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Background: Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare, aggressive malignancy. Only two pediatric and three adult cases of pulmonary NMCs have been documented. In more than two-thirds of NMC cases, a gene fusion between NUT and BRD4 or BRD3 has been documented; other fusions are rare., Case Presentation: A 36-year-old woman was admitted because of a rapidly progressing tumor of the lung with metastases to the breast and bone. A biopsy from the lung tumor revealed an undifferentiated neoplasm exhibiting round to oval nuclei with vesicular chromatin, prominent nucleoli, and scant cytoplasm. Immunohistochemical staining demonstrated focal EMA, cytokeratin AE1/AE3, cytokeratin CAM 5.2, p63, CD138, and vimentin positivity. Finally, the nuclear staining pattern for NUT confirmed a histopathological diagnosis of NMC. A 5'- rapid amplification of the cDNA end (RACE) procedure successfully identified the partner of the NUT translocation as NSD3, a recently discovered partner. Fluorescence in situ hybridization confirmed the NSD3-NUT gene rearrangement, whereas a BRD3/4-NUT fusion gene was not detected., Conclusion: We herein describe the first case of an NSD3-NUT-expressing NMC of the lung. The further accumulation of variant NMCs should provide clues to the establishment of new individualized therapy for NMCs., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Background: NUT (nuclear protein in testis) midline carcinoma (NMC) is a recently described aggressive malignancy that is genetically defined by rearrangements of the NUT locus at 15q14. In approximately two-thirds of cases, the characteristic t(15;19) results in the fusion oncogene BRD4-NUT. Only 10 sinonasal NMCs have been documented, none of which were Japanese cases., Case Presentation: An 18-year-old woman was admitted because of a rapidly progressing tumor in the nasal cavity. A biopsy revealed an undifferentiated neoplasm without squamous differentiation. The tumor cells had round to oval nuclei with vesicular chromatin, prominent nucleoli, and scant cytoplasm. Immunohistochemical staining demonstrated a strong positivity for vimentin and NUT, with focal CD138 and only spotty EMA and cytokeratin AE1/AE3 staining. Cytogenetic and fluorescence in situ hybridization analyses revealed a t(15;19) and BRD4-NUT gene rearrangement. Direct sequencing identified the in-frame fusion of exon11 of BRD4 with exon2 of NUT. The patient was transferred to another hospital for chemoradiotherapy., Conclusion: We herein describe the first Japanese case with an NMC of the sinonasal cavity, providing detailed and unambiguous cyto- and molecular genetic information on BRD4-NUT-rearrangement. The accumulation of cases with well-documented genetic data should provide clues to the treatment of this tumor entity., (Copyright © 2014 Elsevier GmbH. All rights reserved.)