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The Biological and Clinical Aspects of Merkel Cell Carcinoma
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The Biological and Clinical Aspects of Merkel Cell Carcinoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 47276

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Virve Koljonen

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Guest Editor
Department of Plastic Surgery, University of Helsinki and Helsinki University Hospital, 00029 HUS Helsinki, Finland
Interests: rare cancers; Merkel cell carcinoma; Merkel cell polyoma virus; surgery; complications; outcome; porocarcinoma
Dr. Weng-Onn Lui

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Guest Editor
Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden
Interests: skin cancer; molecular biology; viral carcinogenesis; tumor immunology; biomarker
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jürgen Becker

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Guest Editor
1. Translational Skin Cancer Research, German Cancer Consortium (DKTK), University of Duisburg-Essen, 45117 Essen, Germany
2. Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany
Interests: skin cancers; Merkel cell carcinoma; immunology; tumor cell evolution; tumor cell plasticity; epigenetics; immunotherapy; therapy resistance; biomarker
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Eleven years ago, Professor Moore and his team discovered the Merkel cell polyomavirus (MCPyV) DNA integrated clonally into the tumor genome of most Merkel cell carcinomas (MCC). This finding enkindled both interest and, subsequently, research on this rare skin cancer and inspired many researchers investigating the molecular basis and clinical research on MCC. More recently, interest in MCC was further boosted by the observation that this highly aggressive cancer can be readily treated by an immune checkpoint blockade. Based on these research efforts, our understanding of MCC biology and immunology as well as its treatment has improved significantly. However, many questions in both basic and clinical research have yet to be answered, e.g., the cellular origin of MCC, the role of tumor microenvironment in MCC development and immune evasion, the clinical value of differentiating MCPyV-positive and -negative MCC, predictive biomarkers for therapy responsiveness, and salvage therapies for patients who progress under immunotherapy.

In this Special Issue, we will seek advanced knowledge in both basic and clinical research presented in original articles and comprehensive reviews highlighting the latest advances in MCC. We invite submissions that focus on but are not restricted to the molecular basis of the disease, translational investigations of biomarkers for prospective clinical applications, and innovative diagnostic and therapeutic approaches in MCC.

Dr. Virve Koljonen
Dr. Weng-Onn Lui
Prof. Dr. Jürgen C. Becker
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Biomarker
  • Carcinogenesis
  • Diagnosis and prognosis
  • Gene regulation
  • Immunology and immune escape
  • Merkel cell carcinoma
  • Merkel cell polyomavirus
  • Therapy
  • Tumor microenvironment
  • Viral oncoproteins and host factor interactions

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Published Papers (12 papers)

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Editorial

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3 pages, 174 KiB  
Editorial
New Insights into the Biological and Clinical Aspects of Merkel Cell Carcinoma
by Virve Koljonen, Weng-Onn Lui and Jürgen C. Becker
Cancers 2021, 13(9), 2259; https://doi.org/10.3390/cancers13092259 - 8 May 2021
Viewed by 1663
Abstract
The Special Issue in Cancers, “The Biological and Clinical Aspects of Merkel Cell Carcinoma”, walks the avid reader through the interesting and sometimes even mysterious facets of Merkel cell carcinoma (MCC), starting at its carcinogenesis to also cover innovative treatment options [...] Full article
(This article belongs to the Special Issue The Biological and Clinical Aspects of Merkel Cell Carcinoma)

