Affiliation:
1. Section of Pathology, Department of Translational Research University of Pisa Pisa Italy
2. Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine University of Pisa Pisa Italy
3. Pathology Unit Meyer Children's Hospital IRCCS Florence Italy
4. Unit of Histopathology and Molecular Diagnostic Azienda Ospedaliera Universitaria Careggi Florence Italy
5. Department of Health Sciences University of Florence Florence Italy
Abstract
AimsLow‐grade myofibroblastic sarcoma (LGMS) is a rarely metastasizing myofibroblastic tumour mostly affecting extremities and the head and neck of adults. Histologically, it shows long infiltrative fascicles of spindle cells with moderate nuclear atypia. By immunohistochemistry, it stains positive for smooth muscle actin (SMA) and sometimes for desmin. To date, no recurrent genetic abnormalities have been described. Ubiquitin‐specific peptidase 6 (USP6) gene rearrangement is typically found in some benign bone and soft‐tissue tumours including nodular fasciitis (NF), among others. Nevertheless, rare cases of USP6‐rearranged tumours resembling NF with atypical features have been reported.Methods and ResultsOne index case of LGMS of the deltoid in a 56‐year‐old man presented the THBS2::USP6 translocation by RNA sequencing (Archer FusionPlex Sarcoma v2 panel). Further screening of 11 cases of LGMS using fluorescent in situ hybridization (FISH) analysis with a USP6 break‐apart probe identified two additional cases. These cases were investigated with RNA‐sequencing, and a RRBP1::USP6 translocation was detected in one. The other case was not assessable because of low‐quality RNA. Noteworthy, rearranged LGMSs presented distinctive features including variable multinodular/plexiform architecture, prominent vasculature with occasional wall thickening, scattered osteoclast‐like multinucleated giant cells, and peripheral lymphoid aggregates.ConclusionOur findings support the notion that among soft‐tissue neoplasms with fibroblastic/myofibroblastic phenotype, USP6 rearrangement is not limited to benign tumours, and warrants further investigation of genetic changes in myofibroblastic sarcomas.