LAUSR

AIMS Clear cell (hemangioblastoma-like) stromal tumor of the lung is a newly described, rare pulmonary neoplasm. Recurrent YAP1-TFE3 gene fusions have recently been reported in three cases. We describe two additional cases and confirm the characteristic YAP1-TFE3 gene fusion. METHODS AND RESULTS Two mesenchymal tumors of lung were identified from our soft tissue pathology consultation service and RNA sequencing was performed. Both cases were in male patients, aged 35 and 77 years old. Both presented as solitary lung nodules measuring 3.9 and 7.5 cm in greatest dimension. Histopathologically, the tumors were composed of epithelioid to plump spindled cells arranged in packets and solid sheets. The cells showed fusiform to ovoid nuclei with open chromatin, variably prominent nucleoli, and scant to moderate, clear to eosinophilic cytoplasm. Cytologic atypia and significant mitotic activity were minimal. None of the tumors expressed lineage-specific immunophenotypic markers. Both cases were diffusely positive for nuclear TFE3. Unlike YAP1-TFE3 fused epithelioid hemangioendothelioma, for which the fusion breakpoint occurs in YAP1 exon 1 and TFE3 exons 4 or 6, the fusion breakpoints of these tumors are located in YAP1 exon 4 and TFE3 exon 7. Following complete surgical resection, neither of the tumors has recurred or metastasized (follow-up period 6-7 months). CONCLUSIONS We validate the presence of YAP1-TFE3 gene fusion in a unique primary mesenchymal tumor of lung, adding additional support for clear cell stromal tumor of the lung as a distinct entity.