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1
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Möller K, Gulzar T, Lennartz M, Viehweger F, Kluth M, Hube-Magg C, Bernreuther C, Bawahab AA, Simon R, Clauditz TS, Sauter G, Schlichter R, Hinsch A, Kind S, Jacobsen F, Burandt E, Frost N, Reck M, Marx AH, Krech T, Lebok P, Fraune C, Steurer S. TTF-1 is a highly sensitive but not fully specific marker for pulmonary and thyroidal cancer: a tissue microarray study evaluating more than 17,000 tumors from 152 different tumor entities. Virchows Arch 2024; 485:815-828. [PMID: 39377914 PMCID: PMC11564378 DOI: 10.1007/s00428-024-03926-1] [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: 08/20/2024] [Revised: 08/20/2024] [Accepted: 09/06/2024] [Indexed: 10/09/2024]
Abstract
Thyroid transcription factor 1 (TTF-1) immunohistochemistry (IHC) is routinely used for the distinction of primary pulmonary adenocarcinomas. However, TTF-1 can also occur in other malignancies. A tissue microarray containing 17,772 samples from 152 different tumor types was analyzed. Napsin-A, CK20, SATB2, FABP1, and Villin-1 IHC data were available from previous studies. TTF-1 staining was seen in 82 of 152 tumor categories including thyroidal cancers (19-100%), adenocarcinomas (94%), neuroendocrine tumors (67%) of the lung, small cell neuroendocrine carcinomas (71-80%), mesenchymal tumors (up to 42%), and thymomas (39%). Comparative analysis of TTF-1 and Napsin-A revealed a sensitivity/specificity of 94%/86% (TTF-1), 87%/98% (Napsin-A), and 85%/99.1% (TTF-1 and Napsin-A) for the distinction of pulmonary adenocarcinomas. Combined analysis of TTF-1 and enteric markers revealed a positivity for TTF-1 and at least one enteric marker in 22% of pulmonary adenocarcinomas but also a TTF-1 positivity in 6% of colorectal, 2% of pancreatic, and 3% of gastric adenocarcinomas. TTF-1 is a marker of high sensitivity but insufficient specificity for pulmonary adenocarcinomas. A small fraction of TTF-1-positive gastrointestinal adenocarcinomas represents a pitfall mimicking enteric-type pulmonary adenocarcinoma. Combined analysis of TTF-1 and Napsin-A improves the specificity of pulmonary adenocarcinoma diagnosis.
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Affiliation(s)
- Katharina Möller
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Tayyaba Gulzar
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Maximilian Lennartz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Florian Viehweger
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Martina Kluth
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Claudia Hube-Magg
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Christian Bernreuther
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Ahmed Abdulwahab Bawahab
- Department of Basic Medical Sciences, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia
| | - Ronald Simon
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
| | - Till S Clauditz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Guido Sauter
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Ria Schlichter
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Andrea Hinsch
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Simon Kind
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Frank Jacobsen
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Eike Burandt
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Nikolaj Frost
- Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Martin Reck
- Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany
| | - Andreas H Marx
- Department of Pathology, Academic Hospital Fuerth, Fuerth, Germany
| | - Till Krech
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
- Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany
| | - Patrick Lebok
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
- Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany
| | - Christoph Fraune
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
- Department of Pathology, Academic Hospital Fuerth, Fuerth, Germany
| | - Stefan Steurer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
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2
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Singh A, Kumar G, Singh US, Sagar M. Large cell neuroendocrine carcinoma of oral cavity: A rare case report with review of literature. J Oral Maxillofac Pathol 2024; 28:474-477. [PMID: 39670137 PMCID: PMC11633935 DOI: 10.4103/jomfp.jomfp_522_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 08/03/2024] [Accepted: 08/08/2024] [Indexed: 12/14/2024] Open
Abstract
Neuroendocrine tumours (NETs) primarily affect the lungs and larynx. Primary neuroendocrine carcinomas (NECs) rarely occur in the oral cavity. The classification of these tumours is ambiguous; however, the literature acknowledges their aggressiveness. Merkel cell carcinoma (MCC) is rare and more common in the skin but could occur intraorally. MCC and NECs are aggressive neoplasms and recommend intensive treatment. In this case report, a 22-year-old female presented with an ulceroinfiltrative lesion in the left buccal mucosa of the cheek, which was diagnosed as primary NEC in the oral cavity. This patient underwent wide local lesion excision of oral cavity mass, ipsilateral selective neck node dissection of levels 1-4 and postoperative chemotherapy. This aggressive tumour type requires large local excisions with margins like Merkel cell skin carcinomas. To our knowledge, this is the youngest oral cavity primary neuroendocrine cancer patient to date in the literature.
