YAP1–TFE3 gene fusion variant in clear cell stromal tumour of lung: report of two cases in support of a distinct entity

Abstract

YAP1-TFE3 gene fusion variant in clear cell stromal tumour of lung: report of two cases in support of a distinct entity Aims: Clear cell (haemangioblastoma-like) stromal tumour 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 tumours of lung were identified from our soft tissue pathology consultation services and RNA sequencing was performed. Both cases were in male patients, aged 35 and 77 years. Both presented as solitary lung nodules measuring 3.9 and 7.5 cm in greatest dimension. Histopathologically, the tumours were composed of epithelioid to plump spindle 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. Cytological atypia and significant mitotic activity were minimal. None of the tumours expressed lineage-specific immunophenotypical markers. Both cases were diffusely positive for nuclear TFE3. Unlike YAP1-TFE3-fused epithelioid haemangioendothelioma, for which the fusion breakpoint occurs in YAP1 exon 1 and TFE3 exons 4 or 6, the fusion breakpoints of these tumours were located in YAP1 exon 4 and TFE3 exon 7. Following complete surgical resection, neither of the tumours has recurred or metastasised (follow-up period 6-7 months). Conclusions: We validate the presence of YAP1-TFE3 gene fusion in a unique primary mesenchymal tumour of lung, adding additional support for clear cell stromal tumour of the lung as a distinct entity.

Case Report: Hemangioblastoma- Like Clear Cell Stromal Tumor of the Left Lower Lung

“…The PAS staining was also negative. YAP1-TFE3 gene fusions have recently been reported in 5 cases ( 8 ). The YAP1-TFE3 fusion has only been described in a rare subset of epithelioid hemangioendothelioma (EHE), which was lacked the classic WW domain containing transcription regulator 1-Calmodulin binding transcription activator 1 ( WWTR1-CAMTA1 ) fusion ( 9 ).…”

Unraveling the Biology of Epithelioid Hemangioendothelioma, a TAZ–CAMTA1 Fusion Driven Sarcoma

“…When compared with the behavior of WWTR1–CAMTA1 EHE, patients harboring YAP1–TFE3 -fused HE were more likely to have soft-tissue disease and had an improved 5-year progression-free survival [ 47 , 50 ]. Since the initial discovery of this fusion, the YAP1–TFE3 fusion has also been identified in the clear-cell stromal tumor of the lung and in a case of cutaneous low-grade fibromyxoid neoplasm; no additional cancers have been identified that harbor the WWTR1–CAMTA1 fusion [ 62 , 63 , 64 ].…”

Spindle cell tumors of the pleura and the peritoneum: pathologic diagnosis and updates

“…Based on studies including use of murine models, WWTR1-CAMTA1 fusion represents a necessary and sufficient driver in EHE oncogenesis and perturbs signaling of TAZ (encoded by WWTR1) and Hippo pathway [107]. To date, while the WWTR1-CAMTA1 fusion appears to be specific for EHE, YAP1-TFE3 fusion has been identified in non-EHE tumors including clear cell (hemangioblastoma-like) stromal tumor of the lung [108,109].…”