Pheochromocytoma in von Hippel-Lindau disease: Distinct histopathologic phenotype compared to pheochromocytoma in multiple endocrine neoplasia type 2

Pheochromocytomas are rare neuroendocrine tumors that arise from chromaffin tissue. In a small subset of patients, pheochromocytomas occur as a manifestation of von Hippel-Lindau (VHL) disease. The histology of VHL-associated pheochromocytomas has not been reported in detail. In this article, we describe histopathologic features of 14 pheochromocytomas in eight patients with VHL disease and demonstrate that VHL-associated pheochromocytomas have a distinct histologic phenotype as compared with pheochromocytomas in patients with multiple endocrine neoplasia type 2 (MEN 2). VHL tumors are characterized by a thick vascular tumor capsule; myxoid and hyalinized stroma; round, small to medium tumor cells intermixed with small vessels; predominantly amphophilic and clear cytoplasm; absence of cytoplasmic hyaline globules; and lack of nuclear atypia or mitoses. In contrast to MEN 2, there is no extratumoral adrenomedullary hyperplasia in the VHL adrenal gland. Our findings of a distinct histologic phenotype of VHL pheochromocytoma may further help in subdividing patients who clinically present with multiple, bilateral pheochromocytomas.