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Li R, Zhang Y, Liu Q, Gao A, Dang Q. Targeted combination chemotherapy effective in nuclear protein in testis carcinoma of lung origin: A case report and review of the literature. Medicine (Baltimore) 2024; 103:e38881. [PMID: 39969296 PMCID: PMC11688100 DOI: 10.1097/md.0000000000038881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 06/20/2024] [Indexed: 02/20/2025] Open
Abstract
RATIONALE Nuclear protein in testis carcinoma (NC) is a rare, aggressive, poorly differentiated squamous cell carcinoma. By reviewing the entire treatment process of the patient, we aim to explore the treatment experience of NC. PATIENT CONCERNS We report the case of a 27-year-old female patient with NC whose initial symptoms were occasional cough and chest tightness with abdominal distension for more than half a month without any other specific discomfort. DIAGNOSES Computed tomography showed right lung hilar and right middle and lower lobe mass, malignant, right hilar and mediastinal lymph node metastasis, and bilateral cystic solid masses in the adnexal region, malignant possibility. Pathological diagnosis showed nuclear protein in the testis (+). INTERVENTIONS After the failure of first-line chemotherapy with immunocombination, second-line chemotherapy was switched to bevacizumab, which resulted in a progression-free survival of 6 months. OUTCOMES The disease then reprogressed, and she died on November 7, 2022. LESSONS The patient achieved survival of nearly 1 year on multiple courses of therapy, well beyond the currently reported median survival. The patient achieved a 6-month progression-free survival, suggesting that combination therapy with antivascular endothelial growth factor class-targeted agents is a potential approach.
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Affiliation(s)
- Ran Li
- Shandong Second Medical University, Weifang, China
| | - Ye Zhang
- Shandong Second Medical University, Weifang, China
| | - Qian Liu
- Shandong Second Medical University, Weifang, China
| | - Aiqin Gao
- Department of Thoracic Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, China
| | - Qi Dang
- Department of Oncology, Phase I Clinical Trial Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
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2
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Liang Z, Tang Y, Li C, Xie G, Chen M, Zhou P, Li M, Wang Y, Yu X, Tang Y, Wang J, Bao J, Jiang L, Wang W. Oral and oropharyngeal NUT carcinoma: a multicentre screening study of poorly differentiated oral cancer. Histopathology 2024; 85:868-878. [PMID: 39031601 DOI: 10.1111/his.15245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 05/15/2024] [Accepted: 05/29/2024] [Indexed: 07/22/2024]
Abstract
BACKGROUND AND AIMS Nuclear protein testis (NUT) carcinoma (NC) is a rare and highly aggressive tumour characterised by chromosomal rearrangement of the nuclear protein testis family member 1 (NUTM1) gene, also known as the NUT gene. NC occurs mainly in the head and neck, mediastinum and lung. In general, primary NC in the oral cavity is extremely rare and reported sporadically. METHODS A total of 111 formalin-fixed and paraffin-embedded specimens of poorly differentiated oral and oropharyngeal tumours were collected from 10 hospitals. NUT protein IHC staining was performed on these samples, and fluorescence in-situ hybridisation (FISH) and RNA sequencing detection were further carried out for NUT IHC-positive cases. RESULTS The expression of NUT protein in tumour cells was detected in five cases (five of 111, 4.5%). The tumours in these cases were located in the oral floor, lip, base of the tongue, gingiva and hard palate. FISH detection results showed BRD4::NUT rearrangement in three patients and a non-BRD4::NUT rearrangement pattern in two patients. RNA sequencing results confirmed BRD4::NUT rearrangement in two cases. CONCLUSIONS To our knowledge, this is the first and largest retrospective study of oral NC, and we found that NC is easily misdiagnosed as poorly differentiated oral squamous cell carcinoma (SCC) or poorly differentiated carcinoma. The morphology and immunophenotype of four NC cases were similar to SCC, and abrupt keratinisation was observed in three cases. Therefore, it is necessary to detect NUT protein for NC screening in oral malignant tumours with these morphologies, especially for young patients who are more likely to be misdiagnosed with other types of cancer.
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Affiliation(s)
- Zuoyu Liang
- Department of Pathology of West China Hospital, Sichuan University, Chengdu, China
| | - Yaling Tang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Ci Li
- Department of Pathology of Affiliated Hospital of Chengdu University, Chengdu, China
| | - Gang Xie
- Department of Pathology of Mianyang Central Hospital, Mianyang, China
| | - Min Chen
- Department of Pathology of West China Hospital, Sichuan University, Chengdu, China
| | - Ping Zhou
- Department of Pathology of West China Hospital, Sichuan University, Chengdu, China
| | - Mengqian Li
- Department of Pathology of West China Hospital, Sichuan University, Chengdu, China
| | - Yan Wang
- Department of Pathology of West China Hospital, Sichuan University, Chengdu, China
| | - Xuejiao Yu
- Department of Pathology of West China Hospital, Sichuan University, Chengdu, China
| | - Yuan Tang
- Department of Pathology of West China Hospital, Sichuan University, Chengdu, China
| | - Jing Wang
- Precision Medicine Center, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Ji Bao
- Institute of Clinical Pathology of West China Hospital, Sichuan University, Chengdu, China
| | - Lili Jiang
- Department of Pathology of West China Hospital, Sichuan University, Chengdu, China
| | - Weiya Wang
- Department of Pathology of West China Hospital, Sichuan University, Chengdu, China
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Zhao D, Cao W, Zha S, Wang Y, Pan Z, Zhang J, Hu K. Primary pulmonary nuclear protein of the testis midline carcinoma: case report and systematic review with pooled analysis. Front Oncol 2024; 13:1308432. [PMID: 38264746 PMCID: PMC10803636 DOI: 10.3389/fonc.2023.1308432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Accepted: 12/21/2023] [Indexed: 01/25/2024] Open
Abstract
Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare tumor, with particularly low incidence in the lungs, and a correspondingly poor prognosis. To determine the clinicopathological characteristics, outcomes, and prognostic factors of primary pulmonary NMC, a case was reported and a systematic review was performed. Twenty-nine records, including ours, involving 62 cases, were finally included. The median age at diagnosis was 29.5 years. At presentation, the most common symptoms at presentation were cough (47.50%) and chest/back pain (37.50%). In terms of diagnosis, 32.14% of NMC cases were identified through immunohistochemistry (IHC); However, a greater number of cases may be misdiagnosed initially, and ultimately, the diagnosis of NMC was confirmed through a combination of IHC and fluorescence in situ hybridization (FISH). Despite the clinical application of various chemotherapy-based treatments, the actual effectiveness remains unsatisfactory. Furthermore, Cox regression analysis of multiple factors identified male gender and concurrent presence of pleural effusion as indicators of shorter survival time in patients. These results emphasize the importance of increased diagnostic awareness among clinical and pathology practitioners concerning NMC. While there is currently no established standard for treating NMC, a treatment approach combining multiple methods shows promise for future research. Concurrently, clinical and foundational investigations addressing variables such as gender and the presence of pleural effusion may yield valuable insights into the diagnosis and treatment of NMC.
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Affiliation(s)
- Dong Zhao
- Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China
| | - Wei Cao
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shiqian Zha
- Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yixuan Wang
- Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China
| | - Zhou Pan
- Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China
| | - Jingyi Zhang
- Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China
| | - Ke Hu
- Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China
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4
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Huang WP, Gao G, Qiu YK, Yang Q, Song LL, Chen Z, Gao JB, Kang L. Multimodality imaging and treatment of paranasal sinuses nuclear protein in testis carcinoma: A case report. World J Clin Cases 2022; 10:12395-12403. [PMID: 36483827 PMCID: PMC9724541 DOI: 10.12998/wjcc.v10.i33.12395] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 09/28/2022] [Accepted: 10/26/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Nuclear protein in testis (NUT) carcinoma is a rare aggressive malignant epithelial cell tumor, previously known as NUT midline carcinoma (NMC), characterized by an acquired rearrangement of the gene encoding NUT on chromosome 15q14. Due to the lack of characteristic pathological features, it is often underdiagnosed and misdiagnosed. A variety of methods can be used to diagnose NMC, including immunohistochemistry, karyotyping, fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, and next-generation sequencing. So far, there is no standard treatment plan for NMC and the prognosis is poor, related to its rapid progression, easy recurrence, and unsatisfactory treatment outcome.
CASE SUMMARY A 58-year-old female came to our hospital with a complaint of eye swelling and pain for 8 d. The diagnosis of NMC was confirmed after postoperative pathology and genetic testing. The patient developed nausea and vomiting, headache, and loss of vision in both eyes to blindness after surgery. Magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) performed after 1.5 mo postoperatively suggested tumor recurrence. The patient obtained remission after radiation therapy to some extent and after initial treatment with anti-angiogenic drugs and sonodynamic therapy (SDT), but cannot achieve long-term stability and eventually developed distant metastases, with an overall survival of only 17 mo.
CONCLUSION For patients with rapidly progressing sinus tumors and poor response to initial treatment, the possibility of NMC should be considered and immunohistochemical staining with anti-NUT should be performed as soon as possible, combined with genetic testing if necessary. CT, MRI, and PET/CT imaging are essential for the staging, management, treatment response assessment and monitoring of NMC. This case is the first attempt to apply heat therapy and SDT in the treatment of NMC, unfortunately, the prognosis remained poor.
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Affiliation(s)
- Wen-Peng Huang
- Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China
| | - Ge Gao
- Department of Medical Imaging, Peking University First Hospital, Beijing 100034, China
| | - Yong-Kang Qiu
- Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China
| | - Qi Yang
- Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China
| | - Le-Le Song
- Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China
| | - Zhao Chen
- Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China
| | - Jian-Bo Gao
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Lei Kang
- Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China
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5
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Vo NH, Shashi KK, Winant AJ, Liszewski MC, Lee EY. Imaging evaluation of the pediatric mediastinum: new International Thymic Malignancy Interest Group classification system for children. Pediatr Radiol 2022; 52:1948-1962. [PMID: 35476071 DOI: 10.1007/s00247-022-05361-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 02/07/2022] [Accepted: 03/18/2022] [Indexed: 10/18/2022]
Abstract
Mediastinal masses are commonly identified in the pediatric population with cross-sectional imaging central to the diagnosis and management of these lesions. With greater anatomical definition afforded by cross-sectional imaging, classification of mediastinal masses into the traditional anterior, middle and posterior mediastinal compartments - as based on the lateral chest radiograph - has diminishing application. In recent years, the International Thymic Malignancy Interest Group (ITMIG) classification system of mediastinal masses, which is cross-sectionally based, has garnered acceptance by multiple thoracic societies and been applied in adults. Therefore, there is a need for pediatric radiologists to clearly understand the ITMIG classification system and how it applies to the pediatric population. The main purpose of this article is to provide an updated review of common pediatric mediastinal masses and mediastinal manifestations of systemic disease processes in the pediatric population based on the new ITMIG classification system.
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Affiliation(s)
- Nhi H Vo
- Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - Kumar K Shashi
- Department of Radiology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Ave., Boston, MA, 02115, USA
| | - Abbey J Winant
- Department of Radiology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Ave., Boston, MA, 02115, USA
| | - Mark C Liszewski
- Department of Radiology and Pediatrics, The Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Edward Y Lee
- Department of Radiology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Ave., Boston, MA, 02115, USA.
