Skip to main content
SpringerLink
Log in

NUT Carcinoma

  • Chapter
  • First Online:
Mediastinal Lesions

  • 607 Accesses

Abstract

NUT carcinoma (NC) is a genetically defined, highly aggressive, and incurable squamous cell carcinoma associated with chromosomal rearrangements of NUT, most commonly resulting in BRD4-NUT fusion oncogenes or, less commonly, BRD3-NUT, NSD3-NUT, or NUT-variant fusion oncogenes. NC most often arises in the thorax (especially the mediastinum) and in the head and neck (especially the sinonasal tract), but can arise at virtually any site. The karyotype of NCs is uniquely simple compared with that of other squamous cell carcinomas, suggesting that it arises through a genetic or epigenetic shortcut to the phenotype of squamous cell carcinoma. NC is almost certainly underdiagnosed, in part because it has a relatively nonspecific histologic and immunophenotypic profile. NC has a cytopathologic appearance that mimics other primitive small round cell tumors or basaloid neoplasms. Once a difficult diagnosis to make, NC is now diagnosable in most cases by immunohistochemical staining with an anti-NUT monoclonal antibody. No specific chemotherapeutic regimen has demonstrated efficacy in treating NC, but trials investigating the treatment of NC with bromodomain inhibitors that directly target the BRD-NUT oncoproteins are ongoing (www.clinicaltrials.gov).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Shehata BM, Steelman CK, Abramowsky CR, Olson TA, French CA, Saxe DF, et al. NUT mid line carcinoma in a newborn with multiorgan disseminated tumor and a 2-year-old with a pancreatic/hepatic primary. Pediatr Dev Pathol. 2010;13(6):481–5. PubMed PMID: WOS:000288185300008. English.

    Google Scholar 

  2. French CA, Kutok JL, Faquin WC, Toretsky JA, Antonescu CR, Griffin CA, et al. Midline carcinoma of children and young adults with NUT rearrangement. J Clin Oncol Official J Am Soc Clin Oncol. 2004;22(20):4135–9.

    Article  CAS  Google Scholar 

  3. Stelow EB, Bellizzi AM, Taneja K, Mills SE, LeGallo RD, Kutok JL, et al. NUT rearrangement in undifferentiated carcinomas of the upper aerodigestive tract. Am J Surg Pathol. 2008;32A(6):828–34. PubMed PMID: WOS:000256553000003. English.

    Google Scholar 

  4. Bauer DE, Mitchell CM, Strait KM, Lathan CS, Stelow EB, Luer SC, et al. Clinicopathologic features and long-term outcomes of NUT midline carcinoma. Clin Cancer Res Official J Am Assoc Cancer Res. 2012;18(20):5773–9. PubMed PMID: 22896655. Pubmed Central PMCID: 3473162.

    Google Scholar 

  5. Stelow EB, Bellizzi AM, Taneja K, Mills SE, Legallo RD, Kutok JL, et al. NUT rearrangement in undifferentiated carcinomas of the upper aerodigestive tract. Am J Surg Pathol. 2008;32(6):828–34.

    Article  PubMed  Google Scholar 

  6. Evans AG, French CA, Cameron MJ, Fletcher CD, Jackman DM, Lathan CS, et al. Pathologic characteristics of NUT midline carcinoma arising in the mediastinum. Am J Surg Pathol. 2012;36(8):1222–7. PubMed PMID: 22790861. Pubmed Central PMCID: 3396884.

    Google Scholar 

  7. Sholl LM, Nishino M, Pokharel S, Mino-Kenudson M, French CA, Janne PA, et al. Primary pulmonary NUT midline carcinoma: clinical, radiographic, and pathologic characterizations. J Thorac Oncol Official Publ Int Assoc Study Lung Cancer. 2015;10(6):951–9. PubMed PMID: 26001144. Pubmed Central PMCID: 4443847.

    Google Scholar 

  8. French CA, Kutok JL, Faquin WC, Toretsky JA, Antonescu CR, Griffin CA, et al. Midline carcinoma of children and young adults with NUT rearrangement. J Clin Oncol. 2004;22(20):4135–9. PubMed PMID: WOS:000224573400015. English.

    Google Scholar 

  9. Chau NG, Hurwitz S, Mitchell CM, Aserlind A, Grunfeld N, Kaplan L, et al. Intensive treatment and survival outcomes in NUT midline carcinoma of the head and neck. Cancer. 2016. PubMed PMID: 27509377.

    Google Scholar 

  10. French CA. Demystified molecular pathology of NUT midline carcinomas. J Clin Pathol. 2010;63(6):492–6. PubMed PMID: WOS:000277941500004. English.

    Google Scholar 

  11. den Bakker MA, Beverloo BH, van den Heuvel-Eibrink MM, Meeuwis CA, Tan LM, Johnson LA, et al. NUT midline carcinoma of the parotid gland with mesenchymal differentiation. Am J Surg Pathol. 2009;33(8):1253–8.

