title: Renal carcinoma associated with a novel succinate dehydrogenase A mutation: a case report and review of literature of a rare subtype of renal carcinoma.
abstract: Renal cell carcinoma (RCC) linked to germline mutation of succinate dehydrogenase subunits A, B, C, and D (SDHA, SDHB, SDHC, and SDHD, respectively) has been recently included as a provisional entity in the 2013 International Society of Urological Pathology Vancouver classification. Most SDH-deficient tumors show SDHB mutation, with only a small number of RCC with SDHC or SDHD having been reported to date. Only one case of SDH-deficient renal carcinoma known to be SDHA mutated has been previously reported. Here we report an additional RCC harboring an SDHA mutation occurring in a 62-year-old man with right flank pain and nodal metastasis. The tumor was characterized by an infiltrative pattern with solid, acinar, and papillary components. Loss of SDHA and SDHB protein by immunohistochemistry confirmed the diagnosis. Hybrid capture-based comprehensive genomic profiling identified 3 genomic alterations in tumor tissue: (i) a novel single-nucleotide splice site deletion in SDHA gene, (ii) single-nucleotide deletion in NF2 gene, and (iii) EGFR gene amplification of 19 copies. This is the second report of SDHA-mutated RCC. With increased awareness, this rare tumor can be recognized on the basis of distinctive morphology and confirmation by immunohistochemistry and genomic profiling.
authors.affiliation: Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Ozluk
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD; Department of Pathology, Isfahan Kidney Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Diana
authors.initials: D
authors.lastname: Taheri
authors.affiliation: Department of Pathology, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI.
authors.forename: Andres
authors.initials: A
authors.lastname: Matoso
authors.affiliation: Department of Urology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Oner
authors.initials: O
authors.lastname: Sanli
authors.affiliation: Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Neslihan Kayisoglu
authors.initials: NK
authors.lastname: Berker
authors.affiliation: Department of Urology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Yakirevich
authors.affiliation: Foundation Medicine Inc, Cambridge, MA.
authors.forename: Sohail
authors.initials: S
authors.lastname: Balasubramanian
authors.affiliation: Foundation Medicine Inc, Cambridge, MA; Department of Pathology and Laboratory Medicine, Albany Medical School, Albany, NY.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
authors.affiliation: Foundation Medicine Inc, Cambridge, MA.
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: Departments of Pathology, Urology, and Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD. Electronic address: gnetto1@jhmi.edu.
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics*; D004252:DNA Mutational Analysis; D042963:Electron Transport Complex II / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017422:Sequence Analysis, DNA
chemical_list: D042963:Electron Transport Complex II; C511268:SDHA protein, human
keywords: Immunohistochemistry; Renal carcinoma; SDHA; SDHB; Succinate dehydrogenase