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6
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Saiki A, Sakamoto K, Bee Y, Izumo T. Nuclear protein of the testis midline carcinoma of the thorax. Jpn J Clin Oncol 2022; 52:531-538. [PMID: 35325167 PMCID: PMC9157292 DOI: 10.1093/jjco/hyac033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 03/02/2022] [Indexed: 11/14/2022] Open
Abstract
Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare tumor that typically presents in the head, neck, and chest region. NMC is characterized by rearrangement of the NUTM1 gene. It mainly affects children and young adults and is rapidly progressive and lethal. Reportedly, the prognoses of NMCs of the head and neck improve following aggressive initial surgical resection +/- postoperative chemoradiotherapy (CRT) or radiotherapy (RT). However, as NMC of the thorax was identified later, treatments to improve its prognosis are yet to be identified. Our review reveals that NMC is an extremely rare cancer, and most patients remain undiagnosed. Furthermore, this review outlines the clinical characteristics of NMC of the thorax and the prospects for its treatment.
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Affiliation(s)
- Ayae Saiki
- Department of Respiratory Medicine, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Keita Sakamoto
- Department of Respiratory Medicine, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Yuan Bee
- Department of Pathology, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Takehiro Izumo
- Department of Respiratory Medicine, Japanese Red Cross Medical Center, Tokyo, Japan
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7
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Lantuejoul S, Pissaloux D, Ferretti GR, McLeer A. NUT carcinoma of the lung. Semin Diagn Pathol 2021; 38:72-82. [PMID: 34176698 DOI: 10.1053/j.semdp.2021.06.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 06/05/2021] [Accepted: 06/07/2021] [Indexed: 11/11/2022]
Abstract
NUT carcinoma of the thorax is a rare and very aggressive tumor, whose definition is based on the demonstration of a nuclear protein in testis (NUTM1; also known as NUT) gene fusion on 15q14 with different partners from the bromodomain-containing proteins gene family. This fusion results in an activation of MYC oncoprotein responsible for the tumor's aggressivity. NUT carcinoma arises preferentially in young adults, presenting a large thoracic mass frequently associated with lymph nodes, bone or pleural metastases. At histology, this tumor is often poorly differentiated, mainly composed of sheets of small cells with scant cytoplasm, a round nucleus with a central nucleolus. Focal areas of squamous differentiation can be observed. Mitoses and necrosis are frequent, as well as neutrophilic infiltrate. The diagnosis is based on the detection of NUT protein expression by immunohistochemistry using the rabbit monoclonal antibody C52B1 in more than 50% of the tumor nuclei. This technique offers 87% sensitivity and nearly 100% specificity with reference to FISH or RT-PCR, which confirm the NUTM1 rearrangement. The differential diagnoses include basaloid carcinoma of the lung, small cell carcinoma, thymic carcinoma (basaloid variant), SMARCA4_deficient thoracic sarcoma, other NUTM1 rearranged undifferentiated tumors, small round cell tumors, non-Hodgkin lymphoma/leukemia, and melanoma. The prognosis of NUT carcinoma remains very poor, with a median survival of 6.7 months, and 1- and 2-year overall survival rates of 30% and 19%, respectively. NUT carcinoma is often refractory to conventional chemotherapy, but ifosfamide-based regimens or BET inhibitors could represent promising therapies.
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Affiliation(s)
- Sylvie Lantuejoul
- Centre Léon Bérard, Department of biopathology, 28 rue Laënnec, 69373 Lyon, France; University of Grenoble Alpes, F-38000, Grenoble, France; Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Lyon, France.
| | - Daniel Pissaloux
- Centre Léon Bérard, Department of biopathology, 28 rue Laënnec, 69373 Lyon, France; Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Lyon, France
| | - Gilbert R Ferretti
- University of Grenoble Alpes, F-38000, Grenoble, France; CHU Grenoble-Alpes, Department of radiology, 38043 Grenoble, France; Institute for Advanced Biosciences, CNRS UMR5309, Inserm U1209, Grenoble Alpes, University F-38000, Grenoble, France
| | - Anne McLeer
- University of Grenoble Alpes, F-38000, Grenoble, France; CHU Grenoble-Alpes, Department of pathology, 38043 Grenoble, France; Institute for Advanced Biosciences, CNRS UMR5309, Inserm U1209, Grenoble Alpes, University F-38000, Grenoble, France
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8
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Lee EY, Winant AJ. Invited Commentary: New Paradigm for Imaging Evaluation of Pediatric Mediastinal Masses-ITMIG Classification System. Radiographics 2021; 41:E123-E125. [PMID: 34086499 DOI: 10.1148/rg.2021210015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Edward Y Lee
- From the Department of Radiology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115
| | - Abbey J Winant
- From the Department of Radiology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115
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9
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NUT Midline Carcinoma of the Lung: Computed Tomography Findings in 10 Patients. J Comput Assist Tomogr 2021; 45:330-336. [PMID: 33661151 DOI: 10.1097/rct.0000000000001133] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE The aim of the study was to evaluate computed tomography (CT) findings of pulmonary NUT midline carcinoma. METHODS We assessed clinical and CT features of pulmonary NUT carcinoma in 10 consecutive patients (M:F, 7:3; mean, 39 years). RESULTS The primary tumors (size range, 15-65 mm) manifested as either a peripheral tumor (5/10) or a central tumor (5/10). All tumors showed relatively low-attenuation at contrast-enhanced CT (mean net enhancement, 26 HU). Associated CT findings were metastatic hilar or mediastinal lymphadenopathy (8/10), ipsilateral pleural seeding with malignant pleural effusion (2/10), and distant metastasis (2/10). Five patients with low tumor-node-metastasis stages after optimal treatment showed no evidence of disease (50%) for 6 to 35 months. CONCLUSIONS Pulmonary NUT carcinoma presented as a peripheral or a central lung mass showing mild degree of contrast enhancement, frequent metastatic regional lymphadenopathy, affecting relatively young adults. Although known to be highly aggressive, an early diagnosis in low TNM stages can lead to a favorable prognosis.
