title: Ovarian sex cord-stromal tumors in patients with probable or confirmed germline DICER1 mutations.
abstract: The DICER1 gene encodes an endoribonuclease involved in the production of mature microRNAs which regulates gene expression through several mechanisms. Recent studies have demonstrated somatic mutations in DICER1 in approximately 60% of ovarian Sertoli-Leydig cell tumors. Furthermore, patients with germline mutations in DICER1 are predisposed to developing a range of rare neoplasms including ovarian sex cord-stromal tumors most of which have been classified as Sertoli-Leydig cell tumor. However, the histologic features of these tumors have not been reported in detail. We describe the morphologic and immunophenotypic findings of 4 sex cord-stromal tumors arising in patients with proven or likely germline DICER1 mutations including 3 individuals from 1 family. Three tumors showed similar appearances characterized by marked architectural and cytologic heterogeneity including sertoliform, juvenile granulosa cell tumor-like, and unclassifiable elements. The remaining case mainly showed heterologous mucinous epithelial and neuroendocrine differentiation with only a minor intermediate-grade Sertoli cell component. This tumor and one of the 3 former cases arose in related patients with identical germline DICER1 mutations indicating that additional factors influence tumor morphology. All tumors were positive for steroidogenic factor-1 and FOXL2 on immunohistochemical analysis, whereas there was more variable expression of inhibin, calretinin, CD56, CD99, and hormone receptors. The present small series suggests that some ovarian Sertoli-Leydig cell tumor associated with germline DICER1 mutations may show distinctive histologic features in particular admixed Sertoli cell and juvenile granulosa cell tumor-like features. Larger studies are required to establish whether heterologous elements are also a more common feature of these tumors.
authors.affiliation: Departments of Histopathology (E.E.O., H.S.), SJOG Pathology King Edward Memorial Hospital (C.J.R.S.) Schools for Paediatrics and Child Health (A.C., C.S.C.) School for Women's and Infants' Health (Y.L., S.S., J.T., C.J.R.S.), University of Western Australia Department of Medical Genetics (S.T.), King Edward Memorial Hospital, Perth, WA Program in Cancer Genetics (L.W., W.D.F.), Departments of Oncology and Human Genetics, McGill University Department of Medical Genetics (L.W., W.D.F.), Segal Cancer Centre and Lady Davis Institute, McGill University Health Centre, Montreal, QC, Canada.
authors.forename: E Ebo
authors.initials: EE
authors.lastname: Oost
authors.forename: Adrian
authors.initials: A
authors.lastname: Charles
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Choong
authors.forename: Yee C
authors.initials: YC
authors.lastname: Leung
authors.forename: Stuart
authors.initials: S
authors.lastname: Salfinger
authors.forename: Hein
authors.initials: H
authors.lastname: Sonnendecker
authors.forename: Jason
authors.initials: J
authors.lastname: Tan
authors.forename: Sharron
authors.initials: S
authors.lastname: Townshend
authors.forename: Leora
authors.initials: L
authors.lastname: Witkowski
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
authors.forename: Colin J R
authors.initials: CJ
authors.lastname: Stewart
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D043244:Ribonuclease III / Q000235:genetics*; D018312:Sex Cord-Gonadal Stromal Tumors / Q000235:genetics* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases