Novel recurrent PHF1‐TFE3 PHF1‐TFE3 fusions in ossifying fibromyxoid tumors

摘要

Abstract Ossifying fibromyxoid tumor (OFMT) is an uncommon mesenchymal neoplasm of uncertain differentiation and intermediate malignant potential. Recurrent PHF1 gene rearrangements are detected in up to 80% of OFMTs. We describe the clinicopathologic features of five OFMTs harboring a novel PHF1 ‐ TFE3 fusion. In two cases, RNA sequencing identified a fusion transcript composed of PHF1 exon 11 fused to TFE3 exon 3, whereas in a third case PHF1 exon 12 was fused to TFE3 exon 7. A FISH break‐apart assay revealed rearrangements in both PHF1 and TFE3 genes in all cases. The cohort included three males and two females with a median age of 64?years. One OFMT originated in the scapula, while four occurred in the deep soft tissues. Two OFMTs had typical features, whereas three were classified as malignant. Despite uniform cytologic features and fibromyxoid stroma compatible with an OFMT diagnosis, none showed a peripheral shell of lamellar bone. S100 expression was focally present in only one case, while desmin was positive in three cases. All tumors showed strong nuclear immunopositivity for TFE3. All three malignant OFMTs developed metastases, either regionally or to the lung. One patient died of disease 1 year after diagnosis, while the remaining two are alive with disease. In summary, we report novel recurrent PHF1 ‐ TFE3 fusions in a subset of OFMTs with aggressive clinical behavior. The PHF1 ‐ TFE3 fusions resulted in consistent protein TFE3 overexpression which can be used as a reliable screening tool, adding OFMT as another tumor driven by TFE3 oncogenic activation pathway.