Tsai, Jen-WeiJen-WeiTsaiJEN-CHIEH LEEHsieh, Tsung-HanTsung-HanHsiehHuang, Shih-ChiangShih-ChiangHuangLee, Pei-HangPei-HangLeeLiu, Ting-TingTing-TingLiuKao, Yu-ChienYu-ChienKaoChang, Ching-DiChing-DiChangWeng, Te-FuTe-FuWengLi, Chien-FengChien-FengLiLin, Jung-ChiaJung-ChiaLinLiang, Cher-WeiCher-WeiLiangSu, Yu-LiYu-LiSuChang, Ian Yi-FengIan Yi-FengChangWang, Yu-TingYu-TingWangChang, Nien-YiNien-YiChangYu, Shih-ChenShih-ChenYuWang, Jui-ChuJui-ChuWangHuang, Hsuan-YingHsuan-YingHuang2022-07-262022-07-2620220893-3952https://scholars.lib.ntu.edu.tw/handle/123456789/615846NTRK-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.enCONGENITAL INFANTILE FIBROSARCOMA; SOFT-TISSUE SARCOMAS; CERVICAL SARCOMA; GENE FUSIONS; CASE SERIES; ETV6-NTRK3; SUBSET; EXPRESSION; TUMOR; COLON[SDGs]SDG3journal article10.1038/s41379-021-01005-3351497692-s2.0-85124515932WOS:000754139200001https://scholars.lib.ntu.edu.tw/handle/123456789/597452