Adult NTRK-rearranged spindle cell neoplasms of the viscera: with an emphasis on rare locations and heterologous elements
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
Journal Volume
35
Journal Issue
7
Pages
911
Date Issued
2022
Author(s)
Tsai, Jen-Wei
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
Abstract
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.
Subjects
CONGENITAL INFANTILE FIBROSARCOMA; SOFT-TISSUE SARCOMAS; CERVICAL SARCOMA; GENE FUSIONS; CASE SERIES; ETV6-NTRK3; SUBSET; EXPRESSION; TUMOR; COLON
SDGs
Publisher
SPRINGERNATURE
Type
journal article