FOSB is a Useful Diagnostic Marker for Pseudomyogenic Hemangioendothelioma
FOSB is a Useful Diagnostic Marker for Pseudomyogenic Hemangioendothelioma
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DOI：
10.1097/pas.0000000000000795
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发表时间：
2017-05-01
影响因子：
5.6
通讯作者：
Hornick, Jason L.
中科院分区：
文献类型：
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作者：
Hung, Yin P.;Fletcher, Christopher D. M.;Hornick, Jason L.
假肌源性（上皮样肉瘤样）血管内皮瘤是一种独特的血管肿瘤的中间生物学潜力，好发于年轻人和频繁的多灶性表现。假性肌源性血管内皮瘤的特征是疏松的梭形细胞和上皮样细胞，胞浆丰富，同时表达角蛋白和内皮标志物。最近，SERPINE 1-FOSB融合已被确定为假肌源性血管内皮瘤中一致的遗传改变。FOSB基因融合也已报告在一个子集的上皮样血管瘤。本研究的目的是评估与其他内皮肿瘤和组织学模拟相比，FOSB免疫组化对假性肌源性血管内皮瘤的潜在诊断价值。我们评估了274例患者的全组织切片，包括50例假肌源性血管内皮瘤，84例其他血管肿瘤（24例上皮样血管瘤[包括6例血管淋巴样增生伴嗜酸性粒细胞增多组织学]，20例上皮样血管瘤，20例上皮样血管内皮瘤[17例CAMTA 1阳性，2例TFE 3阳性]，10例梭形细胞血管瘤和10例上皮样血管瘤结节），和140个其他组织学类似物（上皮样肉瘤、增殖性筋膜炎、结节性筋膜炎、细胞良性纤维组织细胞瘤、梭形细胞鳞状细胞癌、梭形细胞横纹肌肉瘤和平滑肌肉瘤各20个）。免疫组织化学FOSB进行高压锅抗原修复后，使用兔单克隆抗体。在50例假肌源性血管内皮瘤中的48例（96%）和24例上皮样血管瘤（包括所有嗜酸性粒细胞增多型血管淋巴样增生）中的13例（54%）中观察到FOSB弥漫性核免疫反应（> 50%的细胞）。两例FOSB阴性的假肌源性血管内皮瘤病例均为脱钙骨肿瘤。仅7例其他肿瘤表现出弥漫性FOSB表达：2例增殖性筋膜炎，2例结节性筋膜炎，1例上皮样血管肉瘤，1例梭形细胞血管肉瘤和1例上皮样血管内皮瘤。值得注意的是，FOSB阳性上皮样血管内皮瘤CAMTA 1和TFE 3阴性。在一部分组织学模拟物中观察到局灶性弱FOSB染色，因此没有诊断意义。总之，FOSB是假肌源性血管内皮瘤的一个高度敏感和诊断有用的标志物。免疫组化FOSB可能有助于鉴别假肌源性血管内皮瘤与组织学拟态，包括上皮样肉瘤和其他血管肿瘤。正如预期，一部分上皮样血管瘤表达FOSB，包括血管淋巴样增生伴嗜酸性粒细胞增多。虽然结节性和增生性筋膜炎的病例偶见FOSB阳性，但根据形态学和其他免疫表型结果，这些肿瘤类型与假肌源性血管内皮瘤之间的区别通常是直接的。
Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma is a distinctive vascular neoplasm of intermediate biological potential with a predilection for young adults and frequent multifocal presentation. Pseudomyogenic hemangioendothelioma is characterized by loose fascicles of plump spindled and epithelioid cells with abundant eosinophilic cytoplasm and coexpression of keratins and endothelial markers. Recently, a SERPINE1-FOSB fusion has been identified as a consistent genetic alteration in pseudomyogenic hemangioendothelioma. FOSB gene fusions have also been reported in a subset of epithelioid hemangiomas. The purpose of this study was to assess the potential diagnostic utility of FOSB immunohistochemistry for pseudomyogenic hemangioendothelioma compared with other endothelial neoplasms and histologic mimics. We evaluated whole-tissue sections from 274 cases including 50 pseudomyogenic hemangioendotheliomas, 84 other vascular tumors (24 epithelioid hemangiomas [including 6 cases with angiolymphoid hyperplasia with eosinophilia histology], 20 epithelioid angiosarcomas, 20 epithelioid hemangioendotheliomas [17 CAMTA1 positive, 2 TFE3 positive], 10 spindle-cell angiosarcomas, and 10 epithelioid angiomatous nodules), and 140 other histologic mimics (20 each epithelioid sarcoma, proliferative fasciitis, nodular fasciitis, cellular benign fibrous histiocytoma, spindle-cell squamous cell carcinoma, spindle-cell rhabdomyosarcoma, and leiomyosarcoma). Immunohistochemistry for FOSB was performed following pressure cooker antigen retrieval using a rabbit monoclonal antibody. Diffuse nuclear immunoreactivity for FOSB (> 50% of cells) was observed in 48 of 50 (96%) pseudomyogenic hemangioendotheliomas and 13 of 24 (54%) epithelioid hemangiomas (including all angiolymphoid hyperplasia with eosinophilia type). Both FOSB-negative pseudomyogenic hemangioendothelioma cases were decalcified bone tumors. Only 7 other tumors showed diffuse FOSB expression: 2 proliferative fasciitis, 2 nodular fasciitis, 1 epithelioid angiosarcoma, 1 spindle-cell angiosarcoma, and 1 epithelioid hemangioendothelioma. Of note, the FOSB-positive epithelioid hemangioendothelioma was negative for CAMTA1 and TFE3. Focal weak FOSB staining was observed in a subset of histologic mimics and is therefore not diagnostically meaningful. In conclusion, FOSB is a highly sensitive and diagnostically useful marker for pseudomyogenic hemangioendothelioma. Immunohistochemistry for FOSB may be helpful to distinguish pseudomyogenic hemangioendothelioma from histologic mimics including epithelioid sarcoma and other vascular neoplasms. As expected, a subset of epithelioid hemangiomas expresses FOSB, including angiolymphoid hyperplasia with eosinophilia. Although occasional cases of nodular and proliferative fasciitis are positive for FOSB, distinction between these tumor types and pseudomyogenic hemangioendothelioma is usually straightforward based on morphology and other immunophenotypic findings.