NUT carcinoma of the head and neck: A case report and literature review

Abstract

Nuclear protein in testis (NUT) carcinoma is a rare and highly aggressive cancer, characterized by rearrangements involving theNUTgene located on chromosome 15q14. In this report, wepresent the case of a 52-year-old female diagnosed with primary parotid NUT carcinoma. Despite undergoing surgery, adjuvant chemotherapy, and incomplete regional radiotherapy, the patient succumbed to the disease after an overall survival duration of 7 months. We retrospectively discuss patient clinical and pathological features, as well as therapeutic approaches of NUT carcinoma of the head and neck.

Keywords

chromosome 15q14 / head and neck / nuclear protein in testis carcinoma / radiation therapy

References

[1] McLean-Holden AC, Moore SA, Gagan J, et al. NUT Carcinoma in a PatientwithUnusually Long Survival and False Negative FISH Results. Head Neck Pathol. 2021;15(2):698-703.

[2] Lauer UM, Hinterleitner M, Horger M, Ohnesorge PV, Zender L. NUT Carcinoma-An Underdiagnosed Malignancy. Front Oncol. 2022;12:914031.

[3] Napolitano M, Venturelli M, Molinaro E, Toss A. NUT midline carcinoma of the head and neck: current perspectives. Onco Targets Ther. 2019;12:3235-3244.

[4] Lantuejoul S, Pissaloux D, Ferretti GR, McLeer A. NUT carcinoma of the lung. Semin Diagn Pathol. 2021;38(5):72-82.

[5] Thompson LDR, Bishop JA. Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: nasal Cavity, Paranasal Sinuses and Skull Base. Head Neck Pathol. 2022;16(1):1-18.

[6] Thawani R, Kim MS, Arastu A, et al. The contemporary management of cancers of the sinonasal tract in adults. CACancer J Clin. 2023;73(1):72-112.

[7] Yuan J, Xu Z, Guo Y. Diagnosis, Treatment and Prognosis of Primary Pulmonary NUT Carcinoma: a Literature Review. Curr Oncol. 2022;29(10):6807-6815.

[8] Haack H, Johnson LA, Fry CJ, et al. Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody. Am J Surg Pathol. 2009;33(7):984-991.

[9] Hung YP, Chen AL, Taylor MS, et al. Thoracic nuclear protein in testis (NUT) carcinoma: expanded pathological spectrum with expression of thyroid transcription factor-1 and neuroendocrine markers. Histopathology. 2021;78(6):896-904.

[10] Prall OWJ, Thio N, Yerneni S, Kumar B, McEvoy CR. A NUT carcinoma lacking squamous differentiation and expressing TTF1. Pathology. 2021;53(5):663-666.

[11] French CA, Rahman S, Walsh EM, et al. NSD3-NUT fusion oncoprotein in NUT midline carcinoma: implications for a novel oncogenic mechanism. Cancer Discov. 2014;4(8):928-941.

[12] Shiota H, Elya JE, Alekseyenko AA, et al. “Z4” Complex Member Fusions in NUT Carcinoma: implications for a Novel Oncogenic Mechanism. Mol Cancer Res. 2018;16(12):1826-1833.

[13] Stevens TM, Morlote D, Xiu J, et al. NUTM1-rearranged neoplasia: a multi-institution experience yields novel fusion partners and expands the histologic spectrum. Mod Pathol. 2019;32(6):764-773.

[14] Dickson BC, Sung YS, Rosenblum MK, et al. NUTM1 Gene Fusions Characterize a Subset of Undifferentiated Soft Tissue and Visceral Tumors. Am J Surg Pathol. 2018;42(5):636-645.

[15] French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res. 2003;63(2):304-307.

[16] Agaimy A, Tögel L, Haller F, Zenk J, Hornung J, Märkl B. YAP1-NUTM1 Gene Fusion in Porocarcinoma of the External Auditory Canal. Head Neck Pathol. 2020;14(4):982-990.

[17] Hartsough EM, Moran J, Devins K, Wszolek M, Cornejo KM. An Unusual Case of a Scrotal Porocarcinoma and Review of the Literature. Am J Dermatopathol. 2023;45(1):51-55.

[18] Allison DB, Rueckert J, Cornea V, Lee CY, Dueber J, Bocklage T. Thyroid Carcinoma with NSD3::NUTM1 Fusion: a Case with Thyrocyte Differentiation and Colloid Production. Endocr Pathol. 2022;33(2):315-326.

[19] Arellano Zameza P, Karklins SP, Pena J, et al. High-Grade Spindle Cell Sarcoma of the Scalp With an MGA::NUTM1 Gene Fusion in aPediatric Patient. Am J Dermatopathol. 2024;46(2):101-103.

