NUT midline carcinoma: an aggressive intrathoracic neoplasm.
Nuclear protein in testis (NUT) midline carcinoma (NMC) is a poorly differentiated squamous cell carcinoma that is characterized by a balanced translocation between chromosomes 15 and 19 [t(15;19)(q14;p13.1)]. This genetic aberration results in the fusion of the NUT gene on chromosome 15 to the bromodomain containing 4 (BRD4) gene on chromosome 19. The resultant BRD4-NUT fusion oncogene leads to global hypoacetylation and transcriptional repression of genes required for differentiation." Although it was first reported in 1991 by Kubonishi et al., awareness of this condition remains low and the diagnosis is overlooked initially in a number of patients. A 36-year-old man complained of cough and right-sided chest pain for 3 weeks before presentation. Imaging studies revealed a right hilar mass, and a bronchoscopic biopsy was consistent with an aggressive poorly differentiated neoplasm. A combination of cisplatin, ifosfamide, and etoposide was administered for two cycles without any improvement. A repeat core biopsy showed focal squamous differentiation; and given the clinical presentation along with the histologic features, NMC was considered in the differential diagnosis. Immunohistochemical staining for NUT was positive, and dual-color break-apart fluorescence in situ hybridization demonstrated BRD4-NUT rearrangement, thereby confirming a diagnosis of NMC. Our patient was subsequently enrolled on a phase 1 clinical trial of a novel, orally bioavailable bromodomain and extra terminal inhibitor, GSK525762 (NCT01587703). This report illustrates the challenges in diagnosing this rare malignancy, and highlights new treatment options for these patients.
*Department of Oncology, Mayo Clinic, Rochester, Minnesota; †Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts; ‡Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; §GlaxoSmithKline, Philadelphia, Pennsylvania; and ‖Early Drug Development Center, Dana Farber Cancer Institute, Boston, Massachusetts.
Sameer A
SA
Parikh
Christopher A
CA
French
Brian A
BA
Costello
Randolph S
RS
Marks
Roxana S
RS
Dronca
Craig L
CL
Nerby
Anja C
AC
Roden
Vijay G
VG
Peddareddigari
John
J
Hilton
Geoffrey I
GI
Shapiro
Julian R
JR
Molina
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D002945:Cisplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D015321:Gene Rearrangement; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D013899:Thoracic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D014178:Translocation, Genetic
C471990:BRD4-NUT fusion oncogene protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D005047:Etoposide; D002945:Cisplatin; D007069:Ifosfamide