Review of succinate dehydrogenase-deficient renal cell carcinoma with focus on clinical and pathobiological aspects

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare subtype, integrated into the WHO classification in 2016.
• SDH is an enzyme complex with four subunits (SDHA, SDHB, SDHC, SDHD); mutations in these genes cause this specific RCC.
• This rare tumor accounts for 0.05–0.2% of all renal carcinomas, with about 30% of patients developing multiple tumors.

Purpose of the Study:

• To detail the characteristics of SDH-deficient RCC.
• To outline diagnostic methods including histology, ultrastructural, immunohistochemical, and molecular genetic analyses.
• To discuss the clinical behavior and potential for aggressive features in SDH-deficient RCC.

Main Methods:

• Histological examination of tumor morphology, including cell shape, cytoplasm, and borders.
• Ultrastructural analysis to identify cellular features like mitochondrial abundance.
• Immunohistochemistry to assess SDH subunit expression (SDHA, SDHB).
• Molecular genetic analysis to detect germline mutations in SDHB, SDHC, or SDHD genes.

Main Results:

• SDHB-deficient RCC is the most common form, characterized by specific histological features and abundant mitochondria.
• Immunohistochemistry shows SDHA positivity but SDHB negativity in SDHB-, SDHC-, and SDHD-deficient RCCs; SDHA-deficient RCC is negative for both.
• Germline mutations in SDHB, SDHC, or SDHD genes are identified in patients, regardless of family history.

Conclusions:

• SDH-deficient RCC diagnosis relies on a combination of histological, immunohistochemical, and genetic findings.
• While often low-grade, SDH-deficient RCC can exhibit aggressive behavior, particularly with high nuclear grade, necrosis, or sarcomatoid changes.
• Understanding SDH mutations is crucial for diagnosing and managing this rare renal malignancy.