Research

Jump to: Editorial, Review

12 pages, 1488 KiB  
Article
Distinct Signatures of Genomic Copy Number Variants Define Subgroups of Merkel Cell Carcinoma Tumors
by Natasha T. Hill, David Kim, Klaus J. Busam, Emily Y. Chu, Clayton Green and Isaac Brownell
Cancers 2021, 13(5), 1134; https://doi.org/10.3390/cancers13051134 - 6 Mar 2021
Cited by 7 | Viewed by 2335
Abstract
Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer. Most MCC tumors contain integrated Merkel cell polyomavirus DNA (virus-positive MCC, VP-MCC) and carry a low somatic mutation burden whereas virus-negative MCC (VN-MCC) possess numerous ultraviolet-signature mutations. In contrast to viral oncogenes [...] Read more.
Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer. Most MCC tumors contain integrated Merkel cell polyomavirus DNA (virus-positive MCC, VP-MCC) and carry a low somatic mutation burden whereas virus-negative MCC (VN-MCC) possess numerous ultraviolet-signature mutations. In contrast to viral oncogenes and sequence mutations, little is known about genomic structural variants in MCC. To identify copy number variants in commonly altered genes, we analyzed genomic DNA from 31 tumor samples using the Nanostring nCounter copy number cancer panel. Unsupervised clustering revealed three tumor groups with distinct genomic structural variant signatures. The first cluster was characterized by multiple recurrent deletions in genes such as RB1 and WT1. The second cluster contained eight VP-MCC and displayed very few structural variations. The final cluster contained one VP-MCC and four VN-MCC with predominantly genomic amplifications in genes like MDM4, SKP2, and KIT and deletions in TP53. Overall, VN-MCC contained more structure variation than VP-MCC but did not cluster separately from VP-MCC. The observation that most MCC tumors demonstrate a deletion-dominated structural group signature, independent of virus status, suggests a shared pathophysiology among most VP-MCC and VN-MCC tumors. Full article
(This article belongs to the Special Issue The Biological and Clinical Aspects of Merkel Cell Carcinoma)
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15 pages, 2272 KiB  
Article
Mutational Landscape of Virus- and UV-Associated Merkel Cell Carcinoma Cell Lines Is Comparable to Tumor Tissue
by Kai Horny, Patricia Gerhardt, Angela Hebel-Cherouny, Corinna Wülbeck, Jochen Utikal and Jürgen C. Becker
Cancers 2021, 13(4), 649; https://doi.org/10.3390/cancers13040649 - 5 Feb 2021
Cited by 16 | Viewed by 3528
Abstract
Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous malignancy that is either associated with the integration of the Merkel cell polyomavirus or chronic UV exposure. These two types of carcinogenesis are reflected in characteristic mutational features present in MCC tumor lesions. [...] Read more.
Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous malignancy that is either associated with the integration of the Merkel cell polyomavirus or chronic UV exposure. These two types of carcinogenesis are reflected in characteristic mutational features present in MCC tumor lesions. However, the genomic characteristics of MCC cell lines used as preclinical models are not well established. Thus, we analyzed the exomes of three virus-negative and six virus-positive MCC cell lines, all showing a classical neuroendocrine growth pattern. Virus-negative cell lines are characterized by a high tumor mutational burden (TMB), UV-light-induced DNA damage, functionally relevant coding mutations, e.g., in RB1 and TP53, and large amounts of copy number variations (CNVs). In contrast, virus-positive cell lines have a low TMB with few coding mutations and lack prominent mutational signatures, but harbor characteristic CNVs. One of the virus-negative cell lines has a local MYC amplification associated with high MYC mRNA expression. In conclusion, virus-positive and -negative MCC cell lines with a neuroendocrine growth pattern resemble mutational features observed in MCC tissue samples, which strengthens their utility for functional studies. Full article
(This article belongs to the Special Issue The Biological and Clinical Aspects of Merkel Cell Carcinoma)
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10 pages, 1617 KiB  
Article
Sex Differences in Overall Survival and the Effect of Radiotherapy in Merkel Cell Carcinoma—A Retrospective Analysis of A Swedish Cohort
by Hannah Björn Andtback, Viveca Björnhagen-Säfwenberg, Hao Shi, Weng-Onn Lui, Giuseppe V. Masucci and Lisa Villabona
Cancers 2021, 13(2), 265; https://doi.org/10.3390/cancers13020265 - 12 Jan 2021
Cited by 9 | Viewed by 2235
Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer where Merkel cell Polyomavirus (MCPyV) contributes to the pathogenesis. In an adjuvant setting, radiotherapy (RT) is believed to give a survival benefit. The prognostic impact of sex related to MCPyV-status and adjuvant [...] Read more.
