Potential neuroendocrine differentiation in poorly differentiated colorectal adenocarcinoma: A hidden trait?

Neuroendocrine carcinoma (NEC) of the colon and rectum is a rare malignancy with a poor prognosis that is characterized by distinct clinical and histopathological features that differ significantly from those of more prevalent adenocarcinomas. Poorly differentiated colorectal adenocarcinoma (PDC) is also rare and carries a poor prognosis. Considering the morphological similarities between these two rare, poorly differentiated cancers of the colon and rectum, it is plausible that certain cases of colorectal cancer (CRC) diagnosed as PDC may contain NEC as well. In the present study, cases of CRC that were diagnosed as PDC at our institution were investigated, searching for patients who exhibited NEC characteristics based on the expression of neuroendocrine markers (NEMs), including chromogranin A, synaptophysin and insulinoma-associated 1 (INSM1), and the loss of retinoblastoma 1 (Rb). Of 816 total CRC cases, 74 cases (9.1%) were identified as PDC. These were further divided into 13 (17.5%) cases that were positive for NEMs and others. Of these 13 cases, the expression rates for chromogranin A and synaptophysin were 69.2% each, while that of INSM1 was 100%. Upon re-examination of the 13 PDC cases, two cases were morphologically identified as NEC, including one large- and one small-cell NEC. A total of two cases showed loss of Rb in their PDC lesions. NEM positivity was considered an independent prognostic factor in the 74 PDC cases. Among these cases, some may exhibit characteristics of NEC. Unraveling the molecular mechanisms using CRC that harbors both PDC and NEC will be a task for future research.