Abstract：
Several high-grade pleomorphic sarcoma cases that cannot be classified into any existing established categories have been reported. These cases were provisionally classified into undifferentiated pleomorphic sarcoma (UPS). Some dedifferentiated liposarcoma (DDLS) cases may also have been classified into the UPS category due to the absence of MDM2 amplification or an atypical lipomatous tumor/well-differentiated liposarcoma component. We retrieved and reviewed 77 high-grade pleomorphic sarcoma cases, initially diagnosed as UPS in 66 cases and DDLS in 11 cases. Fluorescence in situ hybridization (FISH) analyses of DDIT3 and MDM2 were performed for available cases. Of the cases successfully subjected to DDIT3 FISH (n = 56), nine (7 UPS and 2 DDLS) showed DDIT3 amplification but no MDM2 amplification. Two UPS cases showed both telomeric (5\') and centromeric (3\') amplification of DDIT3 or low polysomy of chromosome 12, whereas 5 UPS and 2 DDLS cases showed 5\'-predominant DDIT3 amplification. Histopathologically, all cases showed UPS-like proliferation of atypical pleomorphic tumor cells. Immunohistochemically, only one case showed focal nuclear positivity for DDIT3, supporting the previous finding that DDIT3 expression was not correlated with DDIT3 amplification. All three cases with focal MDM2 expression involved 5\'-predominant amplification, two of which showed DDLS-like histological features. The majority of cases (7/9) showed decreased expression in p53 staining, suggesting that DDIT3 amplification regulates the expression of TP53 like MDM2. From a clinicopathological perspective, we hypothesize that DDIT3-amplified sarcoma, especially with 5\'-predominant amplification, can be reclassified out of the UPS category.
摘要：
已报告了几例无法归类为任何现有已确定类别的高级多形性肉瘤病例。这些病例暂时分为未分化多形性肉瘤（UPS）。由于缺乏MDM2扩增或非典型脂肪瘤/高分化脂肪肉瘤成分，一些去分化脂肪肉瘤（DDLS）病例也可能被归类为UPS类别。我们检索并回顾了77例高级别多形性肉瘤病例，最初诊断为UPS66例，DDLS11例。对可用病例进行了DDIT3和MDM2的荧光原位杂交（FISH）分析。在成功接受DDIT3FISH的病例中（n=56），9个(7个UPS和2个DDLS)显示DDIT3扩增，但没有MDM2扩增。2例UPS病例显示DDIT3的端粒（5'）和着丝粒（3'）扩增或12号染色体的低多体，而5例UPS和2例DDLS病例显示5'主导的DDIT3扩增。组织病理学,所有病例均表现为非典型多形性肿瘤细胞的UPS样增殖。免疫组织化学，只有一例显示DDIT3的局灶性核阳性,支持之前的发现,即DDIT3表达与DDIT3扩增不相关.所有三例局灶性MDM2表达均涉及5'-优势扩增，其中两个显示DDLS样组织学特征。大多数病例（7/9）在p53染色中表达降低，这表明DDIT3扩增像MDM2一样调节TP53的表达。从临床病理角度来看，我们假设DDIT3扩增的肉瘤，尤其是5'-优势扩增，可以从UPS类别中重新分类。
