Comprehensive Screening for MED12 Mutations in Gynecological Mesenchymal Tumors Identified Morphologically Distinctive Mixed Epithelial and Stromal Tumors2016-12-21 16:17:53
Histopathology; 21 December 2016: /DOI:10.1111/his.13156
Wen-Chih Huang, Cheng-Han Lee, Ming-Chieh Lin, Chen-Hui Lee, Yu-Chien Kao, Hsuan-Ying Huang, Kuan-Ting Kuo,
MED12 exon 2 mutations have been identified in most uterine leiomyomas and mammary fibroepithelial tumors. MED12 has not been genotyped in most other gynecological mesenchymal tumors.
68 uncommon gynecological mesenchymal tumors were genotyped for MED12 exon 2, including 27 müllerian adenosarcomas (including 3 tentatively diagnosed as “variant adenosarcomas”), 6 cellular angiofibromas, 6 aggressive angiomyxomas, 5 angiomyofibroblastomas, 5 superficial myofibroblastomas, 5 atypical polypoid adenomyomas, and 14 endometrial stromal sarcomas. Immunohistochemistry for CD10, myogenic markers, hormone receptors, MDM2, and CDK4, as well as FISH for JAZF1, PHF1, and YWHAE rearrangement, was performed on selected cases.
The 3 “variant adenosarcomas” harbored 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 harbored unprecedented mutations (p.D54G in 2 and p.Q48* in 1). All remaining tumors were wild-type. The 3 MED12-mutated “variant adenosarcomas” showed distinctive morphological features, including a “fibromyomatous” cytomorphology, close association with adenomyosis, clustered thick-walled vessels, focal conspicuous hyalinization, and intralymphovascular tumor growth. Features of conventional adenosarcomas, including nuclear atypia, mitotic activity, periglandular condensation, and phyllodes-like architecture, were inconspicuous. All 3 cases exhibited immunoreactivity to desmin and hormone receptors, while being negative for MDM2 and CDK4; they showed no JAZF1, PHF1, or YWHAE rearrangement. Despite deep myoinvasion, these tumors followed indolent clinical courses.
These MED12-mutated adenosarcoma-like tumors might represent a distinct entity, which requires more studies to determine. MED12 exon 2 mutations seemed to have no significant role in other uncommon gynecological mesenchymal tumors.
Empire Genomic's PHF1 Break Apart FISH Probe was used in this publication.
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