Abstract：
Extraskeletal myxoid chondrosarcoma (EMC) is an ultrarare sarcoma typically exhibiting myxoid/reticular histology and NR4A3 translocation. However, morphologic variants and the relevance of non-EWSR1::NR4A3 fusions remain underexplored. Three challenging pan-Trk-expressing cases, featuring cellular to solid histology, were subjected to RNA exome sequencing (RES), unveiling different NR4A3-associated fusions. Alongside RES-analyzed cases, fluorescence in situ hybridization was performed to confirm 58 EMCs, with 48 available for pan-Trk immunostaining and KIT sequencing. Except for 1 (2%) NR4A3-rearranged EMC without identifiable partners, 46 (79%), 9 (16%), and 2 (3%) cases harbored EWSR1::NR4A3, TAF15::NR4A3, and TCF12::NR4A3 fusions, respectively. Five EWSR1::NR4A3-positive EMCs occurred in the subcutis (3) and bone (2). Besides 43 classical cases, there were 8 cellular, 4 rhabdoid/anaplastic, 2 solid, and 1 mixed tumor-like variants. Tumor cells were oval/spindle to pleomorphic and formed loose myxoid/reticular to compact sheet-like or fascicular patterns, imparting broad diagnostic considerations. RES showed upregulation of NTRK2/3, KIT, and INSM1. Moderate-to-strong immunoreactivities of pan-Trk, CD117, and INSM1 were present in 35.4%, 52.6%, and 54.6% of EMCs, respectively. KIT p. E554K mutation was detected in 2/48 cases. TAF15::NR4A3 was significantly associated with size >10 cm (78%, P = .025). Size >10 cm, moderate-to-severe nuclear pleomorphism, metastasis at presentation, TAF15::NR4A3 fusion, and the administration of chemotherapy portended shorter univariate disease-specific survival, whereas only size >10 cm (P = .004) and metastasis at presentation (P = .032) remained prognostically independent. Conclusively, EMC may manifest superficial or osseous lesions harboring EWSR1::NR4A3, underrecognized solid or anaplastic histology, and pan-Trk expression, posing tremendous challenges. Most TAF15::NR4A3-positive cases were >10 cm in size, ie, a crucial independent prognosticator, whereas pathogenic KIT mutation rarely occurred.
摘要：
骨外粘液样软骨肉瘤（EMC）是一种超肉瘤，通常表现为粘液样/网状组织学和NR4A3易位。然而,形态变异和非EWSR1::NR4A3融合的相关性仍未充分开发。三个具有挑战性的泛Trk表达案例，具有细胞到实体的组织学特征，进行RNA外显子组测序（RES），推出不同的NR4A3相关融合。除了RES分析的案例，进行荧光原位杂交以确认58个EMC，48可用于pan-Trk免疫染色和KIT测序。除了一个（2%）NR4A3重新排列的EMC没有可识别的合作伙伴，46（79%），9（16%），2例（3％）具有EWSR1：：NR4A3，TAF15：：NR4A3和TCF12：：NR4A3融合，分别。五个EWSR1::NR4A3阳性EMC发生在皮下组织(3)和骨(2)中。除了43个经典案例，有8个细胞，4横纹肌/间变性，2个固体，和1个混合肿瘤样变体。肿瘤细胞呈卵形/梭形至多形性，并形成松散的粘液样/网状至紧密的片状或束状图案。赋予广泛的诊断考虑。RES显示NTRK2/3，KIT，INSM1pan-Trk的中度至强免疫反应性，CD117和INSM1占35.4%，52.6%,和54.6%的EMC。在2/48例中检测到KITp.E554K突变。TAF15::NR4A3与尺寸>10厘米(78%，P=0.025)。尺寸>10厘米，中度/重度核多态性，出现时转移，TAF15::NR4A3融合，和化疗的管理预示着较短的单变量疾病特异性生存期，而仅大小>10cm（P=0.004）和转移（P=0.032）仍然是预后独立的。最后，EMC可能表现为带有EWSR1的浅表或骨病变::NR4A3，未被识别的实体或间变性组织学，和pan-Trk表达式，带来巨大挑战。大多数TAF15::NR4A3阳性病例的大小>10厘米，即，关键的独立预言家，而致病性KIT突变很少发生。
