NUT midline carcinoma of the larynx

An international series and review of the literature

Henrik Hellquist, Christopher A. French, Justin A. Bishop, Andrés Coca-Pelaz, Evan J. Propst, António Paiva Correia, Bo Yee Ngan, Ronald Grant, Nicole A. Cipriani, David Vokes, Rui Henrique, Fernando Pardal, Jose Ramon Vizcaino, Alessandra Rinaldo, Alfio Ferlito

Research output: Contribution to journalArticle

Abstract

Aims: 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. Methods and 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.

Original languageEnglish (US)
JournalHistopathology
DOIs
StateAccepted/In press - 2017

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Larynx
Carcinoma
Oncogene Fusion
Epithelioid Cells
Gene Rearrangement
Mediastinum
Fluorescence In Situ Hybridization
Reverse Transcription
Registries
Neoplasms
Neck
Language
Immunohistochemistry
Head
Polymerase Chain Reaction
Antibodies

Keywords

  • NUT
  • BRD4
  • Larynx
  • NUT midline carcinoma
  • T(15;19)
  • Undifferentiated carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Hellquist, H., French, C. A., Bishop, J. A., Coca-Pelaz, A., Propst, E. J., Paiva Correia, A., ... Ferlito, A. (Accepted/In press). NUT midline carcinoma of the larynx: An international series and review of the literature. Histopathology. https://doi.org/10.1111/his.13143

NUT midline carcinoma of the larynx : An international series and review of the literature. / Hellquist, Henrik; French, Christopher A.; Bishop, Justin A.; Coca-Pelaz, Andrés; Propst, Evan J.; Paiva Correia, António; Ngan, Bo Yee; Grant, Ronald; Cipriani, Nicole A.; Vokes, David; Henrique, Rui; Pardal, Fernando; Vizcaino, Jose Ramon; Rinaldo, Alessandra; Ferlito, Alfio.

In: Histopathology, 2017.

Research output: Contribution to journalArticle

Hellquist, H, French, CA, Bishop, JA, Coca-Pelaz, A, Propst, EJ, Paiva Correia, A, Ngan, BY, Grant, R, Cipriani, NA, Vokes, D, Henrique, R, Pardal, F, Vizcaino, JR, Rinaldo, A & Ferlito, A 2017, 'NUT midline carcinoma of the larynx: An international series and review of the literature', Histopathology. https://doi.org/10.1111/his.13143
Hellquist H, French CA, Bishop JA, Coca-Pelaz A, Propst EJ, Paiva Correia A et al. NUT midline carcinoma of the larynx: An international series and review of the literature. Histopathology. 2017. https://doi.org/10.1111/his.13143
Hellquist, Henrik ; French, Christopher A. ; Bishop, Justin A. ; Coca-Pelaz, Andrés ; Propst, Evan J. ; Paiva Correia, António ; Ngan, Bo Yee ; Grant, Ronald ; Cipriani, Nicole A. ; Vokes, David ; Henrique, Rui ; Pardal, Fernando ; Vizcaino, Jose Ramon ; Rinaldo, Alessandra ; Ferlito, Alfio. / NUT midline carcinoma of the larynx : An international series and review of the literature. In: Histopathology. 2017.
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abstract = "Aims: 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. Methods and 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.",
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T2 - An international series and review of the literature

AU - Hellquist, Henrik

AU - French, Christopher A.

AU - Bishop, Justin A.

AU - Coca-Pelaz, Andrés

AU - Propst, Evan J.

AU - Paiva Correia, António

AU - Ngan, Bo Yee

AU - Grant, Ronald

AU - Cipriani, Nicole A.

AU - Vokes, David

AU - Henrique, Rui

AU - Pardal, Fernando

AU - Vizcaino, Jose Ramon

AU - Rinaldo, Alessandra

AU - Ferlito, Alfio

PY - 2017

Y1 - 2017

N2 - Aims: 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. Methods and 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.

AB - Aims: 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. Methods and 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.

KW - NUT

KW - BRD4

KW - Larynx

KW - NUT midline carcinoma

KW - T(15;19)

KW - Undifferentiated carcinoma

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