To define a classification schema for von Hippel-Lindau (VHL) patients who have a pheochromocytoma predominant phenotyope.

VHL patients who underwent adrenalectomy with pathology-proven pheochromocytoma at our institution were included. We defined pheochromocytoma-predominant VHL a priori as patients with one or more of the following traits: early onset [age at first pheochromocytoma below the cohort’s median age (28.2years)], family history of pheochromocytomas, multiple pheochromocytomas, and paraganglioma(s). Patients with pheochromocytoma-predominant disease were compared to the remaining cohort to determine differences in genotype and phenotype.

One-hundred thirty-nine VHL patients were examined. Preliminary analysis showed that three characteristics (early onset, family history, and multiple pheochromocytomas) were associated. Having paraganglioma(s) did not correlate with the other factors, so it was excluded from the definition of pheochromocytoma-predominant disease. The majority of our patients (110/139, 79%) met the final definition. Pheochromocytoma-predominant patients were less likely to have most additional VHL tumor types, including renal cell carcinoma (P<.001) whereas they were more likely to have missense mutations (P<.001) than the remaining cohort. Overall, pheochromocytoma-predominant patients were most likely to have 0 (P<.001) or 1 (P=.008) extra-adrenal tumor types while non-pheochromocytoma-predominant patients were most likely to have 4 (P=.02) or 5 (P=.02).

Pheochromocytoma-predominant VHL patients are phenotypically distinct from their non-pheochromocytoma-predominant counterparts and are significantly less likely to have more than one other VHL manifestation, including renal carcinoma.