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer where Merkel cell Polyomavirus (MCPyV) contributes to the pathogenesis. In an adjuvant setting, radiotherapy (RT) is believed to give a survival benefit. The prognostic impact of sex related to MCPyV-status and adjuvant RT were analyzed in patients referred to Karolinska University Hospital. Data were collected from 113 patients’ hospital records and MCPyV analyses were made in 54 patients (48%). We found a significantly better overall survival (OS) for women compared to men and a significant difference in OS in patients receiving adjuvant RT. Furthermore, we found that men with virus negative MCC have an increased risk for earlier death (HR 3.6). This indicates that MCPyV positive and negative MCC act as two different diseases, and it might be due to different mechanism in the immune response between male and female patients. This could have significance in tailoring treatment and follow-up in MCC patients in the future. Full article
(This article belongs to the Special Issue The Biological and Clinical Aspects of Merkel Cell Carcinoma)
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19 pages, 2152 KiB  
Article
The Merkel Cell Polyomavirus T Antigens Function as Tumor Promoters in Murine Skin
by Megan E. Spurgeon, Amy Liem, Darya Buehler, Jingwei Cheng, James A. DeCaprio and Paul F. Lambert
Cancers 2021, 13(2), 222; https://doi.org/10.3390/cancers13020222 - 9 Jan 2021
Cited by 9 | Viewed by 2417
Abstract
Merkel cell polyomavirus (MCPyV) causes the majority of human Merkel cell carcinomas (MCC), a rare but highly aggressive form of skin cancer. We recently reported that constitutive expression of MCC tumor-derived MCPyV tumor (T) antigens in the skin of transgenic mice leads to [...] Read more.
Merkel cell polyomavirus (MCPyV) causes the majority of human Merkel cell carcinomas (MCC), a rare but highly aggressive form of skin cancer. We recently reported that constitutive expression of MCC tumor-derived MCPyV tumor (T) antigens in the skin of transgenic mice leads to hyperplasia, increased proliferation, and spontaneous epithelial tumor development. We sought to evaluate how the MCPyV T antigens contribute to tumor formation in vivo using a classical, multi-stage model for squamous cell carcinoma development. In this model, two chemical carcinogens, DMBA and TPA, contribute to two distinct phases of carcinogenesis—initiation and promotion, respectively—that are required for tumors to develop. By treating the MCPyV transgenic mice with each chemical carcinogen, we determined how the viral oncogenes contributed to carcinogenesis. We observed that the MCPyV T antigens synergized with the tumor initiator DMBA, but not with the tumor promoter TPA, cause tumors. Therefore, the MCPyV tumor antigens function primarily as tumor promoters, similar to that seen with human papillomavirus (HPV) oncoproteins. These studies provide insight into the role of MCPyV T antigen expression in tumor formation in vivo and contribute to our understanding of how MCPyV may function as a human DNA tumor virus. Full article
(This article belongs to the Special Issue The Biological and Clinical Aspects of Merkel Cell Carcinoma)
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20 pages, 4254 KiB  
Article
Merkel Cell Polyomavirus T Antigens Induce Merkel Cell-Like Differentiation in GLI1-Expressing Epithelial Cells
by Thibault Kervarrec, Mahtab Samimi, Sonja Hesbacher, Patricia Berthon, Marion Wobser, Aurélie Sallot, Bhavishya Sarma, Sophie Schweinitzer, Théo Gandon, Christophe Destrieux, Côme Pasqualin, Serge Guyétant, Antoine Touzé, Roland Houben and David Schrama
Cancers 2020, 12(7), 1989; https://doi.org/10.3390/cancers12071989 - 21 Jul 2020
Cited by 25 | Viewed by 3503
Abstract
Merkel cell carcinoma (MCC) is an aggressive skin cancer frequently caused by the Merkel cell polyomavirus (MCPyV). It is still under discussion, in which cells viral integration and MCC development occurs. Recently, we demonstrated that a virus-positive MCC derived from a trichoblastoma, an [...] Read more.
Merkel cell carcinoma (MCC) is an aggressive skin cancer frequently caused by the Merkel cell polyomavirus (MCPyV). It is still under discussion, in which cells viral integration and MCC development occurs. Recently, we demonstrated that a virus-positive MCC derived from a trichoblastoma, an epithelial neoplasia bearing Merkel cell (MC) differentiation potential. Accordingly, we hypothesized that MC progenitors may represent an origin of MCPyV-positive MCC. To sustain this hypothesis, phenotypic comparison of trichoblastomas and physiologic human MC progenitors was conducted revealing GLI family zinc finger 1 (GLI1), Keratin 17 (KRT 17), and SRY-box transcription factor 9 (SOX9) expressions in both subsets. Furthermore, GLI1 expression in keratinocytes induced transcription of the MC marker SOX2 supporting a role of GLI1 in human MC differentiation. To assess a possible contribution of the MCPyV T antigens (TA) to the development of an MC-like phenotype, human keratinocytes were transduced with TA. While this led only to induction of KRT8, an early MC marker, combined GLI1 and TA expression gave rise to a more advanced MC phenotype with SOX2, KRT8, and KRT20 expression. Finally, we demonstrated MCPyV-large T antigens’ capacity to inhibit the degradation of the MC master regulator Atonal bHLH transcription factor 1 (ATOH1). In conclusion, our report suggests that MCPyV TA contribute to the acquisition of an MC-like phenotype in epithelial cells. Full article
