Large cell neuroendocrine carcinoma arising in a sessile serrated adenoma: a novel observation.

A 68-year-old woman underwent polypectomy of 2 right-sided colonic polyps identified by screening colonoscopy. Histologic examination of both polyps showed features of sessile serrated adenoma. The larger polyp harbored an invasive tumor composed of large, high-grade cells arranged in nests and cords without tumoral mucin production. Immunohistochemistry demonstrated synaptophysin, cdx-2, cytokeratin 7, and cytokeratin 20 positivity. Both invasive carcinoma and sessile serrated adenoma showed a decreased expression level to focal negative expression of hMLH-1 by immunohistochemistry. Combined morphologic and immunohistochemical features favored large cell neuroendocrine carcinoma arising in a sessile serrated adenoma. Specific carcinoma subtypes and special histologic features (eg, tumor-infiltrating lymphocytes) have been previously reported in carcinomas arising from sessile serrated adenomas. Large cell neuroendocrine carcinoma has not yet been reported in association with sessile serrated adenomas, with this case suggesting a rare but potentially novel end point for the microsatellite instability pathway.

Diverticular disease of the vermiform appendix: a diagnostic clue to underlying appendiceal neoplasm.

Acquired diverticula of the vermiform appendix are rare and arise as a result of different pathogenetic mechanisms. One of the etiologies includes proximally located, often unsuspected small neoplasms. Although the association of appendiceal diverticulosis and neoplasia is known, it remains underemphasized in the teaching and practice of surgical pathology. To investigate the frequency of appendiceal neoplasms with acquired diverticulosis, we conducted a retrospective analysis of all appendectomy specimens received in our institution for a 55-month period (January 2002-July 2006). A total of 1361 appendectomy specimens were identified. Diverticulosis was diagnosed in 23 (1.7%) of all cases. Eleven (48%) appendectomy specimens with diverticulosis also harbored an appendiceal neoplasm. The association of appendiceal neoplasms with diverticulosis was statistically significant (P < .0001, 2-sided Fisher exact test). Neoplastic processes included 5 well-differentiated neuroendocrine tumors (carcinoids), 3 mucinous adenomas, 1 tubular adenoma, and 2 adenocarcinomas. In one case, routine representative sections sampled only a small focus of carcinoma, which originally went undiagnosed. We stress the need for meticulous gross assessment with histologic examination of the entire appendectomy specimen in cases of appendiceal diverticulosis. Thorough examination is required to rule out an underlying neoplasm as a cause of diverticulosis. As acquired diverticula represent a rare finding, examination of the entire appendix in this setting does not create a significant impact on the workload within the pathologic laboratory.

Sessile serrated polyp mimicry in patients with solitary rectal ulcer syndrome: is there evidence of preneoplastic change?

CONTEXT: Solitary rectal ulcer syndrome (SRUS) is associated with erythema and ulceration of the rectal wall. Serrated lesions of the colon are divided into conventional hyperplastic polyps and a new set of lesions that are variably called sessile serrated polyps (SSPs) and sessile serrated adenomas. The SSPs are epithelial proliferative lesions that appear to act as a unique pathway to colorectal carcinogenesis. No association between SRUS and SSPs has been previously reported. OBJECTIVE: To assess a possible association between SRUS and morphologic features that mimic SSPs. DESIGN: Twenty-six patients with SRUS, who presented to our institution between January 1, 1999, and November 14, 2004, were retrospectively reviewed for SSP-type morphologic features by 3 pathologists. Ki-67 and hMLH1 immunohistochemical stains were used. Control tissues included 10 conventional left-sided hyperplastic polyps, 10 right-sided large SSPs, 7 adenocarcinomas with known loss of hMLH1 gene expression, and 4 normal human tonsil tissues. RESULTS: Ten (38%) of 26 SRUS specimens demonstrated histologic features consistent with SSPs. These features included exaggerated serration within the lower crypt compartments, crypt branching, hypermucinous appearance of epithelium, and horizontal extension of crypt bases along the muscularis mucosa. All 10 cases of SRUS had positive basal Ki-67 staining in 10% to 20% of cells. Two (20%) of the 10 cases demonstrated focal superficial loss of hMLH1 mismatch repair gene expression within areas of serrated morphologic features. One hyperplastic polyp superimposed on SRUS showed a reduced number of surface epithelial cells that express hMLH1 protein. CONCLUSIONS: Up to 38% of patients with SRUS have histologic changes that mimic SSPs. More importantly, 20% of these serrated lesions were found to have focal loss of hMLH1 gene expression, indicating a potential of preneoplastic change. This phenomenon may reflect an increased propensity for neoplastic progression in response to repeated trauma and repair process in certain cases of SRUS.