title: NSD3-NUT-expressing midline carcinoma of the lung: first characterization of primary cancer tissue.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pathology, Iwata City Hospital, Japan. Electronic address: shiosuzuki-path@umin.net.
authors.forename: Shioto
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Tumor Pathology, Hamamatsu University School of Medicine, Japan.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Kurabe
authors.affiliation: Division of Pathology, Iwata City Hospital, Japan.
authors.forename: Ippei
authors.initials: I
authors.lastname: Ohnishi
authors.affiliation: Division of Respiratory Medicine, Iwata City Hospital, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Division of Respiratory Medicine, Iwata City Hospital, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Aoshima
authors.affiliation: Division of Radiology, Iwata City Hospital, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Naito
authors.affiliation: Division of Pathology, Iwata City Hospital, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Tanioka
authors.affiliation: Department of Tumor Pathology, Hamamatsu University School of Medicine, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*
chemical_list: C000630260:NUTM1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D011495:Histone-Lysine N-Methyltransferase; C432968:NSD3 protein, human
keywords: Lung; NSD3-NUT; NUT midline carcinoma; Nuclear receptor binding SET domain (NSD) protein