{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T09:03:23Z","timestamp":1776071003827,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:00:00Z","timestamp":1775865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer, with prognosis influenced by tumor location and primary status. This study evaluated clinicopathological features and survival outcomes in patients with MCC from multiple centers in Israel. Methods: Data on demographics, tumor characteristics, lymph node (LN) involvement, treatment, and survival were collected. Patients were stratified by primary tumor status (known vs. unknown) and tumor location (sun-exposed vs. non-sun-exposed). Disease-free survival (DFS) and overall survival (OS) were estimated using Kaplan\u2013Meier analysis, and multivariate analyses were performed. Results: The cohort included 80 patients diagnosed with stage 3 (with LN involvement) MCC, of whom 52 (65%) had primary MCC with lymph node involvement, and 28 patients (35%) with unknown primary MCC. The majority were male (81.3%), with a median age of 71.2 years (range, 37\u201392). The median DFS and OS for the entire cohort were 24 and 32 months, respectively. Patients with unknown primary tumors had longer DFS (34 vs. 18 months; p = 0.0503) and OS (43 vs. 28 months; p = 0.0362) compared with those with known primary MCC. Non-sun-exposed tumors were associated with longer median DFS (32 vs. 18.5 months; p = 0.0663) and OS (41 vs. 23 months; p = 0.0353). Five-year survival analysis showed improved outcomes in patients with unknown primary tumors (DFS 54% vs. 35%, p = 0.04; OS 57% vs. 42%, p = 0.03) and in non-sun-exposed tumors (DFS 51% vs. 33%, p = 0.05; OS 57% vs. 40%, p = 0.04). Conclusions: Unknown primary status and non-sun-exposed tumor location are potentially associated with improved long-term survival in patients with MCC. These findings highlight the prognostic importance of tumor origin and anatomical site in MCC management.<\/jats:p>","DOI":"10.3390\/medsci14020193","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T07:29:29Z","timestamp":1776065369000},"page":"193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Survival Outcomes in Lymph Node-Positive Merkel Cell Carcinoma (Stage III): A Comparison Between Known and Unknown Primary Tumors and Their Sun Exposure Sites"],"prefix":"10.3390","volume":"14","author":[{"given":"Ronen","family":"Brenner","sequence":"first","affiliation":[{"name":"Oncology Institute, Edith Wolfson Medical Center, Holon 58220, Israel"},{"name":"Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna T. Frumin","family":"Edri","sequence":"additional","affiliation":[{"name":"Oncology Institute, Edith Wolfson Medical Center, Holon 58220, Israel"},{"name":"Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabri","family":"El-Saied","sequence":"additional","affiliation":[{"name":"Medical School for International Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilia","family":"Berezhnov","sequence":"additional","affiliation":[{"name":"Oncology Institute, Edith Wolfson Medical Center, Holon 58220, Israel"},{"name":"Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Ievko","sequence":"additional","affiliation":[{"name":"Oncology Institute, Edith Wolfson Medical Center, Holon 58220, Israel"},{"name":"Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8273-4723","authenticated-orcid":false,"given":"Keren","family":"Rouvinov","sequence":"additional","affiliation":[{"name":"Medical School for International Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel"},{"name":"The Legacy Heritage Cancer Center, Dr. Larry Norton Institute, Soroka Medical Center, Beer Sheva 84105, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofiia","family":"Turaieva","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amichay","family":"Meirovitz","sequence":"additional","affiliation":[{"name":"Medical School for International Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel"},{"name":"The Legacy Heritage Cancer Center, Dr. Larry Norton Institute, Soroka Medical Center, Beer Sheva 84105, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanzilya","family":"Tairov","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shlomit","family":"Fenig","sequence":"additional","affiliation":[{"name":"Institute of Oncology, Kaplan Medical Center, Faculty of Medicine, Hebrew University, Jerusalem 91905, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nashat Abu","family":"Yasin","sequence":"additional","affiliation":[{"name":"Medical School for International Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel"},{"name":"The Legacy Heritage Cancer Center, Dr. Larry Norton Institute, Soroka Medical Center, Beer Sheva 84105, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Yakobson","sequence":"additional","affiliation":[{"name":"Medical School for International Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel"},{"name":"The Legacy Heritage Cancer Center, Dr. Larry Norton Institute, Soroka Medical Center, Beer Sheva 84105, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eyal","family":"Fenig","sequence":"additional","affiliation":[{"name":"Institute of Oncology, Davidoff Center, Rabin Medical Center, Beilinson Hospital, Petah Tikva 49414, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3330-2959","authenticated-orcid":false,"given":"Abed","family":"Agbarya","sequence":"additional","affiliation":[{"name":"Oncology Department, Bnai Zion Medical Center, Haifa 31047, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7570-4550","authenticated-orcid":false,"given":"Walid","family":"Shalata","sequence":"additional","affiliation":[{"name":"Medical School for International Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel"},{"name":"The Legacy Heritage Cancer Center, Dr. Larry Norton Institute, Soroka Medical Center, Beer Sheva 84105, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"375","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":"ref_2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.jaad.2017.12.004","article-title":"Merkel cell carcinoma: An update and review: Current and future therapy","volume":"78","author":"Tello","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.jaad.2017.10.028","article-title":"Merkel cell carcinoma: Current US incidence and projected increases based on changing demographics","volume":"78","author":"Paulson","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","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":"ref_5","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1002\/jso.27010","article-title":"Merkel cell carcinoma of unknown primary: Clinical presentation and outcomes","volume":"126","author":"Broida","year":"2022","journal-title":"J. Surg. