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Abstract：
Small cell osteosarcoma (SCOS), a variant of conventional high-grade osteosarcoma (COS), may mimic fusion-driven round cell sarcomas (FDRCS) by overlapping clinico-radiological and histomorphological/immunohistochemical characteristics, hampering accurate diagnosis and consequently proper therapy. We retrospectively analyzed decalcified formalin-fixed paraffin-embedded (FFPE) samples of 18 bone tumors primarily diagnosed as SCOS by methylation profiling, fusion gene analysis, and immunohistochemistry.In eight cases, the diagnosis of SCOS was maintained, and in 10 cases it was changed into FDRCS, including three Ewing sarcomas (EWSR1::FLI1 in two cases and no identified fusion gene in the third case), two sarcomas with BCOR alterations (KMT2D::BCOR, CCNB3::BCOR, respectively), three mesenchymal chondrosarcomas (HEY1::NCOA2 in two cases and one case with insufficient RNA quality), and two sclerosing epithelioid fibrosarcomas (FUS::CREBL3 and EWSR1 rearrangement, respectively).Histologically, SCOS usually possessed more pleomorphic cells in contrast to the FDRCS showing mainly monomorphic cellular features. However, osteoid was seen in the latter tumors as well, often associated with slight pleomorphism. Also, the immunohistochemical profile (CD99, SATB2, and BCOR) overlapped.Clinically and radiologically, similarities between SCOS and FDRCS were observed, with by imaging only minimal presence or lack of (mineralized) osteoid in most of the SCOSs.In conclusion, discrimination of SCOS, epigenetically related to COS, versus FDRCS of bone can be challenging but is important due to different biology and therefore therapeutic strategies. Methylation profiling is a reliable and robust diagnostic test especially on decalcified FFPE material. Subsequent fusion gene analysis and/or use of specific immunohistochemical surrogate markers can be used to substantiate the diagnosis.
摘要：
小细胞骨肉瘤（SCOS），常规高级别骨肉瘤（COS）的变体，可以通过重叠的临床放射学和组织形态学/免疫组织化学特征来模拟融合驱动的圆形细胞肉瘤（FDRCS），妨碍准确的诊断和适当的治疗。我们回顾性分析了18个骨肿瘤的脱钙福尔马林固定石蜡包埋（FFPE）样品，主要通过甲基化分析诊断为SCOS。融合基因分析,和免疫组织化学。在八个案例中，SCOS的诊断得以维持，在10个案例中，它变成了FDRCS，包括三个尤因肉瘤（EWSR1::FLI1在两个病例中，在第三个病例中没有发现融合基因），两种具有BCOR改变的肉瘤（KMT2D::BCOR，CCNB3::BCOR,分别)，三种间充质软骨肉瘤（HEY1::NCOA22例，RNA质量不足1例），和两个硬化性上皮样纤维肉瘤（FUS：：CREBL3和EWSR1重排，分别)。组织学上,SCOS通常具有更多的多形性细胞，而FDRCS则主要表现出单形性细胞特征。然而,在后者的肿瘤中也可以看到类骨，通常与轻微的多态性有关。此外，免疫组织化学谱(CD99,SATB2和BCOR)重叠.临床和放射学，观察到SCOS和FDRCS之间的相似性，通过成像，在大多数SCOSs中仅存在或缺乏（矿化）类骨质。总之,对SCOS的歧视，表观遗传学与COS相关，与骨的FDRCS相比可能具有挑战性，但由于生物学和治疗策略的不同而很重要。甲基化分析是一种可靠且可靠的诊断测试，尤其是在脱钙的FFPE材料上。随后的融合基因分析和/或特异性免疫组织化学替代标记的使用可用于证实诊断。
