Expanding the clinicopathological spectrum of succinate dehydrogenase-deficient renal cell carcinoma with a focus on variant morphologies: a study of 62 new tumors in 59 patients

Fuchs TL, Maclean F, Turchini J, Vargas AC, Bhattarai S, Agaimy A, Hartmann A, Kao CS, Ellis C, Bonert M, Leroy X, Kunju LP, Schwartz L, Matsika A, Williamson SR, Rao P, Divatia M, Guarch R, Algaba F, Balancin ML, Zhou M, Samaratunga H, Da Cunha IW, Brimo F, Ryan A, Clouston D, Aron M, O'Donnell M, Chan E, Hirsch MS, Moch H, Pang CY, Wah C, Yin W, Perry-Keene J, Yilmaz A, Chou A, Clarkson A, Van Der Westhuizen G, Morrison E, Zwi J, Hes O, Trpkov K, Gill AJ (2021)

Publication Type: Journal article

Publication year: 2021

Journal

DOI: 10.1038/s41379-021-00998-1

Abstract

Most succinate dehydrogenase (SDH)-deficient renal cell carcinomas (RCCs) demonstrate stereotypical morphology characterized by bland eosinophilic cells with frequent intracytoplasmic inclusions. However, variant morphologic features have been increasingly recognized. We therefore sought to investigate the incidence and characteristics of SDH-deficient RCC with variant morphologies. We studied a multi-institutional cohort of 62 new SDH-deficient RCCs from 59 patients. The median age at presentation was 39 years (range 19-80), with a slight male predominance (M:F = 1.6:1). A relevant family history was reported in 9 patients (15%). Multifocal or bilateral tumors were identified radiologically in 5 patients (8%). Typical morphology was present at least focally in 59 tumors (95%). Variant morphologies were seen in 13 (21%) and included high-grade nuclear features and various combinations of papillary, solid, and tubular architecture. Necrosis was present in 13 tumors, 7 of which showed variant morphology. All 62 tumors demonstrated loss of SDHB expression by immunohistochemistry. None showed loss of SDHA expression. Germline SDH mutations were reported in all 18 patients for whom the results of testing were known. Among patients for whom follow-up data was available, metastatic disease was reported in 9 cases, 8 of whom had necrosis and/or variant morphology in their primary tumor. Three patients died of disease. In conclusion, variant morphologies and high-grade nuclear features occur in a subset of SDH-deficient RCCs and are associated with more aggressive behavior. We therefore recommend grading all SDH-deficient RCCs and emphasize the need for a low threshold for performing SDHB immunohistochemistry in any difficult to classify renal tumor, particularly if occurring at a younger age.

Authors with CRIS profile

Involved external institutions

University of Sydney (USYD) Australia (AU) Kolling Institute Australia (AU) Leeds Teaching Hospitals NHS Trust United Kingdom (GB) Stanford University United States (USA) (US) Northwestern University United States (USA) (US) McMaster University Canada (CA) Centre hospitalier universitaire de Brest (CHRU Brest) France (FR) University of Michigan United States (USA) (US) University of Pennsylvania United States (USA) (US) Mater Health Services Australia (AU) University of Texas MD Anderson Cancer Center United States (USA) (US) St. Teresa's Hospital Hong Kong (HK) Queen Elizabeth Hospital United Kingdom (GB) Peking University (PKU) / 北京大学 China (CN) Aquesta Specialized Uropathology Australia (AU) University of Calgary Canada (CA) Mediclinic Bloemfontein South Africa (ZA) National Health Laboratory Services South Africa (ZA) Auckland City Hospital New Zealand (NZ) Alberta Precision Laboratories Canada (CA) Cleveland Clinic United States (USA) (US) The Methodist Hospital System United States (USA) (US) Complejo Hospitalario de Navarra - Hospital de Navarra Spain (ES) Autonomous University of Barcelona (UAB) / Universitat Autònoma de Barcelona Spain (ES) Fundacao Oncocentro de Sao Paulo Brazil (BR) Tufts University United States (USA) (US) University of Queensland Australia (AU) Hospitais Rede D'Or São Luiz Brazil (BR) McGill University Canada (CA) Tissupath Australia (AU) University of Southern California (USC) United States (USA) (US) NHS Lothian United Kingdom (GB) University of California San Francisco (UCSF) United States (USA) (US) Brigham and Women's Hospital (BWH) United States (USA) (US) Universitätsspital Zürich (USZ) Switzerland (CH)

How to cite

APA:

Fuchs, T.L., Maclean, F., Turchini, J., Vargas, A.C., Bhattarai, S., Agaimy, A.,... Gill, A.J. (2021). Expanding the clinicopathological spectrum of succinate dehydrogenase-deficient renal cell carcinoma with a focus on variant morphologies: a study of 62 new tumors in 59 patients. Modern Pathology. https://dx.doi.org/10.1038/s41379-021-00998-1

MLA:

Fuchs, Talia L., et al. "Expanding the clinicopathological spectrum of succinate dehydrogenase-deficient renal cell carcinoma with a focus on variant morphologies: a study of 62 new tumors in 59 patients." Modern Pathology (2021).

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