BACKGROUND: Clear cell (hemangioblastoma-like) stromal tumor of the lung (CCSTL) is a rare pulmonary neoplasm. Recently, 9 cases of CCSTL harboring the YAP1-TFE3 gene fusion have been described, and it has been suggested that this aberration could be a characteristic feature of this tumor. CASE PRESENTATION: We here report another case of CCSTL in a 57-year-old male, which presented as a solitary lung nodule 45 mm in the greatest dimension. Microscopically, the tumor consisted of epithelioid to spindled cells with mild-to-moderate nuclear atypia, finely granular or vesicular chromatin, and small nucleoli. Nuclear indentations were a common finding. There were up to 3 mitoses per 10 HPF. The cytoplasm was slightly eosinophilic or clear. Scattered non-tumor large multinucleated cells were present. Immunohistochemically, the tumor cells showed diffuse positivity for TFE3, CD10, vimentin, and IFITM1. Other markers examined were negative, and the expression of lineage-specific markers was not found. NGS analysis revealed a fusion transcript of the YAP1 and TFE3 genes, and a pathogenic variant of the MUTYH gene. CONCLUSION: Our finding supports the recent data suggesting that CCSTL represents a distinct entity characterized by the recurrent YAP1-TFE3 fusion.

• Klíčová slova
• Clear cell (hemangioblastoma-like) stromal tumor, Lung, YAP1-TFE3 fusion,
• MeSH
• fúze genů MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery genetika   analýza   MeSH
• nádory plic * genetika   MeSH
• obrovské buňky chemie   MeSH
• plíce MeSH
• transkripční faktory BHLH-Zip * genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• nádorové biomarkery MeSH
• TFE3 protein, human MeSH Prohlížeč
• transkripční faktory BHLH-Zip * MeSH

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.

• MeSH
• adaptorové proteiny signální transdukční genetika   MeSH
• dospělí MeSH
• fenotyp MeSH
• fúze genů * MeSH
• genetická predispozice k nemoci MeSH
• hemangioblastom genetika   sekundární   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery genetika   MeSH
• nádory plic genetika   patologie   chirurgie   MeSH
• pneumektomie MeSH
• senioři MeSH
• signální proteiny YAP MeSH
• solitární plicní uzel genetika   patologie   chirurgie   MeSH
• transkripční faktory BHLH-Zip genetika   MeSH
• transkripční faktory genetika   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• nádorové biomarkery MeSH
• signální proteiny YAP MeSH
• TFE3 protein, human MeSH Prohlížeč
• transkripční faktory BHLH-Zip MeSH
• transkripční faktory MeSH
• YAP1 protein, human MeSH Prohlížeč

We report two cases (male patients 50 and 55 years old) of clear cell sarcoma ("melanoma of soft parts") arising in the lung, of which one case showed regional lymph node metastases. Histologically, both tumors displayed varying clear epithelioid and spindle neoplastic cells arranged in storiform and nested growth patterns, separated by thin fibrovascular septa. Immunohistochemical studies demonstrated positive expression of S-100 protein, HMB-45 and Melan-A in one case and S-100 protein only in the other. Fluorescence in situ hybridization showed positive EWSR1 gene rearrangement, and a presence of EWS-ATF1 fusion transcript was confirmed by RT-PCR and sequencing in one case.

• Klíčová slova
• ATF1, Clear cell sarcoma, EWS, Lung, Melanoma of soft parts,
• MeSH
• genová přestavba fyziologie   MeSH
• hybridizace in situ fluorescenční metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory měkkých tkání genetika   patologie   MeSH
• protein EWS vázající RNA MeSH
• proteiny S100 metabolismus   MeSH
• proteiny vázající kalmodulin genetika   metabolismus   MeSH
• proteiny vázající RNA genetika   metabolismus   MeSH
• sarkom z jasných buněk diagnóza   genetika   MeSH
• translokace genetická genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• EWSR1 protein, human MeSH Prohlížeč
• protein EWS vázající RNA MeSH
• proteiny S100 MeSH
• proteiny vázající kalmodulin MeSH
• proteiny vázající RNA MeSH