Primary Renal Sclerosing Epithelioid Fibrosarcoma With EWSR1::CREB3L1 Fusion: A Diagnostic Pitfall With a...

Sclerosing epithelioid fibrosarcoma (SEF) is a rare malignant soft tissue sarcoma with morphologic and molecular overlap with low-grade fibromyxoid sarcoma (LGFMS). Although most commonly arising in deep soft tissues, primary involvement of the kidney is exceptionally uncommon and represents a significant diagnostic pitfall. We report a primary renal SEF in a 22-year-old woman, characterized by classic histomorphology, diffuse MUC4 immunoreactivity, and definitive molecular confirmation by next-generation sequencing demonstrating an EWSR1::CREB3L1 fusion. Radiologic evaluation revealed a solid renal mass suspicious for malignancy, prompting partial nephrectomy. Histologically, the tumor was composed of epithelioid and spindle cells embedded in a densely sclerotic stroma with characteristic filigree collagen. Accurate recognition of renal SEF is critical, as it may be misdiagnosed as sarcomatoid renal cell carcinoma, sclerosing clear cell sarcoma of the kidney, epithelioid angiomyolipoma, or other primary renal neoplasms. In addition, a comprehensive review of the literature was performed. Including recently reported tumors identified within molecularly characterized series, a total of 19 patients with primary renal SEF have been documented to date. Notably, within the genitourinary tract, available data suggest a relative predilection for renal involvement. This tumor confirms the broad anatomic spectrum of SEF and underscores the essential role of MUC4 immunohistochemistry and molecular testing in the evaluation of renal tumors with epithelioid cytology and prominent stromal sclerosis.