NUT Midline Carcinoma: A Case Report with a Novel Translocation and Review of the Literature

Abstract

NUT midline carcinoma (NMC) is a rare, genetically defined, highly lethal undifferentiated carcinoma occurring in the midline location of the neck, head or mediastinum. We present the case of a 23 year-old otherwise healthy Chinese male immigrant who presented with complaints of sore throat and right sided neck mass. The initial treatment was for likely EBV infection with streptococcal superinfection. Although continued investigation was pursued shortly after initial presentation, the mass had enlarged and become necrotic with significant nodal involvement. The mass was diagnosed as an NMC tumor with a novel three-way translocation t(9;15;19; q34;q13; p13.1). Despite aggressive treatment, the patient's condition progressed rapidly and he died within 3 months of initial diagnosis. Standard therapeutic interventions have been ineffective in the treatment of NMC. Earlier diagnosis could allow characterization of the natural progression of this entity, and allow more time for intervention or development of novel therapies, potentially related to molecular targets. This continues to require a high index of suspicion and early imaging with cytogenetic and immunohistochemical confirmation.

NUT midline carcinoma of the mediastinum showing two types of poorly differentiated tumor cells: A case report and a literature review

“…Sections in which >20% of the cells showed split signals or 3 signals only were considered positive for NUT rearrangement. We reviewed previous reports [1][2][3][10][11][12][13][14][15][16][17][18][19][20][22][23][24][25][26][27] published between 1991 and 2013 that described the details of immunohistochemical findings of NMC.…”

NUT midline carcinoma: Two case reports and review of the literature

“…In approximately 70% of cases, NUT (15q14) is fused to BRD4 (19p13.1), resulting in a BRD4-NUT fusion gene (3). In the remaining 30% of cases, NUT-variant tumors arise from fusion of the NUT gene to another partner gene such as BRD3, NSD3 (8p 11.23), or other uncharacterized genes (1,28).…”

“…Its function remains equivocal (1,29). It has been suggested that the normal function of NUT is to increase histone acetylation by binding to and activating p300 histone acetyltransferase (28).…”

“…The mechanisms by which BRD4-NUT causes NMC progression remain uncertain (30). BRD4, and possibly NUT, are involved in chromatin modification, suggesting that the fusion protein BRD4-NUT may somehow regulate chromatin so as to suppress the expression of genes required for epithelial maturation and squamous differentiation (1,28). Thus, BRD4-NUT may block cellular differentiation and promote proliferation of carcinoma cells, making it a potential therapeutic target (1).…”

“…NMCs with a translocation involving three chromosomes are also rare, though an example is an invasive hypopharyngeal NMC in a 23-year-old male (28). Pathologic evaluation showed a three-way translocation resulting in the novel karyotype 46XY, t(9;15;19; q34;q13;p13.1) (28).…”