A distinctive, low-grade oncocytic fumarate hydratase-deficient renal cell carcinoma, morphologically reminiscent of succinate dehydrogenase-deficient renal cell carcinoma

作者：Smith Steven C; Sirohi Deepika; Ohe Chisato; McHugh Jonathan B; Hornick Jason L; Kalariya Jigna; Karia Sushil; Snape Katie; Hodgson Shirley V; Cani Andi K; Hovelson Daniel; Luthringer Daniel J; Martignoni Guido; Chen Ying Bei; Tomlins Scott A; Mehra Rohit; Amin Mahul B^*

来源：Histopathology, 2017, 71(1): 42-52.

DOI：10.1111/his.13183

• fumarate hydratase-deficient renal cell carcinoma
• hereditary leiomyomatosis-renal cell carcinoma syndrome
• oncocytic carcinoma
• renal cell carcinoma
• succinate dehydrogenase-deficient renal cell carcinoma

Aims: Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a high-grade, aggressive tubulopapillary carcinoma, arising predominantly in the setting of the hereditary leiomyomatosis-RCC syndrome of familial uterocutaneous leiomyomatosis and deficiency of FH. In contrast, succinate dehydrogenase (SDH)-deficient RCC is a lower-grade oncocytic carcinoma with cytoplasmic flocculence/vacuolation and inclusions, arising mostly in individuals harbouring germline mutations of subunit B of the SDH complex (SDHB). Herein we aim to report the clinicopathologic features of a novel form of FH-deficient RCC showing a low grade oncocytic morphology, reminiscent of SDH-deficient RCC.
Methods and results: These distinctive, low-grade oncocytic neoplasms, with solid, nested and focally tubular architecture (2-90 mm), arose in four males (aged 11-41 years). Uniform cytology of polygonal cells, with flocculent, vacuolated eosinophilic cytoplasm with scattered inclusions, fine chromatin, and inconspicuous nucleoli, was apparent. Despite these features suggestive of SDH-deficient RCC, each tumour was confirmed as an FH-deficient carcinoma with retained SDHB expression. One case showed a synchronous, anatomically separate, typical highgrade FH-deficient RCC; one other showed such a tumour at nephrectomy 4 years later. No progression has been noted at 3 and 7 years in the cases with only the SDH-like lesions; the two cases with separate, typical FH-deficient RCCs progressed.
Conclusions: In summary, we characterize a novel oncocytic type of FH-deficient RCC with a striking resemblance to SDH-deficient RCC, posing a diagnostic challenge and raising concerns about sampling and multifocality for syndrome-associated cases under surveillance protocols.

• 出版日期2017-7