Extended Hormone Profiling Identifies a Wider Network of Duodenal Neuroendocrine Tumor Subtypes.

We studied transcription factors and hormones expressed by duodenal neuroendocrine cells in a consecutively diagnosed series of 53 patients with well-differentiated duodenal NETs. There were 30 men; the mean age was 65 years (33 to 81). The study included biopsies (n = 18), endoscopic mucosal resections (n = 19), and surgical resections (n = 16). Three patients had multifocal disease; two had MEN1. Two patients had neurofibromatosis. Metastases were identified in 15/23 patients with biopsied lymph nodes. PAX6 was expressed in 85%, followed by CDX2 in 65%; ARX was expressed in 33%, and no tumors expressed PAX4. The commonest hormone expressed was gastrin; 23 (43%) had diffuse expression, and 12 (23%) had focal reactivity. Pancreatic polypeptide was diffuse and strong in 17 tumors (32%) classified as PP cell NETs; another 3 tumors had focal staining (total n = 20, 38%). Serotonin was identified only focally in 14 tumors (26%). Somatostatin was positive in 13 tumors (25%), 3 classical D cell tumors and 10 tumors with focal positivity. PYY was expressed in 10 tumors (19%), diffusely in 1 and focally in 9. CCK was identified in 6 tumors (11%), diffusely in 1 and focally in 5. Staining for glucagon/GLPs, insulin, and motilin was completely negative in all tumors. Thirty tumors (57%) expressed more than one hormone; gastrin was the most frequent. In 2 composite gangliocytoma/NETs (CoGNETs), the NET component expressed PP, and both NET and ganglion cells expressed ARX. These data identify a broad spectrum of duodenal NETs including novel cell types and a high incidence of plurihormonality.