    Article  Google Scholar 

  12. Shehata BM, Steelman CK, Abramowsky CR, Olson TA, French CA, Saxe DF, et al. NUT midline carcinoma in a newborn with multiorgan disseminated tumor and a 2-year-old with a pancreatic/hepatic primary. Pediatr Dev Pathol Official J Soc Pediatr Pathol Paediatr Pathol Soc. 2010;13(6):481–5. PubMed PMID: 20017639.

    Google Scholar 

  13. French CA. Pathogenesis of NUT midline carcinoma. Annu Rev Pathol. 2012;7:247–65.

    Article  CAS  PubMed  Google Scholar 

  14. Mertens F, Wiebe T, Adlercreutz C, Mandahl N, French CA. Successful treatment of a child with t (15;19)-positive tumor. Pediatr Blood Cancer. 2007;49(7):1015–7.

    Article  PubMed  Google Scholar 

  15. Nelson BA, Lee EY, French CA, Bauer DE, Vargas SO. BRD4-NUT carcinoma of the mediastinum in a pediatric patient: multidetector computed tomography imaging findings. J Thorac Imaging. 2010;25(3):W93–6.

    Article  PubMed  Google Scholar 

  16. Lee AC, Kwong YI, Fu KH, Chan GC, Ma L, Lau YL. Disseminated mediastinal carcinoma with chromosomal translocation (15;19). A distinctive clinicopathologic syndrome. Cancer. 1993;72(7):2273–6.

    Article  CAS  PubMed  Google Scholar 

  17. Tanaka M, Kato K, Gomi K, Yoshida M, Niwa T, Aida N, et al. NUT midline carcinoma: report of 2 cases suggestive of pulmonary origin. Am J Surg Pathol. 2012;36(3):381–8.

    Article  PubMed  Google Scholar 

  18. Polsani A, Braithwaite KA, Alazraki AL, Abramowsky C, Shehata BM. NUT midline carcinoma: an imaging case series and review of literature. Pediatr Radiol. 2012;42(2):205–10.

    Article  PubMed  Google Scholar 

  19. Vargas SO, French CA, Faul PN, Fletcher JA, Davis IJ, Dal Cin P, et al. Upper respiratory tract carcinoma with chromosomal translocation 15;19: evidence for a distinct disease entity of young patients with a rapidly fatal course. Cancer. 2001;92(5):1195–203.

    Article  CAS  PubMed  Google Scholar 

  20. Engleson J, Soller M, Panagopoulos I, Dahlen A, Dictor M, Jerkeman M. Midline carcinoma with t (15;19) and BRD4-NUT fusion oncogene in a 30-year-old female with response to docetaxel and radiotherapy. BMC Cancer. 2006;6:69. PubMed PMID: 16542442. Pubmed Central PMCID: 1456975.

    Google Scholar 

  21. Ball A, Bromley A, Glaze S, French CA, Ghatage P, Kobel M. A rare case of NUT midline carcinoma. Gynecol Oncol Case Rep. 2012;3:1–3. PubMed PMID: 24371650. Pubmed Central PMCID: 3862205.

    Google Scholar 

  22. Puliyel MM, Mascarenhas L, Zhou S, Sapra A, Dal Cin P, French CA, et al. Nuclear protein in testis midline carcinoma misdiagnosed as adamantinoma. J Clin Oncol Official J Am Soc Clin Oncol. 2014. PubMed PMID: 24470009.

    Google Scholar 

  23. Stelow EB, French CA. Carcinomas of the upper aerodigestive tract with rearrangement of the nuclear protein of the testis (NUT) gene (NUT midline carcinomas). Adv Anat Pathol. 2009;16(2):92–6.

    Article  CAS  PubMed  Google Scholar 

  24. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, et al. Selective inhibition of BET bromodomains. Nature. 2010;468(7327):1067–73. PubMed PMID: 20871596. Pubmed Central PMCID: 3010259.

    Google Scholar 

  25. Stathis A, Zucca E, Bekradda M, Gomez-Roca C, Delord JP, de La Motte Rouge T, et al. Clinical response of carcinomas harboring the BRD4-NUT oncoprotein to the targeted bromodomain inhibitor OTX015/MK-8628. Cancer Discovery. 2016;6(5):492–500. PubMed PMID: 26976114. Pubmed Central PMCID: 4854801.

    Google Scholar 

  26. den Bakker MA, Beverloo BH, van den Heuvel-Eibrink MM, Meeuwis CA, Tan LM, Johnson LA, et al. NUT midline carcinoma of the parotid gland with mesenchymal differentiation. Am J Surg Pathol. 2009;33(8):1253–8. PubMed PMID: WOS:000268850300019. English.

