Succinate dehydrogenase-deficient renal cell carcinoma represents between 0.05 and 0.2% of all renal cell carcinoma (RCCs) and is found in young adults. Mean patient age at presentation was 37 years (range, 14 to 76 y), with a slight male predominance (M:F=1.7:1).

Bilateral tumors were observed in 26% of patients. Patients with germ line mutations in succinate dehydrogenase deficient (SDH) subunit genes (SDHA ,B,C and D) are highly sensitive to certain types of neoplasms such as paragangliomas, pheochromocytomas, gastrointestinal stromal tumorsand renal cell carcinomas (Gill AJ .2012).

Sarcomatoid changes and necrosis are rare but are associated with poorer outcomes.

Two hit process The two hit process (germ line mutations and loss of the wild-type allele) is involved in the development of SDHB-deficient renal cell carcinoma (Schmidt and Linehan 2016).The risk of renal tumors seems highest for SDHB mutation. The germ line mutations reported were extensively found in exons coding the mitochondrial targeting sequence or 2FE-2S ferredoxin-type iron-sulfur binding domain.
Next-generation sequencing dataAdditionally, a targeted next-generation sequencing panel did not reveal alterations in other key genes involved in RCC pathogenesis, such as VHL, PIK3CA, AKT, MTOR, MET, or TP53 (Williamson et al. 2015).

Succinate dehydrogenase (SDH) genes; SDHA, SDHB, SDHC, SDHD, SDHAF2.

Succinate dehydrogenase (SDH) is a key respiratory enzyme complex that converts succinate to fumarate in the citric acid cycle (CAC) and also functions in the mitochondrial electron transport chain. It comprises 4 subunits, SDHA, SDHB, SDHC, and SDHD