{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T11:58:00Z","timestamp":1776945480215,"version":"3.51.4"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T00:00:00Z","timestamp":1639699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. The incidence of the disease has undergone a significant increase in recent years, which is caused by an increase in the average age of the population and in the use of immunosuppressive therapies. MCC is an aggressive pathology, which metastasizes early to the lymph nodes. These characteristics impose an accurate diagnostic analysis of the regional lymph node district with radiography, clinical examination and sentinel node biopsy. In recent years, there has been a breakthrough in the treatment of the advanced pathology thanks to the introduction of monoclonal antibodies acting on the PD-1\/PD-L1 axis. This study aimed to describe the clinico-pathological characteristics, treatment strategies and prognostic factors of MCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective cohort study was conducted involving 143 consecutive patients who were diagnosed and\/or treated for MCC. These patients were referred to the Veneto Institute of Oncology IOV-IRCCS and to the University Hospital of Padua (a third-level center) in the period between December 1991 and January 2020. In the majority of cases, diagnosis took place at the IOV. However, some patients were diagnosed elsewhere and subsequently referred to the IOV for a review of the diagnosis or to begin specific therapeutic regimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>143 patients, with an average age of 71 years, were affected mainly with autoimmune and neoplastic comorbidities. Our analysis has shown that age, autoimmune comorbidities and the use of therapy with immunomodulating drugs (which include corticosteroids, statins and beta-blockers) are associated with a negative prognosis. In this sense, male sex is also a negative prognostic factor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Autoimmune and neoplastic comorbidities were frequent in the studied population. The use of drugs with immunomodulatory effects was also found to be a common feature of the population under examination. The use of this type of medication is considered a negative prognostic factor. The relevance of a multidisciplinary approach to the patient with MCC is confirmed, with the aim of assessing the risks and benefits related to the use of immunomodulating therapy in the individual patient.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2021.737842","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T04:53:46Z","timestamp":1639716826000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Merkel Cell Carcinoma: Evaluation of the Clinico-Pathological Characteristics, Treatment Strategies and Prognostic Factors in a Monocentric Retrospective Series (n=143)"],"prefix":"10.3389","volume":"11","author":[{"given":"Marco","family":"Rastrelli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Del Fiore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Russo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacopo","family":"Tartaglia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Dal Monico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rocco","family":"Cappellesso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Nicol\u00e8","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Piccin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessio","family":"Fabozzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernardo","family":"Biffoli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Di Prata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Ferrazzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Dall\u2019Olmo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Vecchiato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romina","family":"Spina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Russano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Bezzon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Cingarlini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renzo","family":"Mazzarotto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Parisi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Scarzello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacopo","family":"Pigozzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tito","family":"Brambullo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saveria","family":"Tropea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Vindigni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco","family":"Bassetto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Bertin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Gregianin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo Paolo","family":"Dei Tos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Cavallin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Alaibac","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanna","family":"Chiarion-Sileni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Mocellin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/ced.14530","article-title":"Merkel Cell Carcinoma","volume":"46","author":"Patel","year":"2020","journal-title":"Clin Exp Dermatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-017-2099-3","article-title":"Epidemiology, Biology and Therapy of Merkel Cell Carcinoma: Conclusions From the EU Project IMMOMEC","volume":"67","author":"Becker","year":"2018","journal-title":"Cancer Immunol Immunother"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1177\/000313481508100819","article-title":"Dramatic Increase in the Incidence and Mortality From Merkel Cell Carcinoma in the United States","volume":"81","author":"Fitzgerald","year":"2015","journal-title":"Am Surg"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00529","article-title":"A Therapeutic and Diagnostic Multidisciplinary Pathway for Merkel Cell Carcinoma Patients","volume":"10","author":"Rastrelli","year":"2020","journal-title":"Front Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1610-0387.2008.06830.x","article-title":"Merkel Cell Carcinoma: Molecular Pathogenesis, Clinical Features and Therapy","volume":"6","author":"Becker","year":"2008","journal-title":"J Dtsch Dermatol Ges"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2005.02158.x","article-title":"Clinicopathological and Immunohistochemical Analysis of 20 Cases of Merkel Cell Carcinoma in Search of Prognostic Markers","volume":"46","author":"Llombart","year":"2005","journal-title":"Histopathology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.18632\/oncoscience.358","article-title":"Understanding the Influence of Patient Demographics on Disease Severity, Treatment Strategy, and Survival