Thway Khin, Gonzalez David, Wren Dorte, Dainton Melissa, Swansbury John, Fisher Cyril
Sarcoma Unit, Royal Marsden Hospital, London, UK.
Molecular Diagnostics, Royal Marsden Hospital, Sutton, Surrey, UK.
Ann Diagn Pathol. 2015 Jun;19(3):137-42. doi: 10.1016/j.anndiagpath.2015.03.004. Epub 2015 Mar 14.
Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue neoplasm of intermediate biologic potential and uncertain differentiation, most often arising in the extremities of children and young adults. Although it has characteristic histologic features of a lymphoid cuff surrounding nodules of ovoid cells with blood-filled cystic cavities, diagnosis is often difficult due to its morphologic heterogeneity and lack of specific immunoprofile. Angiomatoid fibrous histiocytoma is associated with recurrent chromosomal translocations, leading to characteristic EWSR1-CREB1, EWSR1-ATF1, and, rarely, FUS-ATF1 gene fusions; fluorescence in situ hybridization (FISH), detecting EWSR1 or FUS rearrangements, and reverse transcription-polymerase chain reaction (RT-PCR) for EWSR1-CREB1 and EWSR1-ATF1 fusion transcripts have become routine ancillary tools. We present a large comparative series of FISH and RT-PCR for AFH. Seventeen neoplasms (from 16 patients) histologically diagnosed as AFH were assessed for EWSR1 rearrangements or EWSR1-CREB1 and EWSR1-ATF1 fusion transcripts. All 17 were positive for either FISH or RT-PCR or both. Of 16, 14 (87.5%) had detectable EWSR1-CREB1 or EWSR1-ATF1 fusion transcripts by RT-PCR, whereas 13 (76.5%) of 17 had positive EWSR1 rearrangement with FISH. All 13 of 13 non-AFH control neoplasms failed to show EWSR1-CREB1 or EWSR1-ATF1 fusion transcripts, whereas EWSR1 rearrangement was present in 2 of these 13 cases (which were histopathologically myoepithelial neoplasms). This study shows that EWSR1-CREB1 or EWSR1-ATF1 fusions predominate in AFH (supporting previous reports that FUS rearrangement is rare in AFH) and that RT-PCR has a comparable detection rate to FISH for AFH. Importantly, cases of AFH can be missed if RT-PCR is not performed in conjunction with FISH, and RT-PCR has the added advantage of specificity, which is crucial, as EWSR1 rearrangements are present in a variety of neoplasms in the histologic differential diagnosis of AFH, that differ in behavior and treatment.
血管样纤维组织细胞瘤（AFH）是一种生物学潜能中等且分化不确定的罕见软组织肿瘤，最常见于儿童和青年的四肢。尽管它具有特征性的组织学特征，即围绕卵圆形细胞结节的淋巴样袖套伴充满血液的囊腔，但由于其形态学异质性和缺乏特异性免疫表型，诊断往往很困难。血管样纤维组织细胞瘤与反复出现的染色体易位有关，导致特征性的EWSR1-CREB1、EWSR1-ATF1，以及罕见的FUS-ATF1基因融合；检测EWSR1或FUS重排的荧光原位杂交（FISH），以及针对EWSR1-CREB1和EWSR1-ATF1融合转录本的逆转录聚合酶链反应（RT-PCR）已成为常规辅助手段。我们展示了一系列针对AFH的FISH和RT-PCR的大型对比研究。对17例（来自16名患者）组织学诊断为AFH的肿瘤进行了EWSR1重排或EWSR1-CREB1和EWSR1-ATF1融合转录本的评估。所有17例FISH或RT-PCR或两者均为阳性。16例中，14例（87.5%）通过RT-PCR可检测到EWSR1-CREB1或EWSR1-ATF1融合转录本，而17例中的13例（76.5%）FISH检测EWSR1重排呈阳性。13例非AFH对照肿瘤均未显示EWSR1-CREB1或EWSR1-ATF1融合转录本，而这13例中有2例（组织病理学为肌上皮肿瘤）存在EWSR1重排。本研究表明，EWSR1-CREB1或EWSR1-ATF1融合在AFH中占主导（支持先前关于FUS重排在AFH中罕见的报道），并且RT-PCR对AFH的检测率与FISH相当。重要的是，如果不结合FISH进行RT-PCR，可能会漏诊AFH病例，并且RT-PCR具有特异性这一额外优势，这至关重要，因为在AFH的组织学鉴别诊断中，多种肿瘤存在EWSR1重排，而这些肿瘤在行为和治疗上有所不同。
