巨大琥珀酸去氫酶缺乏型腎細胞癌：外科臨床診斷陷阱及其遺傳學意義

洪健哲、王世鋒

國泰綜合醫院 外科部 泌尿科

A Giant SDH-Deficient Renal Cell Carcinoma: A Diagnostic Trap and Its Genetic Implications for Surgical Practice

Chien-Che Hung¹ MD, Shih-Feng Wang^1,2 MD

1.      Division of Urology, Department of Surgery, Cathay General Hospital, Taipei, Taiwan

2.      School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is an exceedingly rare subtype, accounting for <0.2% of all renal tumors. Classified as a distinct entity by the WHO in 2016, it is strongly associated with germline mutations in SDH subunits (SDHA/B/C/D). We present a case of a 7.5 cm SDH-deficient RCC, highlighting the critical role of immunohistochemical (IHC) screening and the prognostic implications of tumor necrosis. A 40-year-old female with a maternal history of renal cancer presented with an incidental left renal mass. Computed tomography (CT) revealed a 9.1 cm hypervascular tumor with central necrosis and liquefaction, confined within the renal capsule (cT2aN0M0). Laparoscopic radical nephrectomy was performed. Macroscopically, the tumor was a 7.5 cm, well-demarcated, solid, yellow-to-brown mass.

Microscopic examination showed a solid and nodular growth pattern. Tumor cells exhibited eosinophilic cytoplasm with characteristic intracytoplasmic vacuoles and inconspicuous nucleoli (WHO/ISUP Grade 1). Notably, focal coagulative necrosis was present. IHC staining showed positivity for PAX8 and Vimentin, while CK7, CD117, and CA9 were negative. Crucially, IHC for SDHB showed a total loss of cytoplasmic expression (with internal positive controls in endothelial cells), confirming the diagnosis of SDH-deficient RCC (pT2aNxM0).

While many SDH-deficient RCCs follow an indolent course, the risk of metastasis in this subtype is reported to be approximately 10%–33%. Our case is particularly noteworthy due to its significant size (7.5 cm) and the presence of necrosis. Literature suggests that coagulative necrosis and high-grade nuclear features (ISUP Grade 3/4) are the strongest predictors of aggressive behavior and metastatic potential. Even in cases with low ISUP grades, the presence of necrosis warrants stringent, long-term oncological surveillance, as recurrences have been documented decades after initial resection.

Furthermore, because SDH deficiency often signals a hereditary syndrome (Hereditary Paraganglioma-Pheochromocytoma), identifying this pathology is vital. We emphasize that for any eosinophilic renal tumor lacking typical markers like CK7 or CD117, SDHB IHC is mandatory to initiate appropriate genetic counseling and screening for extra-renal manifestations, including paragangliomas and gastrointestinal stromal tumors (GIST).