title: NUT midline carcinoma of the larynx: an international series and review of the literature.
abstract: OBJECTIVE
  NUT midline carcinoma (NMC) is a rare undifferentiated and aggressive carcinoma that locates characteristically to the midline of the head and neck, and mediastinum. NMC is characterized by chromosomal rearrangements of the gene NUT, at 15q14. The BRD4 gene on 19q13 is the most common translocation partner forming a fusion oncogene, BRD4-NUT. By the end of 2014, the International NUT Midline Carcinoma Registry had 48 patients treated for NMC. Laryngeal NMC are exceedingly rare, and we report a case series of seven cases.
  
  
  RESULTS
  We searched for cases in files of different hospitals as well as a thorough search of the English language literature. The diagnosis of NMC is made by demonstration of NUT rearrangement either by immunohistochemistry, fluorescence in-situ hybridization (FISH) or reverse transcription-polymerase chain reaction (RT-PCR). We found three previously published cases, and in this series add four cases of our own.
  
  
  CONCLUSIONS
  NMC consists of monomorphic, often discohesive, cells with an epithelioid appearance and distinct nucleoli. The tumours typically show abrupt squamous differentiation. The mean age of the patients was 34 years, hence significantly lower than that for conventional laryngeal carcinoma. All tumours were located in the supraglottis and five patients died of the disease after 3, 7, 8, 9 and 11 months. Laryngeal NMC may be underdiagnosed, and an increased awareness among pathologists is warranted. NMC has characteristic morphological features, and positive immunostaining with the NUT antibody is diagnostic. Its aggressive behaviour demands a very intense treatment strategy and the need for its recognition is emphasized further by new promising treatment strategies.
authors.affiliation: Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal.
authors.forename: Henrik
authors.initials: H
authors.lastname: Hellquist
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: French
authors.affiliation: Departments of Pathology and Otolaryngology - Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Bishop
authors.affiliation: Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Coca-Pelaz
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Propst
authors.affiliation: University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: António
authors.initials: A
authors.lastname: Paiva Correia
authors.affiliation: Division of Pathology, Department of Pediatric Laboratory Medicine, Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Bo-Yee
authors.initials: BY
authors.lastname: Ngan
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, Hospital for Sick Children, Toronto, Canada.
authors.forename: Ronald
authors.initials: R
authors.lastname: Grant
authors.affiliation: Department of Pathology, The University of Chicago Medicine and Biological Sciences, Chicago, IL, USA.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Cipriani
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Auckland City Hospital and Department of Surgery, University of Auckland, Auckland, New Zealand.
authors.forename: David
authors.initials: D
authors.lastname: Vokes
authors.affiliation: Department of Pathology, Portuguese Institute of Oncology, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Henrique
authors.affiliation: Anatomic Pathology Department, Braga Hospital, Braga, Portugal.
authors.forename: Fernando
authors.initials: F
authors.lastname: Pardal
authors.affiliation: Anatomic Pathology Department, St Antonio General Hospital, Porto Hospitals Centre, Porto, Portugal.
authors.forename: Jose Ramon
authors.initials: JR
authors.lastname: Vizcaino
authors.affiliation: University of Udine School of Medicine, Udine, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rinaldo
authors.affiliation: University of Udine School of Medicine, Udine, Italy.
authors.forename: Alfio
authors.initials: A
authors.lastname: Ferlito
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*
chemical_list: C000630260:NUTM1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins
keywords: 
  NUT
  ; BRD4; NUT midline carcinoma; larynx; t(15;19); undifferentiated carcinoma