NUT midline carcinomas of the sinonasal tract

Justin A. Bishop, William H. Westra

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

NUT midline carcinoma (NMC) is a highly lethal tumor defined by translocations involving the NUT gene on chromosome 15q14. NMC involves midline structures including the sinonasal tract, but its overall incidence at this midline site and its full morphologic profile are largely unknown because sinonasal tumors are not routinely tested for the NUT gene translocation. The recent availability of an immunohistochemical probe for the NUT protein now permits a more complete characterization of sinonasal NMCs. The archival files of The Johns Hopkins Hospital Surgical Pathology were searched for all cases of primary sinonasal carcinomas diagnosed from 1995 to 2011. Tissue microarrays were constructed, and NUT immunohistochemical analysis was performed. All NUT-positive cases underwent a more detailed microscopic and immunohistochemical analysis. Among 151 primary sinonasal carcinomas, only 3 (2%) were NUT positive. NUT positivity was detected in 2 of 13 (15%) carcinomas diagnosed as sinonasal undifferentiated carcinoma and in 1 of 87 (1%) carcinomas diagnosed as squamous cell carcinoma. All occurred in men (26, 33, and 48 y of age). The NMCs grew as nests and sheets of cells with a high mitotic rate and extensive necrosis. Two were entirely undifferentiated, and 1 tumor showed abrupt areas of squamous differentiation. Each case had areas of cell spindling, and 2 were heavily infiltrated by neutrophils. Immunohistochemical staining was observed for cytokeratins (3 of 3), epithelial membrane antigen (3 of 3), p63 (2 of 3), CD34 (1 of 3), and synaptophysin (1 of 3). All patients died of the disease (survival time range, 8 to 16 mo; mean, 12 mo) despite combined surgery and chemoradiation. NMC represents a rare form of primary sinonasal carcinoma, but its incidence is significantly increased in those carcinomas that exhibit an undifferentiated component. Indiscriminant analysis for evidence of the NUT translocation is unwarranted. Instead, NUT analysis can be restricted to those carcinomas that demonstrate undifferentiated areas. The availability of an immunohistochemical probe has greatly facilitated this analysis and is helping to define the full demographic, morphologic, and immunohistochemical spectrum of sinonasal NMC.

Original languageEnglish (US)
Pages (from-to)1216-1221
Number of pages6
JournalAmerican Journal of Surgical Pathology
Volume36
Issue number8
DOIs
StatePublished - Aug 1 2012

Fingerprint

Carcinoma
Keratin-3
Mucin-1
Neoplasms
Surgical Pathology
Synaptophysin
Incidence
Genes
Squamous Cell Carcinoma
Neutrophils
Necrosis
Chromosomes
Demography
Staining and Labeling
Survival
Proteins

Keywords

  • 19) translocation
  • BRD4-NUT
  • NUT midline carcinoma
  • sinonasal tract
  • sinonasal undifferentiated carcinoma
  • t(15

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery

Cite this

NUT midline carcinomas of the sinonasal tract. / Bishop, Justin A.; Westra, William H.

In: American Journal of Surgical Pathology, Vol. 36, No. 8, 01.08.2012, p. 1216-1221.

Research output: Contribution to journalArticle

Bishop, Justin A. ; Westra, William H. / NUT midline carcinomas of the sinonasal tract. In: American Journal of Surgical Pathology. 2012 ; Vol. 36, No. 8. pp. 1216-1221.
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