Carcinoid tumours are neoplasms that arise from mature endocrine cells or their stem cells within the epithelial layer of the gastrointestinal tract. In 1979, Hay and Curt6
reported a case of carcinoid tumour complicating UC. Since then, 21 cases of UC complicated by histologically verified carcinoid tumour have been described in the English literature.4–16
As has been the case in our patient, almost all carcinoids were diagnosed histologically in the surgically removed specimens. Although the incidence of carcinoid in UC remains obscure, our review of the literature suggests that the occurrence of carcinoid is an exceptional event in patients with UC. In addition, it should be noted that there is a considerable heterogeneity in the histology and the site of carcinoids.4–16
There has been controversy as to the association of carcinoid and UC. Greenstein et al
reported five cases of UC accompanied by carcinoids.5
However, their patients had carcinoids at sites apparently unaffected by UC (the appendix and the ileum), where the tumour occurs predominantly in the general population.17,18
Thus, Greenstein et al
suggested that the development of carcinoids is independent of UC.5
Another case of appendiceal carcinoid complicating UC was described by LeMarc’hadour et al
However, the development of carcinoid in the appendix in UC does not exclude the possible correlation of the two conditions, because recent investigations have confirmed that the appendix can be affected by UC.19,20
Miller and Summer15
suggested a possible contribution of chronic inflammation to the development of carcinoids, because they found enteroendocrine cell hyperplasia in the flat mucosa of patients with UC complicated by solid carcinoid tumour.
“It is possible that microcarcinoids in UC are a reactive phenomenon induced by chronic inflammation”
Our case was characterised by a 17 year history of intractable UC and the development of multiple microcarcinoids. There have been two reported cases of UC accompanied microcarcinoids similar to those found in our patient.12,13
In those earlier reports, microcarcinoids were found in the left side of the large bowel. In a patient of McNeely et al
multiple carcinoids were identified in a hemicolectomised specimen, which also contained invasive sigmoid colon cancers and dysplasia. In the other case, a solitary microcarcinoid was incidentally found in the rectum of a patient operated on because of intractable UC.13
It has been shown that enteroendocrine cell hyperplasia is a common histological feature in UC.14
Furthermore, epithelial stem cells, in addition to columnar cells, can be damaged by inflammation. Thus, it is possible that microcarcinoids in UC are a reactive phenomenon induced by chronic inflammation.
Even if carcinoids in UC can be presumed to be a consequence of chronic inflammation, it still remains unclear how and to what extent the inflammation contributes to the pathogenesis of carcinoids. However, it is possible that microcarcinoids remain undetected in patients with UC, because they can easily be missed by colonoscopy, as in our patient.4
In addition, biopsy specimens are inappropriate for the diagnosis because of the predominant submucosal nature of the tumour. Whereas diagnostic and therapeutic strategies for dysplasia and cancer in UC have been rigorously investigated during the past 30 years, such strategies need to be investigated for carcinoid tumours.
Take home messages
- We report a patient with intractable ulcerative colitis of the entire type in whom multiple microcarcinoids were found in the resected colorectum after total proctocolectomy, although they were not noted on previous biopsies
- Carcinoids may be more common than previously thought, and they may be a reactive phenomenon to a variety of factors in ulcerative colitis
- Diagnostic and therapeutic strategies for carcinoid tumours need to be investigated