Retroperitoneal paraganglioma with loss of heterozygosity of the von Hippel–Lindau gene: a case report and review of the literature

• Published in: Endocrine Journal Vol. 69; no. 9; pp. 1137 - 1147
• Main Authors: Anno, Mari, Izawa, Shoichiro, Fujioka, Yohei, Matsuzawa, Kazuhiko, Saito, Kohei, Hikita, Katsuya, Makishima, Karen, Nosaka, Kanae, Takenaka, Atsushi, Usui, Takeshi, Yamamoto, Kazuhiro
• Format: Journal Article
• Language: English
• Published: Japan The Japan Endocrine Society 01-01-2022; Japan Science and Technology Agency
• Subjects: Case reports; Copy number; Exons; Heterozygosity; Kidney cancer; Literature reviews; Loss of heterozygosity; Multiplex ligation-dependent probe amplification; Mutation; Paraganglioma; Patients; Pheochromocytoma; Polymorphic microsatellite; Renal cell carcinoma; Sequence analysis; Tumors; VHL protein; Von Hippel-Lindau disease; Paraganglioma; Von Hippel–Lindau disease; Multiplex ligation-dependent probe amplification; Polymorphic microsatellite; Loss of heterozygosity
• ISSN: 0918-8959; 1348-4540
• DOI: 10.1507/endocrj.EJ21-0611

Von Hippel–Lindau (VHL) disease is an autosomal dominant disease related to germline mutations in VHL. In VHL disease, pheochromocytoma develops in 10%–20% of patients because of germline mutations and loss of heterozygosity of VHL. However, the rate of paraganglioma associated with VHL is low compared with that of pheochromocytoma, and the reason is unknown. In this study, we performed germline and somatic mutation analyses of retroperitoneal paraganglioma that developed in a patient with clinically diagnosed VHL disease and investigated the tumorigenic mechanism of paraganglioma. The patient was a 25-year-old woman who was considered to have VHL disease on the basis of her family history. She was referred to our clinic to investigate a tumor at the bifurcation of the common iliac artery. The tumor was diagnosed as retroperitoneal paraganglioma by clinical evaluations. A left renal cell carcinoma was also suspected. Polymerase chain reaction direct sequencing analysis and polymorphic microsatellite analysis within the VHL locus suggested that loss of heterozygosity of VHL was associated with paraganglioma and renal cell carcinoma. Multiplex ligation-dependent probe amplification analysis showed a loss of the copy number of VHL exons in paraganglioma. These results suggest that VHL disease contributes to the development of paraganglioma. A literature review showed no reported common missense variants involved in the progression of paraganglioma. The loss of heterozygosity of VHL can be a tumorigenic mechanism of retroperitoneal paraganglioma in VHL disease. However, the low rate of paraganglioma compared with pheochromocytoma is not explained by their genetic background alone.