Grade 3 Neuroendocrine Tumor (G3 NET) in a Background of Multiple Serotonin Cell Neoplasms of the Ileum Associated with Carcinoid Syndrome and Aggressive Behavior

Grade 3 well-differentiated neuroendocrine tumors (G3 NETs) have been characterized in the pancreas and stomach and distinguished from low-to-intermediate grade (G1-G2) NETs, as well as from highly malignant, poorly differentiated neuroendocrine carcinomas (NECs). Up to now, no G3 NET has been thoroughly described in the distal small intestine. We herein report a case of a 61-year-old man presenting with carcinoid syndrome. The surgical specimen showed, in a background of small G1 ileal NETs, a larger, grade 3 NET, which retained the nesting pattern and the expression of serotonin, chromogranin-A, and type 2A somatostatin receptors, typical of well-differentiated jejuno-ileal NETs. The patient had G3 NET metastasis to the liver and he died 14 months after surgery, due to deterioration in his clinical conditions.