Long-standing inflammatory bowel disease (IBD), either ulcerative colitis or Crohn disease, is associated with a high risk of developing colorectal adenocarcinoma (CAC). However, histomorphology of IBD-associated CAC has not been thoroughly examined, and it is unclear whether and how these patients should be screened for Lynch syndrome (LS). We evaluated the demographic and morphologic features of 108 IBD-associated CACs, including ulcerative colitis-associated (n = 95) and Crohn disease-associated CACs (n = 13), against 93 control cases of sporadic microsatellite-stable (MSS) CAC, 20 cases of sporadic microsatellite instability high (MSI-H) CAC, and 23 CAC cases of LS. The mean age of patients with IBD-associated CAC was 50 years, which was lower compared with the mean age of 63.7 years of the sporadic MSS controls and 76.5 years of the sporadic MSI-H group but not statistically different from that of the LS patients. Synchronous CACs were noted in 20.4% of the IBD patients and 13% of LS patients but in only 2.1% of the sporadic MSS controls and in none of the MSI-H patients. Right-sided CACs were significantly less frequent in the IBD group than in sporadic MSS controls, MSI-H group, and LS patients (P < 0.05 for all). In contrast to sporadic MSS CAC, IBD-associated CACs are characterized by lack of tumor necrosis, Crohn-like reaction, tumor histologic heterogeneity, the presence of mucin, and signet ring cell differentiation and tumor well differentiation. The histomorphologic similarity among IBD-associated and MSI-H tumors, either sporadic MSI-H or LS-related, is independent of MSI status. The young age of patients with IBD-associated CAC and the morphological similarities among IBD-associated, sporadic MSI-H, and LS-related CAC suggest that an age-based and morphology-based strategy before the screening test for LS may be less effective in IBD patients than in the non-IBD population.
[Show abstract][Hide abstract] ABSTRACT: This review summarizes diagnostic problems, challenges and advances in ulcerative colitis (UC). It emphasizes that, although histopathological examination plays a major role in the diagnosis and management of UC, it should always be interpreted in the context of clinical, endoscopic, and radiological findings. Accurate diagnosis requires knowledge of the classic morphological features of UC, as well as a number of atypical pathological presentations that may cause mis-classification of the disease process, either in resection or biopsy specimens. These atypical pathological presentations include rectal sparing and patchiness of disease at initial presentation of UC in pediatric patients or in the setting of medically treated UC, cecal or ascending colon inflammation in left-sided UC, and backwash ileitis in patients with severe ulcerative pancolitis. Loosely formed microgranulomas, with pale foamy histiocytes adjacent to a damaged crypt or eroded surface, should not be interpreted as evidence of Crohn's disease. Indeterminate colitis should only be used in colectomy specimens as a provisional pathological diagnosis. Patients with UC are at risk for the development of dysplasia and carcinoma; optimal outcomes in UC surveillance programs require familiarity with the diagnostic criteria and challenges relating to UC-associated dysplasia and malignancy. Colon biopsy from UC patients should always be evaluated for dysplasia based on cytological and architectural abnormalities. Accurate interpretation and classification of dysplasia in colon biopsy from UC patients as sporadic adenoma or UC-related dysplasia [flat, adenoma-like, or dysplasia-associated lesion or mass (DALM)] requires clinical and endoscopic correlation. Isolated polypoid dysplastic lesions are considered to be sporadic adenoma if occurring outside areas of histologically proven colitis, or adenoma-like dysplasia if occurring in the diseased segment. Recent data suggest that such lesions may be treated adequately by polypectomy in the absence of flat dysplasia in the patient. UC patients with DALM or flat high-grade dysplasia should be treated by colectomy because of the high probability of adenocarcinoma. The natural history of low-grade dysplasia (LGD) is more controversial: while multifocal LGD, particularly if detected at the time of initial endoscopic examination, is treated with colectomy, unifocal flat LGD detected during surveillance may be managed by close follow-up with increased surveillance. The surveillance interval and treatment options for UC patients with dysplasia are reviewed in detail.
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