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Endocrine Pathology

, Volume 28, Issue 3, pp 253–268 | Cite as

Primary Renal Paragangliomas and Renal Neoplasia Associated with Pheochromocytoma/Paraganglioma: Analysis of von Hippel–Lindau (VHL), Succinate Dehydrogenase (SDHX) and Transmembrane Protein 127 (TMEM127)

  • Sounak Gupta
  • Jun Zhang
  • Dragana Milosevic
  • John R. Mills
  • Stefan K. Grebe
  • Steven C. Smith
  • Lori A. Erickson
Article

Abstract

Alterations of von Hippel-Lindau (VHL), succinate dehydrogenase (SDHX), and TMEM127 have been associated with the development of pheochromocytomas (PCs) and paragangliomas (PGLs) and are also associated with the development of renal neoplasms. This study involved 2 primary renal PGL and 12 cases of PC/PGL with associated renal neoplasia with a mean follow up of 74 months. Germline VHL and SDHX mutation status was obtained from the medical record. Immunohistochemistry for SDHB and mutation analysis for TMEM127 was performed, in addition to analysis of The Cancer Genome Atlas datasets for SDHX and TMEM127 mutated renal cell carcinomas (RCCs). The spectrum of renal neoplasia included clear cell and tubulocystic and papillary RCC, as well as a case of multiple papillary adenomas. Three patients had metastatic PC/PGL and three patients had VHL syndrome. Previously unreported TMEM127 alterations were identified in two patients, both without evidence of VHL syndrome or SDH-deficiency, and were classified as variants of uncertain significance. Primary renal PGL and neoplasia was associated with about 2% of 710 cases of PC/PGL. These were diagnosed concurrently or on average 27 months prior to the PC/PGL, and most were low-grade, low-stage clear cell RCCs. Up to half of patients with PC/PGL and renal neoplasia had VHL syndrome, SDH deficiency, or alterations in TMEM127. One (of three) case of metastatic PC/PGL had SDHB mutation and loss of SDHB by immunohistochemistry. The other two cases had retained SDHB expression.

Keywords

Paraganglioma Pheochromocytoma Renal cell carcinoma Succinate dehydrogenase SDHA SDHB SDHC SDHD SDHAF1 SDHAF2 TMEM127 Von Hippel–Lindau VHL 

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Sounak Gupta
    • 1
  • Jun Zhang
    • 2
  • Dragana Milosevic
    • 1
  • John R. Mills
    • 1
  • Stefan K. Grebe
    • 1
  • Steven C. Smith
    • 3
  • Lori A. Erickson
    • 1
  1. 1.Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA
  2. 2.Department of Laboratory Medicine and PathologyMayo ClinicPhoenixUSA
  3. 3.Departments of Pathology and UrologyVCU HealthRichmondUSA

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