The knowledge of clinical features and, particularly, histopathological spectrum of EWSR1-PATZ1-rearranged spindle and round cell sarcomas (EPS) remains limited. For this reason, we report the largest clinicopathological study of EPS to date. Nine cases were collected, consisting of four males and five females ranging in age from 10 to 81 years (average: 49 years). Five tumors occurred in abdominal wall soft tissues, three in the thorax, and one in the back of the neck. Tumor sizes ranged from 2.5 to 18 cm (average 6.6 cm). Five patients had follow-up with an average of 38 months (range: 18-60 months). Two patients had no recurrence or metastasis 19 months after diagnosis. Four patients developed multifocal pleural or pulmonary metastasis and were treated variably by surgery, radiotherapy, and chemotherapy. The latter seemed to have little to no clinical benefit. One of the four patients was free of disease 60 months after diagnosis, two patients were alive with disease at 18 and 60 months, respectively. Morphologically, low, intermediate, and high-grade sarcomas composed of a variable mixture of spindled, ovoid, epithelioid, and round cells were seen. The architectural and stromal features also varied, resulting in a broad morphologic spectrum. Immunohistochemically, the following markers were most consistently expressed: S100-protein (7/9 cases), GFAP (7/8), MyoD1 (8/9), Pax-7 (4/5), desmin (7/9), and AE1/3 (4/9). By next-generation sequencing, all cases revealed EWSR1-PATZ1 gene fusion. In addition, 3/6 cases tested harbored CDKN2A deletion, while CDKN2B deletion and TP53 mutation were detected in one case each. Our findings confirm that EPS is a clinicopathologic entity, albeit with a broad morphologic spectrum. The uneventful outcome in some of our cases indicates that a subset of EPS might follow a more indolent clinical course than previously appreciated. Additional studies are needed to validate whether any morphological and/or molecular attributes have a prognostic impact.

Central Customs Hospital Baku Azerbaijan

Department of Laboratories Seattle Children's Hospital Seattle WA USA

Department of Laboratory Medicine and Pathology University of Washington School of Medicine Seattle WA USA

Department of Pathology and Laboratory Medicine Dartmouth Hitchcock Medical Center and Geisel School of Medicine Lebanon NH USA

Department of Pathology and Molecular Genetics Bioptical Laboratory Ltd Plzen Czech Republic

Department of Pathology Faculty of Medicine Hacettepe University Ankara Turkey

Department of Pathology Faculty of Medicine in Plzen Charles University Plzen Czech Republic

Department of Pathology Oklahoma University Health Sciences Center Oklahoma City OK USA

Department of Pathology Oregon Health and Science University Portland OR USA

Department of Pathology Robert J Tomsich Pathology and Laboratory Medicine Institute Cleveland Clinic Cleveland OH USA

Department of Pathology University of Pittsburgh Pittsburgh PA USA

Institute of Pathology Friedrich Alexander University Erlangen Nürnberg University Hospital Erlangen Germany

Laboratory of Pathology CSD Health Care Ltd Kyiv Ukraine

Mod Pathol. 2021 Nov;34(11):2092. doi: 10.1038/s41379-021-00740-x. PubMed

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PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum