SPP 08-01 DX: Midline Carcinoma with BRD4-NUT rearrangement - 5% of respondents

The sections show a high-grade malignancy with primitive – undifferentiated morphology, infiltrating dermis and subcutaneous soft tissues. This tumor has no particular pattern of growth or specific apparent line of differentiation. Cytologically it corresponds to primitive cells, some with cytoplasm including rhabdoid features. Focal areas show myxoid background and short spindle-cell morphology. No matrix assembled, no evidence of squamoid or epithelial, glandular or organoid differentiation. A vague alveolar pattern is focally discerned. Immunohistochemistry showed variable, focal but strong positivity for vimentin, CK 18, CD99, AE1/AE3 and CD34, and evident nuclear expression of INI1 (BAF47) throughout. Markers for Epithelial Membrane Antigen, actin, desmin, myogenin and CD45 were negative. Cytogenetics revealed various abnormalities including a distinctive chromosomal translocation t(15:19)(q15; p13.1) resulting in the fusion of BRD4-NUT oncogene confirmed by FISH (at Dr. French’s Laboratory, Boston MA), establishing this diagnosis.