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Affiliation(s)
- Anurag Singh
- Department of Pathology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Gulshan Kumar
- Department of Pathology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Uma S. Singh
- Department of Pathology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Mala Sagar
- Department of Pathology, King George Medical University, Lucknow, Uttar Pradesh, India
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3
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Chowdhary S, Deka R, Panda K, Kumar R, Solomon AD, Das J, Kanoujiya S, Gupta AK, Sinha S, Ruokolainen J, Kesari KK, Gupta PK. Recent Updates on Viral Oncogenesis: Available Preventive and Therapeutic Entities. Mol Pharm 2023; 20:3698-3740. [PMID: 37486263 PMCID: PMC10410670 DOI: 10.1021/acs.molpharmaceut.2c01080] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 06/13/2023] [Accepted: 06/14/2023] [Indexed: 07/25/2023]
Abstract
Human viral oncogenesis is a complex phenomenon and a major contributor to the global cancer burden. Several recent findings revealed cellular and molecular pathways that promote the development and initiation of malignancy when viruses cause an infection. Even, antiviral treatment has become an approach to eliminate the viral infections and prevent the activation of oncogenesis. Therefore, for a better understanding, the molecular pathogenesis of various oncogenic viruses like, hepatitis virus, human immunodeficiency viral (HIV), human papillomavirus (HPV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV), could be explored, especially, to expand many potent antivirals that may escalate the apoptosis of infected malignant cells while sparing normal and healthy ones. Moreover, contemporary therapies, such as engineered antibodies antiviral agents targeting signaling pathways and cell biomarkers, could inhibit viral oncogenesis. This review elaborates the recent advancements in both natural and synthetic antivirals to control viral oncogenesis. The study also highlights the challenges and future perspectives of using antivirals in viral oncogenesis.
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Affiliation(s)
- Shivam Chowdhary
- Department
of Industrial Microbiology, Sam Higginbottom
University of Agriculture, Technology and Sciences, Prayagraj 211007, Uttar Pradesh India
| | - Rahul Deka
- Department
of Bioengineering and Biotechnology, Birla
Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India
| | - Kingshuk Panda
- Department
of Applied Microbiology, Vellore Institute
of Technology, Vellore 632014, Tamil Nadu, India
| | - Rohit Kumar
- Department
of Life Sciences, Sharda School of Basic Sciences and Research, Sharda University, Greater Noida 201310, Uttar Pradesh, India
| | - Abhishikt David Solomon
- Department
of Molecular & Cellular Engineering, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj 211007, Uttar Pradesh, India
| | - Jimli Das
- Centre
for
Biotechnology and Bioinformatics, Dibrugarh
University, Assam 786004, India
| | - Supriya Kanoujiya
- School
of
Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India
| | - Ashish Kumar Gupta
- Department
of Biophysics, All India Institute of Medical
Sciences, New Delhi 110029, India
| | - Somya Sinha
- Department
of Biotechnology, Graphic Era Deemed to
Be University, Dehradun 248002, Uttarakhand, India
| | - Janne Ruokolainen
- Department
of Applied Physics, School of Science, Aalto
University, 02150 Espoo, Finland
| | - Kavindra Kumar Kesari
- Department
of Applied Physics, School of Science, Aalto
University, 02150 Espoo, Finland
- Division
of Research and Development, Lovely Professional
University, Phagwara 144411, Punjab, India
| | - Piyush Kumar Gupta
- Department
of Life Sciences, Sharda School of Basic Sciences and Research, Sharda University, Greater Noida 201310, Uttar Pradesh, India
- Department
of Biotechnology, Graphic Era Deemed to
Be University, Dehradun 248002, Uttarakhand, India
- Faculty
of Health and Life Sciences, INTI International
University, Nilai 71800, Malaysia
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4
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Weissferdt A, Sepesi B, Ning J, Hermsen M, Ferrarotto R, Glisson B, Hanna E, Bell D. Optimal Combination of Neuroendocrine Markers for the Detection of High-Grade Neuroendocrine Tumors of the Sinonasal Tract and Lung. Curr Oncol Rep 2023; 25:1-10. [PMID: 36422794 DOI: 10.1007/s11912-022-01346-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/19/2022] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Identification of neuroendocrine (NE) differentiation is critical to the classification of head and neck (HN) and lung tumors. In combination with tumor morphology, immunohistochemical (IHC) documentation of NE differentiation is necessary for the diagnosis of NE tumors. The purpose of this study is to determine the sensitivity and concordance of two novel NE markers (mASH1, INSM1) across a group of high-grade NE tumors of the sinonasal tract and lung, and to compare their expression with the current widespread use of conventional NE markers, synaptophysin (SYN) and chromogranin A (CGA). In addition, expression of PARP1 is examined as a potential novel therapeutic target. RECENT FINDINGS Thirty-nine high-grade NE tumors, 23 of the HN and 16 of the lung, were reevaluated by two subspecialized HN and thoracic pathologists, and subsequently stained with mASH1, INSM1, and PARP1. Sensitivity and degree of concordance of all possible combinations of markers were assessed. Sensitivities (standard error) were as follows: mASH1 41% (0.08), INSM1 44% (0.08), SYN 56% (0.08), and CGA 42% (0.09); combination of all four NE markers: 73% (0.08). Sensitivity and standard error for PARP1 was 90% and 0.05, respectively. Highest sensitivity to detect NE differentiation in high-grade NE tumors of the HN and thoracic region was achieved with a combination of four NE markers. Moderate concordance was found with combinations of mASH1 and INSM1 and traditional NE markers, respectively. Consistent overexpression of PARP1 in high-grade tumors with NE differentiation in the HN and lung opens eligibility for PARP1 inhibitor trials.
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Affiliation(s)
- Annikka Weissferdt
- Department of Pathology, MD Anderson Cancer Center, Houston, TX, USA.,Department of Thoracic Surgery, MD Anderson Cancer Center, Houston, TX, USA
| | - Boris Sepesi
- Department of Thoracic Surgery, MD Anderson Cancer Center, Houston, TX, USA
| | - Jing Ning
- Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA
| | - Mario Hermsen
- Head and Neck Oncology, University Hospital of Oviedo, Oviedo, Spain
| | - Renata Ferrarotto
- Department of Head and Neck/Thoracic Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Bonnie Glisson
- Department of Head and Neck/Thoracic Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Ehab Hanna
- Department of Head and Neck Surgery, MD Anderson Cancer Center, Houston, TX, USA
| | - Diana Bell
- Department of Pathology and Head and Neck Disease Team Alignment, City of Hope Comprehensive Cancer Center, Duarte, CA, 91010, USA.
