"Fibrosarcoma-like" Tumors of the Gynecologic Tract Show Distinct Molecular Subgroups: Tyrosine Kinase Fusions and Recurrent ERBB2/3 Mutations.

In recent years, rare fibrosarcoma-like tumors have been identified in the gynecologic tract, characterized by variable CD34 and S-100 positivity and recurrent tyrosine kinase gene fusions in many cases. We identified 17 of these tumors by searching for gynecologic sarcomas expressing S-100 and/or CD34 and supplementing these with cases contributed by collaborating institutions. Tumors involved the uterine cervix (n = 11), uterine corpus (n = 4), and vagina (n = 2). Patients ranged from 28 to 64 (median, 50 years) years. Fifteen tumors showed overlapping morphologic features, including haphazard or fascicular growth of relatively monotonous spindled to ovoid cells with minimal to moderate cytoplasm. Tyrosine kinase gene fusions were identified in 9 tumors, including NTRK fusions in 6 and COL1A1::PDGFB in 3 tumors. Oncogenic variants in ERBB2/ERBB3 were identified in 6 additional tumors. These 2 subgroups showed distinct immunohistochemical profiles, with all tyrosine kinase fusion-positive tumors being CD34 positive, variably S-100 positive, and SOX10 negative. In contrast, the ERBB-altered tumors were CD34 negative and diffusely positive for S-100 and SOX10. The remaining 2 tumors showed morphologic and immunohistochemical overlap with the tyrosine kinase fusion-positive sarcomas; 1 was negative for fusion or sequence variants, and sequencing failed in the other. In conclusion, most fibrosarcoma-like tumors of the gynecologic tract are defined by either tyrosine kinase fusions or ERBB2/3 mutations. Immunohistochemistry can be used to predict these subgroups to guide confirmatory genetic testing and targeted therapies.