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Comprehensive screening for MED 12 mutations in gynaecological mesenchymal tumours identified morphologically distinctive mixed epithelial and stromal tumours
Author(s) -
Yuan ChangTsu,
Huang WenChih,
Lee ChengHan,
Lin MingChieh,
Lee ChenHui,
Kao YuChien,
Huang HsuanYing,
Kuo KuanTing,
Lee JenChieh
Publication year - 2017
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13156
Subject(s) - pathology , biology , fluorescence in situ hybridization , cancer research , stromal cell , medicine , chromosome , gene , biochemistry
Aims MED 12 exon 2 mutations have been identified in most uterine leiomyomas and mammary fibroepithelial tumours. MED 12 has not been genotyped in most other gynaecological mesenchymal tumours. The purpose of this study was to determine the prevalence of MED 12 mutations in uncommon gynaecological mesenchymal tumours. Methods and results Sixty‐eight uncommon gynaecological mesenchymal tumours were genotyped for MED 12 exon 2, including 27 Müllerian 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 CD 10, myogenic markers, hormone receptors, MDM 2, and CDK 4, and fluorescence in‐situ hybridization ( FISH ) for JAZF 1 , PHF 1 and YWHAE rearrangement, were performed on selected cases. The three ‘variant adenosarcomas’ harboured MED 12 exon 2 mutations (including p.L36R hotspot mutation, recurrent p.L39_A50del, and a novel splice site mutation). Three endometrial stromal sarcomas with JAZF 1– SUZ 12 or JAZF 1– PHF 1 fusion harboured unprecedented mutations (p.D54G in two, and p.Q48* in one). All remaining tumours were wild‐type. The three MED 12 ‐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 MDM 2 and CDK 4; they showed no JAZF 1 , PHF 1 or YWHAE rearrangement. Despite deep myoinvasion, these tumours followed an indolent clinical course. Conclusions These MED 12 ‐mutated adenosarcoma‐like tumours might represent a distinct entity that requires more studies for its identification. MED 12 exon 2 mutations seemed to have no significant role in other uncommon gynaecological mesenchymal tumours.