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5
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Dum D, Menz A, Völkel C, De Wispelaere N, Hinsch A, Gorbokon N, Lennartz M, Luebke AM, Hube-Magg C, Kluth M, Fraune C, Möller K, Bernreuther C, Lebok P, Clauditz TS, Jacobsen F, Sauter G, Uhlig R, Wilczak W, Steurer S, Minner S, Marx AH, Simon R, Burandt E, Krech T. Cytokeratin 7 and cytokeratin 20 expression in cancer: A tissue microarray study on 15,424 cancers. Exp Mol Pathol 2022; 126:104762. [PMID: 35390310 DOI: 10.1016/j.yexmp.2022.104762] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 03/23/2022] [Accepted: 03/30/2022] [Indexed: 01/15/2023]
Abstract
Combined analysis of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) is often used for assessing the origin of metastatic cancer. To evaluate the diagnostic utility of CK7 and CK20, tissue microarrays containing 15,424 samples from 120 different tumor types and subtypes and 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. CK7 positivity was seen in 52% (8.7% weak, 5.9% moderate, 37% strong) and CK20 positivity in 23% (5.1% weak, 3.4% moderate, 15% strong) of interpretable tumors. Of 8390 positive tumors, 1181 (14%) showed positivity for CK7 and CK20, 5380 (64%) showed positivity for CK7 alone, and 1829 (22%) showed positivity for CK20 alone. CK20 predominated in gastrointestinal tract, urothelial and Merkel cell carcinomas. CK7 was usually negative in prostate cancer and colorectal cancer. Combined evaluation of CK7/CK20 revealed the best diagnostic utility in CK20 positive tumors, where CK7 negativity is often linked to colorectal origin while CK7 positivity argues for urothelial origin or mucinous ovarian cancer. Associations with unfavorable tumor features were found for cytokeratin 7 loss in breast cancer of no special type, urothelial and renal cell carcinomas, for CK7 overexpression in high-grade serous ovarian and gastric cancer, and for CK20 overexpression in urothelial carcinoma. CK20 loss was linked to MSI in gastric (p = 0.0291) and colorectal adenocarcinoma (p < 0.0001). These analyses provide comprehensive data on the frequency of CK7 and CK20 immunostaining - alone or in combination - in human cancers. These data facilitate interpretation of CK7/CK20 immunostaining in cancers.
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Affiliation(s)
- David Dum
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Anne Menz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Cosima Völkel
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Noémi De Wispelaere
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andrea Hinsch
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Natalia Gorbokon
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Maximilian Lennartz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andreas M Luebke
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Claudia Hube-Magg
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Martina Kluth
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph Fraune
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Katharina Möller
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christian Bernreuther
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Patrick Lebok
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Till S Clauditz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Frank Jacobsen
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Guido Sauter
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ria Uhlig
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Waldemar Wilczak
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Stefan Steurer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sarah Minner
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andreas H Marx
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Pathology, Academic Hospital Fuerth, Fuerth, Germany
| | - Ronald Simon
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
| | - Eike Burandt
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Till Krech
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany
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6
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Fjaeldstad AW, Villadsen GE, Dam G, Hamilton-Dutoit SJ, Frederiksen TW. Incidental finding of a neuroendocrine neoplasm in a suspected ear canal exostosis. OTOLARYNGOLOGY CASE REPORTS 2022. [DOI: 10.1016/j.xocr.2022.100394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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7
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Merkel-type oral small cell neuroendocrine carcinoma as second malignancy of tongue. J Dent Sci 2021; 16:1290-1292. [PMID: 34484597 PMCID: PMC8403886 DOI: 10.1016/j.jds.2021.06.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 06/24/2021] [Indexed: 11/21/2022] Open
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8
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DeCaprio JA. Molecular Pathogenesis of Merkel Cell Carcinoma. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE 2020; 16:69-91. [PMID: 33228463 DOI: 10.1146/annurev-pathmechdis-012419-032817] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin with two distinct etiologies. Clonal integration of Merkel cell polyomavirus DNA into the tumor genome with persistent expression of viral T antigens causes at least 60% of all MCC. UV damage leading to highly mutated genomes causes a nonviral form of MCC. Despite these distinct etiologies, both forms of MCC are similar in presentation, prognosis, and response to therapy. At least three oncogenic transcriptional programs feature prominently in both forms of MCC driven by the virus or by mutation. Both forms of MCC have a high proliferative growth rate with increased levels of cell cycle-dependent genes due to inactivation of the tumor suppressors RB and p53, a strong MYC signature due to MYCL activation by the virus or gene amplification, and an attenuated neuroendocrine differentiation program driven by the ATOH1 transcription factor.
