NUT Midline Carcinoma of the Sinonasal Tract
Justin A Bishop, William H Westra. The Johns Hopkins Hospital, Baltimore, MD
Background: NUT midline carcinoma (NMC) is a malignancy defined by translocations involving the NUT gene on chromosome 15q14. NMC is important to recognize because it is highly lethal and because its chromosomal rearrangement offers the potential for targeted therapies. NMC involves midline structures including the head and neck. Six cases of the sinonasal tract have been reported, but its true incidence at this midline site is unknown because its morphologic features are not well known or recognized, and because sinonasal tumors are not routinely tested for the NUT gene translocation. Translocations involving NUT result in expression of the NUT protein which is otherwise detected only in normal germ cells, and identification of NMCs has been facilitated by the recent availability of a highly sensitive and specific NUT immunostain.
Design: We searched The Johns Hopkins Hospital surgical pathology archives for all cases of sinonasal carcinoma from 1995 to 2011 and constructed tissue microarrays from the blocks. Immunohistochemistry with the NUT monoclonal antibody was performed.
Results: Among the 141 primary sinonasal carcinomas tested, three (2%) NMCs were identified. Two of 12 (17%) sinonasal undifferentiated carcinomas (SNUCs) and 1 of 80 (1%) squamous cell carcinomas were revealed to be NMC. All occurred in men, aged 26, 33, and 48 years (mean 36). The NMCs grew as nests and sheets of cells with abundant mitoses/apoptosis and necrosis. While two showed no histologic evidence of differentiation, one case had scattered "abrupt" nests of keratin. The nuclei of the NMCs were uniform, round to oval with open chromatin, and had one or more prominent eosinophilic nucleoli. Immunohistochemistry showed each carcinoma to be positive for cytokeratins and EMA. P63 was strongly positive in two, but was entirely negative in one. One of the cases was strongly CD34-positive, and the same case also showed focal positivity for neuroendocrine markers. Each patient died of his disease, with survivals of 8, 11, and 16 (mean 12) months despite combined surgery and chemoradiation.
Conclusions: We found that NMCs comprise 2% of all sinonasal carcinomas including 17% of tumors previously classified as SNUC. Although we tested a variety of histologic types, the morphologic features of the positive cases conformed to those previously described for NMC. Although NMC is uncommon in the nasal passages, it should be considered in the differential diagnosis of a poorly differentiated malignancy of that site. Abrupt keratinization and nuclear uniformity in a high grade carcinoma are morphologic clues, and NUT immunohistochemistry is a useful confirmatory tool.
Category: Head & Neck
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 169, Tuesday Afternoon