NUT Midline Carcinoma: Diagnostic Ultrastructural Features
EP Wartchow, TS Moore, CA French, GW Mierau. The Children's Hospital, Aurora, CO; Brigham and Women's Hospital, Boston, MA
Background: Nuclear protein in testis (NUT) midline carcinoma is a recently described entity which typically arises in children and young adults. NUT midline carcinomas tend to metastasize early, are almost uniformly lethal, and are most often characterized by a balanced t(15;19)(q13,p13.1) chromosomal translocation that results in a BRD4-NUT fusion oncogene. Although NUT midline carcinomas can be detected by cytogenetic and immunohistochemical means, electron microscopy remains a viable diagnostic tool. The electron microscopic (EM) findings associated with this highly aggressive tumor have thus far received only brief mention in the literature and have never previously been illustrated.
Design: The ultrastructural findings in a typical case of NUT midline carcinoma, confirmed by cytogenetic and fluorescence in situ hybridization studies, are presented to illustrate and characterize features which allow discrimination of this tumor from other entities with which this tumor is likely to be confused. Tissue from a thoracic mass arising in a 5-year-old child was fixed in glutaraldehyde and examined by electron microscopy. Representative micrographs were obtained and analyzed.
Results: Key ultrastructural findings included an often irregularly shaped nucleus containing one or more large nucleoli exhibiting a very prominent nucleonema, and an abundant electron dense cytoplasm containing numerous relatively short bundles of tonofilaments, clusters of pleomorphic granules, and deposits of lipid and glycogen. Stubby microvillous projections extended from the cell surfaces, and frequent punctate well formed desmosomal-type intercellular junctions were found. This constellation of features enables differentiation from thymic carcinoma, thymoma, germ cell tumor, Ewing's sarcoma, or mesothelioma.
Conclusions: Although NUT midline carcinomas are very aggressive tumors with a propensity for early hematogenous spread, they may be sensitive to specific chemotherapeutic regimens. NUT midline carcinoma displays a constellation of distinctive ultrastructural features which may allow earlier diagnosis and intervention. Electron microscopy can, particularly when genetic testing is unproductive or unavailable, prove helpful in discriminating NUT midline carcinoma from other similarly appearing entities.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 256, Wednesday Morning