Other carcinomas

NUT carcinoma

Last author update: 23 January 2023
Last staff update: 23 January 2023

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PubMed Search: NUT carcinoma lung

Kyriakos Chatzopoulos, M.D., Ph.D.
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Cite this page: Chatzopoulos K. NUT carcinoma. website. Accessed April 15th, 2024.
Definition / general
  • NUT carcinoma is an aggressive malignancy characterized by NUT gene rearrangements
  • Monotonous, poorly differentiated morphology with foci of abrupt keratinization
Essential features
  • NUT carcinoma is an aggressive malignancy more frequently arising in the thorax or aerodigestive tract, affecting patients of any age with equal gender distribution
  • Morphologically it shows diffuse architecture and consists of monotonous cells with frequent cytoplasmic clearing, large nuclei with prominent nucleoli and foci of abrupt keratinization
  • Due to its largely nonspecific morphology, the differential diagnosis is broad
  • Speckled nuclear immunohistochemical expression of NUT protein in ≥ 50% of cells is a diagnostic hallmark
  • NUT gene rearrangements are present and can be detected by FISH
  • NUT midline carcinoma (no longer recommended)
ICD coding
  • ICD-O: 8023/3 - NUT carcinoma
Clinical features
  • Diagnosis of NUT carcinoma can be challenging because of nonspecific morphologic features
  • Features may not be uniformly present in small biopsy specimens
  • A combination of subtle morphologic changes with NUT immunohistochemistry can aid in the diagnosis (Virchows Arch 2021;478:21)
Prognostic factors
Case reports
Gross description
  • Because of the advanced stage at diagnosis, examination of complete resection specimens is rare
  • Tumor can be deceivingly well demarcated from adjacent structures (Int J Surg Pathol 2016;24:85)
Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Kyriakos Chatzopoulos, M.D., Ph.D. and Kassiani Boulogeorgou, M.D.

Cytomorphology of NUT carcinoma

NUT abrupt keratinization

NUT immunostain

Cytology description
Positive stains
Negative stains
Electron microscopy description
Molecular / cytogenetics description
Sample pathology report
  • Mediastinum, anterior, excisional biopsy:
    • NUT carcinoma (see comment)
    • Comment: Infiltrative, poorly differentiated carcinoma, with extensive necrosis and focal keratinization. Immunohistochemically, tumor cells express p63, p40, keratins 5/6 and NUT. Break apart FISH is positive for NUT rearrangement. These findings support the diagnosis.
Differential diagnosis
Board review style question #1

A 36 year old man presents with cough and shortness of breath and is diagnosed with a large mediastinal mass and undergoes open surgical biopsy. A low power hematoxylin and eosin microscopic picture is shown above. If the mass undergoes genetic testing, which of the following is the most likely finding?

  1. BRD4::NUT fusion transcript
  2. Isochromosome 12p
  3. MYC amplification
  4. SMARCA4 point mutation
Board review style answer #1
A. BRD4::NUT fusion transcript

BRD4::NUT fusion transcript is detected in 70% of NUT carcinomas. Answer B is incorrect because isochromosome 12p is a common finding in mediastinal germ cell tumors. Answer C is incorrect: although MYC is overexpressed in NUT carcinoma, this is because it is downstream in the BRD4::NUT fusion transcript cascade and not because of gene amplification. Answer D is incorrect because SMARCA4 point mutations are frequent in SMARCA4 deficient thoracic tumors (Cancer Genet Cytogenet 2010;203:16, Histopathology 2021;78:593, Oncogene 2014;33:1736, Virchows Arch 2021;478:21).

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Reference: NUT carcinoma
Board review style question #2
A 42 year old woman presents with hemoptysis and bone pain. Imaging reveals a right hilar pulmonary mass and multiple lytic bone lesions. The patient mentions a history of facial nodule removed a year ago. Biopsy of a bone lesion reveals metastatic carcinoma with monomorphous morphology and foci of abrupt keratinization. Immunohistochemistry shows nuclear positivity for NUT protein. Which of the following genetic findings would make the diagnosis of NUT carcinoma more likely?

  1. Detection of YAP1::NUT fusion transcript
  2. Positive break apart NUT FISH
  3. Presence of a complex karyotype
  4. Wild type TP53 gene
Board review style answer #2
B. Positive break apart NUT FISH

Although rare NUT fusions are nondetectable by FISH, the combination of this finding with a positive NUT immunostain has high sensitivity and specificity for diagnosing NUT carcinoma. Answer A is incorrect because a YAP1::NUT fusion, along with the patients reported history of facial nodule would be consistent with the diagnosis of porocarcinoma rather than NUT carcinoma. Answer C is incorrect because most NUT carcinomas have noncomplex karyotypes, with the only finding being a t(15;19) reciprocal translocation. Answer D is incorrect because TP53 is frequently mutated in NUT carcinoma (Lung Cancer 2015;90:484, J Cutan Pathol 2021;48:403, Pathol Int 2018;68:583, Cancer Med 2021;10:5757).

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Reference: NUT carcinoma
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