Recurrent YAP1-TFE3 gene fusions in clear cell stromal tumor of the lung Journal Article
| Authors: | Agaimy, A.; Stoehr, R.; Michal, M.; Christopoulos, P.; Winter, H.; Zhang, L.; Stenzinger, A.; Michal, M.; Mechtersheimer, G.; Antonescu, C. R. |
| Article Title: | Recurrent YAP1-TFE3 gene fusions in clear cell stromal tumor of the lung |
| 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. |
| Keywords: | lung; yap1; hemangioblastoma; pecoma; tfe3; defines; subset; vhl; pecomas; clear cell sugar tumor |
| Journal Title: | American Journal of Surgical Pathology |
| Volume: | 45 |
| Issue: | 11 |
| ISSN: | 0147-5185 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2021-11-01 |
| Start Page: | 1541 |
| End Page: | 1549 |
| Language: | English |
| ACCESSION: | WOS:000706785000011 |
| DOI: | 10.1097/pas.0000000000001719 |
| PROVIDER: | wos |
| PMCID: | PMC8516668 |
| PUBMED: | 33899786 |
| Notes: | Article -- Source: Wos |
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