Answer: NUT midline carcinoma

Histology: The tumor is an infiltrative, high grade malignancy, with numerous mitoses and necrosis. There is no evidence of differentiation by routine H&E staining. Despite its high grade features, the nuclei of the tumor are actually monotonous, with every nucleus looking very similar in size and shape. Immunostaining showed that the tumor is diffusely positive for AE1/AE3, p63, CD34, and NUT.

Discussion: NUT midline carcinoma (NMC) is a relatively recently described entity. NMC is rare, with only about 30 cases reported. As its name implies, NMC most often occurs in midline structures of the head and neck or thorax, including the sinonasal tract, mediastinum, nasopharynx, etc. NMC usually, but not always, occurs in young patients. NMC is defined by translocations involving the NUT gene at 15q14; the most common (75%) translocation is t(15;19) (q13;p13.1), where NUT fuses with the BRD4 gene. NMC usually appears high grade and undifferentiated at the histological level, and SNUC is the most common entity considered in the differential diagnosis. As expected from a translocation tumor, the nuclei are typically uniform. Occasionally, squamous differentiation, which is often abrupt, can be seen. At the immunohistochemical level, NMC marks as poorly differentiated squamous carcinoma, with consistent reactivity to cytokeratins and p63. Surprisingly, CD34 expression, rare in carcinomas, is seen in about half of cases. Other markers of high grade malignancies in the sinonasal tract (e.g., melanoma markers, neuroendocrine markers, muscle markers) are consistently negative. The gold standard for the diagnosis of NMC is FISH, but recently a highly sensitive and specific monoclonal antibody to NUT has become commercially available. NMC is almost uniformly lethal, with an average survival time of less than a year.

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