ZFP36-FOSB Fusion Defines a Subset of Epithelioid Hemangioma with Atypical Features
ZFP36-FOSB Fusion Defines a Subset of Epithelioid Hemangioma with Atypical Features
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DOI：
10.1002/gcc.22206
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发表时间：
2014-11-01
影响因子：
3.7
通讯作者：
Fletcher, Christopher D.
中科院分区：
文献类型：
--
作者：
Antonescu, Cristina R.;Chen, Hsiao-Wei;Fletcher, Christopher D.
上皮样血管瘤(EH)是一种具有独特血管形成特征的良性肿瘤，偶尔表现为细胞增多、细胞学异型性和/或局部侵袭性生长，导致与恶性血管肿瘤的鉴别诊断具有挑战性。基于两例骨内高血压的组织学特征令人担忧的病例，如坏死的存在，RNA测序被用于可能的融合基因发现和潜在的新的非典型高血压亚群的亚型分类。1例检测到ZFP36-FosB融合，另1例检测到WWTR1-FosB嵌合转录本，均经荧光原位杂交(FISH)和逆转录聚合酶链式反应(RT-PCR)进一步验证。这些异常随后通过FISH在44个EH中从不同的位置进行筛选，另外7个EH揭示了FosB基因重排，除了一个外，所有的EH都与ZFP36融合。有趣的是，所研究的4/6阴茎EH显示FosB异常。虽然在FosB重排的EH中观察到了一些不典型的组织学特征，包括实性生长、细胞增多、轻到中度的核多形性和坏死，但没有明显的肉瘤区域来客观区分融合阴性的EH。到目前为止，没有患者出现复发，但随访相对有限，而且时间较短，无法得出有关行为的明确结论。尽管FosB重排的EH与SERPINE1-FosB融合阳性的假性肌源性血管内皮瘤在形态上没有明显的重叠，但FosB致癌激活正在成为这些良性和中度血管肿瘤中的一个重要事件。(C)2014年威利期刊公司。
Epithelioid hemangioma (EH) is a benign neoplasm with distinctive vasoformative features, which occasionally shows increased cellularity, cytologic atypia, and/or loco-regional aggressive growth, resulting in challenging differential diagnosis from malignant vascular neoplasms. Based on two intraosseous EH index cases with worrisome histologic features, such as the presence of necrosis, RNA sequencing was applied for possible fusion gene discovery and potential subclassification of a novel atypical EH subset. A ZFP36-FOSB fusion was detected in one case, while a WWTR1-FOSB chimeric transcript in the other, both were further validated by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR). These abnormalities were then screened by FISH in 44 EH from different locations with seven additional EH revealing FOSB gene rearrangements, all except one being fused to ZFP36. Interestingly, 4/6 penile EH studied showed FOSB abnormalities. Although certain atypical histologic features were observed in the FOSB-rearranged EH, including solid growth, increased cellularity, mild to moderate nuclear pleomorphism, and necrosis in 3/9 cases, no overt sarcomatous areas were discerned to objectively separate the lesions from the fusion-negative EH. No patient has developed recurrence to date, but the follow-up was relatively limited and short to draw definitive conclusions regarding behavior. Although FOSB-rearranged EH do not show significant morphologic overlap with SERPINE1-FOSB fusion-positive pseudomyogenic hemangioendothelioma, FOSB oncogenic activation is emerging as an important event in these benign and intermediate groups of vascular tumors. (c) 2014 Wiley Periodicals, Inc.