Diagnosis and Discussion

Diagnosis

NUT carcinoma.

Discussion

NUT carcinoma is a highly aggressive poorly differentiated carcinoma define by rearrangement of NUT (Nuclear protein in Testis) gene, due to chromosomal translocations involving the NUT gene (15q14), most commonly with BRD4 (19p13),  which occurs in ~70% of cases. The other reported translocations BRD3-NUT and NSD3-NUT, are less common variant fusions seen in NUT carcinoma. In our case FISH for NUT-BRD4 was positive. P40 is frequently positive, indicating squamous lineage.

NUT carcinoma has been reported primarily in the head, neck, and mediastinum of young individuals. Although more common in midline sites, it can occur anywhere in the body.

Grossly it appears as a highly infiltrative, very aggressive tumor that frequently presents with metastasis. It has nonspecific white-tan cut surface commonly demonstrating prominent necrosis.

Histologically the tumor cells demonstrate monotonous round to oval nuclei with prominent nucleoli, and variable amounts of cytoplasm, mostly clear to eosinophilic, with a high mitotic rate, and prominent multifocal areas of necrosis. Keratinization may be present and mostly leads us to think about squamous or adenosquamous carcinoma if p40 and TTF-1 are expressed. Characteristically NUT carcinoma show unique speckled nuclear positivity for NUT1 immunohistochemistry which is highly sensitive (76%) and specific (100%) for the diagnosis. Other stains used are pan-cytokeratin and P40 which are commonly positive. Chromogranin, synaptophysin, and TTF-1 may occasionally be positive.

In general MRI signals of NUT carcinoma are nonspecific and may mimic other pathological entities like lymphoma, metastatic carcinoma, or sarcoma.

NUT carcinoma has a poor prognosis with a median overall survival of 7 months. There is no sex predilection reported for this tumor. This is a very rare and under-recognized entity, unfortunately, chemotherapy has been inadequate and there is a need for targeted therapy. Surgery and radiotherapy might be associated with better survival. Given the rapid progression of this tumor, increased awareness and detection of this tumor in early stages before metastasis occur is important to initiate quick treatment.

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References

Edgar, M., et al., NUT Midline Carcinoma of the Nasal Cavity. Head Neck Pathol. 2017. 11(3): 389-392.

Evans, A.G., et al., Pathologic characteristics of NUT midline carcinoma arising in the mediastinum. AJSP. 2012. 36(8): 1222-1227.

French, C.A., The importance of diagnosing NUT midline carcinoma. Head Neck Pathol. 2013. 7(1): 11-6