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.
Pediatric and Reporoductive ENdocinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA.
Christian A
CA
Koch
David
D
Mauro
McClellan M
MM
Walther
W Marston
WM
Linehan
Alexander O
AO
Vortmeyer
Ronald
R
Jaffe
Karel
K
Pacak
George P
GP
Chrousos
Zhengping
Z
Zhuang
Irina A
IA
Lubensky
D000310:Adrenal Gland Neoplasms / Q000150:complications / Q000473:pathology*; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000150:complications / Q000473:pathology*; D010673:Pheochromocytoma / Q000150:complications / Q000473:pathology*; D006623:von Hippel-Lindau Disease / Q000150:complications / Q000473:pathology*