Ovarian Sex Cord-Stromal Tumors in Patients With Probable or Confirmed Germline DICER1 Mutations. (May 2015)

• Record Type: Journal Article
• Authors: Oost, E. Ebo; Charles, Adrian; Choong, Catherine S.; Leung, Yee C.; Salfinger, Stuart; Sonnendecker, Hein; Tan, Jason; Townshend, Sharron; Witkowski, Leora; Foulkes, William D.; Stewart, Colin J. R.
• Is Part Of: International journal of gynecological pathology. Volume 34:Number 3(2015:May)
• Publication Date: 2015-05
• Subjects: Gynecologic pathology -- Periodicals; Gynecology -- Periodicals; Generative organs, Female -- Diseases -- Periodicals; 618.10705
• DOI: 10.1097/PGP.0000000000000150
• Languages: English
• ISSNs: 0277-1691

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>The <italic>DICER1</italic> 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 <italic>DICER1</italic> in approximately 60% of ovarian Sertoli-Leydig cell tumors. Furthermore, patients with germline mutations in <italic>DICER1</italic> 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 <italic>DICER1</italic> 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 <italic>DICER1</italic> 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 <italic>DICER1</italic> 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.</p> </sec> </abstract>