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10
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Saik WN, Da Forno P, Thway K, Khurram SA. NUT Carcinoma Arising from the Parotid Gland: A Case Report and Review of the Literature. Head Neck Pathol 2020; 15:1064-1068. [PMID: 33351171 PMCID: PMC8384986 DOI: 10.1007/s12105-020-01254-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 11/17/2020] [Indexed: 02/06/2023]
Abstract
NUT carcinoma is an aggressive carcinoma with an overall poor survival outcome. The mediastinum and head and neck area, especially the sinonasal region, are among the common sites of disease. Histopathological diagnosis of NUT carcinoma is often very challenging due to its overlapping features with other poorly differentiated carcinomas. We report a case of NUT carcinoma arising from the parotid gland of a young female patient. Primary NUT carcinoma of salivary gland is very rare, with only 15 such cases reported in the literature to date. Our case highlights the diagnostic challenges associated with such lesions.
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Affiliation(s)
- Wei-Ning Saik
- Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, 19 Claremont Crescent, Sheffield, S10 2TA UK
| | - Philip Da Forno
- Department of Histopathology, Leicester Royal Infirmary, University Hospitals of Leicester, Leicester, UK
| | - Khin Thway
- Head and Neck Unit; Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London, UK
| | - Syed Ali Khurram
- Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, 19 Claremont Crescent, Sheffield, S10 2TA UK ,Head and Neck Unit; Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London, UK
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11
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Virarkar M, Saleh M, Ramani NS, Morani AC, Bhosale P. Imaging spectrum of NUT carcinomas. Clin Imaging 2020; 67:198-206. [PMID: 32866821 DOI: 10.1016/j.clinimag.2020.07.025] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 07/03/2020] [Accepted: 07/23/2020] [Indexed: 12/22/2022]
Abstract
Nuclear protein of the testis (NUT) carcinoma (NC) (formerly known as NUT midline carcinoma) is an aggressive pleomorphic squamous cell carcinoma with a dismal prognosis. Primary NC tumors are commonly located in the chest or head and neck regions. Imaging plays an indispensable role in the staging, management, treatment response assessment, and surveillance of NC. Primary pulmonary NC usually presents as a large mass with lymphadenopathy and pleural involvement. Primary head and neck NC presents as a large expansile necrotic mass in the sinonasal region with locoregional destruction and occasional cervical lymph node involvement. These imaging features are relatively non-specific but are consistent among patients. Currently, there are no standardized guidelines for the treatment of NC. Because of its rarity, paucity of reports in the medical literature, and the lack of awareness among radiologists, NUT carcinoma (NC) has been largely underdiagnosed and misdiagnosed. Clinical aggressive features and pleomorphic/undifferentiated squamous cell carcinoma should prompt genetic evaluation for NUT translocation to diagnose NC. In this article, we discuss NC's clinicopathologic and imaging features and treatment options, including emerging new treatments.
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Affiliation(s)
- Mayur Virarkar
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
| | - Mohammed Saleh
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America
| | - Nisha Subhashchandra Ramani
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America
| | - Ajaykumar C Morani
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America
| | - Priya Bhosale
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America
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12
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Huang QW, He LJ, Zheng S, Liu T, Peng BN. An Overview of Molecular Mechanism, Clinicopathological Factors, and Treatment in NUT Carcinoma. BIOMED RESEARCH INTERNATIONAL 2019; 2019:1018439. [PMID: 31815119 PMCID: PMC6877965 DOI: 10.1155/2019/1018439] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Accepted: 10/15/2019] [Indexed: 12/13/2022]
Abstract
NUT carcinoma (NC) is a rare and poorly differentiated tumor, with highly aggressive and fatal neoplasm. NC is characterized by chromosomal rearrangement involving NUTM1 gene, but lack of specific clinical and histomorphological features. It is more common in midline anatomic sites, such as head and neck, mediastinum, and other midline organs. NC may occur at any age, but mainly in children and young adults. In addition, male and female are equally affected. Most clinicians lack a clear understanding of the disease, and NC diagnostic reagents are still not widely used; therefore, misdiagnosis often occurs in clinic. Due to the highly aggressive nature of the disease and the insensitivity to nonspecific chemotherapy or radiotherapy, many patients have died before the confirmation of NC. In fact, the true incidence of NC is much higher than the current statistics. In recent years, targeted therapy for NC has also made some progress. This article aims to summarize the molecular mechanisms, clinicopathological characteristics, and treatment of NC.