(This article belongs to the Special Issue The Biological and Clinical Aspects of Merkel Cell Carcinoma)
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16 pages, 838 KiB  
Article
Merkel Cell Carcinoma Treatment in Finland in 1986–2016—A Real-World Data Study
by Helka Sahi, Jenny Their, Mika Gissler and Virve Koljonen
Cancers 2020, 12(5), 1224; https://doi.org/10.3390/cancers12051224 - 13 May 2020
Cited by 5 | Viewed by 2798
Abstract
Merkel cell carcinoma (MCC) is a rare cutaneous carcinoma that has gained enormous interest since the discovery of Merkel cell polyoma virus, which is a causative oncogenic agent in the majority of MCC tumours. Increased research has focused on effective treatment options with [...] Read more.
Merkel cell carcinoma (MCC) is a rare cutaneous carcinoma that has gained enormous interest since the discovery of Merkel cell polyoma virus, which is a causative oncogenic agent in the majority of MCC tumours. Increased research has focused on effective treatment options with immuno-oncology. In this study, we reviewed the real-world data on different treatments given to MCC patients in Finland in 1986–2016. We used the Finnish Cancer Registry database to find MCC patients and the Hospital Discharge Register and the Cause-of-Death Register to obtain treatment data. We identified 376 MCC patients and 33 different treatment entities and/or combinations of treatment. An increase was noted in the incidence of MCC since 2005. Therefore, the cohort was divided into two groups: the “early“ group with time of diagnosis between years 1986 and 2004 and the “late” group with time of diagnosis between 2005 and 2016. The multitude of different treatment combinations is a relatively new phenomenon; before the year 2005, only 11 treatments or treatment combinations were used for MCC patients. Our data show that combining radiation therapy with simple excision provided a survival advantage, which was, however, lost after adjustment for stage or age. Our registry study serves as a baseline treatment efficacy comparison as we move into the age of immunotherapy in MCC. Standardizing the treatment of MCC patients in Finland requires more work on awareness and multidisciplinary co-operation. Full article
(This article belongs to the Special Issue The Biological and Clinical Aspects of Merkel Cell Carcinoma)
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15 pages, 1839 KiB  
Article
Artesunate Affects T Antigen Expression and Survival of Virus-Positive Merkel Cell Carcinoma
by Bhavishya Sarma, Christoph Willmes, Laura Angerer, Christian Adam, Jürgen C. Becker, Thibault Kervarrec, David Schrama and Roland Houben
Cancers 2020, 12(4), 919; https://doi.org/10.3390/cancers12040919 - 9 Apr 2020
Cited by 19 | Viewed by 4688
Abstract
Merkel cell carcinoma (MCC) is a rare and highly aggressive skin cancer with frequent viral etiology. Indeed, in about 80% of cases, there is an association with Merkel cell polyomavirus (MCPyV); the expression of viral T antigens is crucial for growth of virus-positive [...] Read more.
Merkel cell carcinoma (MCC) is a rare and highly aggressive skin cancer with frequent viral etiology. Indeed, in about 80% of cases, there is an association with Merkel cell polyomavirus (MCPyV); the expression of viral T antigens is crucial for growth of virus-positive tumor cells. Since artesunate—a drug used to treat malaria—has been reported to possess additional anti-tumor as well as anti-viral activity, we sought to evaluate pre-clinically the effect of artesunate on MCC. We found that artesunate repressed growth and survival of MCPyV-positive MCC cells in vitro. This effect was accompanied by reduced large T antigen (LT) expression. Notably, however, it was even more efficient than shRNA-mediated downregulation of LT expression. Interestingly, in one MCC cell line (WaGa), T antigen knockdown rendered cells less sensitive to artesunate, while for two other MCC cell lines, we could not substantiate such a relation. Mechanistically, artesunate predominantly induces ferroptosis in MCPyV-positive MCC cells since known ferroptosis-inhibitors like DFO, BAF-A1, Fer-1 and β-mercaptoethanol reduced artesunate-induced death. Finally, application of artesunate in xenotransplanted mice demonstrated that growth of established MCC tumors can be significantly suppressed in vivo. In conclusion, our results revealed a highly anti-proliferative effect of the approved and generally well-tolerated anti-malaria compound artesunate on MCPyV-positive MCC cells, suggesting its potential usage for MCC therapy. Full article
