I read with interest the report by Matsumoto and colleagues¹ of a patient with ulcerative colitis and multiple microcarcinoid tumours, and would like to describe a similar recent case encountered in our department. A 44 year old man with an 18 year history of ulcerative colitis underwent total colectomy after a diagnosis of high grade dysplasia in a rectal biopsy. The resection specimen revealed a mucinous adenocarcinoma of the rectum invading the submucosa, but not involving the muscularis propria, perirectal fat, or lymph nodes. There was also active ulcerative colitis of mild to moderate severity involving the distal 200 mm of the colon and rectum. The inflamed segment was extensively sampled and all sections showed multifocal endocrine cell proliferation within the muscularis mucosae and the superficial submucosa (fig 1). Most foci comprised clusters of between five and 50 cells, which were typically arranged in small nests and cords, but there were four larger endocrine cell aggregates from 1 to 2.5 mm maximum diameter. Some of the submucosal nests were closely apposed to nerves and ganglion cells. Immunohistochemistry on representative sections showed expression of cytokeratin, chromogranin, synaptophysin, and CD56 within the endocrine cells and close apposition to S100 protein positive nerves and dendritic cells. There was no evidence of endocrine cell hyperplasia within the overlying mucosa or in the normal proximal bowel.

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Figure 1

 Endocrine cell proliferation within thickened rectal muscularis mucosae. There is no evidence of mucosal endocrine hyperplasia.

Although there are several reports of neuroendocrine tumours arising in patients with inflammatory bowel disease, the finding of microscopic and multifocal endocrine cell proliferations is much more rare. Indeed, the most appropriate terminology for these lesions is not clear. Matsumoto and colleagues¹ used the term “microcarcinoids” to describe the endocrine proliferations in their patient. The lesions were described as “multiple small islands of cells” but the sizes of the lesions were not documented. Maruyama and colleagues² described a non-colitic patient with multiple, variably sized endocrine cell proliferations and five typical grossly evident carcinoid tumours in the colon. They suggested that the microscopic lesions should be subdivided into microcarcinoids, endocrine cell microproliferations (ECMPs), and transitional forms. The smaller ECMPs and transitional lesions did not exhibit expansile growth or intervening fibrous stroma. Abe et al,³ in describing a case of multiple duodenal endocrine cell proliferations, defined carcinoid tumours as greater than 3 mm diameter, microcarcinoids as between 0.5 and 2.9 mm, and lesions smaller than 0.5 mm (which they interpreted as hyperplastic) as “endocrine cell micronests”. According to these criteria, most of the lesions in our case would be classified as ECMPs or micronests. Regardless of the terminology, it would appear that these cases show a spectrum of endocrine cell proliferation, but whether these are truly hyperplastic or neoplastic is not clear.

As discussed by Matsumoto et al,¹ it has been suggested previously that colonic endocrine cell hyperplasia in association with inflammatory bowel disease may represent a response to injury or inflammation. However, although this hypothesis may reasonably explain mucosal endocrine cell proliferation, the distribution of the lesions within the submucosa and muscularis mucosae in our patient and in some previous reports^1,2,4 is less readily understood, particularly because the crypt endocrine population was not hyperplastic in these cases. Maruyama and colleagues² noted in their case that the submucosal endocrine cells were often associated with ganglion cells and S100 positive dendritic cells, and postulated that the proliferation involved a subpopulation of endocrine cells associated with submucosal nerve fibres. This suggestion is supported by the findings in our case. As noted by Matsumoto et al,¹ deeply located endocrine cell proliferations are unlikely to be identified on endoscopic biopsies. Indeed, our patient underwent four colonoscopic examinations in the 12 months before surgery and no endocrine lesions were identified in a total of 24 biopsy samples examined during that period. Therefore, the incidence of such lesions may be underestimated, although whether this is a clinically relevant finding is not clear.