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Affiliation(s)
- Qian W. Huang
- Department of Medical Oncology, People's Hospital of Boluo County, Huizhou 516000, China
| | - Li J. He
- Department of Medical Oncology, People's Hospital of Liaoning Province, Shenyang 110000, China
| | - Shuang Zheng
- Department of Medical Oncology, People's Hospital of Liaoning Province, Shenyang 110000, China
| | - Tao Liu
- Department of Orthopaedics, People's Hospital of Gaotang County, Liaocheng 252000, China
| | - Bei N. Peng
- Dalian Medical University, Dalian 116000, China
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13
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Lichtenberger JP, Biko DM, Carter BW, Pavio MA, Huppmann AR, Chung EM. Primary Lung Tumors in Children: Radiologic-Pathologic Correlation From the Radiologic Pathology Archives. Radiographics 2019; 38:2151-2172. [PMID: 30422774 DOI: 10.1148/rg.2018180192] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Primary lung tumors in children are rare, with a narrow range of diagnostic considerations. However, the overlapping imaging appearances of these tumors necessitate attention to key discriminating imaging and pathologic features. In the neonate and infant, the important considerations include pleuropulmonary blastoma (PPB), infantile fibrosarcoma, and fetal lung interstitial tumor. Among these tumors, imaging findings such as air-filled cysts in type 1 PPB and homogeneously low attenuation of fetal lung interstitial tumors are relatively specific. Key pathologic and genetic discriminators among this group of tumors include the DICER1 germline mutation found in PPB and the t(12,15)(p13;q25) translocation and ETV6-NTRK3 fusion gene seen in infantile fibrosarcoma. Primary lung tumors in older children include inflammatory myofibroblastic tumors (IMTs), carcinoid salivary gland-type tumors of the lung, recurrent respiratory papillomatosis, and other rare entities. IMT, a spindle-cell proliferation with inflammatory elements, is the most common lung tumor in children. Anaplastic lymphoma kinase, a receptor-type protein tyrosine kinase, is present in 50% of these tumors, and this finding may support an imaging diagnosis of IMT. Carcinoid tumors account for a substantial portion of childhood lung tumors, and their characteristic avid enhancement on images corresponds to the compressed fibrovascular stroma histologically. Furthermore, novel imaging agents used with somatostatin receptor analogs have an emerging role in the evaluation of carcinoid tumors. Although less common than mucoepidermoid carcinoma, adenoid cystic carcinoma tends to recur given the perineural spread seen histologically. Integrating radiologic and pathologic knowledge is critical to accurate diagnosis, treatment planning, and surveillance of primary lung tumors in children.
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Affiliation(s)
- John P Lichtenberger
- From the Department of Radiology and Radiological Sciences (J.P.L., E.M.C.) and Department of Pathology (J.P.L., A.R.H., E.M.C.), Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814; Thoracic Radiology Section (J.P.L., D.M.B.) and Pediatric Radiology Section (D.M.B., E.M.C.), American Institute for Radiologic Pathology, Silver Spring, Md; Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pa (D.M.B.); Department of Diagnostic Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, Tex (B.W.C.); and Department of Radiology, Walter Reed National Military Medical Center, Bethesda, Md (M.A.P.)
| | - David M Biko
- From the Department of Radiology and Radiological Sciences (J.P.L., E.M.C.) and Department of Pathology (J.P.L., A.R.H., E.M.C.), Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814; Thoracic Radiology Section (J.P.L., D.M.B.) and Pediatric Radiology Section (D.M.B., E.M.C.), American Institute for Radiologic Pathology, Silver Spring, Md; Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pa (D.M.B.); Department of Diagnostic Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, Tex (B.W.C.); and Department of Radiology, Walter Reed National Military Medical Center, Bethesda, Md (M.A.P.)
| | - Brett W Carter
- From the Department of Radiology and Radiological Sciences (J.P.L., E.M.C.) and Department of Pathology (J.P.L., A.R.H., E.M.C.), Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814; Thoracic Radiology Section (J.P.L., D.M.B.) and Pediatric Radiology Section (D.M.B., E.M.C.), American Institute for Radiologic Pathology, Silver Spring, Md; Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pa (D.M.B.); Department of Diagnostic Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, Tex (B.W.C.); and Department of Radiology, Walter Reed National Military Medical Center, Bethesda, Md (M.A.P.)
| | - Michael A Pavio
- From the Department of Radiology and Radiological Sciences (J.P.L., E.M.C.) and Department of Pathology (J.P.L., A.R.H., E.M.C.), Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814; Thoracic Radiology Section (J.P.L., D.M.B.) and Pediatric Radiology Section (D.M.B., E.M.C.), American Institute for Radiologic Pathology, Silver Spring, Md; Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pa (D.M.B.); Department of Diagnostic Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, Tex (B.W.C.); and Department of Radiology, Walter Reed National Military Medical Center, Bethesda, Md (M.A.P.)
| | - Alison R Huppmann
- From the Department of Radiology and Radiological Sciences (J.P.L., E.M.C.) and Department of Pathology (J.P.L., A.R.H., E.M.C.), Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814; Thoracic Radiology Section (J.P.L., D.M.B.) and Pediatric Radiology Section (D.M.B., E.M.C.), American Institute for Radiologic Pathology, Silver Spring, Md; Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pa (D.M.B.); Department of Diagnostic Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, Tex (B.W.C.); and Department of Radiology, Walter Reed National Military Medical Center, Bethesda, Md (M.A.P.)
| | - Ellen M Chung
- From the Department of Radiology and Radiological Sciences (J.P.L., E.M.C.) and Department of Pathology (J.P.L., A.R.H., E.M.C.), Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814; Thoracic Radiology Section (J.P.L., D.M.B.) and Pediatric Radiology Section (D.M.B., E.M.C.), American Institute for Radiologic Pathology, Silver Spring, Md; Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pa (D.M.B.); Department of Diagnostic Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, Tex (B.W.C.); and Department of Radiology, Walter Reed National Military Medical Center, Bethesda, Md (M.A.P.)
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14
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Storck S, Kennedy AL, Marcus KJ, Teot L, Vaughn J, Gnekow AK, Märkl B, Leuschner I, DuBois SG, French CA, Frühwald MC. Pediatric NUT-midline carcinoma: Therapeutic success employing a sarcoma based multimodal approach. Pediatr Hematol Oncol 2017; 34:231-237. [PMID: 29040054 DOI: 10.1080/08880018.2017.1363839] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
A subset of poorly differentiated squamous cell carcinomas, NUT midline carcinomas (NMC) are characterized by a translocation t(15;19)(q13;p13) [ 1 ]. The prognosis is generally dismal [ 2 ] and therapeutic success has been limited to exceptional cases [ 3 ]. We present two cases of pediatric NMC from two different institutions treated according to a multimodal sarcoma approach involving surgery, chemotherapy, and focal radiotherapy. One patient has remained in complete continuous remission for over 6 years, while the other is in CR in early follow-up off therapy. Our proposed multimodal strategy apparently meets the aggressive biologic nature of NMC and should be considered for further evaluation in this context potentially in the setting of a clinical trial.
