[Succinate dehydrogenase (SDH)-deficient renal cell carcinoma]

Area of Science:

• Biochemistry
• Oncology
• Molecular Biology

Background:

• Succinate dehydrogenase (SDH) is a mitochondrial complex II enzyme involved in the respiratory chain and Krebs cycle.
• SDH comprises four subunits (SDHA, SDHB, SDHC, SDHD) and has recognized oncogenic signaling and tumor suppressor roles.
• SDH deficiency is implicated in familial paraganglioma syndromes and various tumors like GIST, hypophyseal adenomas, and pancreatic neuroendocrine neoplasms.

Purpose of the Study:

• To review the clinicopathological, immunohistochemical, and genetic features of SDH-deficient renal cell carcinoma (RCC).
• To discuss SDH-deficient RCC within the context of its differential diagnosis.
• To highlight the significance of SDH deficiency in oncogenesis, particularly the universal loss of SDHB expression in SDH-deficient neoplasms.

Main Methods:

• Literature review focusing on clinicopathological, immunohistochemical, and genetic studies of SDH-deficient RCC.
• Analysis of the role of SDH subunits, especially SDHB, in tumor development.
• Inclusion of SDH-deficient RCC in the latest World Health Organization (WHO) classification.

Main Results:

• SDH-deficient RCC is a distinct subtype recognized in the 2016 WHO classification.
• Loss of SDHB expression is a hallmark of all SDH-deficient neoplasms, regardless of the specific mutated SDH subunit.
• SDH-deficient tumors share common features due to the central role of SDHB in complex integrity.

Conclusions:

• SDH-deficient RCC is a rare but well-characterized entity with specific diagnostic criteria.
• Immunohistochemistry for SDHB is crucial for identifying SDH-deficient tumors.
• Understanding SDH deficiency is vital for the diagnosis and potential therapeutic strategies in various cancers.