A variety of histologies is often mixed in neuroendocrine carcinoma (NEC) called mixed neuroendocrine–non-neuroendocrine neoplasm (MiNEN). However, tumors consisting of both large-cell NEC and squamous cell carcinoma (SCC) are rare. NEC of the large intestine is aggressive; however, an ideal treatment strategy has not been established. In this study, we have reported a case of rectal MiNEN containing large-cell NEC and SCC that was covered by tubulovillous adenoma. A 73-year-old man was referred to our hospital for the treatment of an upper rectal tumor. The results of preoperative biopsy indicated tubulovillous adenoma, whereas computed tomography revealed multiple liver tumors and swollen lymph nodes around the rectum. Laparotomy was performed because of severe dyschezia caused by rectal stenosis. Hartmann’s operation was performed because of peritoneal metastases. Histopathological examination of the rectal tumor revealed MiNEN containing large-cell NEC, SCC, well-differentiated adenocarcinoma, and tubulovillous adenoma covering the surface of the tumor. The patient died 73 days after surgery due to liver metastases. It is important to consider NEC in the differential diagnosis and tissue sampling should be performed to ensure appropriate management when pathological findings and clinical diagnosis do not match. More research is required to determine the ideal treatment for these rare and aggressive tumors.
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