Pheochromocytoma in von hippel-lindau disease: distinct histopathologic phenotype compared to pheochromocytoma in multiple endocrine neoplasia type 2

Endocr Pathol. Spring 2002;13(1):17-27. doi: 10.1385/ep:13:1:17.


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.

Publication types

  • Comparative Study

MeSH terms

  • Adrenal Gland Neoplasms / complications
  • Adrenal Gland Neoplasms / pathology*
  • Adult
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Endocrine Neoplasia Type 2a / complications
  • Multiple Endocrine Neoplasia Type 2a / pathology*
  • Pheochromocytoma / complications
  • Pheochromocytoma / pathology*
  • von Hippel-Lindau Disease / complications
  • von Hippel-Lindau Disease / pathology*