Recurrent YAP1-TFE3 Gene Fusions in Clear Cell Stromal Tumor of the Lung

Agaimy A, Stöhr R, Michal M, Christopoulos P, Winter H, Zhang L, Stenzinger A, Michal M, Mechtersheimer G, Antonescu CR (2021)

Publication Type: Journal article

Publication year: 2021

Journal

American Journal of Surgical Pathology Lippincott, Williams & Wilkins

Book Volume: 45

Pages Range: 1541-1549

Journal Issue: 11

DOI: 10.1097/PAS.0000000000001719

Abstract

Clear cell (hemangioblastoma-like) stromal tumor of the lung (CCST-L) is a recently described distinctive rare pulmonary neoplasm of unknown histogenesis and molecular pathogenesis. Only 7 cases have been reported in 2 recent studies, although additional cases might have been reported under the heading of extraneural pulmonary hemangioblastoma. We herein describe 4 CCST-L cases, 3 of them harboring a YAP1-TFE3 fusion. The fusion-positive tumors occurred in 3 women, aged 29, 56, and 69 years. All presented with solitary lung nodules measuring 2.3 to 9.5 cm. Histologically, all tumors showed similar features being composed of relatively uniform medium-sized epithelioid to ovoid cells with clear cytoplasm and small round monomorphic nuclei. Scattered larger cells with enlarged hyperchromatic nuclei and marked pleomorphism were noted in 2 cases. The tumors were associated with a hypervascularized stroma with variable but essentially subtle resemblance to capillary hemangioblastoma and perivascular epithelioid cell tumor (PEComa). Immunohistochemistry was negative for all lineage-specific markers. Targeted RNA sequencing showed a YAP1-TFE3 fusion in 3 of 4 cases. All 3 tumors showed homogeneous nuclear TFE3 immunoreactivity. Two patients were disease free at 36 and 12 months. The third patient had biopsy-proven synchronous renal and hepatic metastases, but extended follow-up is not available (recent case). The fourth case lacking the fusion affected a 66-year-old woman and showed subtle histologic differences from the fusion-positive cases, but had comparable TFE3 immunoreactivity. CCST-L represents a distinctive entity unrelated to hemangioblastoma and likely driven by recurrent YAP1-TFE3 fusions in most cases. The relationship of our cases to the recently reported "hemangioblastoma-like" CCST-L remains to be determined. Analysis of larger series is paramount to delineate the morphologic spectrum and biological behavior of this poorly characterized entity.

Authors with CRIS profile

Abbas Agaimy Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Robert Stöhr Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

Univerzita Karlova v Praze / Charles University in Prague CZ Czech Republic (CZ) Universitätsklinikum Heidelberg DE Germany (DE) Deutsches Zentrum für Lungenforschung e.V. (DZL) DE Germany (DE) Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Memorial Sloan Kettering Cancer Center US United States (USA) (US)

How to cite

APA:

Agaimy, A., Stöhr, R., Michal, M., Christopoulos, P., Winter, H., Zhang, L.,... Antonescu, C.R. (2021). Recurrent YAP1-TFE3 Gene Fusions in Clear Cell Stromal Tumor of the Lung. American Journal of Surgical Pathology, 45(11), 1541-1549. https://doi.org/10.1097/PAS.0000000000001719

MLA:

Agaimy, Abbas, et al. "Recurrent YAP1-TFE3 Gene Fusions in Clear Cell Stromal Tumor of the Lung." American Journal of Surgical Pathology 45.11 (2021): 1541-1549.

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