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Affiliation(s)
- James A DeCaprio
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; .,Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.,Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
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9
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Zhou Y, Zhou HC, Peng H, Zhang ZH. Primary small cell neuroendocrine carcinoma of the right posterior tongue. World J Meta-Anal 2020; 8:285-291. [DOI: 10.13105/wjma.v8.i4.285] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 07/30/2020] [Accepted: 08/21/2020] [Indexed: 02/06/2023] Open
Abstract
Small cell neuroendocrine carcinoma (SNEC) is an extremely aggressive tumor and mainly occurs in the lung. Primary extra-pulmonary SNEC is rare. To date, only 11 primary SNECs occurring in the oral cavity have been reported in the English literature. We describe a case of primary SNEC of the right posterior tongue in a 46-year-old man. The patient had stage IVA disease and received adjuvant chemotherapy, followed by radical surgery and radiotherapy. He remained tumor-free for 20 mo before death due to gastrointestinal metastasis. The relevant literature on the 11 previously reported patients was reviewed, and the clinical features, histopathological characteristics, differential diagnosis and therapeutic strategies of this rare tumor were analyzed.
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Affiliation(s)
- Yu Zhou
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Hang-Cheng Zhou
- Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Hui Peng
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Zhi-Hong Zhang
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
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10
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Csoboz B, Rasheed K, Sveinbjørnsson B, Moens U. Merkel cell polyomavirus and non-Merkel cell carcinomas: guilty or circumstantial evidence? APMIS 2020; 128:104-120. [PMID: 31990105 DOI: 10.1111/apm.13019] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 12/02/2019] [Indexed: 12/11/2022]
Abstract
Merkel cell polyomavirus (MCPyV) is the major causative factor of the rare but aggressive cancer, Merkel cell carcinoma (MCC). Two characteristics of MCPyV-positive MCCs are integration of the viral genome and expression of a truncated version of one of its oncogenic proteins, namely large T antigen. The strong association of MCPyV with MCC development has incited researchers to further investigate a possible role of this virus in other cancers. However, many of the examples displaying the presence of the virus in the various non-MCC cancers are not able to clearly demonstrate a direct connection between cellular transformation and the presence of the virus. The prevalence of the virus is significantly lower in non-MCC cancers compared to MCCs, with a lower level of viral load and sparse viral protein expression. Moreover, the state of the viral genome, and whether a truncated large T antigen is expressed, has rarely been investigated. Nonetheless, considering the strong oncogenic potential of MCPyV proteins in MCC, the plausible contribution of MCPyV to transformation and cancer growth in non-MCC tumors cannot be ruled out. Furthermore, the absence of MCPyV in cancers does not exclude a hit-and-run mechanism, or the oncoproteins of MCPyV may potentiate the neoplastic process mediated by co-infecting oncoviruses such as high-risk human papillomaviruses and Epstein-Barr virus. The current review is focusing on the available data describing the presence of MCPyV in non-MCC tumors, with an aim to provide a comprehensive overview of the corresponding literature and to discuss the potential contribution of MCPyV to non-MCC cancer in light of this.
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Affiliation(s)
- Balint Csoboz
- Molecular Inflammation Research Group, Department of Medical Biology, University of Tromsø - The Arctic University of Norway, Tromsø, Norway
| | - Kashif Rasheed
- Molecular Inflammation Research Group, Department of Medical Biology, University of Tromsø - The Arctic University of Norway, Tromsø, Norway
| | - Baldur Sveinbjørnsson
- Molecular Inflammation Research Group, Department of Medical Biology, University of Tromsø - The Arctic University of Norway, Tromsø, Norway
| | - Ugo Moens
- Molecular Inflammation Research Group, Department of Medical Biology, University of Tromsø - The Arctic University of Norway, Tromsø, Norway
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11
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Cancer Biology and Carcinogenesis: Fundamental Biological Processes and How They Are Deranged in Oral Cancer. TEXTBOOK OF ORAL CANCER 2020. [DOI: 10.1007/978-3-030-32316-5_29] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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12
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Neuroendocrine Key Regulator Gene Expression in Merkel Cell Carcinoma. Neoplasia 2018; 20:1227-1235. [PMID: 30414538 PMCID: PMC6226622 DOI: 10.1016/j.neo.2018.10.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 10/07/2018] [Accepted: 10/11/2018] [Indexed: 01/26/2023] Open
Abstract
Merkel cell carcinoma (MCC) is a highly aggressive non-melanoma skin cancer of the elderly which is associated with the Merkel cell polyomavirus (MCPyV). MCC reveals a trilinear differentiation characterized by neuroendocrine, epithelial and pre/pro B-cell lymphocytic gene expression disguising the cellular origin of MCC. Here we investigated the expression of the neuroendocrine key regulators RE1 silencing transcription factor (REST), neurogenic differentiation 1 (NeuroD1) and the Achaete-scute homolog 1 (ASCL1) in MCC. All MCCs were devoid of REST and were positive for NeuroD1 expression. Only one MCC tissue revealed focal ASCL1 expression. This was confirmed in MCPyV-positive MCC cell lines. Of interest, MCPyV-negative cell lines did express REST. The introduction of REST expression in REST-negative, MCPyV-positive MCC cells downregulated the neuroendocrine gene expression. The lack of the neuroendocrine master regulator ASCL1 in almost all tested MCCs points to an important role of the absence of the negative regulator REST towards the MCC neuroendocrine phenotype. This is underlined by the expression of the REST-regulated microRNAs miR-9/9* in REST-negative MCC cell lines. These data might provide the basis for the understanding of neuroendocrine gene expression profile which is expected to help to elucidate the cellular origin of MCC.
