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肺透明细胞间质瘤中存在 YAP1-TFE3 基因融合变异体:两例支持该实体存在的报告。

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

机构信息

Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.

Diagnostic and Research Institute of Pathology, Translational Sarcoma Pathology, Medical University of Graz, Graz, Austria.

出版信息

Histopathology. 2021 Dec;79(6):940-946. doi: 10.1111/his.14437. Epub 2021 Aug 22.


DOI:10.1111/his.14437
PMID:34156713
Abstract

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.

摘要

目的:肺透明细胞(血管外皮瘤样)间质瘤是一种新描述的罕见肺肿瘤。最近有三例报道了 YAP1-TFE3 基因融合的复发病例。我们描述了另外两例病例,并证实了特征性的 YAP1-TFE3 基因融合。

方法和结果:我们从软组织病理学咨询服务中确定了两个肺间叶性肿瘤,并进行了 RNA 测序。这两个病例均为男性患者,年龄分别为 35 岁和 77 岁。两个病例均表现为单发肺结节,最大径分别为 3.9 和 7.5cm。组织病理学上,肿瘤由上皮样至饱满的梭形细胞组成,呈束状和实性片状排列。细胞的核呈梭形至卵圆形,染色质开放,核仁大小不一,显著或不显著,胞质稀少至中等量,透明或嗜酸性。细胞学异型性和明显的有丝分裂活性最小。肿瘤均不表达谱系特异性免疫表型标记物。两个病例均弥漫性表达核 TFE3。与 YAP1-TFE3 融合的上皮样血管内皮细胞瘤不同,后者的融合断点发生在 YAP1 外显子 1 和 TFE3 外显子 4 或 6,而这些肿瘤的融合断点位于 YAP1 外显子 4 和 TFE3 外显子 7。完全手术后切除后,两个肿瘤均未复发或转移(随访期 6-7 个月)。

结论:我们在一个独特的原发性肺间叶性肿瘤中证实了 YAP1-TFE3 基因融合的存在,为肺透明细胞间质瘤作为一个独特实体提供了更多的支持。

相似文献

[1]
YAP1-TFE3 gene fusion variant in clear cell stromal tumour of lung: report of two cases in support of a distinct entity.

Histopathology. 2021-12

[2]
Clear cell stromal tumour of the lung with YAP1::TFE3 fusion: four cases including a case with highly aggressive clinical course.

Histopathology. 2022-8

[3]
Recurrent YAP1-TFE3 Gene Fusions in Clear Cell Stromal Tumor of the Lung.

Am J Surg Pathol. 2021-11-1

[4]
YAP1-TFE3-fused hemangioendothelioma: a multi-institutional clinicopathologic study of 24 genetically-confirmed cases.

Mod Pathol. 2021-12

[5]
A YAP1::TFE3 cutaneous low-grade fibromyxoid neoplasm: A novel entity!

Genes Chromosomes Cancer. 2022-4

[6]
Clear cell stromal tumor of the lung with multinucleated giant cells: a report of a case with YAP1-TFE3 fusion.

Diagn Pathol. 2023-1-27

[7]
Inflammatory spindle cell PEComa of the lung with YAP1::TFE3 fusion: a report of two cases and a potential relationship with clear cell stromal tumour.

Histopathology. 2025-2

[8]
Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma.

Genes Chromosomes Cancer. 2013-6-5

[9]
YAP1-TFE3 epithelioid hemangioendothelioma: a case without vasoformation and a new transcript variant.

Virchows Arch. 2015-4

[10]
Cytologic features of hepatic YAP1-TFE3 rearranged epithelioid hemangioendothelioma.

Diagn Cytopathol. 2021-12

引用本文的文献

[1]
C-terminal fusion partner activity contributes to the oncogenic functions of YAP1::TFE3.

Sci Rep. 2025-8-31

[2]
YAP, TAZ, and Hippo-Dysregulating Fusion Proteins in Cancer.

Annu Rev Cancer Biol. 2024-6

[3]
"Putting the cart before the horse": an update on promiscuous gene fusions in soft tissue tumors.

Virchows Arch. 2025-5

[4]
Perivascular Epithelioid Cell Tumor of the Lung With a Novel Fusion.

Int J Surg Pathol. 2025-9

[5]
YAP1::TFE3 fusion in a case of malignant TFE3-rearranged PEComa of the lung: expanding the spectrum of pulmonary PEComa-like mesenchymal neoplasms.

Virchows Arch. 2025-3

[6]
Small blue round cell tumor with focal epithelial differentiation harboring a novel YAP1::LEUTX fusion with poor prognosis.

Virchows Arch. 2024-8

[7]
Clear cell stromal tumor of the lung with multinucleated giant cells: a report of a case with YAP1-TFE3 fusion.

Diagn Pathol. 2023-1-27

[8]
Unraveling the Biology of Epithelioid Hemangioendothelioma, a TAZ-CAMTA1 Fusion Driven Sarcoma.

Cancers (Basel). 2022-6-16

[9]
Case Report: Hemangioblastoma- Like Clear Cell Stromal Tumor of the Left Lower Lung.

Front Med (Lausanne). 2022-4-18

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