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A distinctive, low‐grade oncocytic fumarate hydratase‐deficient renal cell carcinoma, morphologically reminiscent of succinate dehydrogenase‐deficient renal cell carcinoma
Author(s) -
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,
Martigi Guido,
Chen YingBei,
Tomlins Scott A,
Mehra Rohit,
Amin Mahul B
Publication year - 2017
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13183
Subject(s) - sdhb , fumarase , renal cell carcinoma , pathology , oncocytoma , clear cell , carcinoma , biology , clear cell carcinoma , cancer research , medicine , germline mutation , mutation , biochemistry , gene , enzyme
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 high‐grade 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 RCC s 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.