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

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Abstract

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 phenochromocytoma may further help in subdividing patients who clinically present with multiple, bilateral pheochromocytomas.

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Author notes

  1. Christian A. Koch MD

    Present address: Department of Medicine III, University of Leipzig, Philipp-Rosenthal-Str. 27, 04103, Leipzig, Germany

Authors and Affiliations

  1. Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, USA

    Christian A. Koch MD, Karel Pacak MD, PhD & George P. Chrousos MD

  2. Laboratory of Pathology, National Cancer Institute, USA

    David Mauro MD, PhD

  3. Urologic Oncology Branch, National Cancer Institute, USA

    McClellan M. Walther MD & W. Marston Linehan MD

  4. National Institutes of Health, Bethesda, MD

    Ronald Jaffe MD

  5. Department of Pathology, University of Pittsburgh and Children’s Hospital, Pittsburgh, PA

    Ronald Jaffe MD

  6. Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH, Building 10, Room 5D37, 10 Center Drive, 20892, Bethesda, MD

    Alexander O. Vortmeyer MD, Zhengping Zhuang MD, PhD &  Irina A. Lubensky MD

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  1. Christian A. Koch MD
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Correspondence to Irina A. Lubensky MD.

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Koch, C.A., Mauro, D., Walther, M.M. et al. Pheochromocytoma in von hippel-lindau disease: Distinct histopathologic phenotype compared to pheochromocytoma in multiple endocrine neoplasia type 2. Endocr Pathol 13, 17–27 (2002). https://doi.org/10.1385/EP:13:1:17

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