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Am J Surg Pathol. 2012 Aug;36(8):1216-21. doi: 10.1097/PAS.0b013e318254ce54.

NUT midline carcinomas of the sinonasal tract.

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  • 1Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.


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.

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