Spindle Cell Spindle Sarcoma Harboring a Novel RECQL::ROS1 Gene Fusion

Abstract

Soft tissue sarcomas are a heterogeneous group of malignancies arising from mesenchymal cells. Recent advancements in genomic profiling have identified novel gene fusions in these tumors, offering new insights into their pathogenesis and potential therapeutic targets. Here, we describe a spindle cell sarcoma harboring a novel RECQL::ROS1 gene fusion. A 21-year-old female patient presented with a painless mass in the left thigh for over one month. Magnetic resonance imaging revealed a well-circumscribed, heterogeneously enhancing lesion within the vastus lateralis muscle. Histopathological examination demonstrated the tumor with alternating hypocellular and hypercellular areas infiltrating surrounding skeletal muscle. The hypocellular zones featured hyalinized collagenous stroma containing bland spindle cells exhibiting nuclei with inconspicuous nucleoli, eosinophilic cytoplasm, and mitotic figures were minimal (<1/2 mm²). In contrast, hypercellular regions displayed palisading necrosis with hemorrhagic foci, fascicular proliferation of pleomorphic spindle cells, marked nuclear atypia with prominent nucleoli, and frequent mitotic figures (>10/2 mm²). Immunohistochemically, tumor cells were positive for S100 and CD34. Tumor cells were negative for pan-keratin, SMA, desmin, ALK, p63, SOX10, TRK(Pan), MyoD1, STAT6, CDK4, MDM2, EMA, TLE1, CD21, and ROS1. A novel RECQL::ROS1 fusion was identified through RNA-based next-generation sequencing and whole-exome sequencing. Fluorescence in situ hybridization confirmed ROS1 rearrangement. The tumor was ultimately classified as a spindle cell sarcoma with RECQL::ROS1 fusion. The patient undergone radiotherapy after surgery and recovered well without recurrence and metastasis 8 months after surgery. This study extends the spectrum of ROS1-rearrangements in the spindle cell sarcoma, while underscoring the pivotal role of comprehensive molecular profiling in providing diagnostic clarity and identifying actionable therapeutic targets.