Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:NUT midline carcinoma: an aggressive intrathoracic neoplasm. 2445 44

NUT midline carcinoma (NMC) is a poorly differentiated tumor typically driven by a t(15;19) rearrangement leading to a NUT fusion event. This rare and uniformly fatal tumor arises in multiple organ sites; however the clinical, radiographic, and pathologic characteristics of primary pulmonary NMC are poorly defined. We identified eight cases of primary pulmonary NMC in our consult practice over 4 years and, using a NUT immunohistochemistry screen, retrospectively identified one additional case from 166 (0.6%) consecutive in-house biopsies of lung carcinomas lacking glandular differentiation. Eight cases had available clinical and radiographic data and shared a remarkable degree of similarity. The median age at presentation was 30 (range 21-68). Six patients had little or no smoking history. All complained of 1 to 3 months of cough at presentation. Computed tomography scans showed a large, centrally located primary mass with confluent involvement of mediastinal lymph nodes, pleural disease, and sparing of the contralateral lung. Lytic bone metastases were common but brain metastases were absent in all cases. Pathologically, all cases showed primitive-appearing round to epitheloid cells growing in nests and sheets. All tumors expressed keratin, p63 or p40, and NUT protein. Eight cases had a fluorescence in situ hybridization-proven BRD4-NUT or BRD3-NUT rearrangement; one case was presumed to have a NUT-variant fusion event. Median overall survival was 2.2 months. Despite the rarity of primary pulmonary NMC, it is important to recognize this entity to counsel patients regarding outcome and to identify candidates for targeted BRD inhibitors currently in clinical trials.
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PMID:Primary Pulmonary NUT Midline Carcinoma: Clinical, Radiographic, and Pathologic Characterizations. 2600 Nov 44

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a clinically lethal malignancy affecting all age group often located in the midline structures such as mediastinum, larynx and nasopharynx. It is characterized by chromosomal translocation between chromosomes 15 and 19 with the formation of chimeric gene BRD-NUT. We present the cytologic findings of NMC including the immunohistochemical stains performed. The patient is a 34-year-old man who presented with 1 month history of dyspnea and interscapular pain followed by nonproductive cough a week before consultation. He was initially diagnosed with pneumonia. Due to progression of symptoms, a chest CT scan was performed revealing a large hilar mass and mediastinal adenopathy. A core biopsy with touch preparations of the hilar mass was performed which revealed cohesive malignant cells with ovoid to elongated nuclei, fine to coarse chromatin pattern, irregular nuclear contour, prominent nucleoli, and scant ill-defined cytoplasm arranged in sheets and focally pseudoglandular pattern. Although focal nuclear overlapping and crush artifact were identified, karyorrhectic debris and mitotic figures were rare. Squamous differentiation was absent. The core biopsy showed discohesive malignant cells with tumor necrosis. No nuclear molding, glandular or squamous differentiation was identified. The tumor was immunoreactive for p63 and NUT with high Ki-67 (>80%). The tumor was negative for keratin, lymphoid, myeloid, neuroendocrine markers and S-100. This case emphasizes that cytologic features of NMC can mimic poorly differentiated, undifferentiated and neuroendocrine carcinomas and the importance of immunohistochemical stains especially NUT monoclonal antibody in arriving at the diagnosis.
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PMID:Cytologic findings of NUT midline carcinoma in the hilum of the lung. 2613 51

NUT carcinoma (NC) is an aggressive squamous tumor characterized by NUT gene rearrangement, and the most common fusion form is BRD4-NUT. However, NC diagnosis is difficult for its rareness and often being confused with a variety of poorly differentiated tumors. A 21-year-old Chinese woman was referred to our hospital for cough and intermittent fever. Chest computed tomography (CT) imaging revealed a left lobe hilar mass. Fiberoptic bronchoscopy results showed that tumor cells were poorly differentiated. In combination with immunohistochemistry staining, she was misdiagnosed with Ewing's sarcoma/primitive neuroectodermal tumor. Next-generation sequencing (NGS) revealing BRD4-NUT fusion, and NUT immunohistochemistry confirmed the diagnosis of NC. Subsequently, left pneumonectomy and lymph node dissection were performed, and the patient received pemetrexed and lobaplatin treatment. NGS technology played an important role in NC diagnosis in this case, and it may have clinical use for rare cancer diagnosis and guidance of potential targeted therapies.
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PMID:Diagnosis of NUT carcinoma of lung origin by next-generation sequencing: case report and review of the literature. 3030 75

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare and aggressive subset of poorly differentiated squamous cell carcinoma that is defined by t(15,19) and typically presents in the midline structures of the head, neck, and mediastinum. We report two cases of NMC that presented uniquely with malignant pleural and pericardial effusions including one with cardiac tamponade at presentation. The first case is of a 25-year-old male patient who presented with progressive dyspnea associated with palpitations and dizziness on standing, found to have large bilateral pleural effusions. The second case is of a previously healthy 29-year-old male patient who presented with progressive dyspnea, cough with expectoration, and a large right lower neck mass of 3 months onset, and a large left pleural effusion and left lung infiltrate on imaging studies. Both cases showed malignant cells on cytology suggestive of poorly differentiated carcinoma. Subsequent histopathological and immunochemistry studies were consistent with the diagnosis of NMC. Both patients had a rapid decline in status and suffered comorbidities secondary to their carcinoma, inevitably leading to their death. It is important to consider NUT midline carcinomas can present in a variety of clinical scenarios, and it is important to consider in the differential diagnoses when evaluating malignant effusion cytology. Utilization of ancillary testing with a broad immunostain profile including NUT studies, as well as fluorescent in-situ hydridization (FISH) studies are helpful and necessary in making the appropriate diagnosis.
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PMID:Midline carcinoma expressing NUT in malignant effusion cytology. 3073 27