NUT midline carcinoma: report of 2 cases suggestive of pulmonary origin.
In this study, we report 2 pediatric cases of nuclear protein of the testis (NUT) midline carcinoma (NMC) suggestive of pulmonary origin: case 1 was a 14-year-old Japanese boy and case 2 was a 7-year-old Japanese girl. Initial symptoms of both cases were prolonged cough and chest pain, and the case 2 patient also complained of lumbago and lumbar mass due to bone metastases. Imaging studies revealed that pulmonary tumors from both patients were located at the hilar region of the lower lobe. Biopsies of the tumors showed undifferentiated carcinoma in case 1 and combined undifferentiated and squamous cell carcinoma in case 2. Despite intensive treatment with chemotherapy and radiation, progression of neither tumor was controlled, and both patients died of the tumors at 1 year (case 1) and 4 months (case 2) after onset of disease. Both tumors were diffusely positive for p63 and NUT expression and were partially positive for various cytokeratins. Reverse transcription polymerase chain reaction analysis and subsequent direct sequencing revealed that the bromodomain-containing protein 4-NUT chimeric gene was present in tumor tissue of both patients, leading to a diagnosis of NMC. The tumor cells of case 1 were also positive for thyroid transcription factor-1 expression, but those of case 2 were negative. Histologic examination of the surgically removed lung tumor of case 1 indicated that the origin of the tumor was basal cells of the bronchiolar epithelia.
Kanagawa Children's Medical Center, Division of Pathology, Yokohama, Japan. mio@zc4.so-net.ne.jp
Mio
M
Tanaka
Keisuke
K
Kato
Kiyoshi
K
Gomi
Mariko
M
Yoshida
Tetsu
T
Niwa
Noriko
N
Aida
Hisato
H
Kigasawa
Yokatsu
Y
Ohama
Yukichi
Y
Tanaka
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000235:genetics / Q000556:secondary / Q000628:therapy; D002454:Cell Differentiation; D002648:Child; D018450:Disease Progression; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008175:Lung Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D008297:Male; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000032:analysis* / Q000235:genetics; D015513:Oncogene Proteins / Q000032:analysis* / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013125:Spinal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000556:secondary / Q000628:therapy; D000074482:Thyroid Nuclear Factor 1; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014157:Transcription Factors / Q000032:analysis; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000032:analysis
C471990:BRD4-NUT fusion oncogene protein, human; D014408:Biomarkers, Tumor; C000614412:NKX2-1 protein, human; C000630260:NUTM1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; C115051:TP63 protein, human; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D007633:Keratins