Endocrine Abstracts

Background: Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous, with grade (G) defined by Ki67 proliferation index (<3% G1, 3-20% G2, >20% G3) or mitotic rate. The G3 NEN subgroup is further divided into well differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NEC). Grade progression can occur over time, with low-to-high grade progression (L-to-H; G1/2 to G3) the most clinically relevant form. It is associated w...

Background: Small intestinal neuroendocrine tumor (SI-NET) is one of the major cancer subtypes of the small bowel. Most SI-NETs locate in the terminal ileum with a high incidence of multiple synchronous primary tumors. The only essentially curative treatment of SI-NETs is complete surgical resection; however, most SI-NET patients cannot undergo surgery as they typically present with an extensive metastatic disease. Several high-throughput sequencing studies have reported low s...

Background: Gastrointestinal neuroendocrine tumors (GI NETs) are subdivided into grades (G) G1-G3 based on Ki-67 proliferation index (%) (G1<3%, G2 3-20%, and G3 >20%) or mitotic rate, with tumor grade informing prognosis and treatment. Grade progression (GP) over time in GI and pancreatic NETs has recently been identified, with low(G1/2)-to-high(G3) grade progression (L-to-H) the most clinically relevant form. L-to-H is associated with worse survival, yet the timefram...

Background: Grade 3 pancreatic neuroendocrine tumor (G3-PanNET) and neuroendocrine carcinoma (PanNEC) are both defined by Ki67>20% and/or mitoses >20 per 2mm2. PanNET and PanNEC are thought to be molecularly distinct entities and progression from PanNET to PanNEC is considered rare. MEN1, ATRX, DAXX, and TSC1/2 mutations are common in PanNET, while TP53, RB1, KRAS, and SMAD4 mutations are typical of PanNEC. Immunostains for ATRX/DAXX/p53/Rb aid in the classification of...

Background: Pancreatic neuroendocrine tumors (panNETs) are heterogeneous, with grade (G) defined by Ki67 proliferation index (<3% G1, 3-20% G2, and >20% G3) or mitotic rate. Previous studies suggest that baseline Ki67 index may be confounded by biopsy site (primary or metastasis), biopsy technique and primary tumor size. Ki67 differences leading to grade discordance in PanNETs at baseline is relatively understudied. Our study aims to evaluate grade discordance in synch...

Background: Germline pathogenic or likely pathogenic (P/LP) variants occur in approximately 10% of NEN patients with recent data suggesting a higher frequency in pancreatic NENs or paraganglioma/pheochromocytoma (PPGL). However, identification of VUS can complicate interpretation of germline results, particularly when diverse populations are under study and the optimal gene panel size for testing remains unclear.Methods: A single-center retrospective cha...

Background: G3NETs demonstrate variable clinical behavior (Ki-67>20-100%). Treatment extrapolated from grade 1/2 (G1/2) NETs and neuroendocrine carcinomas depending on clinicopathologic features. Therapy for treatment-emergent G3NETs remains especially ill-defined.Methods: Retrospective chart review of patients with de novo G3NETs or progressing from low-to-high grade (L-H) (G1/2 at diagnosis and G3 >=3 months later). Treatment patterns compared ...

Background: Serotonin produced by ileum neuroendocrine tumors (i-NETs) promotes development of the mesenteric mass (MM) associated with lymph node metastases. We previously reported that more extensive MM progression along the superior mesenteric vessels predicts a lower rate of complete surgical resection. In this study, we hypothesized that tumoral serotonin production is associated not only with the development of MM but also its progression, and we examined serotonin level...

Background: Serotonin production by ileum neuroendocrine tumors (i-NETs) is considered a critical mediator of the fibrotic reaction in mesenteric mass (MM)/ lymph node metastasis. Antidepressants modify serotonin dynamics: however, their role in MM formation is uncertain. We hypothesized that histories of antidepressant use affect MM formation. This study examined the correlation between antidepressant use and MM formation.Methods: One hundred eighty-two...