PHF1::TFE3-positive fibromyxoid sarcoma? Report of 2 cases and review of 13 cases of PHF1::TFE3-positive ossifying fibromyxoid tumor in the literature.

ABSTRACT

OBJECTIVES: Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain histogenesis. Most OFMTs have benign behavior, and many harbor gene fusions involving the PHD finger protein 1 (PHF1), such as EP400PHF1, MEAF6PHF1, EPC1PHF1, and PHF1TFE3. The PHF1TFE3 fusion is unique because PHF1 is at 5' instead of residing at 3' in the other fusions. In this study, we describe 2 cases of OFMT harboring PHF1TFE3 fusions and review 13 published cases. METHODS: Two cases of PHF1TFE3-positive OFMT were investigated using RNA Next-Generation Sequencing and immunohistochemistry. RESULTS: Most (12/15) of the PHF1TFE3 OFMTs we studied were located at proximal and distal extremities, with a multinodular growth pattern. Only 1 case (1/10) had a shell of bone at the periphery. Areas morphologically similar to sclerosing epithelioid fibrosarcoma or low-grade fibromyxoid sarcoma were found in 8 of 12 (66.7%) cases. Eleven cases (11/15 [73.3%]) were regarded as malignant based on more than 2/50 high-power field mitotic figures, increased cellularity, or the presence of necrosis. Among the 9 cases with follow-up data, 2 patients died of disease (with metastases), 1 patient is alive with metastases, and 1 patient had multiple local recurrences. CONCLUSIONS: Because PHF1 is located at 3' in all the PHF1 fusions in OFMTs except PHF1TFE3, the different driver molecular alterations suggest that OFMTs with 3'-PHF1 fusions and OFMTs with PHF1TFE3 are different tumors. Immunohistochemistry confirmed TFE3 expression in all PHF1TFE3 OFMTs. Because PHF1TFE3-positive OFMTs have increased mitotic figures and tumor cellularity, with a high rate of metastasis, using the name PHF1TFE3 positive fibromyxoid sarcoma may be appropriate.