The Role of the Surgical Pathologist in the Recognition of Hereditary SDH-Deficient Tumor Syndromes

Succinate dehydrogenase (SDH)-deficient tumors form an expanding, clinically important group of neoplasms driven by disruption of mitochondrial complex II through germline or somatic alterations in SDHA-D or SDHAF2, or by epigenetic silencing within the pathway. For the surgical pathologist, recognition of SDH deficiency has immediate implications for risk stratification, treatment selection, and identification of patients who may require genetic counseling and family surveillance. This review provides a practical, pathology-focused overview of SDH-deficient tumor syndromes, emphasizing the clinicopathologic spectrum of paraganglioma-pheochromocytoma syndromes (PGL1-5), SDH-deficient gastrointestinal stromal tumor, SDH-deficient renal cell carcinoma, Carney-Stratakis syndrome, and Carney triad. We highlight recurring morphologic cues across tumor types, outline a stepwise workflow integrating histology, SDHB and SDHA immunohistochemistry and targeted molecular testing, and discuss interpretive pitfalls.