Sporadic and von Hippel-Lindau Disease-related Pancreatic Neuroendocrine Tumors Definitions are not Consistent between the Various Classification Criteria

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\visceral lesion) or Danish criteria (any two clinical manifestations, one clinical manifestation and family background of VHL\self-genetic diagnosis). PNET in VHL seems distinct from sporadic PNET, as most are non-functioning with lower grade and rate of metastases, yet head-to-head comparisons are scarce.

Aim:
Compare VHL-related and sporadic PNET and Internation vs Danish-based diagnosis of VHL.

Methods:
PNET cases identified via MDClone, data gathered included demographic, tumor-specific characteristics, and clinical features\genetic diagnosis\family background of VHL.

Results:
Twenty-nine patients with VHL (17 (58%) with PNET) and 65 with sporadic PNET were identified. PNET diagnosis age was younger for VHL 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, grade, progression, or survival.

Age at diagnosis of PNET, RCC, and VHL was younger in the International vs Danish group. Hemangioblastomas diagnosed in 90% of patients in the International vs none in the Danish. The first manifestation was hemangioblastomas (47%), then pheochromocytoma (31%) in the International, and RCC (62%) and PNET (37%) in the Danish group. Fifty percent had family\genetic background in the International and none in the Danish group.

Conclusions:
Diagnosis of VHL according to International or Danish criteria form two distinct clinical groups, with greater similarity of the Danish group to sporadic PNET patients.