been described in young women and has been associated with the use of oral contracep- tives (13). Ischemia may not be considered clinically in these patients because of their young age and atypical disease distribution. Fortu- nately the histologic features of acute ischemic colitis are quite characteristic. There are only very minimal neutrophilic infiltrates, limited to areas of erosion or ulceration, and lymphoplasmacytic infiltrates are Fig. 7. Infectious colitis. Normal crypt architecture is well maintained. Scat- tered neutrophils are evident within the superficial lamina propria. A stool culture grew Campylobacter jejuni. 338 Hart never present. Ischemia preferentially produces damage to the superficial portion of the mucosa, a pattern not seen in IBD. Hemorrhage and deposits of proteinaceous material within the lamina propria are also characteristic of acute ischemia and are not seen in IBD (Fig. 8). Chronic ischemic colitis can result in focal ulceration or stricture formation, which can clinically and endoscopically resemble Crohn’s disease. Again, ischemia may not be considered clinically because a watershed zone may not be affected. Ischemia owing to thrombosis, emboli, or vasculitis can involve any colonic segment, including so- called protected zones like the cecum and rectum. Biopsies will reveal significant crypt architectural distortion, similar to that seen in IBD, but will also demonstrate prominent lamina propria fibrosis. In addition, the neutrophilic and lymphoplasmacytic infiltrates typical of untreated IBD are never present in chronic ischemic colitis. Nonetheless, focal ulceration owing to chronic ischemia is sometimes misdiagnosed as Crohn’s disease by the unwary pathologist and clinician. This is particularly true in cases with cecal involvement (solitary cecal ulceration), where ischemia may be one of several contributing factors (along with uremia, CMV infection, and/or drug toxicity). Fig. 8. Acute ischemic colitis. Normal crypt architecture is maintained, although detachment of the surface epithelium and withering of the superficial portions of the crypts is evident. Also note the lack of significant inflammatory cell infiltrates and the deposition of pinkish proteinaceous material in the lamina propria. Chapter 17 / Pathologic Features of IBD 339 NSAID COLITIS The diagnosis of NSAID colitis is often not considered by either the clinician or pathologist. Patients may not be forthcoming regarding their usage of NSAIDs, and the endoscopist may not directly ask about these agents. The histologic features of NSAID colitis have not been completely documented, and some pathologists may not consider the possibility, particularly if a history of NSAID use is not mentioned in the pathology requisition form. Chronic NSAID use can result in the formation of a focal ulcer or stricture, and therefore a diagnosis of Crohn’s colitis might be entertained (14). NSAIDs can also produce diffuse mild colitis, which can be confused with ulcerative colitis colonoscopically (15,16). Histologic examination reveals mild neutrophilic infiltrates, but maintenance of normal crypt architecture and an absence of a lymphoplasmacytic infiltrate in the lamina propria, ruling out IBD. In addition, there may be a patchy thickening of the subepithelial collagen layer, similar to that seen in collagenous colitis. However, the absence of a significant increase in intra-epithelial lymphocytes, the presence of colitis colonoscopically, and the absence of a history of chronic watery diarrhea eliminates collagenous colitis as diagnostic consideration. O THER FORMS OF COLITIS Chronic radiation colitis and chronic graft vs host disease both produce crypt architectural distortion and therefore could be theoretical in histologic differential diagnosis of treated IBD. The clinical history would obviously be important in these cases, and there are other histologic features of these conditions that are helpful in arriving at the cor- rect diagnosis. Drugs other than NSAIDs can rarely cause colitis and must be considered in problematic cases. Distal colitis can also be pro- duced factitciously by the instillation of toxic agents via enema. FULMINANT IBD AND INDETERMINANT IBD Although a more common complication of ulcerative colitis, fulminant colitis and toxic megacolon can also occur in Crohn’s disease or as a complication of various infections (Shigella, Salmonella, Campylobacter, and Clostridium) (3). Unfortunately, many of the histologic features characteristic of either ulcerative colitis or Crohn’s disease cannot be evaluated because of the presence of very severe inflammation and necrosis. Typically a colon affected by fulminant colitis exhibits confluent areas of deep ulceration. The remaining mucosa is severely congested, friable, and hemorrhagic. Ulceration often extends into the muscularis propria and sections from these areas may show inflamma- 340 Hart tory cells extending into the serosa. This transmural inflammation is