    Google Scholar 

  27. Bishop JA, French CA, Ali SZ. Cytopathologic features of NUT midline carcinoma: a series of 26 specimens from 13 patients. Cancer Cytopathol. 2016;n/a–n/a.

    Google Scholar 

  28. Bellizzi AM, Bruzzi C, French CA, Stelow EB. The cytologic features of NUT midline carcinoma. Cancer. 2009;117(6):508–15.

    PubMed  Google Scholar 

  29. Policarpio-Nicolas MLC, de Leon EMB, Jagirdar J. Cytologic Findings of NUT midline carcinoma in the hilum of the lung. Diagn Cytopathol. 2015;43(9):739–42. PubMed PMID: WOS:000359703200014. English.

    Google Scholar 

  30. Kuroda S, Suzuki S, Kurita A, Muraki M, Aoshima Y, Tanioka F, et al. Cytological features of a variant NUT midline carcinoma of the lung harboring the NSD3-NUT fusion gene: a case report and literature review. Case Rep Pathol. 2015;2015:572951. PubMed PMID: 25685583. Pubmed Central PMCID: 4320876.

    Google Scholar 

  31. Wartchow EP, Moore TS, French CA, Mierau GW. Ultrastructural features of NUT midline carcinoma. Ultrastruct Pathol. 2012;36(4):280–4.

    Article  PubMed  Google Scholar 

  32. Bishop JA, French CA, Ali SZ. Cytopathologic features of NUT midline carcinoma: a series of 26 specimens from 13 patients. Cancer Cytopathol. 2016. PubMed PMID: 27400194.

    Google Scholar 

  33. Zhu B, Laskin W, Chen Y, French CA, Cameron MJ, Nayar R, et al. NUT midline carcinoma: a neoplasm with diagnostic challenges in cytology. Cytopathol Official J Brit Soc Clin Cytol. 2011;22(6):414–7.

    Article  CAS  Google Scholar 

  34. Stelow EB. A review of NUT midline carcinoma. Head Neck Pathol. 2011;5(1):31–5. PubMed PMID: 21221870. Pubmed Central PMCID: 3037455.

    Google Scholar 

  35. French CA, Ramirez CL, Kolmakova J, Hickman TT, Cameron MJ, Thyne ME, et al. BRD-NUT oncoproteins: a family of closely related nuclear proteins that block epithelial differentiation and maintain the growth of carcinoma cells. Oncogene. 2008;27(15):2237–42. PubMed PMID: WOS:000254621300014. English.

    Google Scholar 

  36. French CA, Miyoshi I, Aster JC, Kubonishi I, Kroll TG, Dal Cin P, et al. BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t (15;19). Am J Pathol. 2001;159(6):1987–92. PubMed PMID: WOS:000172457400003. English.

    Google Scholar 

  37. Schwartz BE, Hofer MD, Lemieux ME, Bauer DE, Cameron MJ, West NH, et al. Differentiation of NUT midline carcinoma by epigenomic reprogramming. Cancer Res. 2011;71(7):2686–96. PubMed PMID: WOS:000289057600029. English.

    Google Scholar 

  38. Engleson J, Soller M, Panagopoulos I, Dahlen A, Dictor M, Jerkeman M. Midline carcinoma with t (15;19) and BRD4-NUT fusion oncogene in a 30-year-old female with response to docetaxel and radiotherapy. BMC Cancer. 2006;6. PubMed PMID: WOS:000237264000001. English.

    Google Scholar 

  39. Haack H, Johnson LA, Fry CJ, Crosby K, Polakiewicz RD, Stelow EB, et al. Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody. Am J Surg Pathol. 2009;33(7):984–91. PubMed PMID: WOS:000268043400003. English.

    Google Scholar 

  40. French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res. 2003;63(2):304–7.

    CAS  PubMed  Google Scholar 

  41. Haack H, Johnson LA, Fry CJ, Crosby K, Polakiewicz RD, Stelow EB, et al. Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody. Am J Surg Pathol. 2009;33(7):984–91. PubMed PMID: 19363441. Pubmed Central PMCID: 2783402.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Harvard Medical School, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115, USA

    Lucian R. Chirieac & Christopher A. French

Authors
  1. Lucian R. Chirieac
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christopher A. French
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lucian R. Chirieac .

Editor information

Editors and Affiliations

  1. Department of Pathology, Mayo Clinic School of Medicine, Rochester, Minnesota, USA

    Anja C. Roden

  2. Department of Pathology, New York University Langone Medical Center, New York, New York, USA

    Andre L. Moreira

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Chirieac, L.R., French, C.A. (2017). NUT Carcinoma. In: Roden, A., Moreira, A. (eds) Mediastinal Lesions. Springer, Cham. https://doi.org/10.1007/978-3-319-48379-5_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-48379-5_7

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-48377-1

  • Online ISBN: 978-3-319-48379-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation