Succinate dehydrogenase (SDH)-deficient neoplasia
Anthony J Gill1,2,3
1Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia.
Histopathology
|December 15, 2017
Summary
Loss of succinate dehydrogenase B (SDHB) immunohistochemistry indicates syndromic disease, often linked to mutations in SDH subunits. This finding is crucial for identifying SDH-deficient tumors like pheochromocytoma, paraganglioma, GISTs, and renal carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The succinate dehydrogenase (SDH) complex is vital for cellular respiration.
- Loss of SDHB expression via immunohistochemistry is a marker for SDH-deficient tumors, often resulting from germline mutations.
- Syndromic diseases are frequently associated with SDH mutations.
Purpose of the Study:
- To highlight the significance of SDHB immunohistochemistry as a diagnostic marker for SDH-deficient tumors.
- To detail the characteristics and associations of SDH-deficient tumors in various cancer types.
- To recommend SDHB screening for specific tumor types.
Main Methods:
- Immunohistochemistry for SDHB and SDHA expression.
- Genetic mutation analysis (germline and somatic).
- Review of clinical and pathological features of SDH-deficient tumors.
Main Results:
- Loss of SDHB immunohistochemistry indicates bi-allelic SDH inactivation and is a marker for syndromic disease.
- Fifteen percent of pheochromocytoma/paraganglioma cases are SDH-deficient, warranting SDHB screening.
- SDH-deficient GISTs have unique features and are linked to SDHA mutations or SDHC epimutation (Carney triad).
- SDH-deficient renal carcinoma and pituitary adenomas are also recognized, associated with specific SDH subunit mutations.
Conclusions:
- SDHB immunohistochemistry is a critical tool for identifying SDH-deficient tumors and associated syndromic diseases.
- Routine SDHB screening is recommended for pheochromocytoma and paraganglioma.
- Understanding the distinct features of SDH-deficient tumors aids in diagnosis, prognosis, and treatment strategies.
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