(This article belongs to the Special Issue The Biological and Clinical Aspects of Merkel Cell Carcinoma)
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11 pages, 1128 KiB  
Article
Tumor Ulceration, Reduced Infiltration of CD8-Lymphocytes, High Neutrophil-to-CD8-Lymphocyte Ratio and Absence of MC Virus are Negative Prognostic Markers for Patients with Merkel Cell Carcinoma
by Simon Naseri, Torben Steiniche, Jeanette Bæhr Georgsen, Rune Thomsen, Morten Ladekarl, Martin Heje, Tine Engberg Damsgaard and Marie Louise Bønnelykke-Behrndtz
Cancers 2020, 12(4), 888; https://doi.org/10.3390/cancers12040888 - 6 Apr 2020
Cited by 12 | Viewed by 3474
Abstract
(1) Background: Merkel cell carcinoma (MCC) is caused by the Merkel cell polyomavirus and UV radiation. Understanding of the underlying biology is limited, but identification of prognostic markers may lead to better prognostic stratification for the patients. (2) Methods: Ninety patients diagnosed with [...] Read more.
(1) Background: Merkel cell carcinoma (MCC) is caused by the Merkel cell polyomavirus and UV radiation. Understanding of the underlying biology is limited, but identification of prognostic markers may lead to better prognostic stratification for the patients. (2) Methods: Ninety patients diagnosed with MCC (1996–2012) were included. Virus status was estimated by polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Ulceration status, PD-L1, cd66b neutrophils, cd8 lymphocytes and biomarkers of vascularization (cd34 endothelial cells) and migration (e-cadherin) were estimated by IHC and analyzed with digital pathology. (3) Results: Virus was present in 47% of patient samples and correlated with lower E-cadherin expression (p = 0.0005), lower neutrophil-to-CD8 lymphocyte ratio (N:CD8 ratio) (p = 0.02) and increased PD-L1 expression (p = 0.03). Ulceration was associated with absence of virus (p = 0.03), increased neutrophil infiltration (p < 0.0001) and reduced CD8 lymphocyte infiltration (p = 0.04). In multivariate analysis, presence of virus (p = 0.01), ulceration (p = 0.05) and increased CD8 lymphocyte infiltration (p = 0.001) showed independent prognostic impacts on MCC-specific survival. (3) Conclusions: In this study, we found that a high N:CD8 ratio, ulceration, virus-negative status and absence of CD8 lymphocytes are negative prognostic markers. Accurate prognostic stratification of the patients may be important in the clinical setting for determination of adjuvant treatment. Full article
(This article belongs to the Special Issue The Biological and Clinical Aspects of Merkel Cell Carcinoma)
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12 pages, 1586 KiB  
Article
Highly Expressed miR-375 is not an Intracellular Oncogene in Merkel Cell Polyomavirus-Associated Merkel Cell Carcinoma
by Kaiji Fan, Armin Zebisch, Kai Horny, David Schrama and Jürgen C. Becker
Cancers 2020, 12(3), 529; https://doi.org/10.3390/cancers12030529 - 25 Feb 2020
Cited by 16 | Viewed by 4886
Abstract
miR-375 is a highly abundant miRNA in Merkel cell carcinoma (MCC). In other cancers, it acts as either a tumor suppressor or oncogene. While free-circulating miR-375 serves as a surrogate marker for tumor burden in patients with advanced MCC, its function within MCC [...] Read more.
miR-375 is a highly abundant miRNA in Merkel cell carcinoma (MCC). In other cancers, it acts as either a tumor suppressor or oncogene. While free-circulating miR-375 serves as a surrogate marker for tumor burden in patients with advanced MCC, its function within MCC cells has not been established. Nearly complete miR-375 knockdown in MCC cell lines was achieved using antagomiRs via nucleofection. The cell viability, growth characteristics, and morphology were not altered by this knockdown. miR-375 target genes and related signaling pathways were determined using Encyclopedia of RNA Interactomes (ENCORI) revealing Hippo signaling and epithelial to mesenchymal transition (EMT)-related genes likely to be regulated. Therefore, their expression was analyzed by multiplexed qRT-PCR after miR-375 knockdown, demonstrating only a limited change in expression. In summary, highly effective miR-375 knockdown in classical MCC cell lines did not significantly change the cell viability, morphology, or oncogenic signaling pathways. These observations render miR-375 an unlikely intracellular oncogene in MCC cells, thus suggesting that likely functions of miR-375 for the intercellular communication of MCC should be addressed. Full article
(This article belongs to the Special Issue The Biological and Clinical Aspects of Merkel Cell Carcinoma)
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Review

