Nasal cavity, paranasal sinuses, nasopharynx
Sinonasal carcinoma
NUT carcinoma

Editorial Board Member: Kelly Magliocca, D.D.S., M.P.H.
Editor-in-Chief: Debra Zynger, M.D.
Lisa Rooper, M.D.

Topic Completed: 29 January 2019

Revised: 5 February 2019

Copyright: (c) 2019, PathologyOutlines.com, Inc.

PubMed Search: NUT carcinoma nasal

See Also: NUTM1

Lisa Rooper, M.D.
Page views in 2018: 1,214
Page views in 2019 to date: 6,930
Cite this page: Rooper L. NUT carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/nasalnutcarcinoma.html. Accessed October 13th, 2019.
Definition / general
  • Aggressive carcinoma defined by translocations involving the NUT gene and frequent squamous differentiation
Essential features
  • Highly aggressive malignancy with median survival of < 1 year
  • Histologically defined by primitive round cells with areas of abrupt keratinization
  • Caused by translocations involving the NUT gene (15q14), most commonly with BRD4 (19p13)
  • Speckled nuclear positivity for NUT1 immunohistochemistry is sensitive and specific for diagnosis
Terminology
  • NUT stands for nuclear protein in testis
  • Formerly called NUT midline carcinoma due to proclivity for midline sites
Epidemiology
Clinical features
Radiology images

Images hosted on other servers:

Large nasal mass

Case reports
Treatment
  • Tumors generally show minimal response to radiation and conventional chemotherapy (Head Neck Pathol 2013;7:11)
  • In clinical trials, some patients show rapid response to extraterminal bromodomain inhibitors although prognosis remains poor (Cancer Discov 2016;6:492)
Clinical images

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Lacrimal mass

Nasopharyngeal endoscopy

Gross description
  • Highly infiltrative tumor frequently involving multiple anatomic subsites
  • Nonspecific white-tan cut surface commonly demonstrating prominent necrosis
Microscopic (histologic) description
  • Primitive small to medium sized cells with minimal indistinct to clear cytoplasm
  • Monotonous round to oval nuclei with variably prominent nucleoli
  • High mitotic rate with prominent tumor necrosis
  • Foci of abrupt squamous differentiation with clear to eosinophilic cytoplasm and keratin pearl formation
  • Areas of spindled cells frequently present
  • Dense neutrophil infiltrate seen in subset of cases
Microscopic (histologic) images

Contributed by Lisa Rooper, M.D.

Primitive small to medium cells

Highly infiltrative growth

Monotonous nuclei

Prominent necrosis


Abrupt keratinization

Prominent spindled foci

Infiltrating neutrophils

NUT1



Contributed by Brendan Dickson, M.D.

Abrupt keratinization

Necrosis

Undifferentiated areas

p63

NUT1

AE1 / 3

Cytology images

Images hosted on other servers:

Aspirate of metastasis

Positive stains
Negative stains
Electron microscopy description
Molecular / cytogenetics description
Sample pathology report
  • NUT carcinoma; see note:
    • Note: Immunostains show that the tumor cells are positive for AE1 / AE3, p40 and NUT1 and negative for CD99 and synaptophysin, supporting the above diagnosis. NUT carcinoma is a rare, highly aggressive malignancy that is defined by translocations involving the NUT gene. Please see www.nmcregistry.org for information about enrolling the patient into the International NUT Carcinoma Registry and opportunities for clinical trials.
Differential diagnosis
Board review question #1
An 18 year old woman presented with a destructive sinonasal tumor; biopsy findings are shown below. What immunohistochemical finding would you expect?



  1. Cytoplasmic positivity for cytokeratin without significant reactivity for any other markers
  2. Diffuse strong positivity for synaptophysin and INSM1
  3. Loss of nuclear INI1 expression
  4. Speckled nuclear positivity for NUT1
Board review answer #1
D. Speckled nuclear positivity for NUT1. The picture depicts a NUT carcinoma, diagnosis of which is suggested by the presence of monotonous primitive cells interspersed with areas of abrupt keratinization. The correct immunohistochemical finding for this tumor is speckled nuclear positivity for NUT1, a sensitive and specific marker of this tumor type. The other immunoprofiles listed would be more characteristic of tumors that lack the characteristic keratinization pattern depicted in this photomicrograph, including sinonasal undifferentiated carcinoma (A. Cytoplasmic positivity for cytokeratin without significant reactivity for any other markers), small cell carcinoma (B. Diffuse strong positivity for synaptophysin and INSM1) and SMARCB1 deficient sinonasal carcinoma (C. Loss of nuclear INI1 expression).

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Board review question #2
What is the most common genetic abnormality identified in NUT carcinoma?

  1. BRD3-NUT
  2. BRD4-NUT
  3. Deletion of NUT
  4. NSD3-NUT
Board review answer #2
B. BRD4-NUT. The most common genetic abnormality identified in NUT carcinoma is BRD4-NUT fusion, which is present in ~67% of cases. The other translocations listed, BRD3-NUT and NSD3-NUT, are less common variant fusions seen in NUT carcinoma; deletion of NUT has not been reported as a cause of this tumor type.

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