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Affiliation(s)
- Simone Storck
- a Swabian Children's Cancer Centre , Children's Hospital Augsburg , Augsburg , Germany
| | - Alyssa L Kennedy
- f Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School , Boston , USA
| | - Karen J Marcus
- g Dana-Farber/Boston Children's Cancer and Blood Disorders Center , Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School , Boston USA
| | - Lisa Teot
- e Department of Pathology , Boston Children's Hospital, Harvard Medical School , Boston , USA
| | - Jennifer Vaughn
- h Department of Radiology, Boston Children's Hospital, Harvard Medical School , Boston , USA
| | - Astrid K Gnekow
- a Swabian Children's Cancer Centre , Children's Hospital Augsburg , Augsburg , Germany
| | - Bruno Märkl
- b Department of Pathology , Klinikum Augsburg , Augsburg , Germany
| | - Ivo Leuschner
- c Department of Pediatric Pathology , University Hospital of Schleswig-Holstein , Kiel , Germany (deceased)
| | - Steven G DuBois
- f Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School , Boston , USA
| | - Christopher A French
- d Department of Pathology , Brigham and Women's Hospital, Harvard Medical School , Boston , USA
| | - Michael C Frühwald
- a Swabian Children's Cancer Centre , Children's Hospital Augsburg , Augsburg , Germany
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15
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Kundra A, Andrei M, Westra W, Chaudhry R, Moussouris H, Gohari A, Wang JC. Nuclear protein in testis midline carcinoma of larynx: An underdiagnosed entity. Head Neck 2016; 38:E2471-4. [DOI: 10.1002/hed.24418] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Accepted: 12/30/2015] [Indexed: 11/07/2022] Open
Affiliation(s)
- Ajay Kundra
- Division of Hematology and Oncology; Brookdale University Hospital and Medical Center; Brooklyn New York
| | - Mirela Andrei
- Division of Hematology and Oncology; Brookdale University Hospital and Medical Center; Brooklyn New York
| | - William Westra
- Division of Pathology, Oncology, and Otolaryngology/Head and Neck Surgery; The Johns Hopkins Medical Institutions; Baltimore Maryland
| | - Rashid Chaudhry
- Division of Otolaryngology/Head and Neck Surgery; Brookdale University Hospital and Medical Center; Brooklyn New York
| | - Harry Moussouris
- Division of Pathology; Brookdale University Hospital and Medical Center; Brooklyn New York
| | - Arash Gohari
- Division of Radiology; Brookdale University Hospital and Medical Center; Brooklyn New York
| | - Jen C. Wang
- Division of Hematology and Oncology; Brookdale University Hospital and Medical Center; Brooklyn New York
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16
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Imaging Evaluation of Mediastinal Masses in Children and Adults: Practical Diagnostic Approach Based on A New Classification System. J Thorac Imaging 2016; 30:247-67. [PMID: 26086589 DOI: 10.1097/rti.0000000000000161] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
A compartmental approach to the diagnosis of the mediastinal masses in children and adults has been widely used to facilitate the diagnosis and planning of diagnostic interventions and surgical treatment for many years. Recently, a new computed tomography-based mediastinal division scheme, approved by the International Thymic Malignancy Interest Group, has received considerable attention as a potential new standard. In this review article, this new computed tomography-based mediastinal division scheme is described and illustrated. In addition, currently used imaging modalities and techniques, practical imaging algorithm of evaluating mediastinal masses, and characteristic imaging findings of various mediastinal masses that occur in children and adults are discussed. Such up-to-date knowledge has the potential to facilitate better understanding of mediastinal masses in both pediatric and adult populations.
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17
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Intrapericardial NUT Midline Carcinoma: Unusual Presentation of a Rare Tumor and Literature Review with Management Considerations. Pediatr Cardiol 2016; 37:208-11. [PMID: 26667959 DOI: 10.1007/s00246-015-1313-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Accepted: 11/21/2015] [Indexed: 10/22/2022]
Abstract
Rearrangements in the nuclear protein in testis (NUT) gene cause carcinomas that represent a rare but aggressive tumor type that often present at advanced stages in midline structures. Survival rarely exceeds 12 months from the time of diagnosis. There have been no reports of a primary cardiac presentation, and few studies have reported on the numerous treatment strategies. Given their aggressive and invasive nature, NUT midline carcinomas present a therapeutic dilemma. Treatment may include surgical resection, chemotherapy, or radiotherapy, but no consistently successful treatment has been established. Surgical resection is indicated to reduce symptomatic mass effect whenever present. Novel therapies with bromodomain extra-terminal inhibitors may be associated with potential survival benefit. Here, we describe an unusual presentation of this tumor. Literature review with management considerations is underlying.
