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Published on: November 5, 2019
The Role of the Surgical Pathologist in the Recognition of Hereditary SDH-Deficient Tumor Syndromes
C Christofer Juhlin1,2, Ozgur Mete3,4,5
1Department of Oncology-Pathology, Karolinska Institutet.
Abstract:
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.
Insights
Succinate dehydrogenase (SDH)-deficient tumors are increasingly recognized. This review guides pathologists in identifying these neoplasms, aiding diagnosis, risk stratification, and patient management.
Area of Science:
- Oncology
- Pathology
- Genetics
Background:
- Succinate dehydrogenase (SDH) deficiency disrupts mitochondrial complex II, driving tumor formation.
- Alterations in SDHA-D, SDHAF2, or epigenetic silencing lead to SDH deficiency.
- Recognizing SDH deficiency is crucial for surgical pathologists for risk stratification and treatment.
Purpose of the Study:
- To provide a pathology-focused overview of SDH-deficient tumor syndromes.
- To highlight clinicopathologic features and diagnostic approaches.
- To guide pathologists in identifying and managing these tumors.
Main Methods:
- Review of clinicopathologic spectrum of SDH-deficient tumors.
- Emphasis on paraganglioma-pheochromocytoma syndromes, GIST, RCC, Carney-Stratakis, and Carney triad.
- Integration of histology, immunohistochemistry (SDHB, SDHA), and molecular testing.
Main Results:
- Recurring morphologic features across various SDH-deficient tumor types are identified.
- A stepwise diagnostic workflow is proposed.
- Common interpretive pitfalls are discussed.
Conclusions:
- SDH deficiency defines a significant group of neoplasms with distinct syndromes.
- Pathologists play a key role in diagnosis, risk stratification, and guiding genetic counseling.
- Integrated diagnostic strategies improve recognition and management of SDH-deficient tumors.
