Abstract：
Desmoplastic small round cell tumor (DSRCT) is a high-grade, primitive round cell sarcoma classically associated with prominent desmoplastic stroma, coexpression of keratin and desmin, and a characteristic EWSR1::WT1 gene fusion. DSRCT typically arises in the abdominopelvic cavity of young males with diffuse peritoneal spread and poor overall survival. Although originally considered to be pathognomonic for DSRCT, EWSR1::WT1 gene fusions have recently been detected in rare tumors lacking the characteristic morphologic and immunohistochemical features of DSRCT. Here, we report 3 additional cases of neoplasms other than conventional DSCRCT with EWSR1::WT1 gene fusions that occurred outside the female genital tract. Two occurred in the abdominopelvic cavities of a 27-year-old man and a 12-year-old girl, whereas the third arose in the axillary soft tissue of an 85-year-old man. All cases lacked prominent desmoplastic stroma and were instead solid and cystic with peripheral fibrous pseudocapsules and occasional intervening fibrous septa. Necrosis was either absent (1/3) or rare (2/3), and mitotic activity was low (<1 to 3 per 10 hpf). In immunohistochemical studies, there was expression of smooth muscle actin (3/3) and desmin (3/3), rare to focal reactivity for EMA (2/3), and variable expression of CK AE1/AE3 (1/3). Myogenin and MyoD1 were negative, and C-terminus-specific WT1 was positive in both cases tested (2/2). All 3 tumors followed a more indolent clinical course with 2 cases demonstrating no evidence of disease at 20 and 44 months after resection. The patient from case 3 died of other causes at 14 months with no evidence of recurrence. DNA methylation profiling showed that the 3 cases clustered with DSRCT; however, they demonstrated fewer copy number variations with 2 cases having a flat profile (0% copy number variation). Differential methylation analysis with hierarchical clustering further showed variation between the 3 cases and conventional DSRCT. Although further study is needed, our results, in addition to previous reports, suggest that EWSR1::WT1 gene fusions occur in rare and seemingly distinctive tumors other than conventional DSRCT with indolent behavior. Proper classification of these unusual soft tissue tumors with EWSR1::WT1 gene fusions requires direct correlation with tumor morphology and clinical behavior, which is essential to avoid overtreatment with aggressive chemotherapy.
摘要：
促纤维增生性小圆细胞瘤(DSRCT)是一种高度恶性、原始圆形细胞肉瘤，与突出的纤维增生性基质有关，角蛋白和结蛋白的共表达，和特征性的EWSR1::WT1基因融合。DSRCT通常出现在年轻男性的腹肾盂腔中，腹膜弥漫性扩散且总体生存率较差。虽然最初被认为是DSRCT的病态，最近在缺乏DSRCT特征性形态学和免疫组织化学特征的罕见肿瘤中检测到EWSR1::WT1基因融合。在这里，我们报告了另外3例发生在女性生殖道外的EWSR1::WT1基因融合的非常规DSRCT肿瘤。两例发生在一名27岁男性和一名12岁女性的腹盆腔腔中，而第三个出现在一名85岁男性的腋窝软组织中。所有病例均缺乏明显的纤维增生性基质，而是实性和囊性，周围有纤维假囊，偶尔有纤维间隔。坏死不存在（1/3）或罕见（2/3），有丝分裂活性低（每10hpf<1至3）。关于免疫组织化学研究，有SMA（3/3）和desmin（3/3）的表达，罕见于EMA的局灶性反应性（2/3），和差异表达的CKAE1/AE3（1/3）。Myogenin和MyoD1均为阴性，C端特异性WT1在两种情况下都是阳性的（2/2）。所有三个肿瘤都遵循更缓慢的临床过程，其中两个病例在切除后20和44个月没有疾病迹象。病例3的患者在14个月时死于其他原因，没有复发的证据。DNA甲基化分析显示，这3例病例聚集在DSRCT上；然而，他们显示了较少的拷贝数变异（CNV），其中两个病例具有平坦的概况（0％CNV）。分层聚类的差异甲基化分析进一步显示了三例与常规DSRCT之间的差异。虽然需要进一步研究，我们的结果,除了以前的报道，表明EWSR1::WT1基因融合发生在罕见且看似独特的情况下，具有惰性行为的非常规DSRCT肿瘤。EWSR1::WT1基因融合的这些异常软组织肿瘤的正确分类需要与肿瘤形态和临床行为直接相关，这对于避免积极化疗的过度治疗至关重要。
