Mohamed Mustafa, Gonzalez David, Fritchie Karen J, Swansbury John, Wren Dorte, Benson Charlotte, Jones Robin L, Fisher Cyril, Thway Khin
Sarcoma Unit, The Royal Marsden NHS Foundation Trust, 203 Fulham Road, London, SW3 6JJ, UK.
Molecular Diagnostics, Royal Marsden Hospital, Surrey, Sutton, UK.
Virchows Arch. 2017 Nov;471(5):631-640. doi: 10.1007/s00428-017-2207-y. Epub 2017 Jul 26.
Desmoplastic small round cell tumor (DSRCT) is a rare, biologically aggressive soft tissue neoplasm of uncertain differentiation, most often arising in the abdominal and pelvic cavities of adolescents and young adults with a striking male predominance. Histologically, it is characterized by islands of uniform small round cells in prominent desmoplastic stroma, and it has a polyimmunophenotypic profile, typically expressing WT1 and cytokeratin, desmin, and neural/neuroendocrine differentiation markers to varying degrees. Tumors at other sites and with variant morphology are more rarely described. DSRCT is associated with a recurrent t(11;22)(p13;q12) translocation, leading to the characteristic EWSR1-WT1 gene fusion. Fluorescence in situ hybridization (FISH), to detect EWSR1 rearrangement, and reverse transcription-polymerase chain reaction (RT-PCR) to assess for EWSR1-WT1 fusion transcripts are routine diagnostic ancillary tools. We present a large institutional comparative series of FISH and RT-PCR for DSRCT diagnosis. Twenty-six specimens (from 25 patients) histologically diagnosed as DSRCT were assessed for EWSR1 rearrangement and EWSR1-WT1 fusion transcripts. Of these 26 specimens, 24 yielded positive results with either FISH or RT-PCR or both. FISH was performed in 23 samples, with EWSR1 rearrangement seen in 21 (91.3%). RT-PCR was performed in 18 samples, of which 13 (72.2%) harbored EWSR1-WT1 fusion transcripts. The sensitivity of FISH in detecting DSRCT was 91.3%, and that of RT-PCR was 92.8% following omission of four technical failures. Therefore, both methods are comparable in terms of sensitivity. FISH is more sensitive if technical failures for RT-PCR are taken into account, and RT-PCR is more specific in confirming DSRCT. Both methods complement each other by confirming cases that the other method may not. In isolation, FISH is a relatively non-specific diagnostic adjunct due to the number of different neoplasms that can harbor EWSR1 rearrangement, such as Ewing sarcoma. However, in cases with appropriate morphology and a typical pattern of immunostaining, FISH is confirmatory of the diagnosis.
促纤维组织增生性小圆细胞肿瘤（DSRCT）是一种罕见的、生物学行为侵袭性的软组织肿瘤，其分化情况不明，最常发生于青少年和年轻成人的腹腔和盆腔，男性明显居多。组织学上，其特征是在显著的促纤维组织增生性间质中有均匀的小岛状小圆细胞，并且具有多免疫表型特征，通常表达WT1以及细胞角蛋白、结蛋白，并不同程度地表达神经/神经内分泌分化标志物。其他部位及形态变异的肿瘤则较少被描述。DSRCT与复发性t(11;22)(p13;q12)易位相关，导致特征性的EWSR1-WT1基因融合。用于检测EWSR1重排的荧光原位杂交（FISH）以及用于评估EWSR1-WT1融合转录本的逆转录-聚合酶链反应（RT-PCR）是常规的诊断辅助工具。我们展示了一个大型机构关于DSRCT诊断的FISH和RT-PCR的比较系列研究。对26例（来自25名患者）组织学诊断为DSRCT的标本进行了EWSR1重排和EWSR1-WT1融合转录本的评估。在这26例标本中，24例通过FISH或RT-PCR或两者检测均呈阳性结果。对23个样本进行了FISH检测，其中21个（91.3%）出现EWSR1重排。对18个样本进行了RT-PCR检测，其中13个（72.2%）含有EWSR1-WT1融合转录本。排除4例技术失败情况后，FISH检测DSRCT的敏感性为91.3%，RT-PCR的敏感性为92.8%。因此，两种方法在敏感性方面相当。如果考虑RT-PCR的技术失败情况，FISH更敏感，而RT-PCR在确诊DSRCT方面更具特异性。两种方法通过确认对方可能无法确诊的病例相互补充。单独来看，由于许多不同肿瘤都可能存在EWSR1重排，如尤因肉瘤，FISH是一种相对非特异性的诊断辅助手段。然而，在具有合适形态和典型免疫染色模式的病例中，FISH可确诊。
