PMID- 35127482 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220501 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 11 DP - 2021 TI - Primary Thyroid NUT Carcinoma With High PD-L1 Expression and Novel Massive IGKV Gene Fusions: A Case Report With Treatment Implications and Literature Review. PG - 778296 LID - 10.3389/fonc.2021.778296 [doi] LID - 778296 AB - BACKGROUND: Nuclear protein in testis (NUT) carcinoma (NC) is a rare and aggressive undifferentiated carcinoma that typically arises from midline supradiaphragmatic structures. It is uniquely driven by a NUT gene rearrangement on chromosome 15q14. Few thyroid NCs have been reported and there are no established treatment guidelines for NUT carcinoma. METHOD: Ultrasound-guided fine needle aspiration smear was performed for the preoperative diagnosis of thyroid lesions. Cytopathology, histology, and immunochemical staining all indicated NC. Fluorescence in situ hybridization (FISH), qRT-PCR, and next-generation sequencing (NGS) were used to analyze the genetic characteristics of NC. RESULTS: We describe a rare case of thyrogenic NC in a 38-year-old male with cytological, histological, immunohistochemical, and genetic features. Cytological smears and histopathological specimens showed typical features of NC. Immunohistochemistry confirmed strong immunoreactivity with NUT, EMA, P63, TTF-1, and c-myc. CK19 was positive exclusively in sudden keratosis. No immunoreactivity was found for neuroendocrine markers. FISH was applied to isolate the NUT gene on chromosome 15q14. The NGS results revealed a BRD4-NUT gene fusion, which was further confirmed by RT-qPCR. Structural variation (SV) of NUTM1 occurred in the exon region, and the mutation site was 15q14. Moreover, BRD4 single-nucleotide variation (SNV) occurs in the 3' UTR at mutation site 19p13.12. The PD-L1 combined predictive score was over 30%. The patient received chemotherapy, followed by programmed cell death 1 (PD-1) inhibition with camrelizumab, and died 10 months after surgery. CONCLUSION: Thyroid NC is an extremely rare and fatal malignant tumor. It is necessary to consider NC when squamous differentiation is observed cytologically or histologically. NGS is an effective tool for obtaining the final diagnosis and obtaining a better understanding of tumor pathogenesis. A large number of IGKV gene fusions in addition to the BRD4-NUT fusion may play a role in the pathogenesis and immunotherapy response of NC. Immunotherapy for NC remains to be explored due to the rarity of this aggressive malignancy. CI - Copyright (c) 2022 Zhou, Duan, Jiao, Chen, Xing, Su, Tang, Zhang and Liu. FAU - Zhou, Juan AU - Zhou J AD - Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Duan, Miao AU - Duan M AD - Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China. FAU - Jiao, Qiong AU - Jiao Q AD - Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Chen, Chunyan AU - Chen C AD - Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Xing, Aiyan AU - Xing A AD - Department of Pathology, Qilu Hospital of Shandong University, Jinan, China. FAU - Su, Peng AU - Su P AD - Department of Pathology, Qilu Hospital of Shandong University, Jinan, China. FAU - Tang, Juan AU - Tang J AD - Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Zhang, Hui AU - Zhang H AD - Department of Pathology, Qilu Hospital of Shandong University, Jinan, China. FAU - Liu, Zhiyan AU - Liu Z AD - Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. LA - eng PT - Case Reports DEP - 20220119 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC8807656 OTO - NOTNLM OT - BRD4-NUT fusion OT - IGKV gene fusions OT - NUT carcinoma OT - PD-L1 OT - cytopathology OT - thyroid COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/02/08 06:00 MHDA- 2022/02/08 06:01 PMCR- 2021/01/01 CRDT- 2022/02/07 05:34 PHST- 2021/09/16 00:00 [received] PHST- 2021/12/23 00:00 [accepted] PHST- 2022/02/07 05:34 [entrez] PHST- 2022/02/08 06:00 [pubmed] PHST- 2022/02/08 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2021.778296 [doi] PST - epublish SO - Front Oncol. 2022 Jan 19;11:778296. doi: 10.3389/fonc.2021.778296. eCollection 2021.