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NUT carcinoma of the parotid gland: report of two cases, one with a rare ZNF532-NUTM1 fusion

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Abstract

Nuclear protein in testis (NUT) carcinoma (NC) is a rare aggressive tumor with a typical NUTM1 gene rearrangement. Herein, we aimed to investigate the morphological and genetic features of head and neck NC. Immunohistochemistry staining for NUT (C52B1) was performed for 118 samples of head and neck poorly differentiated/undifferentiated carcinoma. Diffuse NUT staining was further confirmed via fluorescence in situ hybridization and next-generation sequencing. Two parotid gland NC cases, one in a 22-year-old man and one in a 52-year-old woman, were confirmed (2/118, 1.6%). Typical morphological features, including squamous cells and abrupt keratinization, were observed. Diffuse pankeratin, CK5/6, p63, and MYC expression were noted, while CD34, CD99, synaptophysin, chromogranin A, TTF1, S-100, and PD-L1 staining and EBER in situ hybridization (EBV-ISH) were negative. Both tumors harbored a NUTM1 rearrangement: a classic BRD4-NUTM1 fusion and a rare ZNF532-NUTM1 fusion. Furthermore, trisomy 8 and three copies of the MYC gene were detected in both cases. Next-generation sequencing revealed six additional somatic alterations, a low tumor mutation burden, and microsatellite stability. Patient 1 died from the disease after 15 months, and patient 2 was alive after 8 months. Parotid gland NC exhibits diverse morphological features and heterogeneous genotypes. To the best of our knowledge, this is the first report of parotid gland NC with a ZNF532-NUTM1 fusion.

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Funding

This study was funded by the Sichuan Science and Technology Program (No. 2020YFS0275) and Sichuan University 1.3.5 Project for Disciplines of Excellence-Clinical Research Incubation (No. 2019HXFH002).

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Authors and Affiliations

  1. Department of Pathology, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu, 610041, Sichuan Province, China

    Min Chen, Sha Zhao, Zuoyu Liang, Weiya Wang, Ping Zhou & Lili Jiang

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  1. Min Chen
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  2. Sha Zhao
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Contributions

Min Chen collected the patients, did the experiments, and wrote the paper; Zuoyu Liang and Ping Zhou did the immunohistochemistry; Sha Zhao and Weiya Wang performed the histopathological examinations; Lili Jiang organized and modified the paper. All authors were involved in providing study data and commenting on the manuscript. All authors approved the final manuscript.

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Correspondence to Lili Jiang.

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The study was conducted as per institutional ethical regulations and was approved by the West China Hospital, Sichuan University.

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Informed consent was obtained from each patient involved.

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Chen, M., Zhao, S., Liang, Z. et al. NUT carcinoma of the parotid gland: report of two cases, one with a rare ZNF532-NUTM1 fusion. Virchows Arch 480, 887–897 (2022). https://doi.org/10.1007/s00428-021-03253-9

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