[20] French CA, Cheng ML, Hanna GJ, et al. Report of the First International Symposium on NUT Carcinoma. Clin Cancer Res. 2022;28(12):2493-2505.

[21] Giridhar P, Mallick S, Kashyap L, Rath GK. Patterns of care and impact of prognostic factors in the outcome of NUTmidline carcinoma: a systematic review and individual patient data analysis of 119 cases. Eur Arch Otorhinolaryngol. 2018;275(3):815-821.

[22] Chau NG, Hurwitz S, Mitchell CM, et al. Intensive treatment and survival outcomes inNUTmidline carcinoma of the head and neck. Cancer. 2016;122(23):3632-3640.

[23] Zhang H, Liu MH, Zhang J, et al. Successful treatment of a case with NUT midline carcinoma in the larynx and review of the literature. Clin Case Rep. 2019;8(1):176-181.

[24] Urbanelli A, Nitro L, Pipolo C, et al. Therapeutic approaches to sinonasalNUT carcinoma: a systematic review. Eur Arch Otorhinolaryngol. 2024;281(7):3361-3369.

[25] Schwartz BE, Hofer MD, Lemieux ME, et al. Differentiation of NUT midline carcinoma by epigenomic reprogramming. Cancer Res. 2011;71(7):2686-2696.

[26] Mertens F, Wiebe T, Adlercreutz C, Mandahl N, French CA. Successful treatment of a child with t(15;19)-positive tumor. Pediatr Blood Cancer. 2007;49(7):1015-1017.

[27] Maher OM, Christensen AM, Yedururi S, Bell D, Tarek N. Histone deacetylase inhibitor forNUT midline carcinoma. Pediatr Blood Cancer. 2015;62(4):715-717.

[28] Filippakopoulos P, Qi J, Picaud S, et al. Selective inhibition of BET bromodomains. Nature. 2010;468(7327):1067-1073.

[29] Esteves G, Ferreira J, Afonso R, Martins C, Zagalo C, Félix A. HDAC Overexpression in a NUT Midline Carcinoma of the Parotid Gland with Exceptional Survival: a Case Report. Head Neck Pathol. 2020;14(4):1117-1122.

[30] Alekseyenko AA, Walsh EM, Wang X, et al. The oncogenic BRD4-NUT chromatin regulator drives aberrant transcription within large topological domains. Genes Dev. 2015;29(14):1507-1523.

[31] Stathis A, Zucca E, Bekradda M, et al. Clinical Response of Carcinomas Harboring the BRD4-NUT Oncoprotein to the Targeted Bromodomain InhibitorOTX015/MK-8628. Cancer Discov. 2016;6(5):492-500.

[32] Lewin J, Soria JC, Stathis A, et al. Phase Ib Trial With Birabresib, a Small-Molecule Inhibitor of Bromodomain and Extraterminal Proteins, in Patients With Selected Advanced Solid Tumors. J Clin Oncol. 2018;36(30):3007-3014.

[33] Piha-Paul SA, Hann CL, French CA, et al. Phase 1 Study of Molibresib (GSK525762), a Bromodomain and Extra-TerminalDomain Protein Inhibitor, in NUT Carcinoma and Other Solid Tumors. JNCI Cancer Spectr. 2019;4(2):pkz093.

[34] Cousin S, Blay JY, Garcia IB, et al. Safety, pharmacokinetic, pharmacodynamic and clinical activity of molibresib for the treatment of nuclear protein in testis carcinoma and other cancers: results of a Phase I/II open-label, dose escalation study. Int J Cancer. 2022;150(6):993-1006.

[35] Schöffski P, Machiels JP, Rottey S, et al. Phase Ia dose-escalation trial with the BET protein inhibitor BI 894999 in patients with advanced or metastatic solid tumours. Eur J Cancer. 2023;191:112987.

[36] Shapiro GI, LoRusso P, Dowlati A, et al. A Phase 1 study ofRO6870810, a novel bromodomain and extra-terminal protein inhibitor, in patients with NUT carcinoma, other solid tumours, or diffuse large B-cell lymphoma. Br J Cancer. 2021;124(4):744-753.

[37] Weichert W. HDAC expression and clinical prognosis in human malignancies. Cancer Lett. 2009;280(2):168-176.

[38] Huang Y, Durall RT, Luong NM, et al. EZH2 Cooperates with BRD4-NUT to Drive NUT Carcinoma Growth by Silencing Key Tumor Suppressor Genes. Cancer Res. 2023;83(23):3956-3973.

[39] Manzotti G, Ciarrocchi A, Sancisi V. Inhibition of BET Proteins andHistone Deacetylase (HDACs): crossing Roads in Cancer Therapy. Cancers (Basel). 2019;11(3):304.

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2024 The Author(s). Precision Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Shandong Cancer Hospital & Institute.