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18
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Harms A, Herpel E, Pfarr N, Penzel R, Heussel CP, Herth FJF, Dienemann H, Weichert W, Warth A. NUT carcinoma of the thorax: Case report and review of the literature. Lung Cancer 2015; 90:484-91. [PMID: 26490121 DOI: 10.1016/j.lungcan.2015.10.001] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Revised: 09/14/2015] [Accepted: 10/03/2015] [Indexed: 12/22/2022]
Abstract
NUT (nuclear protein in testis) carcinomas are exceedingly rare neoplasms with specific molecular alterations and often follow a devastating course. Thus, a precise early diagnosis is of utmost importance. Known from the sinonasal region for years, the new 2015 WHO classification now also recognizes the existence of this entity in the thorax, specifically the lungs and the mediastinum. However, yet available data on this entity are sparse. Here, we report on a 31 years old female patient with an aggressively growing tumor localized in the median line that was initially sampled by endobronchial ultrasound-guided transbronchial biopsies. Pathological assessment of the biopsy specimens revealed a NUT carcinoma with typical morphological characteristics and an uncommon NUT translocation variant with a NSD3-NUT fusion. Diagnosis was further confirmed in the subsequent resection specimen. We describe specific clinical, histomorphological, and molecular characteristics of this tumor and provide a comprehensive review of the current literature on these rare neoplasms.
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Affiliation(s)
- Alexander Harms
- Institute of Pathology, University Hospital Heidelberg, Germany
| | - Esther Herpel
- Institute of Pathology, University Hospital Heidelberg, Germany
| | - Nicole Pfarr
- Institute of Pathology, University Hospital Heidelberg, Germany
| | - Roland Penzel
- Institute of Pathology, University Hospital Heidelberg, Germany
| | - Claus-Peter Heussel
- Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik at Heidelberg University, Germany; Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Germany
| | - Felix J F Herth
- Department of Pneumology and Respiratory Critical Care Medicine, Thoraxklinik at Heidelberg University, Germany
| | - Hendrik Dienemann
- Department of Thoracic Surgery, Thoraxklinik at Heidelberg University, Germany
| | - Wilko Weichert
- Institute of Pathology, University Hospital Heidelberg, Germany; National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Arne Warth
- Institute of Pathology, University Hospital Heidelberg, Germany.
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19
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Demystifying NUT midline carcinoma: radiologic and pathologic correlations of an aggressive malignancy. AJR Am J Roentgenol 2014; 203:W391-9. [PMID: 25247968 DOI: 10.2214/ajr.13.12401] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE NUT midline carcinoma is a rare poorly differentiated aggressive subtype of squamous cell carcinoma. To date, fewer than 100 total cases have been reported. CONCLUSION Given the rarity of this disease process and lack of pathognomonic imaging findings, a definitive diagnosis based solely on imaging findings alone is untenable. Select cases are used to emphasize the particularly infiltrative and aggressive nature of NUT midline carcinoma, which shows a complete disregard for normal tissue boundaries and rapid progression during brief intervals.
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20
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Mills AF, Lanfranchi M, Wein RO, Mukand-Cerro I, Pilichowska M, Cowan J, Bedi H. NUT midline carcinoma: a case report with a novel translocation and review of the literature. Head Neck Pathol 2013; 8:182-6. [PMID: 23912933 PMCID: PMC4022924 DOI: 10.1007/s12105-013-0479-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2013] [Accepted: 07/16/2013] [Indexed: 11/26/2022]
Abstract
NUT midline carcinoma (NMC) is a rare, genetically defined, highly lethal undifferentiated carcinoma occurring in the midline location of the neck, head or mediastinum. We present the case of a 23 year-old otherwise healthy Chinese male immigrant who presented with complaints of sore throat and right sided neck mass. The initial treatment was for likely EBV infection with streptococcal superinfection. Although continued investigation was pursued shortly after initial presentation, the mass had enlarged and become necrotic with significant nodal involvement. The mass was diagnosed as an NMC tumor with a novel three-way translocation t(9;15;19; q34;q13;p13.1). Despite aggressive treatment, the patient's condition progressed rapidly and he died within 3 months of initial diagnosis. Standard therapeutic interventions have been ineffective in the treatment of NMC. Earlier diagnosis could allow characterization of the natural progression of this entity, and allow more time for intervention or development of novel therapies, potentially related to molecular targets. This continues to require a high index of suspicion and early imaging with cytogenetic and immunohistochemical confirmation.
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Affiliation(s)
- Andrew F Mills
- Tufts University School of Medicine, 145 Harrison Ave, Boston, MA, 02111, USA,
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21
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Bauer DE, Mitchell CM, Strait KM, Lathan CS, Stelow EB, Lüer SC, Muhammed S, Evans AG, Sholl LM, Rosai J, Giraldi E, Oakley RP, Rodriguez-Galindo C, London WB, Sallan SE, Bradner JE, French CA. Clinicopathologic features and long-term outcomes of NUT midline carcinoma. Clin Cancer Res 2012; 18:5773-9. [PMID: 22896655 DOI: 10.1158/1078-0432.ccr-12-1153] [Citation(s) in RCA: 283] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer characterized by rearrangement of the NUT gene. Research advances have provided opportunities for targeted therapy in NMC, yet the clinical features of this rare disease have not been systematically characterized. We report on a large population of such patients to identify the disease characteristics and treatments, correlate them with outcome, and to consider clinical recommendations. EXPERIMENTAL DESIGN A clinical database was established using retrospective demographic and outcomes data available on all known cases of NMC. Questionnaires were completed by treating physicians. Pathologic, demographic, and clinical variables were assessed for 63 patients, the largest cohort of patients with NMC studied to date. Outcome data from 54 patients were available for survival analyses. RESULTS The diagnosis of NMC has increased annually since 2007. Since 2009, there has been an observed increase in the age at diagnosis (P < 0.05). Geographic distribution of patients with NMC has been concentrated in the United States (n = 41, 65%). The median overall survival for patients with NMC was 6.7 months. The 2-year progression-free survival (PFS) was 9% with a 95% confidence interval (CI) of 1% to 17% [1-year PFS 15% (5-24%) and 2-year overall survival (OS) was 19% with a 95% CI of 7%-31% (1-year OS: 30% (27-34%)]. Multivariate analysis suggested that extent of surgical resection and initial radiotherapy were independent predictors of PFS and OS. Notably, no chemotherapeutic regimen was associated with improved outcome. CONCLUSIONS NMC portends a poor prognosis among all squamous cell neoplasms and seems to be frequently unrecognized. The finding that conventional chemotherapy has been inadequate indicates a pressing need for the development of targeted therapeutics. Intensive local therapies such as gross total resection and radiotherapy might be associated with enhanced survival.