Jump to: Editorial, Research

38 pages, 825 KiB  
Review
Merkel Cell Polyomavirus and Merkel Cell Carcinoma
by Valeria Pietropaolo, Carla Prezioso and Ugo Moens
Cancers 2020, 12(7), 1774; https://doi.org/10.3390/cancers12071774 - 3 Jul 2020
Cited by 73 | Viewed by 8502
Abstract
Viruses are the cause of approximately 15% of all human cancers. Both RNA and DNA human tumor viruses have been identified, with Merkel cell polyomavirus being the most recent one to be linked to cancer. This virus is associated with about 80% of [...] Read more.
Viruses are the cause of approximately 15% of all human cancers. Both RNA and DNA human tumor viruses have been identified, with Merkel cell polyomavirus being the most recent one to be linked to cancer. This virus is associated with about 80% of Merkel cell carcinomas, a rare, but aggressive cutaneous malignancy. Despite its name, the cells of origin of this tumor may not be Merkel cells. This review provides an update on the structure and life cycle, cell tropism and epidemiology of the virus and its oncogenic properties. Putative strategies to prevent viral infection or treat virus-positive Merkel cell carcinoma patients are discussed. Full article
(This article belongs to the Special Issue The Biological and Clinical Aspects of Merkel Cell Carcinoma)
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13 pages, 900 KiB  
Review
Management Recommendations for Merkel Cell Carcinoma—A Danish Perspective
by Simon Naseri, Torben Steiniche, Morten Ladekarl, Marie Louise Bønnelykke-Behrndtz, Lisbet R. Hölmich, Seppo W. Langer, Alessandro Venzo, Elizaveta Tabaksblat, Siri Klausen, Mathilde Skaarup Larsen, Niels Junker and Annette H. Chakera
Cancers 2020, 12(3), 554; https://doi.org/10.3390/cancers12030554 - 28 Feb 2020
Cited by 16 | Viewed by 5850
Abstract
Merkel cell carcinoma (MCC) is a rare malignant neuroendocrine carcinoma of the skin with a poor prognosis and an apparent increase in incidence. Due to its rarity, evidence-based guidelines are limited, and there is a lack of awareness among clinicians. This review constitutes [...] Read more.
Merkel cell carcinoma (MCC) is a rare malignant neuroendocrine carcinoma of the skin with a poor prognosis and an apparent increase in incidence. Due to its rarity, evidence-based guidelines are limited, and there is a lack of awareness among clinicians. This review constitutes the consensus management recommendations developed by the Danish MCC expert group and is based on a systematic literature search. Patients with localized disease are recommended surgical excision and adjuvant radiotherapy to the primary site; however, this may be omitted in patients with MCC with low risk features. Patients with regional lymph node involvement are recommended complete lymph node removal and adjuvant radiotherapy in case of extracapsular disease. Metastatic disease was traditionally treated with chemotherapy, however, recent clinical trials with immune therapy have been promising. Immune checkpoint inhibitors targeting the programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1) axis should therefore be strongly considered as first-line treatment for fit patients. A 5-year follow-up period is recommended involving clinical exam every 3 months for 2 years and every 6 months for the following 3 years and PET-CT one to two times a year or if clinically indicated. These national recommendations are intended to offer uniform patient treatment and hopefully improve prognosis. Full article
(This article belongs to the Special Issue The Biological and Clinical Aspects of Merkel Cell Carcinoma)
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