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Tripathi M, Swanson PE. Rare tumors of esophageal squamous mucosa. Ann N Y Acad Sci 2016; 1381:122-132. [PMID: 27310830 DOI: 10.1111/nyas.13108] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Revised: 04/22/2016] [Accepted: 04/27/2016] [Indexed: 12/15/2022]
Abstract
In spite of increasing incidence of esophageal adenocarcinoma in the last few decades, esophageal squamous cell carcinoma (SCC) still remains the dominant subtype of esophageal cancer worldwide. Apart from conventional SCC, some rare unconventional tumors of esophageal squamous mucosa are also well known. This study provides an introduction to these and presents a brief review of the literature, including the diagnostic and prognostic importance of each variant.
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Affiliation(s)
- Monika Tripathi
- Department of Histopathology, Cambridge University Hospitals, NHS Foundation Trust, Cambridge, United Kingdom
| | - Paul E Swanson
- Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada.
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Ye B, Cappel J, Findeis-Hosey J, McMahon L, Yang Q, Xiao GQ, Xu H, Li F. hASH1 is a specific immunohistochemical marker for lung neuroendocrine tumors. Hum Pathol 2015; 48:142-7. [PMID: 26596584 DOI: 10.1016/j.humpath.2015.09.019] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2015] [Revised: 09/03/2015] [Accepted: 09/16/2015] [Indexed: 10/23/2022]
Abstract
Mammalian/human achaete-scute homolog 1 (hASH1) regulates neuroendocrine cell development. No detailed comparative study has been conducted to explore the immunohistochemical utility of hASH1 in distinguishing different types of lung cancers. We investigated the expression of hASH1, synaptophysin, chromogranin, and CD56 in 101 squamous cell carcinomas (SCCs), 183 adenocarcinomas (ADCs), 37 typical carcinoids (TCs), 14 atypical carcinoids (ACs), 11 large cell neuroendocrine carcinomas (LCNECs), and 24 small cell lung carcinomas (SCLCs) of the lung by immunohistochemical staining with a monoclonal antibody against hASH1. Staining intensity was graded from 0 to 3, and percentage of tumor cells in each grade was estimated. All cases of ADC and SCC were discreetly negative for hASH1 in contrast to their low percentage positivity for synaptophysin, chromogranin, and CD56. hASH1 positively stained TC (64.9%), AC (64.3%), LCNEC (72.7%), and SCLC (79.2%) as did chromogranin (TC, 100%; AC, 78.6%; LCNEC, 9.0%; and SCLC, 4.2%), synaptophysin (TC, 100%; AC, 78.6%; LCNEC, 81.8%; and SCLC, 83.3%), and CD56 (TC, 59.5%; AC, 57.1%; LCNEC, 36.4%; and SCLC, 79.2%). TC and AC often showed weaker intensity and lower percentage of tumor cells positive for hASH1 (median score, 5) than LCNEC and SCLC (median score, 40 and 170, respectively). There were statistically significant differences in mean intensity scores between SCLC (148.8 ± 20.1) and other neuroendocrine tumors: TC (37.1 ± 9.2) and AC (28.6 ± 10.8) or LCNEC (51.8 ± 18.0). Our findings indicate that hASH1 is a specific marker to distinguish neuroendocrine tumors from SCC and ADC. Additionally, hASH1 is a useful diagnostic marker for segregating SCLC from other neuroendocrine tumors.
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Affiliation(s)
- Bo Ye
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642; Department of Laboratory Medicine and Pathology, University of Minnesota, Dwan Variety Club Cardio vascular Research Center, Minneapolis, MN 55455
| | - Jaclyn Cappel
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642
| | - Jennifer Findeis-Hosey
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642
| | - Loralee McMahon
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642
| | - Qi Yang
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642
| | - Guang-Qian Xiao
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642
| | - Haodong Xu
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095
| | - Faqian Li
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642; Department of Laboratory Medicine and Pathology, University of Minnesota, Dwan Variety Club Cardio vascular Research Center, Minneapolis, MN 55455.
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Zeng M, Yang SD, Zhang JL, Chen XM. Primary small cell neuroendocrine carcinoma of the oral cavity: A case report and review of the literature. Oncol Lett 2015; 10:887-890. [PMID: 26622589 DOI: 10.3892/ol.2015.3298] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2014] [Accepted: 04/13/2015] [Indexed: 12/28/2022] Open
Abstract
Small cell neuroendocrine carcinoma (SNEC) of the oral cavity is a rare and distinctive tumor with aggressive clinical behavior. Thus far, only a small number of cases have been reported and no definitive standard treatment strategy has been determined. The current study reports a case of oral SNEC arising in the lower gingiva in a 73-year-old male. Computed tomography displayed a relatively well-defined mass measuring 2.8×2×1.4 cm in size. The mass was located in the buccal side of the right mandibular posterior gingiva and exhibited no bony involvement. Histopathological examination revealed a proliferation of small cells with ovoid- to spindle-shaped nuclei, fine granular chromatin, inconspicuous nucleoli, scant cytoplasm and high mitotic activity. Immunohistochemically, the tumor cells were positive for cytokeratin AE1/AE3, chromogranin A, synaptophysin and neuron-specific enolase. Surgical resection and radical neck dissection were performed prior to the administration of adjuvant chemotherapy with a combination of cisplatin and etoposide. No evidence of local recurrence or metastasis was observed at 14 months post-surgery.
