Novel PLAG1 gene rearrangement distinguishes a subset of uterine myxoid leiomyosarcoma from other uterine myxoid mesenchymal tumors Journal Article


Authors: Arias-Stella, J. A. 3rd; Benayed, R.; Oliva, E.; Young, R. H.; Hoang, L. N.; Lee, C. H.; Jungbluth, A. A.; Frosina, D.; Soslow, R. A.; Antonescu, C. R.; Ladanyi, M.; Chiang, S.
Article Title: Novel PLAG1 gene rearrangement distinguishes a subset of uterine myxoid leiomyosarcoma from other uterine myxoid mesenchymal tumors
Abstract: Genetic alterations in uterine myxoid leiomyosarcoma are unknown. We investigate the clinicopathologic features of 19 uterine tumors previously diagnosed as myxoid leiomyosarcomas in which tumoral RNA was subjected to targeted RNA sequencing. PLAG1, BCOR, BCORL1, HMGA2, and ALK break-apart fluorescence in situ hybridization (FISH) and BCOR, PLAG1, and ALK immunohistochemistry were performed in cases which failed or lacked fusions by sequencing. The diagnosis of myxoid leiomyosarcoma was confirmed in 15 cases after exclusion of 4 tumors with BCOR and ALK rearrangements. These 15 patients presented at a median age of 50 years with stage I (3), II (2), III (2), and IV (1) tumors, respectively; stage was unknown in 7 cases. Tumor size ranged from 10 to 24 cm. Matrix was myxoid in all tumors and also eosinophilic in 2. Cells were spindled, epithelioid, and both in 10, 2, and 3 tumors and showed mild, moderate, and severe nuclear atypia in 3, 8, and 4 tumors, respectively. Mitotic index ranged from <1 to 14/10 HPF, while tumor necrosis was present in 6 (40%). Novel TRPS1-PLAG1 or RAD51B-PLAG1 fusions were detected by sequencing in 4 tumors, 3 of which were also confirmed by FISH. Diffuse PLAG1 expression was seen in 7 tumors, including 4 with PLAG1 rearrangement. No morphologic differences were seen among PLAG1 fusion-positive and fusion-negative tumors. No PLAG1, HMGA2, ALK, BCOR, or BCORL1 rearrangements were detected by FISH in 11 tumors. On the basis of sequencing and FISH results, PLAG1 rearrangements resulting in PLAG1 expression underpin 25% of myxoid leiomyosarcomas and may serve as a useful diagnostic biomarker. Immunohistochemistry, targeted RNA sequencing, and/or FISH may distinguish myxoid leiomyosarcoma from its morphologic mimics. © 2018 Wolters Kluwer Health, Inc. All rights reserved.
Keywords: alk; endometrial stromal sarcoma; uterine sarcoma; inflammatory myofibroblastic tumor; myxoid leiomyosarcoma; bcor; plag1
Journal Title: American Journal of Surgical Pathology
Volume: 43
Issue: 3
ISSN: 0147-5185
Publisher: Lippincott Williams & Wilkins  
Date Published: 2019-03-01
Start Page: 382
End Page: 388
Language: English
DOI: 10.1097/pas.0000000000001196
PUBMED: 30489320
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 1 April 2019 -- Source: Scopus
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MSK Authors
  1. Cristina R Antonescu
    609 Antonescu
  2. Marc Ladanyi
    870 Ladanyi
  3. Robert Soslow
    643 Soslow
  4. Achim Jungbluth
    340 Jungbluth
  5. Denise Frosina
    84 Frosina
  6. Rym Benayed
    72 Benayed
  7. Sarah   Chiang
    42 Chiang