Primary retroperitoneal myxoid/round cell liposarcoma is a nonexisting disease: an immunohistochemical and molecular biological analysis
Primary retroperitoneal myxoid/round cell liposarcoma is a nonexisting disease: an immunohistochemical and molecular biological analysis
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DOI：
10.1038/modpathol.2008.164
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发表时间：
2009-02-01
期刊：
影响因子：
7.5
通讯作者：
van Coevorden, Frits
中科院分区：
文献类型：
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作者：
de Vreeze, Ronald S. A.;de Jong, Daphne;van Coevorden, Frits
几乎所有的原发性腹膜后脂肪肉瘤都可以被归类为高分化/去分化脂肪肉瘤。然而，很少有原发性腹膜后脂肪肉瘤被分类为粘液样/圆细胞脂肪肉瘤，根据粘液样区域和血管鱼尾纹的存在，这导致了对腹膜后脂肪肉瘤分类的争论。在遗传学上，粘液样/圆细胞脂肪肉瘤和高分化/去分化脂肪肉瘤是不同的疾病。粘液样/圆细胞脂肪肉瘤的特征是易位引起FUS-CHOP或EWSR 1-CHOP融合，而分化良好/去分化的脂肪肉瘤的特征是12 q13 -15区域的扩增，包括MDM 2和CDK 4基因。由于黏液样/圆细胞脂肪肉瘤对放射和化疗高度敏感，亚型之间的分化对于优化治疗非常重要。我们研究了原发性腹膜后脂肪肉瘤诊断为粘液样/圆细胞脂肪肉瘤是否代表真正的粘液样/圆细胞脂肪肉瘤分子或组织病理学模拟，并代表良好/去分化的脂肪肉瘤。原发性腹膜后粘液样/圆细胞脂肪肉瘤（n = 16）与原发性四肢粘液样/圆细胞脂肪肉瘤（n = 20）进行了比较。组织学及免疫组化观察。使用多重连接依赖性探针扩增分析研究12 q13 -15区域的扩增状态，并使用RT-PCR研究FUS-CHOP或EWS-CHOP易位。原发性腹膜后黏液样/圆细胞脂肪肉瘤中，12例MDM 2和CDK 4均为阳性。原发性四肢黏液样/圆细胞脂肪肉瘤中，18/20例MDM 2阴性，CDK 4全部阴性。多重连接依赖探针扩增显示16/16例原发性腹膜后粘液样/圆细胞型脂肪肉瘤和1/20例原发性四肢粘液样/圆细胞型脂肪肉瘤中12 q13 -15区域扩增。所有（18/18）原发性四肢粘液样/圆细胞脂肪肉瘤均存在移位，但所有原发性腹膜后粘液样/圆细胞脂肪肉瘤均无移位。根据免疫组化和分子特征，明显的原发性腹膜后粘液样/圆细胞脂肪肉瘤可以被识别为分化良好/去分化的脂肪肉瘤，其形态特征类似于粘液样/圆细胞脂肪肉瘤。在这些情况下，治疗可能应该特别设计为高分化/去分化的脂肪肉瘤。此外，在腹膜后发现粘液样/圆细胞脂肪肉瘤移位高度提示转移，应立即寻找腹膜后外的原发灶。
Almost all primary retroperitoneal liposarcomas can be classified as well-/dedifferentiated liposarcoma. Rarely, however, primary retroperitoneal liposarcoma is classified as myxoid/round cell liposarcoma, based on the presence of myxoid areas and vascular crow's feet pattern, which has resulted in a debate on the classification of liposarcoma in the retroperitoneum. Genetically, myxoid/round cell liposarcoma and well-/dedifferentiated liposarcoma are different diseases. Myxoid/round cell liposarcoma is characterized by a translocation causing FUS-CHOP or EWSR1-CHOP fusion, whereas well-/dedifferentiated liposarcoma is characterized by an amplification of the 12q13-15 region, including MDM2 and CDK4 genes. As myxoid/round cell liposarcoma is highly radio- and chemosensitive, differentiation between subtypes is important to optimize treatment. We studied whether primary retroperitoneal liposarcomas diagnosed as myxoid/round cell liposarcoma represent molecularly true myxoid/round cell liposarcoma or are histopathological mimics and represent well-/dedifferentiated liposarcoma. Primary retroperitoneal myxoid/round cell liposarcoma (n = 16) were compared to primary extremity myxoid/round cell liposarcoma (n = 20). Histopathological and immunohistochemical features were studied. Amplification status of the 12q13-15 region was studied using a multiplex ligation-dependent probe amplification analysis, and FUS-CHOP or EWS-CHOP translocations were studied using RT-PCR. In primary retroperitoneal myxoid/round cell liposarcoma, MDM2 and CDK4 staining was both positive in 12 of 15 cases. In primary extremity myxoid/round cell liposarcoma, MDM2 was negative in 18/20 and CDK4 was negative in all cases. Multiplex ligation-dependent probe amplification showed the amplification of 12q13-15 region in 16/16 primary retroperitoneal myxoid/round cell liposarcomas and in 1/20 primary extremity myxoid/round cell liposarcomas. Translocation was present in all (18/18) primary extremity myxoid/round cell liposarcomas, but absent in all primary retroperitoneal myxoid/round cell liposarcomas. On the basis of immunohistochemical and molecular characteristics, apparent primary retroperitoneal myxoid/round cell liposarcoma can be recognized as well-/dedifferentiated liposarcoma with morphological features mimicking myxoid/round cell liposarcoma. In these cases, treatment should probably be specifically designed as for well-/dedifferentiated liposarcoma. Moreover, finding of myxoid/round cell liposarcoma translocations in a retroperitoneal localization is highly suggestive of metastasis and should prompt search for a primary localization outside the retroperitoneum.