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Rare Tumors in Children and Adolescents pp 193–204Cite as

NUT Carcinoma

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Part of the book series: Pediatric Oncology ((PEDIATRICO))

Abstract

NUT carcinoma (NC) is defined molecularly by rearrangement of the NUTM1 gene and is most commonly driven by the BRD4-NUT oncoprotein. Patients are typically in their teens or young adulthood. This highly aggressive, incurable subtype of squamous cell carcinoma, with median survivals measured in months, arises most commonly from midline upper airway structures, including head and neck and thorax. Primary sites can occur outside the midline; thus, the term “midline” was dropped from the name of this cancer. The emergence of next-generation sequencing (NGS) technologies has broadened the spectrum of NUTM1-rearranged tumors, and the heterogeneity and number of NUTM1-partner fusion genes continues to expand. Recent NGS data suggest that NC is less rare than originally thought. The diagnosis of NC is easy, owing to the availability of a highly sensitive and specific immunostain for the NUT protein, yet NC continues to be vastly under-tested and underdiagnosed throughout the world. The underdiagnosis of NC is in part due to its pathological overlap with other poorly differentiated neoplasms, and thus utilization of the NUT immunohistochemical stain should be performed more liberally across a large variety of poorly differentiated cancers. In general, we recommend that NC should be ruled out in any poorly differentiated non-cutaneous carcinoma, with or without squamous differentiation, that has a monomorphic histologic appearance. BRD4-NUT drives NC by blocking differentiation; a key oncogenic target is MYC. Although there remains no standard of care treatment of NC, small molecule inhibitors of BRD4-NUT have demonstrated on-target activity in human patients, and the development of novel approaches to treating NC is accelerating. The arrival of specific approaches to treating NC and the limited window in which to treat it impart a crucial need to testing for this cancer.

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Authors and Affiliations

  1. Department of Pathology, Brigham and Women’s Hospital/Harvard Medical School, Boston, MA, USA

    Christopher A. French

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Editors and Affiliations

  1. Clinic of Pediatrics, Municipal Hospital Dortmund, University Witten-Herdecke, Dortmund, Germany

    Dominik T. Schneider

  2. Department of Hematology and Oncology, University Children’s Hospital, Tübingen, Baden-Württemberg, Germany

    Ines B. Brecht

  3. Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta and Emory University, Atlanta, GA, USA

    Thomas A. Olson

  4. Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Milano, Italy

    Andrea Ferrari

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French, C.A. (2022). NUT Carcinoma. In: Schneider, D.T., Brecht, I.B., Olson, T.A., Ferrari, A. (eds) Rare Tumors in Children and Adolescents. Pediatric Oncology. Springer, Cham. https://doi.org/10.1007/978-3-030-92071-5_22

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  • DOI: https://doi.org/10.1007/978-3-030-92071-5_22

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-92070-8

  • Online ISBN: 978-3-030-92071-5

  • eBook Packages: MedicineMedicine (R0)

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