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Affiliation(s)
- Daniel E Bauer
- Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Hematology/Oncology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
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22
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Fang W, French CA, Cameron MJ, Han Y, Liu H. Clinicopathological significance of NUT rearrangements in poorly differentiated malignant tumors of the upper respiratory tract. Int J Surg Pathol 2012; 21:102-10. [PMID: 22777717 DOI: 10.1177/1066896912451651] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Nuclear protein in testis (NUT) midline carcinoma (NMC) is a highly malignant carcinoma originating from the midline of the body. This study investigated the clinicopathological significance of NUT rearrangements in poorly differentiated malignant tumors (PDMTs) of the upper-respiratory tract (URT) in China. The clinical and pathological features of 155 PDMTs of the URT were reviewed. Epstein-Barr virus (EBV)-encoded RNA and NUT were investigated by in situ hybridization and immunohistochemistry (IHC), respectively. NUT-positive cases were examined by fluorescence in situ hybridization (FISH) and immunohistochemical staining with a set of cytokeratins (CKs) and neuroendocrine markers. One case was observed by transmission electron microscopy. Four cases of poorly differentiated squamous cell carcinomas and sinonasal undifferentiated carcinomas were diffuse positive for NUT by IHC and also stained for antibodies to CKs and P63 but were negative for neuroendocrine markers. Only 2 of these 4 cases showed rearrangements of the NUT and BRD4 genes by FISH; both these patients died within 12 months. The remaining 2 patients showed no NUT rearrangement by FISH and did not have an aggressive clinical course. NMC is a rare, poorly differentiated carcinoma, which occurs most often in midline organs, and in this first series from China, affected the sinonasal tract of older adults and was not associated with EBV infection. Determination of NUT protein expression and gene rearrangement can allow the differentiation of NMC from other URT PDMTs. The authors suggest that molecular determination of NUT gene rearrangements should therefore represent the gold standard for NMC diagnosis.
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Affiliation(s)
- Wei Fang
- Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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23
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Rosenbaum DG, Teruya-Feldstein J, Price AP, Meyers P, Abramson S. Radiologic features of NUT midline carcinoma in an adolescent. Pediatr Radiol 2012; 42:249-52. [PMID: 22057302 DOI: 10.1007/s00247-011-2288-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2011] [Revised: 09/29/2011] [Accepted: 10/05/2011] [Indexed: 12/17/2022]
Abstract
We present a case of NUT midline carcinoma (NMC) mimicking lymphoma in an adolescent boy, with attention to multidetector CT appearance and pattern of metastasis on [F-18]2-fluoro-2-deoxyglucose positron emission tomography (FDG PET/CT). Few case reports have focused on the imaging characteristics of this rare tumor in the pediatric imaging literature. A newly described but increasingly recognized disease entity, NMC should enter the differential of pediatric midline tumors displaying particularly aggressive characteristics on imaging.
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Affiliation(s)
- Daniel G Rosenbaum
- Department of Radiology, New York-Presbyterian Hospital/Weill Cornell Medical Center, 525 E. 68th St., Box 141, New York, NY 10065, USA.
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24
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NUT midline carcinoma: an imaging case series and review of literature. Pediatr Radiol 2012; 42:205-10. [PMID: 22033856 DOI: 10.1007/s00247-011-2272-3] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2011] [Revised: 09/02/2011] [Accepted: 09/12/2011] [Indexed: 10/16/2022]
Abstract
BACKGROUND NUT midline carcinoma is a rare and aggressive tumor that has primarily been reported in children and young adults. The tumor is characterized by a rearrangement on the nuclear protein in testis (NUT) gene, located on chromosome 15q14, resulting in the BRD4-NUT fusion oncogene. This carcinoma most commonly presents in the midline and displays an invariably lethal clinical course. OBJECTIVE To highlight the imaging features of NUT midline carcinoma. MATERIALS AND METHODS IRB approval was obtained for chart review. We retrospectively reviewed the chart and imaging studies of three children. All three cases were diagnosed by karyotyping and confirmed by fluorescence in situ hybridization (FISH). Cross-sectional imaging including CT, MRI and, in one patient, PET was available for review. RESULTS Two out of three children presented with midline and multifocal disease. The third case had a medial left thigh mass and no metastatic disease at initial presentation. The common imaging features include heterogeneous low density on CT and T1 hypointensity and low-level T2 hyperintensity on MRI with heterogeneous enhancement. All cases were confirmed pathologically and by molecular studies. CONCLUSION NUT midline carcinoma usually presents in the midline, either in the head, neck or chest. We present three cases with the bulk of the tumor below the diaphragm, which is seen in the minority of patients with NUT midline carcinoma, according to the available literature. Metastatic disease is common at initial presentation and can be quite extensive. The most striking feature of this disease is its aggressive nature with exponential interval growth of tumor.
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25
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26
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Abstract
Nut midline carcinomas are uncommon carcinomas characterized by chromosomal rearrangements that involve the gene encoding the nuclear protein of the testis (NUT). This article reviews the clinicopathologic features of these malignancies. Ancillary testing is discussed as well as the pathologic differential diagnosis.
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Affiliation(s)
- Edward B. Stelow
- Dept of Pathology, UVA Health System, University of Virginia, Jefferson Park Ave., Box 800214, Charlottesville, VA 22908 USA
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