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Affiliation(s)
- Ming Zeng
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei‑MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430072, P.R. China
| | - Shao-Dong Yang
- Department of Pathology, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430072, P.R. China
| | - Jia-Li Zhang
- Department of Pathology, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430072, P.R. China
| | - Xin-Ming Chen
- Department of Pathology, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430072, P.R. China
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Achaete-scute homolog 1 expression closely correlates with endocrine phenotype and degree of differentiation in sinonasal neuroendocrine tumors. Ann Diagn Pathol 2015; 19:154-6. [PMID: 25892663 DOI: 10.1016/j.anndiagpath.2015.03.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2015] [Accepted: 03/28/2015] [Indexed: 11/20/2022]
Abstract
Primary sinonasal tumors with neuroendocrine differentiation (STNDs) are uncommon, with overlapping histology. According to the amount of neuroendocrine component, they can be subcategorized into esthesioneuroblastoma, high-grade sinonasal neuroendocrine carcinoma/small cell carcinoma, and sinonasal undifferentiated carcinoma. Achaete-scute homolog 1 (ASH1) is a master gene for neuroendocrine differentiation and is expressed in fetal and adult neuroendocrine tissues. Expression of ASH1 protein may be a useful marker for cancers with neuroendocrine features. The aim of this study was to compare and assess the value of ASH1 protein expression/levels in STND. We reviewed the morphological features and performed immunohistochemical analyses for ASH1 in 30 samples of surgically resected cancers with neuroendocrine differentiation from our institution. Achaete-scute homolog 1 was found to be expressed in STND, indicating that it is instrumental in the development of a subset of neurons and neuroendocrine cells and plays a key role in regulating neuroendocrine differentiation in tumor cells. Achaete-scute homolog 1 levels were associated with the degree of STND tumor differentiation (high-grade tumors show increased expression of this protein), correlating well with studies indicating that expression of ASH1 appears to be restricted to immature cells.
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Wu BZ, Gao Y, Yi B. Primary neuroendocrine carcinoma in oral cavity: two case reports and review of the literature. J Oral Maxillofac Surg 2013; 72:633-44. [PMID: 24215661 DOI: 10.1016/j.joms.2013.08.020] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2013] [Revised: 08/12/2013] [Accepted: 08/16/2013] [Indexed: 10/26/2022]
Abstract
Neuroendocrine carcinoma (NEC) is a tumor that occurs in different locations, particularly the lungs and larynx. The oral cavity is a rare site for a primary NEC. This report describes 2 cases of primary NEC in the oral cavity. Case 1 occurred in the anterior mandibular gingiva in a 25-year-old woman and presented with a special histologic appearance. This patient showed no evidence of recurrence 13 months after marginal resection of the anterior mandible. Case 2 was a primary NEC with some foci of squamous cell differentiation arising in the right buccal region in a 38-year-old woman. This patient showed no evidence of disease 8 months after tumor resection and postoperative iodine-125 brachytherapy. To the best of the authors' knowledge, case 1 is the youngest patient with NEC reported in the oral cavity to date in the English-language literature, and case 2 is the first report of a primary NEC in the buccal region.
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Affiliation(s)
- Bin-Zhang Wu
- Resident, Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China
| | - Yan Gao
- Professor, Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China
| | - Biao Yi
- Professor, Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China.
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Assigning site of origin in metastatic neuroendocrine neoplasms: a clinically significant application of diagnostic immunohistochemistry. Adv Anat Pathol 2013; 20:285-314. [PMID: 23939147 DOI: 10.1097/pap.0b013e3182a2dc67] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The neuroendocrine epithelial neoplasms (NENs) include well-differentiated neuroendocrine tumors (WDNETs) and poorly differentiated neuroendocrine carcinomas (PDNECs). Whereas PDNECs are highly lethal, with localized Merkel cell carcinoma somewhat of an exception, WDNETs exhibit a range of "indolent" biologic potentials-from benign to widely metastatic and eventually fatal. Within each of these 2 groups there is substantial morphologic overlap. In the metastatic setting, the site of origin of a WDNET has significant prognostic and therapeutic implications. In the skin, Merkel cell carcinoma must be distinguished from spread of a visceral PDNEC. This review intends to prove the thesis that determining the site of origin of a NEN is clinically vital and that diagnostic immunohistochemistry is well suited to the task. It will begin by reviewing current World Health Organization terminology for the NENs, as well as an embryologic and histologic pattern-based classification. It will present population-based data on the relative frequency and biology of WDNETs arising at various anatomic sites, including the frequency of metastases of unknown primary, and comment on limitations of contemporary imaging techniques, as a means of defining the scope of the problem. It will go on to discuss the therapeutic significance of site of origin. The heart of this review is a synthesis of data compiled from >100 manuscripts on the expression of individual markers in WDNETs and PDNECs, as regards site of origin. These include proteins that are considered "key markers" and others that are either useful "secondary markers," potentially very useful markers that need to be further vetted, or ones that are widely applied despite a lack of efficacy. It will conclude with my approach to the metastatic NEN of unknown origin.
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Bates T, McQueen A, Iqbal MS, Kelly C, Robinson M. Small cell neuroendocrine carcinoma of the oropharynx harbouring oncogenic HPV-infection. Head Neck Pathol 2013; 8:127-31. [PMID: 23838856 PMCID: PMC3950381 DOI: 10.1007/s12105-013-0471-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2013] [Accepted: 06/27/2013] [Indexed: 01/16/2023]
Abstract
Small cell carcinoma/neuroendocrine carcinoma (SCNEC) of the oropharynx is uncommon. Recently, an association has been reported between oropharyngeal SCNEC and high-risk human papillomavirus (HPV) infection. While HPV infection confers a better prognosis for oropharyngeal squamous cell carcinoma, HPV infection does not appear to influence the biological behaviour of SCNECs, which are generally associated with poor clinical outcomes. We document two cases of SCNEC arising in the oropharynx with evidence of high-risk HPV infection. The cases highlight the expanding range of malignant oropharyngeal neoplasms that harbour oncogenic HPV infection and support the concept that, irrespective of HPV infection, neuroendocrine differentiation portends a poor prognosis.
