Genomic Profiling Aids Classification of Diagnostically Challenging Uterine Mesenchymal Tumors With Myomelanocytic Differentiation

P. Selenica, N. Conlon, C. Gonzalez, D. Frosina, A.A. Jungbluth, R.G.H. Beets-Tan, M.K. Rao, Y.M. Zhang, R. Benayed, M. Ladanyi, D.B. Solit, S. Chiang, D.M. Hyman, M.L. Hensley, R.A. Soslow, B. Weigelt, R. Murali*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Web of Science)

Abstract

Although diagnosis of high-grade uterine mesenchymal tumors (UMTs) exhibiting classic morphologic features is straightforward, diagnosis is more challenging in tumors in which prototypical features are poorly developed, focal, and/or coexist with features seen in other neoplasms. Here, we sought to define the repertoire of somatic genetic alterations in diagnostically challenging UMTs with myomelanocytic differentiation, including some reported as perivascular epithelioid cell tumors (PEComas). In 17 samples from 15 women, the tumors were histologically heterogenous. Immunohistochemical expression of at least 1 melanocytic marker (HMB45, Melan-A, or MiTF) was identified in all tumors, and of myogenic markers (desmin or smooth muscle actin) in most tumors. Targeted massively parallel sequencing revealed several genetic alterations, most commonly in TP53 (41% mutation, 12% deletion), TSC2 (29% mutation, 6% deletion), RB1 (18% deletion), ATRX (24% mutation), MED12 (12% mutation), BRCA2 (12% deletion), CDKN2A (6% deletion) as well as FGFR3, NTRK1, and ERBB3 amplification (each 6%). Gene rearrangements (JAZF1-SUZ12; DNAJB6-PLAG1; and SFPQ-TFE3) were identified in 3 tumors. Integrating histopathologic, immunohistochemical, and genetic findings, tumors from 4 patients were consistent with malignant PEComa (1 TFE3-rearranged); 6 were classified as leiomyosarcomas; 3 showed overlapping features of PEComa and other sarcoma types (leiomyosarcoma or low-grade endometrial stromal sarcoma); and 2 were classified as sarcoma, not otherwise specified. Our findings suggest that diagnostically challenging UMTs with myomelanocytic differentiation represent a heterogenous group of neoplasms which harbor a diverse repertoire of somatic genetic alterations; these genetic alterations can aid classification.
Original languageEnglish
Pages (from-to)77-92
Number of pages16
JournalAmerican Journal of Surgical Pathology
Volume45
Issue number1
DOIs
Publication statusPublished - 1 Jan 2021

Keywords

  • allelic loss
  • cell neoplasm pecoma
  • endometrial stromal sarcomas
  • expression
  • genetics
  • leiomyoma
  • leiomyosarcoma
  • melanocytic differentiation
  • mutations
  • myomelanocytic differentiation
  • pathology
  • pecoma
  • perivascular epithelioid cell tumor
  • practical issues
  • smooth-muscle tumors
  • somatic mutations
  • tsc2 gene
  • uterus
  • TSC2 GENE
  • CELL NEOPLASM PECOMA
  • LEIOMYOSARCOMA
  • MUTATIONS
  • PEComa
  • ENDOMETRIAL STROMAL SARCOMAS
  • LEIOMYOMA
  • PRACTICAL ISSUES
  • SMOOTH-MUSCLE TUMORS
  • ALLELIC LOSS
  • EXPRESSION

Cite this