https://scholars.lib.ntu.edu.tw/handle/123456789/636700
標題: | Extraskeletal Myxoid Chondrosarcomas: The Uncommon Clinicopathologic Manifestations and Significance of TAF15::NR4A3 Fusion | 作者: | Huang, Shih-Chiang JEN-CHIEH LEE Hsu, Yong-Chen Tsai, Jen-Wei Kao, Yu-Chien Hsieh, Tsung-Han Chang, Yi-Ming Chang, Kung-Chao Wu, Pao-Shu Chen, Paul Chih-Hsueh Chen, Chien-Heng Chang, Ching-Di Lee, Pei-Hang Tai, Hui-Chun Liu, Ting-Ting Wen, Mei-Chin Li, Wan-Shan Yu, Shih-Chen Wang, Jui-Chu Huang, Hsuan-Ying |
關鍵字: | NR4A3; TAF15; extraskeletal myxoid chondrosarcoma; osseous; pan-Trk; solid | 公開日期: | 七月-2023 | 卷: | 36 | 期: | 7 | 來源出版物: | Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc | 摘要: | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/636700 | ISSN: | 08933952 | DOI: | 10.1016/j.modpat.2023.100161 |
顯示於: | 病理學科所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。