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Affiliation(s)
- Timothy Bates
- Department of Cellular Pathology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, NE7 7DN UK
| | - Andrew McQueen
- Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, NE7 7DN UK
| | | | - Charles Kelly
- Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, NE7 7DN UK
| | - Max Robinson
- Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, NE7 7DN UK
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Coursaget P, Samimi M, Nicol JTJ, Gardair C, Touzé A. Human Merkel cell polyomavirus: virological background and clinical implications. APMIS 2013; 121:755-69. [PMID: 23781869 DOI: 10.1111/apm.12122] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2012] [Accepted: 04/11/2013] [Indexed: 11/27/2022]
Abstract
The Merkel cell polyomavirus (MCPyV), identified in humans in 2008, is associated with a relatively rare but aggressive neuroendocrine skin cancer, the Merkel cell carcinoma (MCC). MCC incidence is increasing due to the advancing age of the population, the increase in damaging sun exposure and in the number of immunocompromised individuals. MCPyV must be considered as the etiological agent of MCC and thus is the first example of a human oncogenic polyomavirus. MCPyV infection is common, and seroprevalence studies indicate that widespread exposure begins early in life. The majority of adults have anti-MCPyV antibodies and there is a growing body of evidence that healthy human skin harbors resident or transient MCPyV suggesting that MCPyV infection persists throughout life. However, the mode of transmission, the host cells, and the latency characteristics of this virus remain to be elucidated. In addition, it is still not clear whether MCPyV is associated with diseases or lesions other than Merkel cell carcinoma. The etiologic role of MCPyV in MCC opens up opportunities to improve the understanding of this cancer and to potentially improve its treatment.
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Ishida M, Okabe H. Merkel cell carcinoma concurrent with Bowen's disease: two cases, one with an unusual immunophenotype. J Cutan Pathol 2013; 40:839-43. [DOI: 10.1111/cup.12176] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2013] [Revised: 04/16/2013] [Accepted: 04/22/2013] [Indexed: 11/28/2022]
Affiliation(s)
- Mitsuaki Ishida
- Division of Diagnostic Pathology, Department of Clinical Laboratory Medicine; Shiga University of Medical Science; Shiga; Japan
| | - Hidetoshi Okabe
- Division of Diagnostic Pathology, Department of Clinical Laboratory Medicine; Shiga University of Medical Science; Shiga; Japan
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Small cell neuroendocrine tumour of the anterior tongue: A case report. Int J Surg Case Rep 2013; 4:753-5. [PMID: 23835197 DOI: 10.1016/j.ijscr.2013.04.028] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2013] [Accepted: 04/10/2013] [Indexed: 12/17/2022] Open
Abstract
INTRODUCTION Neuroendocrine carcinomas (NECs) are rare in the oral cavity. There is ambiguity regarding the classification of these tumours, but their aggressive nature is recognised throughout the literature. Merkel cell carcinoma (MCC) is rare and more frequent in skin, though it has also been described intra-orally. High grade neuroendocrine tumours (HGNEC) and MCCs behave aggressively and aggressive treatment strategies have been advocated. We describe the first small cell HGNEC on the anterior tongue. PRESENTATION OF CASE We present the first report of a pT1pN1M0 small cell HGNEC in a 75 year old man on the left lateral anterior tongue. This was widely resected with 20mm peripheral and deep margins to achieve disease clearance. Selective neck dissection of levels 1-4 was also carried out. DISCUSSION Histological analysis of the tumour confirmed a primary poorly differentiated neuroendocrine tumour of small cell type (small cell HGNEC). Resected node bearing tissue from levels 1-4 confirmed metastasis to a level III node with no extra capsular spread giving a pT1pN1M0 classification. Margins of 11.7mm from the invasive tumour to mucosal margin medially and 7.0mm for the deep margin despite surgical 20mm margin resection. To the best of our knowledge small cell neuroendocrine carcinoma has not been described in the anterior tongue. CONCLUSION The aggressive nature of this tumour type mandates aggressive surgical resection with margins similar to those now recommended for skin Merkel cell carcinomas. We advocate a wide excision margin of 20mm to give adequate clearance, with neck dissection in order to pathologically stage this cancer type.
