https://scholars.lib.ntu.edu.tw/handle/123456789/615846
標題: | Adult NTRK-rearranged spindle cell neoplasms of the viscera: with an emphasis on rare locations and heterologous elements | 作者: | Tsai, Jen-Wei JEN-CHIEH LEE Hsieh, Tsung-Han Huang, Shih-Chiang Lee, Pei-Hang Liu, Ting-Ting Kao, Yu-Chien Chang, Ching-Di Weng, Te-Fu Li, Chien-Feng Lin, Jung-Chia Liang, Cher-Wei Su, Yu-Li Chang, Ian Yi-Feng Wang, Yu-Ting Chang, Nien-Yi Yu, Shih-Chen Wang, Jui-Chu Huang, Hsuan-Ying |
關鍵字: | CONGENITAL INFANTILE FIBROSARCOMA; SOFT-TISSUE SARCOMAS; CERVICAL SARCOMA; GENE FUSIONS; CASE SERIES; ETV6-NTRK3; SUBSET; EXPRESSION; TUMOR; COLON | 公開日期: | 2022 | 出版社: | SPRINGERNATURE | 卷: | 35 | 期: | 7 | 起(迄)頁: | 911 | 來源出版物: | Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc | 摘要: | NTRK-rearranged mesenchymal neoplasms mostly affect the soft tissues of pediatric patients. Given the responsiveness to selective NTRK inhibitors, it remains critical to identify those ultra-rare cases occurring in the viscera of adults. In five females and two males aged 18-53 years, we characterized visceral mesenchymal tumors harboring TPM3-NTRK1 [uterine cervix (N = 2), pleura, prostate], LMNA-NTRK1 (lung), SQSTM1-NTRK3 (heart), and NTRK3 rearrangement with unknown fusion partner (colon/mesocolon) with RNA sequencing, FISH, RT-PCR, and immunohistochemistry. The tumors exhibited spindled to ovoid/epithelioid or pleomorphic cells, often arranged in fascicles, and were low-to-intermediate-grade and high-grade in three and four cases, respectively. Keloid-like stromal collagen and perivascular hyalinization was noted in five. Adenosarcoma-like appearances were observed in two, manifesting frond-like protrusions in one cervical tumor and phyllodes-like architecture in the prostatic tumor. Abrupt high-grade transformation into pleomorphic liposarcoma was found in another cervical tumor, while the pleural tumor contained intermixed rhabdomyoblasts. Pan-TRK immunostaining was positive in all cases. All cases expressed CD34, while five were S100-positive. CDKN2A homozygous deletion with concomitant p16 loss occurred in 4/7. Whole-exome sequencing identified TP53 mutation (c.672+2T>C, involving a splice site, with concomitant protein loss) in a cervical sarcoma, limited to its heterologous liposarcomatous component. At least moderate pan-TRK immunoreactivity was present in varying proportions of potential pathologic mimics, with BCOR-positive sarcoma (56%, 5/9), undifferentiated uterine sarcoma (50%, 3/6), and spindle cell/sclerosing rhabdomyosarcoma (33%, 2/6) being among the most frequent. This underscored the unsatisfactory specificity of pan-TRK immunohistochemistry and warranted molecular confirmation in the diagnosis of adult NTRK-rearranged visceral mesenchymal neoplasms. The current report highlights the ever-expanding clinicopathologic and genetic spectrum of this entity by describing the unprecedented cardiac and pleural locations and heterologous differentiation, as well as the second NTRK-rearranged "prostatic stromal sarcoma," while substantiating CDKN2A deletion as a frequent occurrence. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/615846 | ISSN: | 0893-3952 | DOI: | 10.1038/s41379-021-01005-3 |
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。