This investigation describes the clinicoradiologic, pathologic, and molecular features of a unique soft tissue tumor characterized by a peripheral shell of bone and composed of bland myoid spindle and epithelioid cells that are keratin-positive. Our study cohort consists of 6 men and 6 women, with a mean age of 32 years. The tumors arose in the extremities (n = 9) and proximal limb girdle (n = 3) and were equally distributed between deep and superficial soft tissues. Patients reported dull painless masses of several months to >10 years duration (mean: 2.9 years). Imaging demonstrated a complete or partial peripheral shell of bone that could extend centrally, and the tumor's mean size was 5.7 cm. Histologically, the tumors were composed of uniform, eosinophilic myoid spindled cells growing in sheets and intersecting fascicles, surrounded by mature lamellar and/or woven bone. Also present was an admixed component of intermediate-sized epithelioid cells with eosinophilic cytoplasm. Mitotic activity was consistently low. Immunohistochemistry showed strong multifocal staining for keratins, and 50% (5/10) showed focal staining for S100; however, all were negative for SMA, desmin, SOX10, ERG, and CD34. Genetic analysis by multiple targeted RNA sequencing panels was negative (n = 10); however, whole transcriptome sequencing (n = 8) revealed a recurrent and novel in-frame SRSF7::NFATC3 fusion in 4 tumors. Dual fluorescence in situ hybridization probes for SRSF7::NFATC3 successfully confirmed this fusion and identified a fifth case, which had not undergone whole transcriptome sequencing but was negative by a targeted RNA fusion panel. Methylation profiling (n = 8) demonstrated a shared epigenetic profile distinct from other entities. Clinical follow-up (n = 11) showed no evidence of recurrence after primary excision with a mean of 41.6 months. In summary, we describe a novel soft tissue tumor designated "ossifying spindled and epithelioid tumor" as a descriptive histologic term that also emphasizes its close radiologic mimic, ossifying fibromyxoid tumor. All cases have behaved in a benign fashion without recurrence following simple excision. Awareness of this entity is important, so that it can be distinguished from other neoplasms that have more aggressive biological potential.

Department of Pathology and Laboratory Medicine Cleveland Clinic Cleveland Ohio

Department of Pathology and Laboratory Medicine Hospital for Special Surgery Weill Cornell Medical College New York New York

Department of Pathology Baylor University Medical Center Dallas Texas

Department of Pathology Bone Tumor Reference Center at the Institute of Pathology University Hospital Basel and University of Basel Basel Switzerland

Department of Pathology Bone Tumor Reference Center at the Institute of Pathology University Hospital Basel and University of Basel Basel Switzerland; Department of Pathology Basel Research Centre for Child Health Basel Switzerland

Department of Pathology Charles University Faculty of Medicine in Plzeň Plzeň Czech Republic; Department of Pathology Bioptical Laboratory Ltd Plzeň Czech Republic

Department of Pathology Corewell Health William Beaumont University Hospital Royal Oak Michigan

Department of Pathology Experimental and Computational Genomic Core Shared Resource The Sidney Kimmel Comprehensive Cancer Center The Johns Hopkins University School of Medicine Baltimore Maryland

Department of Pathology Institute of Pathology Erlangen University Hospital Friedrich Alexander University of Erlangen Nuremberg Erlangen Germany; Department of Pathology Comprehensive Cancer Center European Metropolitan Area Erlangen Nuremberg Erlangen Germany

Department of Pathology Rutgers University Newark New Jersey

Department of Pathology Stanford University School of Medicine Stanford California

Department of Pathology The Johns Hopkins University School of Medicine Baltimore Maryland

Department of Pathology University of Miami and Miller School of Medicine Miami Florida

Section of Histopathology Department of Pathology and Laboratory Medicine Aga Khan University Hospital Karachi Pakistan

Citace poskytuje Crossref.org