merely a reflection of the severity of the acute disease and should not by itself prompt a diagnosis of Crohn’s colitis. On the other hand, lymphoid aggregates in the muscularis propria or serosal tissues away from areas of deep ulceration are consistent with Crohn’s colitis. Often in cases of fulminant ulcerative colitis, the mucosa of the rectum is grossly less affected in comparison with the sigmoid area, leading to a false impression of Crohn’s colitis. However, histologic sections will show crypt architectural distortion, consistent with involvement by ulcerative colitis. In some cases, a diagnosis of indeterminate colitis must be rendered if no specific features of ulcerative colitis or Crohn’s disease can be recognized. Of course, if the patient has a firm history of either ulcerative colitis or Crohn’s colitis before the onset of the fulminant episode, then there is no reason to change the diagnosis to indeterminate colitis for the colectomy specimen. The problematic situation arises only in patients in whom an established diagnosis has not already been made. Considerable confusion regarding the term indeterminate colitis has developed because it has been used in several different clinical and pathologic contexts. Endoscopists sometimes use the term when the findings observed are not specific for either ulcerative colitis or Crohn’s colitis. Likewise, some pathologists use the term when the histologic features present in biopsy specimens do not allow clear distinction between the two diseases. It is probably best to restrict the term to those cases in which it is impossible to distinguish between ulcerative colitis and Crohn’s disease, despite examination of a colectomy specimen (in a patient without a firm pre-operative diagnosis). ATYPICAL HISTOLOGIC FEATURES IN ULCERATIVE COLITIS Some patients with typical left-sided ulcerative colitis exhibit endoscopic and histologic evidence of an additional isolated focus of disease in the cecum, usually taking the form of a patch of inflamed mucosa near the appendiceal orifice and/or ileocecal valve. This so-called “cecal red patch” may be regarded as a skip lesion and therefore a feature favoring Crohn’s disease by those not aware of its occurrence in ulcerative colitis (17). Histologic sections from these endoscopically abnormal patches reveal changes typical of mildly active ulcerative colitis, with crypt architectural distortion and mild mixed inflammatory cell infiltrates. It should be remembered, however, that cecal biopsies normally contain more intense lamina propria inflammatory cell infiltrates than are Chapter 17 / Pathologic Features of IBD 341 present in biopsies from other parts of the colon. In fact, rare neutrophils may even be present normally in cecal mucosa. The possibility of patchy disease involvement in ulcerative colitis has already been mentioned. It is now well-documented that intensive medical therapy for symptomatic ulcerative colitis can lead to patchy healing, resulting in an endoscopic impression of skip areas. Biopsies from these endoscopically normal regions, which can include the rectum, may reveal no disease activity, but in most cases crypt architectural distortion is still evident, indicating prior disease involvement. In rare cases, the distortion of crypt architecture may be very subtle or simply not apparent (18). There are also cases in which skip areas of normal mucosa are definitely present from the onset (typically a segment in the transverse or descending colon), and yet all other clinical and histologic features are consistent with the diagnosis of ulcerative colitis. The clinical course in such a patient is almost always that of typical ulcerative colitis. DYSPLASIA IN IBD The identification of dysplasia is one of the most important tasks of the pathologist in evaluating colonic biopsies from patients with IBD. Dysplasia is defined as an unequivocal neoplastic change in the colonic epithelium, without invasion past the basement membrane. This prema- lignant change has been shown to be a useful marker of a high risk for the presence or development of invasive adenocarcinoma, and is the basis of surveillance colonoscopy programs. The diagnostic criteria for the diagnosis of dysplasia were established by an international group of expert pathologists who blindly reviewed a collection of slides showing a range of reactive and dysplastic changes (19). The panel recognized that significant interobserver and intraobserver variation was unavoid- able, particularly in the distinction of low grade dysplasia from reactive changes that closely resemble dysplasia. The problem of interobserver variability in the diagnosis of dysplasia has in fact been confirmed in other studies (20–22). A variety of technical problems can hinder the ability of pathologists to make a reproducible diagnosis of dysplasia. Small, crushed, and poorly oriented biopsies are obviously difficult to interpret. Poor fixa- tion, sectioning, and staining of the biopsies compounds the difficulty. In addition, the presence of marked active inflammation and/or ulceration produces cytologic alterations that closely simulate those seen in dysplasia. Even if large, well-oriented, and properly handled biopsies are obtained and prepared, there are still a variety of interpretational [...]... of Inflammatory Bowel Disease Surgical Management of Inflammatory Bowel Disease Ostomy Care Inflammatory Bowel Disease in Children and Adolescents Nutritional/Metabolic Issues in the Management of Inflammatory Bowel Disease Extraintestinal Manifestations of Inflammatory Bowel Disease Cancer in Inflammatory Bowel Disease Gender-Specific Issues in Inflammatory Bowel Disease Economics of Inflammatory Bowel. .. Contents Inflammatory Bowel Disease (Ulcerative Colitis, Crohn's Disease) : Early History, Current Concepts, and 21st Century Directions Epidemiology of Inflammatory Bowel Disease Etiology and Pathogenesis of Inflammatory Bowel Disease Genetics of Inflammatory Bowel Disease Presentation and Diagnosis of Inflammatory Bowel Disease Radiological Findings in Inflammatory Bowel Disease Inflammatory Bowel Disease. .. Inflammatory Bowel Disease Gender-Specific Issues in Inflammatory Bowel Disease Economics of Inflammatory Bowel Disease Pathologic Features of Inflammatory Bowel Disease Index 90000 Clinical Gastroenterology™ INFLAMMATORY BOWEL DISEASE DIAGNOSIS AND THERAPEUTICS ISBN: 0-8 960 3-9 0 9-9 E-ISBN: 1-5 925 9-3 1 1-9 humanapress.com 9 780896 039094 ... nutrition, 236 Ulcerative colitis personality, 4 Ultrasound (US), 101 103 United Kingdom inflammatory bowel disease, 19 Upper GI and small bowel follow-through (UGI-SBFT), 99 Ureteral obstruction, 271 Crohn’s disease, 86 Urinary lactulose/L-rhamnose permeability ratio, 119 Urinary retention ulcerative colitis surgery, 164–167 US, 101 103 Uveitis, 269–270 children, 219 V Vaccine novel, 9 Vagotomy distal,... informative, Inflammatory Bowel Disease: Diagnosis and Therapeutics offers physicians, patients, their families, and public health officials alike a clear, readable account of the many complex issues involved in inflammatory bowel diseases, Crohn’s disease, and ulcerative colitis Features • Comprehensive, concise, and accessible survey of the inflammatory bowel diseases • Expert advice by world-renowned... Immunosuppressants, 9 adverse effects, 289–290 Impotence ulcerative colitis surgery, 167 Imuran See Azathioprine Indeterminant inflammatory bowel disease, 339–340 Indomethacin, 53 Infections children, 35 Infectious colitis distinguished from inflammatory bowel disease, 335–337 Inflammatory bowel disease, 1 10 animal models, 5–7 biopsy diagnosis, 328–329 clinical features, 3–4 complications nutrition therapy, 239–243... 109 ANCA, 108 Anemia, 272–273 Crohn’s disease, 86 megaloblastic, 243 Anemia of chronic disease, 273 Animal models, 5–7 Ankylosing spondylitis, 261–262 Antegren, 143 Antibiotics children, 226 Antibodies, 108 109 , 113–115, 116 natural history, 120–121 Antiinflammatory drugs, 9 Antimicrobials, 135–136 Antineutrophil cytoplasmic antibody (ANCA), 108 Antinuclear antibody (ANA) detection assay, 109 Anti-Saccharomyces... obstruction Crohn’s disease, 188 Intestinal permeability markers, 119 Intestinal resection Crohn’s disease, 183 Intestinal strictureplasty Crohn’s disease, 183–185 Intraabdominal abscess Crohn’s disease, 189 Intracellular adhesion molecule (ICAM), 52 Iritis children, 219 Iron deficiency, 272–273 Irritable bowel syndrome (IBS), 81–82, 103 Ischemic colitis distinguished from inflammatory bowel disease, 337–338... 232–233 Index W–Z Wegener’s granulomatosis, 108 Weight loss children, 217 W pouch, 173 Zinc deficiency, 36, 245 Clinical Gastroenterology™ George Y Wu, MD, PhD, Series Editor Inflammatory Bowel Disease Diagnosis and Therapeutics Edited by Russell D Cohen, MD The University of Chicago Medical Center, Chicago, IL Inflammatory bowel diseases (IBD) are chronic relapsing diseases that unite patients, their families,... d’Alteroche L, et al Non-steroidal anti -inflammatory druginduced colonic strictures: two cases and literature review Am J Gastroenterol 1995;90:2035–2038 15 Bjarnason I, Hayllar J, Macpherson AJ, Russell AS Side effects of nonsteroidal anti -inflammatory drugs on the small and large intestine in humans Gastroenterology 1993 ;104 :1832–1847 16 Davies NM Toxicity of nonsteroidal anti -inflammatory drugs in . nonsteroidal anti -inflammatory drugs on the small and large intestine in humans. Gastroenter- ology 1993 ;104 :1832–1847. 16. Davies NM. Toxicity of nonsteroidal anti -inflammatory drugs in the large intestine Pharmaceuticals Inc. REFERENCES 1. Riddell RH. Pathology of Idiopathic Inflammatory Bowel Disease. In: Inflamma- tory Bowel Disease (4th ed). (Kirsner JB and Sorter RG, eds), 1995. Williams & Wilkins,. cytoplasmic antibody (ANCA), 108 Antinuclear antibody (ANA) detection assay, 109 Anti-Saccharomyces cerevisiae antibody (ASCA), 5, 80–81, 109 test characteristics, 110 Anti-tumor necrosis factor (TNF)