Comprehensive screening for MED12 mutations in gynaecological mesenchymal tumours identified morphologically distinctive mixed epithelial and stromal tumours

Chang Tsu Yuan, Wen Chih Huang, Cheng Han Lee, Ming Chieh Lin, Chen Hui Lee, Yu-Chien Kao, Hsuan Ying Huang, Kuan Ting Kuo, Jen Chieh Lee

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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 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 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.

Original languageEnglish
Pages (from-to)954-965
Number of pages12
JournalHistopathology
Volume70
Issue number6
DOIs
Publication statusPublished - May 1 2017

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Adenosarcoma
Mutation
Exons
Neoplasms
Endometrial Stromal Sarcoma
Muscle Tissue Neoplasms
Adenomyoma
Hormones
Angiofibroma
Adenomyosis
Myxoma
Desmin
Leiomyoma
Fluorescence In Situ Hybridization
Immunohistochemistry
Breast Neoplasms
Growth

Keywords

  • adenosarcoma
  • endometrial stromal sarcoma
  • gynaecological mesenchymal tumour
  • MED12

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Comprehensive screening for MED12 mutations in gynaecological mesenchymal tumours identified morphologically distinctive mixed epithelial and stromal tumours. / Yuan, Chang Tsu; Huang, Wen Chih; Lee, Cheng Han; Lin, Ming Chieh; Lee, Chen Hui; Kao, Yu-Chien; Huang, Hsuan Ying; Kuo, Kuan Ting; Lee, Jen Chieh.

In: Histopathology, Vol. 70, No. 6, 01.05.2017, p. 954-965.

Research output: Contribution to journalArticle

Yuan, Chang Tsu ; Huang, Wen Chih ; Lee, Cheng Han ; Lin, Ming Chieh ; Lee, Chen Hui ; Kao, Yu-Chien ; Huang, Hsuan Ying ; Kuo, Kuan Ting ; Lee, Jen Chieh. / Comprehensive screening for MED12 mutations in gynaecological mesenchymal tumours identified morphologically distinctive mixed epithelial and stromal tumours. In: Histopathology. 2017 ; Vol. 70, No. 6. pp. 954-965.
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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{\"u}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.",
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AU - Lee, Chen Hui

AU - Kao, Yu-Chien

AU - Huang, Hsuan Ying

AU - Kuo, Kuan Ting

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