Comprehensive screening for MED12 mutations in gynaecological mesenchymal tumours identified morphologically distinctive mixed epithelial and stromal tumours
Journal
Histopathology
Journal Volume
70
Journal Issue
6
Pages
954-965
Date Issued
2017
Author(s)
Huang W.-C.
Lee C.-H.
Lin M.-C.
Lee C.-H.
Kao Y.-C.
Huang H.-Y.
Abstract
Aims: MED12 exon 2 mutations have been identified in most uterine leiomyomas and mammary fibroepithelial tumours. MED12 has not been genotyped in most other gynaecological mesenchymal tumours. The purpose of this study was to determine the prevalence of MED12 mutations in uncommon gynaecological mesenchymal tumours. Methods and results: Sixty-eight uncommon gynaecological mesenchymal tumours were genotyped for MED12 exon 2, including 27 M?llerian adenosarcomas (including three tentatively diagnosed as ‘variant adenosarcomas’), six cellular angiofibromas, six aggressive angiomyxomas, five angiomyofibroblastomas, five superficial myofibroblastomas, five atypical polypoid adenomyomas, and 14 endometrial stromal sarcomas. Immunohistochemistry for CD10, myogenic markers, hormone receptors, MDM2, and CDK4, and fluorescence in-situ hybridization (FISH) for JAZF1, PHF1 and YWHAE rearrangement, were performed on selected cases. The three ‘variant adenosarcomas’ harboured MED12 exon 2 mutations (including p.L36R hotspot mutation, recurrent p.L39_A50del, and a novel splice site mutation). Three endometrial stromal sarcomas with JAZF1–SUZ12 or JAZF1–PHF1 fusion harboured unprecedented mutations (p.D54G in two, and p.Q48* in one). All remaining tumours were wild-type. The three MED12-mutated ‘variant adenosarcomas’ showed distinctive morphological features, including ‘fibromyomatous’ cytomorphology, a close association with adenomyosis, clustered thick-walled vessels, focal conspicuous hyalinization, and intralymphovascular tumour growth. Features of conventional adenosarcomas, including nuclear atypia, mitotic activity, periglandular condensation, and phyllodes-like architecture, were inconspicuous. All three cases showed immunoreactivity for desmin and hormone receptors, while being negative for MDM2 and CDK4; they showed no JAZF1, PHF1 or YWHAE rearrangement. Despite deep myoinvasion, these tumours followed an indolent clinical course. Conclusions: These MED12-mutated adenosarcoma-like tumours might represent a distinct entity that requires more studies for its identification. MED12 exon 2 mutations seemed to have no significant role in other uncommon gynaecological mesenchymal tumours. ? 2016 John Wiley & Sons Ltd
Other Subjects
caldesmon; common acute lymphoblastic leukemia antigen; cyclin dependent kinase 4; desmin; protein MDM2; MED12 protein, human; mediator complex; adenomyoma; adenomyosis; adult; aged; Article; blastoma; chromosome rearrangement; disease association; endometrium sarcoma; epithelium tumor; exon; female; female genital tract tumor; fluorescence in situ hybridization; gene; genotype; hemangiofibroma; human; human tissue; hyaline degeneration; immunohistochemistry; immunoreactivity; major clinical study; MED12 gene; middle aged; mitosis rate; mutational analysis; myxoma; priority journal; Sanger sequencing; wild type; young adult; dna mutational analysis; female genital tract tumor; genetics; laser capture microdissection; mutation; polymerase chain reaction; soft tissue tumor; Adult; Aged; DNA Mutational Analysis; Female; Genital Neoplasms, Female; Genotype; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Laser Capture Microdissection; Mediator Complex; Middle Aged; Mutation; Neoplasms, Connective and Soft Tissue; Polymerase Chain Reaction; Young Adult
Publisher
Blackwell Publishing Ltd
Type
journal article