title: Succinate dehydrogenase deficiency is rare in pituitary adenomas.
abstract: Germline mutations in the succinate dehydrogenase genes (SDHA, SDHB, SDHC, and SDHD) are established as causes of pheochromocytoma/paraganglioma, renal carcinoma, and gastrointestinal stromal tumor. It has recently been suggested that pituitary adenomas may also be a component of this syndrome. We sought to determine the incidence of SDH mutation in pituitary adenomas. We performed screening immunohistochemistry for SDHB and SDHA on all available pituitary adenomas resected at our institution from 1998 to 2012. In those patients with an abnormal pattern of staining, we then performed SDH mutation analysis on DNA extracted from paraffin-embedded tissue, fresh frozen tissue, and peripheral blood. One of 309 adenomas (0.3%) demonstrated an abnormal pattern of staining, a 30 mm prolactin-producing tumor from a 62-year-old man showing loss of staining for both SDHA and SDHB. Examination of paraffin-embedded and frozen tissues confirmed double-hit inactivating somatic SDHA mutations (c.725_736del and c.989_990insTA). Neither of these mutations was present in the germline. We conclude that, although pathogenic SDH mutation may occur in pituitary adenomas and can be identified by immunohistochemistry, it appears to be a very rare event and can occur in the absence of germline mutation. SDH-deficient pituitary adenomas may be larger and more likely to produce prolactin than other pituitary adenomas. Unless suggested by family history and physical examination, it is difficult to justify screening for SDH mutations in pituitary adenomas. Surveillance programs for patients with SDH mutation may be tailored to include the possibility of pituitary neoplasia; however, this is likely to be a low-yield strategy.
authors.affiliation: *Department of Anatomical Pathology, Royal North Shore Hospital ‡University of Sydney, Sydney †Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medial Research #Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards §Histopath Pathology, North Ryde ∥Department of Anatomical Pathology, St Vincents Hospital, Darlinghurst, NSW ¶Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Melbourne, Vic., Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Gill
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Toon
authors.forename: Adele
authors.initials: A
authors.lastname: Clarkson
authors.forename: Loretta
authors.initials: L
authors.lastname: Sioson
authors.forename: Angela
authors.initials: A
authors.lastname: Chou
authors.forename: Ingrid
authors.initials: I
authors.lastname: Winship
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Robinson
authors.forename: Diana E
authors.initials: DE
authors.lastname: Benn
authors.forename: Roderick J
authors.initials: RJ
authors.lastname: Clifton-Bligh
authors.forename: Trisha
authors.initials: T
authors.lastname: Dwight
mesh_terms: D000236:Adenoma / Q000201:enzymology / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010911:Pituitary Neoplasms / Q000201:enzymology / Q000235:genetics*; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase / Q000172:deficiency* / Q000235:genetics*; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D013385:Succinate Dehydrogenase