Poorly differentiated neuroendocrine carcinomas of the gastrointestinal tract: A single-institute study of 43 cases

Objectives: To characterize the clinicopathologic and immunohistochemical features of poorly differentiated neuroendocrine carcinomas (NEC) in the gastrointestinal tract. Design: A total of 43 cases were identified and reassessed based on modern classification. Results: The cohort (27M, 16F; median age: 66 years) included 16 (37%) large cell NEC, 12 (28%) small cell NEC, 5 (12%) NEC not otherwise specified, and 10 (23%) mixed adenoneuroendocrine carcinomas. Tumor predominantly involved the colon (n = 14, 33%), rectum (n = 13, 30%), and esophagus (n = 9, 21%). Immunohistochemically, INSM1 was the most sensitive marker for neuroendocrine differentiation (28/28, 100%), followed by synaptophysin (40/43, 93%), CD56 (22/35, 63%), and chromogranin (18/40, 45%). SATB2, CDX2, CK20, CK7, abnormal p53, and PD-L1 was positive in 21/26 (81%), 26/37 (70%), 11/35 (31%), 10/35 (29%), 19/24 (79%), and 12/23 (52%) cases, respectively. Three of 25 (11%) were mismatch repair protein deficient. Of 21 resected tumors, 19 (90%) were >= pT3 and 13 (62%) had nodal metastasis. Twenty-eight (65%) had distant metastasis. The 5-year survival rate was 21%. The prognosis was stage dependent (p < 0.05), but not associated with tumor type, location, or specific immunomarkers. Conclusion: Gastrointestinal NECs are aggressive neoplasms. INSM1, synaptophysin, and SATB2 are sensitive markers, although not site or tumor type specific.