Expanding the spectrum of NR4A3 fusion–positive gynecologic leiomyosarcomas Journal Article
| Authors: | Momeni-Boroujeni, A.; Mullaney, K.; DiNapoli, S. E.; Leitao, M. M. Jr; Hensley, M. L.; Katabi, N.; Allison, D. H. R.; Park, K. J.; Antonescu, C. R.; Chiang, S. |
| Article Title: | Expanding the spectrum of NR4A3 fusion–positive gynecologic leiomyosarcomas |
| Abstract: | Recurrent gene fusions have been observed in epithelioid and myxoid variants of uterine leiomyosarcoma. PGR::NR4A3 fusions were recently described in a subset of epithelioid leiomyosarcomas exhibiting rhabdoid morphology. In this study, we sought to expand the clinical, morphologic, immunohistochemical, and genetic features of gynecologic leiomyosarcomas harboring NR4A3 rearrangements with PGR and novel fusion partners. We identified 9 gynecologic leiomyosarcomas harboring PGR::NR4A3, CARMN::NR4A3, ACTB::NR4A3, and possible SLCO5A1::NR4A3 fusions by targeted RNA sequencing. Tumors frequently affected premenopausal women, involving the uterine corpus, uterine cervix, or pelvis. All were similarly characterized by lobules of monomorphic epithelioid and/or spindled cells arranged in sheets, cords, trabeculae, and micro- and macrocysts associated with abundant myxoid matrix and hemorrhage, creating labyrinth-like or pulmonary edema–like architecture. Myogenic differentiation with frequent estrogen receptor and progesterone receptor staining and no CD10 expression characterized all tumors. All cases showed high NR4A3 RNA expression levels and NOR1 (NR4A3) nuclear staining similar to salivary gland acinic cell carcinomas and a subset of extraskeletal myxoid chondrosarcomas harboring NR4A3 rearrangements. NOR1 (NR4A3) immunohistochemistry may serve as a useful diagnostic marker of NR4A3 fusion–positive gynecologic leiomyosarcomas. © 2024 United States & Canadian Academy of Pathology |
| Keywords: | immunohistochemistry; adult; cancer chemotherapy; human tissue; middle aged; cancer surgery; unclassified drug; human cell; major clinical study; clinical feature; doxorubicin; gemcitabine; cancer radiotherapy; follow up; lymph node dissection; pelvis; cytoreductive surgery; dacarbazine; ovariectomy; protein; cell differentiation; ifosfamide; docetaxel; exemestane; cancer hormone therapy; lung embolism; leuprorelin; lung metastasis; gene rearrangement; pazopanib; immunophenotyping; letrozole; premenopause; trabectedin; leiomyosarcoma; estrogen receptor; progesterone receptor; abdominal hysterectomy; uterine leiomyosarcoma; uterine cervix; megestrol acetate; myomectomy; pgr; beta actin; epithelioid; bone biopsy; lung edema; omentectomy; myxoid; myxoid leiomyosarcoma; olaratumab; salpingectomy; laparoscopic hysterectomy; human; female; article; rna sequencing; nr4a3; pembrolizumab; robot assisted surgery; epithelioid leiomyosarcoma; patient history of hysterectomy; bilateral salpingo-oophorectomy; epithelioid histiocyte; nuclear receptor nr4a3; pelvic sarcoma; carmn protein; slco5a1 protein |
| Journal Title: | Modern Pathology |
| Volume: | 37 |
| Issue: | 5 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2024-05-01 |
| Start Page: | 100474 |
| Language: | English |
| DOI: | 10.1016/j.modpat.2024.100474 |
| PUBMED: | 38508521 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA00848) acknowledged in PDF -- MSK corresponding author is Source: Sarah Chiang -- Scopus |
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