A case of rectal mixed neuroendocrine-non-neuroendocrine neoplasm diagnosed only after radical surgery: implications of diagnostic timing for therapeutic decision-making

Colorectal mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare and aggressive tumors in which accurate preoperative diagnosis remains difficult because of marked intratumoral heterogeneity. A 75-year-old man presented with locally advanced rectal cancer with inguinal lymph node metastasis. Routine biopsy demonstrated moderately to poorly differentiated adenocarcinoma, while retrospective immunohistochemical analysis revealed focal neuroendocrine differentiation insufficient for a diagnosis of MiNEN. Initial systemic chemotherapy with FOLFOXIRI plus bevacizumab was administered for metastatic rectal adenocarcinoma, followed by chemoradiotherapy, and radical surgery was performed after a partial response. Histopathological examination of the resected specimen revealed composite-type MiNEN composed of poorly differentiated adenocarcinoma and large-cell neuroendocrine carcinoma (NEC). The NEC component showed marked lymphovascular invasion and a Ki-67 index exceeding 90%, indicating highly aggressive biological behavior. Multiple liver metastases developed one month after surgery, and postoperative chemotherapy with carboplatin plus etoposide was initiated targeting the NEC component. The patient died of disease 17 months after surgery. This case highlights the diagnostic challenges and therapeutic dilemmas associated with preoperative management of colorectal MiNEN, particularly in patients with locally advanced rectal cancer requiring multidisciplinary management. Comprehensive pathological assessment of the resected specimen remains essential for recognizing the biologically dominant component and optimizing subsequent therapeutic strategy.