S3743 A Rare Case of Colonic MiNEN: Coexisting Large Cell Neuroendocrine Carcinoma and Mucinous Adenocarcinoma

Introduction: Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) of the colon are exceedingly rare, accounting for less than 1% of colorectal tumors. Their dual histology, often combining adenocarcinoma and neuroendocrine carcinoma, presents diagnostic and therapeutic challenges. We present a unique case of colorectal MiNEN with mucinous adenocarcinoma and large cell neuroendocrine carcinoma components. Case Description/Methods: A 74-year-old woman with hypertension and hyperlipidemia was referred for evaluation of iron-deficiency anemia. She denied overt gastrointestinal bleeding but reported increased fatigue. Colonoscopy revealed 2 adjacent lesions in the distal transverse colon: a large circumferential mass approximately 60 cm from the anal verge and a smaller polypoid lesion 5 cm proximally. Biopsy of the larger lesion showed poorly differentiated large cell neuroendocrine carcinoma with a Ki-67 index >90%, prompting urgent oncologic referral. She underwent laparoscopic extended right hemicolectomy with intraoperative tattoo localization. Gross examination revealed a 6.3 × 4.5 cm tumor infiltrating through the colonic wall. Final pathology demonstrated a rare mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN), composed of well-differentiated mucinous adenocarcinoma and high-grade large cell neuroendocrine carcinoma. One of twelve lymph nodes was positive for metastatic mucinous carcinoma. Margins were negative; no lymphovascular or perineural invasion was noted. The tumor was staged as pT3N1a. Immunohistochemistry showed loss of MLH1 and PMS2 with intact MSH2/MSH6, confirming Mismatch Repair Deficiency (dMMR). Focal chromogranin and synaptophysin expression supported neuroendocrine differentiation. She completed 12 cycles of adjuvant FOLFOX. Follow-up positron emission tomography-computed tomography scans at 6 and 12 months showed no recurrence. Discussion: This case highlights the exceptional rarity of colorectal MiNEN with both mucinous adenocarcinoma and large cell neuroendocrine carcinoma components. The coexistence of dual aggressive histologies presents a unique therapeutic challenge and complicates standard management and surveillance algorithms. As long-term outcomes remain unclear, this case reinforces the importance of close multidisciplinary follow-up and contributes to the limited literature on these complex malignancies.