A case of rectal neuroendocrine carcinoma in a patient with long‐standing ulcerative colitis involving alterations of the p16‐Rb pathway

Abstract

The patient was a 54-year-old male who had been suffering from extensive ulcerative colitis (UC) for 17 years. Colonoscopy revealed an elevated lesion in the affected rectum, and its biopsy demonstrated neuroendocrine carcinoma (NEC). The surgical specimen obtained on laparoscopic high anterior resection showed extensive active inflammatory and dysplastic lesions and three grossly visible multifocal malignant lesions: a polypoid fungating tumor of NEC (type 1, 20 mm in diameter, pT3) that had been preoperatively noticed, a polypoid fungating tumor of adenocarcinoma (type 1, 22 mm, pT2) and a protruded sessile polypoid tumor (0-Is, 5 mm, pTis) of adenocarcinoma. The NEC was adjacently accompanied by dysplasia-carcinoma sequential lesions and showed a diffuse immunohistochemical overexpression of p53 and p16 proteins and the loss of Rb with no abnormal immunohistochemical staining of microsatellite instability markers and no KRAS mutations. Fifteen months later, the patient showed liver metastasis from the NEC component, followed by bone and spinal metastasis; he died 22 months after the initial diagnosis. A rare case of lethal NEC arising from long-standing extensive UC was reported. The NEC appeared to be UC-related, not incidental, and complicated by progression from dysplasia to carcinoma involving alterations of the p16-Rb pathway.

Solid Pseudopapillary Neoplasm of the Pancreas with High-Grade Malignant Transformation Involving p16-RB Pathway Alterations

“…These results indicate multistep development involving both morphological Case Reports in Surgery (low-grade pseudopapillary structures to high-grade diffuse sheets) and genetic (β-catenin abnormalities plus changes to the p16-RB pathway) alterations. The combination of diffuse RB protein loss and diffuse p16 protein overexpression has often been found in highly aggressive malignant tumours with high proliferative activities, a finding convincingly suggestive of changes in the p16-RB pathway [9,10]. Therefore, RB and p16 immunostaining seems to be useful for identifying the high-grade component in SPNs, while treatment targeting the p16-RB pathway may be effective for high-grade SPNs.…”

Neuroendocrine carcinoma associated with chronic ulcerative colitis: a case report and review of the literature

“…UC associated with NEC is a rare diagnosis. We searched PubMed for previously published case reports on UC associated with NEC by using the keywords "neuroendocrine carcinoma" and "ulcerative colitis" and found only 14 reported cases (Table 1) [3][4][5][6][7][8][9][10][11][12][13][14]. The median age of occurrence was 54 years, with a range of 35 to 77 years.…”

“…Most cases of NEC in patients with UC become clinically evident abruptly after a few months from the last examination because they are proliferative and easily metastasize by frequent venous invasion [ 12 ]. Although NEC in patients with UC is extremely rare, we have highlighted the importance of including NEC in the differential diagnosis of colorectal tumors considering its aggressive behavior and poor outcomes.…”

“…The histology of UCAC is usually adenocarcinoma, with neuroendocrine carcinoma (NEC) being extremely rare. At the time of writing, only 14 cases of NEC associated with UC have been reported [3][4][5], including cases of colonic NEC [6][7][8][9][10] and rectal NEC [11][12][13][14]. In this article, we report the case of a patient with UC who developed an NEC of the rectum and review the clinicopathological features of the cases reported in the literature.…”