Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden.
Mod Pathol. 2014 Mar;27(3):390-5. doi: 10.1038/modpathol.2013.164. Epub 2013 Sep 13.
Solitary fibrous tumor (SFT) is composed of spindled to ovoid cells in a patternless architecture with prominent stromal collagen and hemangiopericytoma-like vessels. Some tumors show hypercellularity, nuclear atypia, and significant mitotic activity; the latter feature in particular often portends an aggressive clinical course. SFT can sometimes be difficult to distinguish from other benign mesenchymal tumors and sarcomas. The most characteristic (albeit nonspecific) immunohistochemical finding in SFT is CD34 expression. A NAB2-STAT6 gene fusion, resulting in a chimeric protein in which a repressor domain of NGFI-A binding protein 2 (EGR1 binding protein 2) (NAB2) is replaced with a carboxy-terminal transactivation domain from signal transducer and activator of transcription 6, interleukin-4 induced (STAT6), was recently identified as a consistent finding in SFT. However, as these genes are located in close proximity on 12q13, this fusion can only rarely be detected by conventional chromosomal banding or fluorescence in situ hybridization analysis. Nuclear expression of the carboxy terminal part of STAT6 is a consistent finding in SFT of the meninges (so-called 'meningeal hemangiopericytoma'). We investigated STAT6 expression by immunohistochemistry in SFTs and other soft tissue tumors arising outside the central nervous system to validate the diagnostic utility of this novel marker. Whole-tissue sections of 231 tumors were evaluated, including 60 cases of SFT as well as other benign and malignant mesenchymal neoplasms and sarcomatoid mesotheliomas. Fifty-nine of 60 SFT cases (98%) showed nuclear expression of STAT6, which was usually diffuse and intense. All other tumor types were negative for STAT6, except for three dedifferentiated liposarcomas and one deep fibrous histiocytoma, which showed weak staining. In conclusion, STAT6 is a highly sensitive and almost perfectly specific immunohistochemical marker for SFT and can be helpful to distinguish this tumor type from histologic mimics.
孤立性纤维瘤（SFT）由梭形至卵圆形细胞构成，呈无序排列，间质富含胶原，伴血管外皮细胞瘤样血管。部分肿瘤表现为细胞丰富、核异型性和显著的有丝分裂活性；后者特征往往预示着侵袭性临床病程。SFT 有时难以与其他良性间叶肿瘤和肉瘤鉴别。SFT 最具特征性（虽然非特异性）的免疫组化表现是 CD34 表达。最近发现 NAB2-STAT6 基因融合，导致嵌合蛋白，其中 NGFI-A 结合蛋白 2（EGR1 结合蛋白 2）（NAB2）的阻遏结构域被信号转导和转录激活因子 6、白细胞介素 4 诱导（STAT6）的羧基末端转录激活结构域取代。然而，由于这些基因位于 12q13 附近，这种融合在常规染色体带分析或荧光原位杂交分析中很少被检测到。STAT6 羧基末端的核表达是脑膜孤立性纤维瘤（所谓的“脑膜血管外皮细胞瘤”）的一个一致性发现。我们通过免疫组化检测 STAT6 在 SFT 和其他发生于中枢神经系统外的软组织肿瘤中的表达，以验证这一新标志物的诊断效用。评估了 231 个肿瘤的全组织切片，包括 60 例 SFT 以及其他良性和恶性间叶性肿瘤和肉瘤样间皮瘤。60 例 SFT 中有 59 例（98%）显示 STAT6 核表达，通常为弥漫性和强阳性。除了 3 例去分化脂肪肉瘤和 1 例深部纤维组织细胞瘤外，所有其他肿瘤类型均为 STAT6 阴性，后者表现为弱阳性染色。总之，STAT6 是 SFT 的一种高度敏感和几乎完全特异的免疫组化标志物，有助于将这种肿瘤类型与组织学类似物区分开来。