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Li M, Saghafi N, Freymiller E, Basile JR, Lin YL. Metastatic Merkel cell carcinoma of the oral cavity in a human immunodeficiency virus–positive patient and the detection of Merkel cell polyomavirus. Oral Surg Oral Med Oral Pathol Oral Radiol 2013; 115:e66-71. [DOI: 10.1016/j.oooo.2012.09.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2012] [Revised: 08/28/2012] [Accepted: 09/02/2012] [Indexed: 11/26/2022]
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La Rosa S, Marando A, Gatti G, Rapa I, Volante M, Papotti M, Sessa F, Capella C. Achaete-scute homolog 1 as a marker of poorly differentiated neuroendocrine carcinomas of different sites: a validation study using immunohistochemistry and quantitative real-time polymerase chain reaction on 335 cases. Hum Pathol 2013; 44:1391-9. [PMID: 23375646 DOI: 10.1016/j.humpath.2012.11.013] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2012] [Revised: 11/24/2012] [Accepted: 11/28/2012] [Indexed: 11/20/2022]
Abstract
Neuroendocrine carcinomas show overlapping morphological and immunohistochemical features independently of their site of origin, which makes identification of the primary location problematic when they are diagnosed as metastases of unknown origin. Neuroendocrine carcinomas are easily morphologically differentiated from neuroendocrine tumors in surgical material, although this distinction can be difficult when using small biopsy specimens. The diagnostic usefulness of different transcription factors as site-specific markers or as discriminating markers between neuroendocrine carcinomas and neuroendocrine tumors has been previously studied with sometimes contradictory results. In this respect, the role of achaete-scute homolog 1 has been poorly investigated, although some recent findings demonstrate its expression in neuroendocrine carcinomas. Using immunohistochemistry and quantitative real-time polymerase chain reaction, we investigated the expression of achaete-scute homolog 1 in 335 neuroendocrine neoplasms (194 neuroendocrine carcinomas and 141 neuroendocrine tumors) of different sites, to check its possible utility as diagnostic marker. High concordance between immunohistochemical and molecular findings was found. Achaete-scute homolog 1 expression was identified in 82% of lung neuroendocrine carcinomas and 70% of extrapulmonary neuroendocrine carcinomas. Achaete-scute homolog 1 was not detected in any gastroenteropancreatic neuroendocrine tumor and was found in only a minority of lung carcinoids. The diagnostic sensitivity and specificity of achaete-scute homolog 1 expression were 82.4% and 89.7% in distinguishing neuroendocrine carcinomas from neuroendocrine tumors of the lung, 40.6% and 100% to differentiate extrapulmonary neuroendocrine carcinomas from neuroendocrine tumors, and 82.4% and 59.4% in distinguishing lung from extrapulmonary neuroendocrine carcinomas. Our data suggest that achaete-scute homolog 1 is not a site-specific marker. However, achaete-scute homolog 1 may be proposed as a diagnostic marker of poor differentiation and may help to differentiate neuroendocrine carcinomas from neuroendocrine tumors in difficult cases.
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Affiliation(s)
- Stefano La Rosa
- Department of Pathology, Ospedale di Circolo, 21100 Varese, Italy.
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Absence of Merkel Cell Polyomavirus in Primary Parotid High-grade Neuroendocrine Carcinomas Regardless of Cytokeratin 20 Immunophenotype. Am J Surg Pathol 2011; 35:1806-11. [DOI: 10.1097/pas.0b013e318236a9b0] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Chang Y, Moore PS. Merkel cell carcinoma: a virus-induced human cancer. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE 2011; 7:123-44. [PMID: 21942528 DOI: 10.1146/annurev-pathol-011110-130227] [Citation(s) in RCA: 150] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Merkel cell polyomavirus (MCV) is the first polyomavirus directly linked to human cancer, and its recent discovery helps to explain many of the enigmatic features of Merkel cell carcinoma (MCC). MCV is clonally integrated into MCC tumor cells, which then require continued MCV oncoprotein expression to survive. The integrated viral genomes have a tumor-specific pattern of tumor antigen gene mutation that incapacitates viral DNA replication. This human cancer virus provides a new model in which a common, mostly harmless member of the human viral flora can initiate cancer if it acquires a precise set of mutations in a host with specific susceptibility factors, such as age and immune suppression. Identification of this tumor virus has led to new opportunities for early diagnosis and targeted treatment of MCC.
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Affiliation(s)
- Yuan Chang
- Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
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Pellitteri PK, Takes RP, Lewis JS, Devaney KO, Harlor EJ, Strojan P, Rodrigo JP, Suárez C, Rinaldo A, Medina JE, Woolgar JA, Ferlito A. Merkel cell carcinoma of the head and neck. Head Neck 2011; 34:1346-54. [DOI: 10.1002/hed.21787] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/21/2011] [Indexed: 01/30/2023] Open
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Purgina B, Pantanowitz L, Seethala RR. A Review of Carcinomas Arising in the Head and Neck Region in HIV-Positive Patients. PATHOLOGY RESEARCH INTERNATIONAL 2011; 2011:469150. [PMID: 21660273 PMCID: PMC3108450 DOI: 10.4061/2011/469150] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2010] [Accepted: 02/14/2011] [Indexed: 12/30/2022]
Abstract
The majority of malignancies arising in the head and neck among patients with AIDS are Kaposi sarcoma and non-Hodgkin lymphoma. Patients with HIV/AIDS are also at increased risk of developing several carcinomas of the head and neck. This paper focuses on these less common, albeit important, carcinomas. An English language literature search identified numerous population-based studies evaluating carcinomas in the head and neck of HIV-positive patients. Published results indicate that patients with HIV/AIDS are at an increased risk of developing mucosal squamous cell carcinoma, nasopharyngeal carcinoma, lymphoepithelial carcinoma of the salivary gland, and Merkel cell carcinoma in this anatomic region. Data also suggest that HIV-positive patients with these cancers present at a younger age, with more aggressive disease and worse prognosis compared to HIV-negative patients. Treatment involves surgical resection with or without radiation therapy and chemotherapy for locally advanced and metastatic disease. AIDS patients, however, are more likely to suffer radiation treatment complications. Highly active antiretroviral therapy (HAART) has not altered the incidence of these malignancies.
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Affiliation(s)
- Bibianna Purgina
- Department of Pathology, Presbyterian-Shadyside University Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
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