NUT Midline Carcinoma in a Newborn with Multiorgan Disseminated Tumor and a 2-Year-Old with a Pancreatic/Hepatic Primary

• Published in: Pediatric and developmental pathology Vol. 13; no. 6; pp. 481 - 485
• Main Authors: Shehata, Bahig M., Steelman, Charlotte K., Abramowsky, Carlos R., Olson, Thomas A., French, Christopher A., Saxe, Debra F., Ricketts, Richard R., Katzenstein, Howard M.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.11.2010; SAGE PUBLICATIONS, INC
• Subjects: Carcinoma - congenital; Carcinoma - genetics; Carcinoma - pathology; Cell Cycle Proteins; Child, Preschool; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 9; Combined Modality Therapy; Fatal Outcome; Humans; Infant, Newborn; Liver Neoplasms - congenital; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Male; Neoplasms, Multiple Primary; Nuclear Proteins - genetics; Oncogene Proteins - genetics; Oncogene Proteins, Fusion - genetics; Orbital Neoplasms - congenital; Orbital Neoplasms - genetics; Orbital Neoplasms - pathology; Pancreatic Neoplasms - congenital; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Transcription Factors - genetics; Translocation, Genetic; t(15, 19); NUT; BRD; t(9, 15); NUT midline carcinoma; BRD4
• ISSN: 1093-5266; 1615-5742
• DOI: 10.2350/09-10-0727-CR.1

NUT midline carcinoma (NMC) is a rare and aggressive malignant epithelial tumor defined by rearrangement of the NUT gene on chromosome 15. In two thirds of cases, NUT is involved in a balanced translocation with BDR4 on chromosome 19, while in the remaining cases, NUT is rearranged with variant fusion partners such as BRD3. These undifferentiated tumors primarily affect midline structures, usually in the upper aerodigestive tract and mediastinum. Most reported cases have followed a rapidly lethal clinical course. We report the clinical and pathological findings of NMC in the youngest patients identified so far. The 1st case involves a newborn who presented with a supraorbital mass and extensive multiorgan involvement, including the spine, lungs, liver, pancreas, adrenal glands, and subcutaneous tissue. The 2nd patient was a 2-year-old male with an abdominal mass involving the liver and pancreas with pulmonary metastasis. Histopathological analysis of both tumors showed undifferentiated malignant neoplasms, and immunohistochemistry showed positivity for epithelial markers. Both tumors demonstrated t(15;19), and immunohistochemistry with NUT monoclonal antibodies and fluorescent in situ hybridization confirmed NUT rearrangement. The patients died from disease at 1 and 2 months postpresentation. Thus far, 25 cases have been reported, including our 2 current cases. Presentation ages range from 0 to 78 years (mean, 23 years). Herein, we report the 2 youngest reported cases of NMC, including the 1st congenital case and the 1st case arising within the liver/pancreas. Increased awareness and further molecular studies are required for a better understanding of NMC pathobiology and improved therapeutic outcomes.