Primary Bronchial Hybrid Low-Grade Fibromyxoid Sarcoma/Sclerosing Epithelioid Fibrosarcoma With EWSR1::CREB3L1 Fusion: Diagnostic Insights From a Challenging Case in the Respiratory Tract.

Hybrid low-grade fibromyxoid sarcoma/sclerosing epithelioid fibrosarcoma (LGFMS/SEF) is an ultra-rare fibroblastic sarcoma that typically arises in the soft tissues. Primary involvement of the respiratory tract is extremely uncommon, and, to our knowledge, no cases arising in the bronchial wall have previously been reported. We describe a hybrid LGFMS/SEF arising in the right bronchus of a Japanese woman in her 40 s. The 2-cm tumor was incidentally detected, and imaging studies demonstrated no other lesions. Histologically, the tumor consisted predominantly of bland spindle cells within fibromyxoid stroma with collagen rosettes, admixed with epithelioid fibroblasts arranged in cords. Immunohistochemically, the tumor showed diffuse positivity for MUC4. Comprehensive genomic profiling performed for diagnostic purposes identified an EWSR1::CREB3L1 fusion gene, supporting the diagnosis of hybrid LGFMS/SEF. Retrospective review of the transbronchial biopsy specimen revealed subtle spindle cells showing MUC4 expression by immunohistochemistry and EWSR1 rearrangement by fluorescence in situ hybridization, which had initially been interpreted as inflammatory change. This case highlights important diagnostic pitfalls of hybrid LGFMS/SEF and provides the clinicopathological insights into EWSR1::CREB3L1-associated fibroblastic sarcoma arising in the bronchial wall.