AJSP2502 - CME/CMLE - PHF1::TFE3-positive fibromyxoid sarcoma? Report of 2 cases and review of 13 cases of PHF1::TFE3-positive ossifying fibromyxoid tumor in the literature-AJSP2502

AJSP2502 - Educational Activity

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The article in the American Journal of Clinical Pathology (2024) explores ossifying fibromyxoid tumors (OFMTs), a rare soft tissue neoplasm characterized by uncertain origins and typically benign behavior. However, some OFMTs exhibit malignant tendencies, with metastasis risks estimated between 20% to 60%. The focus is on OFMTs with a specific genetic fusion, PHF1::TFE3, which is distinct from other PHF1 fusions due to the 5' positioning of PHF1, as opposed to its typical 3' location. The study describes two new cases and reviews 13 previously published instances of PHF1::TFE3 fusions.<br /><br />Key findings show that PHF1::TFE3-positive OFMTs are generally more aggressive, with increased mitotic activity and cellularity, sometimes leading to metastasis or recurrent tumors. These tumors often exhibit features resembling other sarcomas, such as sclerosing epithelioid fibrosarcoma or low-grade fibromyxoid sarcoma, but with unique molecular alterations. Immunohistochemical testing confirms TFE3 protein expression in these tumors, supporting the oncogenic role of the PHF1::TFE3 fusion.<br /><br />The study presents a detailed methodological approach, utilizing RNA next-generation sequencing (NGS) and immunohistochemistry to identify and characterize the fusions. The results showed that all PHF1::TFE3 OFMTs were positive for nuclear TFE3 staining and had a distinct genetic profile, suggesting they could be classified separately from other OFMTs with different PHF1 fusions.<br /><br />Despite the limited number of cases, the researchers propose renaming these tumors as PHF1::TFE3-positive fibromyxoid sarcoma. The article emphasizes the need for more extensive research and long-term follow-up to understand fully the clinical implications and biological behavior of these tumors. Such studies would confirm whether they should indeed be distinguished from other types of OFMTs in terms of diagnosis and treatment strategies.

Keywords

ossifying fibromyxoid tumors

PHF1::TFE3 fusion

soft tissue neoplasm

malignant tendencies

metastasis risk

RNA next-generation sequencing

immunohistochemistry

sclerosing epithelioid fibrosarcoma

fibromyxoid sarcoma

oncogenic role