LGALS3::POU5F1 gene fusion identified in a low-grade myxoid spindle cell tumor.

Abstract

Myoepithelial tumor (MET) of soft tissue can harbor POU5F1-associated fusions, including EWSR1/FUS::POU5F1 and SS18::POU5F1. We present a low-grade myxoid spindle cell tumor with a novel LGALS3::POU5F1 mimicking MET. Immunohistochemistry, DNA/RNA next-generation sequencing (NGS), and chromosomal microarray were performed. A 54-year-old man presented with a firm 4.5-cm left upper extremity mass superficial to the fascia. Microscopically, the tumor was partially encapsulated with extracapsular invasion and involvement of surrounding fat. The predominantly hypocellular tumor featured a reticular growth pattern with a myxoid stroma, mimicking extraskeletal myxoid chondrosarcoma. The hypercellular areas demonstrated epithelioid tumor cells embedded in sclerotic stroma, mimicking sclerosing epithelioid fibrosarcoma. Tumor necrosis was absent, and mitotic figures were rare. The tumor cells were only focally and weakly positive for S100 and CAM5.2, but negative for MUC4, AE1/3, CD34, EMA, desmin, GFAP, SMA, p63, SOX10, and calponin. Chromosomal microarray showed gains of whole chromosomes or segment of 5, 6, 7, 8, 12, 14q, and 16. DNA NGS did not show pathogenic mutations. More similar cases are needed to determine whether this LGALS3::POU5F1-positive low-grade myxoid spindle cell tumor represents a new tumor entity or a variant of a MET.