Succinate Dehydrogenase-Deficient Renal Cancer Featuring Fructose-1,6-Biphosphatase Loss, Pyruvate Kinase M2 Overexpression, and SWI/SNF Chromatin Remodeling Complex Aberrations: A Rare Case Report

Abstract

SDH (succinate dehydrogenase)-deficient renal cancer is a rare renal cancer (RCC) subtype recently accepted by WHO as an unique RCC subtype with only 59 cases described worldwide. Here we report a case of 17-year old man. The detailed evaluation indicated occurrence of the SDHBdeficient RCC. The genetic testing revealed no germline mutation in SDH genes. Immunohistochemistry showed SDHB deficiency, overexpression of PKM2 and dramatic downregulation of FBP1 metabolic enzymes, unaltered levels of pAMPK and mTOR. Furthermore, the strong upregulation of INI1, BRG1 and overexpression of BAF180 subunits of SWI/SNF ATP-dependent chromatin remodeling complex were found. The identified tumor pathologically did not resemble ccRCC (clear cell renal cell carcinoma) but some metabolic alterations are common for both cancer types. Thus, we postulate that the phenotypical differences between ccRCC and SDHB-deficient RCC may be related to distinct molecular and metabolic alterations.

Succinate dehydrogenase B-deficient renal cell carcinoma with a germline variant in a Japanese patient: a case report

“…The estimated incidence rate of SDH-deficient RCC among all RCCs is 0.05%–0.2% 2 . Sixty cases of SDH-deficient RCC have been reported in the literature 3 . Among SDH-deficient RCCs, SDHB-deficient RCC is the predominant type, whereas SDHA-, SDHC-, and SDHD-deficient RCC are less common 4 , 5 .…”