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36例小细胞骨肉瘤的临床病理、免疫表型及分子学特征

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 Small Cell Osteosarcoma: Clinicopathologic, Immunohistochemical, and Molecular Analysis of 36 Cases.Am J Surg Pathol. 2015,[Epub ahead of print]


 Abstract  Small round cell osteosarcoma is a very rare type of osteosarcoma, histologically mimicking other small round cell malignancies of bone, most notably Ewing sarcoma. To distinguish small cell osteosarcoma from other primary small cell malignancies of bone, we evaluated the immunohistochemical (IHC) expression of CD99 and SATB2, a marker of osteoblastic differentiation. Second, we analyzed EWSR1 and FUS gene aberrations using fluorescence in situ hybridization and/or reverse transcription-polymerase chain reaction (RT-PCR) techniques to assess whether small cell osteosarcoma and Ewing sarcoma share the same genetic alteration analysis. Thirty-six cases of primitive small cell osteosarcoma of bone were included in this study. All the cases of small cell osteosarcoma showed strong nuclear expression of SATB2 associated with negativity for CD99 antibody or weak, cytoplasmic staining in few neoplastic cells. Reverse transcription-polymerase chain reaction was negative for EWS-FLI1 type 1-2, EWS-ERG type 1, and CIC-DUX4 in the 10 available cases of small cell osteosarcoma analyzed. Fluorescence in situ hybridization analysis was feasible with a readable signal in 13 cases of small cell osteosarcoma, and none of these cases showed any EWSR1 and FUS gene rearrangements. In conclusion, it appears extremely useful to combine IHC analysis of SATB2 and CD99 with molecular analysis of Ewing sarcoma-associated genetic aberrations, to differentiate small cell osteosarcoma from other small round cell malignancies of bone. The strong IHC expression of SATB2 associated with CD99 immunonegativity and the absence of EWSR1 and FUS gene rearrangements in small cell osteosarcoma argues against the existence of a morphologic/genetic continuum with Ewing sarcoma.


小圆细胞骨肉瘤是骨肉瘤的一种非常罕见亚型,组织学模拟骨的其它小圆细胞恶性肿瘤,特别是尤文氏肉瘤。为了从骨的原发性小细胞恶性肿瘤中区分小细胞骨肉瘤,作者对36例原发性骨的小细胞骨肉瘤进行了研究,评估了CD99和SATB2(一种成骨细胞分化的标记物)的免疫组化(IHC)表达情况。另外,作者通过荧光原位杂交和逆转录聚合酶链反应(RT-PCR)分析了EWSR1 和 FUS基因突变情况,进一步评估是否小细胞骨肉瘤和尤文氏肉瘤有相同的遗传性学改变。所有的小细胞骨肉瘤显示了核强阳性表达SATB2,而CD99阴性表达或仅少数的肿瘤细胞弱阳性胞浆表达。10例可利用的病例RT-PCR检测发现EWS-FLI1 type 1-2、EWS-ERG type 1和 CIC-DUX4阴性。13例小细胞骨肉瘤行荧光原位杂交检测发现不存在EWSR1和FUS基因重排。总之,通过IHC分析SATB2和CD99的表达,并联合分子遗传学分析尤文氏肉瘤-相关基因的突变,对于从骨的其它小圆细胞恶性肿瘤中区分小细胞骨肉瘤是非常有用的。小细胞骨肉瘤中IHC强表达SATB2,不表达CD99,并缺乏EWSR1和FUS基因重排,这与尤文氏肉瘤显著不同。

标签:小细胞骨肉瘤 临床病理 免疫 分子
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