Outcomes in Merkel Cell Carcinoma: A Surveillance, Epidemiology, and End-Results Study","volume":"4","author":"Ezaldein","year":"2017","journal-title":"Oncoscience"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-016-5266-4","article-title":"Analysis of Prognostic Factors From 9387 Merkel Cell Carcinoma Cases Forms the Basis for the New 8th Edition AJCC Staging System","volume":"23","author":"Harms","year":"2016","journal-title":"Ann Surg Oncol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"17077","DOI":"10.1038\/nrdp.2017.77","article-title":"Merkel Cell Carcinoma","volume":"3","author":"Becker","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2007.11.020","article-title":"Clinical Characteristics of Merkel Cell Carcinoma at Diagnosis in 195 Patients: The AEIOU Features","volume":"58","author":"Heath","year":"2008","journal-title":"J Am Acad Dermatol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/cup.13910","article-title":"Merkel Cell Carcinoma: A Review","volume":"48","author":"Walsh","year":"2021","journal-title":"J Cutan Pathol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdq366","article-title":"Merkel Cell Carcinoma","author":"Becker","year":"2010","journal-title":"Ann Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2015.06.131","article-title":"Diagnosis and Treatment of Merkel Cell Carcinoma. European Consensus-Based Interdisciplinary Guideline","volume":"51","author":"Lebbe","year":"2015","journal-title":"Eur J Cancer"},{"key":"B14","article-title":"Prognostic Value of Immune Cell Infiltration, Tertiary Lymphoid Structures and PD-L1 Expression in Merkel Cell Carcinomas","volume":"7","author":"Behr","year":"2014","journal-title":"Int J Clin Exp Pathol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.7497\/j.issn.2095-3941.2015.0022","article-title":"Tumor Immune Microenvironment Characterization and Response to Anti-PD-1 Therapy","volume":"12","author":"Santarpia","year":"2015","journal-title":"Cancer Biol Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603702","article-title":"PD-1 Blockade With Pembrolizumab in Advanced Merkel-Cell Carcinoma","volume":"374","author":"Nghiem","year":"2016","journal-title":"N Engl J Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-018-02295-4","article-title":"Early Objective Response to Avelumab Treatment is Associated With Improved Overall Survival in Patients With Metastatic Merkel Cell Carcinoma","volume":"68","author":"D'Angelo","year":"2019","journal-title":"Cancer Immunol Immunother"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10100350","article-title":"Prognostic Factors in Merkel Cell Carcinoma: A Retrospective Single-Center Study in 90 Patients","volume":"10","author":"Rastrelli","year":"2018","journal-title":"Cancers (Basel)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-018-6513-7","article-title":"Melanoma Staging: American Joint Committee on Cancer (AJCC) 8th Edition and Beyond [Published Correction Appears in Ann Surg Oncol. 2018 Dec;25(Suppl 3):993-994]","volume":"25","author":"Gershenwald","year":"2018","journal-title":"Ann Surg Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A New Method of Classifying Prognostic Comorbidity in Longitudinal Studies: Development and Validation","volume":"40","author":"Charlson","year":"1987","journal-title":"J Chronic Dis"},{"key":"B21","volume-title":"R: A Language and Environment for Statistical Computing","year":"2020"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2012.05.006","article-title":"Increased Incidence of Merkel Cell Carcinoma Among Younger Statin Users","volume":"36","author":"Sahi","year":"2012","journal-title":"Cancer Epidemiol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107614","article-title":"Statins and Autoimmunity: State-Of-the-Art","volume":"214","author":"Dehnavi","year":"2020","journal-title":"Pharmacol Ther"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2016.1164141","article-title":"Immunological and Pleiotropic Effects of Individual \u03b2-Blockers and Their Relevance in Cancer Therapies","volume":"25","author":"Chung","year":"2016","journal-title":"Expert Opin Investig Drugs"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.388","article-title":"Systemic Immune Suppression Predicts Diminished Merkel Cell Carcinoma-Specific Survival Independent of Stage","volume":"133","author":"Paulson","year":"2013","journal-title":"J Invest Dermatol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1159\/000350757","article-title":"Skin Cancer in Organ Transplant Recipients","volume":"80","author":"Kempf","year":"2013","journal-title":"Pathobiology"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)07668-7","article-title":"Merkel Cell Carcinoma and HIV Infection","volume":"359","author":"Engels","year":"2002","journal-title":"Lancet"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1097\/MLR.0b013e318297429c","article-title":"Why Summary Comorbidity Measures Such As the Charlson Comorbidity Index and Elixhauser Score Work","volume":"53","author":"Austin","year":"2015","journal-title":"Med Care"},{"key":"B29","article-title":"Merkel Cell Carcinoma and Melanoma: Etiological Similarities and Differences [Published Correction Appears in Cancer Epidemiol Biomarkers Prev 1999 May;8(5):485]","volume":"8","author":"Miller","year":"1999","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/","article-title":"Merkel Cell Carcinoma, Chronic Lymphocytic Leukemia and Other Lymphoproliferative Disorders: An Old Bond With Possible New Viral Ties","volume":"22","author":"Tadmor","year":"2011","journal-title":"Ann Oncol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00451","article-title":"Histogenesis of Merkel Cell Carcinoma: A Comprehensive Review","volume":"9","author":"Kervarrec","year":"2019","journal-title":"Front Oncol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2019.0267","article-title":"Evaluation of Lymph Node Ratio Association With Long-Term Patient Survival After Surgery for Node-Positive Merkel Cell Carcinoma","volume":"155","author":"Cheraghlou","year":"2019","journal-title":"JAMA Dermatol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-014-3587-8","article-title":"The Role of Sentinel Lymph Node Biopsy in Patients With Merkel Cell Carcinoma: Uncertainty Prevails","volume":"21","author":"Thompson","year":"2014","journal-title":"Ann Surg Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.737842\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T04:53:52Z","timestamp":1639716832000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.737842\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,17]]},"references-count":33,"alternative-id":["10.3389\/fonc.2021.737842"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2021.737842","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,17]]},"article-number":"737842"}}