Endocrine Abstracts

Background: von Hipple-Lindau (VHL) disease comprises hemangioblastomas, renal cell carcinomas (RCC), pheochromocytomas, and pancreatic neuroendocrine tumors (PNET). Diagnosis is based International (two hemangioblastomas, one hemangioblastoma and one visceral lesion, or VHL family history and hemangioblastoma or visceral lesion) or Danish criteria (any two clinical manifestations, one clinical manifestation and family background of VHL or self-genetic diagnosis). The nature of PNET in VHL appears to be distinct from sporadic PNET, as most VHL-related PNET are non-functioning, are lower grade and have a lower rate of metastases, yet head-to-head comparisons are scarce.

Aim: In the current study we wished to compare the characteristics of VHL-related and sporadic PNET. We also tested the hypothesis that diagnosis of VHL according to the International and Danish criteria may comprise two distinct patient populations.

Methods: Patients with a diagnosis of PNET were identified using the MD Clone platform and data including demographic and tumor specific characteristics were gathered. In addition, the presence of any clinical feature of VHL and presence of a family or genetic diagnoses was noted for each patient. Patients were grouped according to a diagnosis of VHL (following either International or Danish criteria) or sporadic PNET.

Results: Twenty-nine patients with VHL, 17 (58%) with PNET and 65 patients with sporadic PNET were identified. Patients with VHL were younger at PNET diagnosis compared with sporadic PNET (50.1±4.7 vs. 62.8±1.5 years, P<0.001). There was no significant difference between VHL-related or sporadic PNET in stage and grade, nor in progression or survival. Sporadic PNET were more often located in the body and tail of pancreas. In the subgroup comparison of International vs Danish criteria -based VHL diagnosis, age at diagnosis of PNET, RCC and VHL was younger in the International group. Hemangioblastomas were diagnosed in 90% of patients in the International compared with none in the Danish group. First manifestation of VHL was hemangioblastomas (47%) followed by pheochromocytomas (31%) in the International group compared with RCC (62%) and PNET (37%) in the Danish group. Finally, 50% in the International and none in the Danish group had a family or genetic VHL background.

Conclusions: Patients with PNET diagnosed with VHL according to the International and Danish criteria seem to form two distinct clinical groups, with a greater similarity of the Danish group to patients with sporadic PNET. Further comparisons in other cohorts are warranted, as this may call for different clinical management.