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.jaad.2011.09.009","article-title":"Merkel cell carcinoma: The prognostic implications of an occult primary in stage IIIB (nodal) disease","volume":"67","author":"Foote","year":"2012","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zaggana, E., Konstantinou, M.P., Krasagakis, G.H., de Bree, E., Kalpakis, K., Mavroudis, D., and Krasagakis, K. (2022). Merkel Cell Carcinoma-Update on Diagnosis, Management and Future Perspectives. Cancers, 15.","DOI":"10.3390\/cancers15010103"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1001\/jamadermatol.2021.6096","article-title":"Recurrence and Mortality Risk of Merkel Cell Carcinoma by Cancer Stage and Time from Diagnosis","volume":"158","author":"McEvoy","year":"2022","journal-title":"JAMA Dermatol."},{"key":"ref_9","unstructured":"(2025, February 27). NCCN Clinical Practice Guidelines in Oncology: Merkel Cell Carcinoma (Version 2023). Available online: https:\/\/www.nccn.org\/guidelines\/guidelines-detail?category=1&id=1444."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1002\/cam4.4562","article-title":"Merkel cell carcinoma in lymph nodes with and without primary origin","volume":"11","author":"Fennig","year":"2022","journal-title":"Cancer Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fazio, N., Maisonneuve, P., Spada, F., Gervaso, L., Cella, C.A., Pozzari, M., Zerini, D., Pisa, E., Fumagalli, C., and Barberis, M. (2022). Nodal Merkel Cell Carcinoma with Unknown Primary Site and No Distant Metastasis: A Single-Center Series. Cancers, 14.","DOI":"10.3390\/cancers14194777"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Brenner, R., Frumin Edri, H.T., Sarel, I., Levko, A., Turaieva, S., Tairov, T., Berezhnov, I., Fenig, S., Fenig, E., and Ziv-Baran, T. (2025). Worse prognosis of local and locally advanced head and neck Merkel cell carcinoma: Is it time to change the treatment paradigm?. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1691000"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1177\/0300891620944209","article-title":"Multidisciplinary team approach for Merkel cell carcinoma: The European Institute of Oncology experience with focus on radiotherapy","volume":"107","author":"Zerini","year":"2021","journal-title":"Tumori J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1245\/s10434-021-10727-2","article-title":"Merkel Cell Carcinoma: Changing Practice Patterns and Impact on Recurrence-Free and Overall Survival at a Single Institution and Nationally","volume":"29","author":"Esposito","year":"2022","journal-title":"Ann. Surg. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/S0190-9622(03)02108-X","article-title":"Epidemiology of primary Merkel cell carcinoma in the United States","volume":"49","author":"Agelli","year":"2003","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jdcr.2020.11.017","article-title":"Unknown primary Merkel cell carcinoma in the immunosuppressed patient: Case series","volume":"8","author":"Rizzo","year":"2020","journal-title":"JAAD Case Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.jaad.2012.07.035","article-title":"Unknown primary Merkel cell carcinoma: 23 new cases and a review","volume":"68","author":"Tarantola","year":"2013","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1158\/1078-0432.CCR-17-1678","article-title":"Merkel Cell Carcinoma Patients Presenting Without a Primary Lesion Have Elevated Markers of Immunity, Higher Tumor Mutation Burden, and Improved Survival","volume":"24","author":"Vandeven","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1200\/JCO.18.01896","article-title":"Durable Tumor Regression and Overall Survival in Patients with Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy","volume":"37","author":"Nghiem","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Alves, A.S., Scampa, M., Martineau, J., Giordano, S., Kalbermatten, D.F., and Oranges, C.M. (2022). Merkel Cell Carcinoma of the External Ear: Population-Based Analysis and Survival Outcomes. Cancers, 14.","DOI":"10.3390\/cancers14225653"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.ejca.2016.10.022","article-title":"Merkel cell carcinoma: Epidemiology, prognosis, therapy and unmet medical needs","volume":"71","author":"Schadendorf","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1338237","DOI":"10.1080\/2162402X.2017.1338237","article-title":"Immune evasion mechanisms and immune checkpoint inhibition in advanced merkel cell carcinoma","volume":"6","author":"Schadendorf","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"941","DOI":"10.3892\/ol.2010.176","article-title":"Spontaneous regression of malignant tumors: Importance of the immune system and other factors (Review)","volume":"1","author":"Ricci","year":"2010","journal-title":"Oncol. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"76","DOI":"10.12788\/j.sder.0084","article-title":"Merkel cell carcinoma: Current status of targeted and future potential for immunotherapies","volume":"33","author":"Aldabagh","year":"2014","journal-title":"Semin. Cutan. Med. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/bjd.13870","article-title":"Merkel cell carcinoma and Merkel cell polyomavirus: A systematic review and meta-analysis","volume":"173","author":"Fuentes","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"165","DOI":"10.2302\/kjm.54.165","article-title":"Mechanisms of UV-induced immunosuppression","volume":"54","author":"Schwarz","year":"2005","journal-title":"Keio J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"155668","DOI":"10.1016\/j.prp.2024.155668","article-title":"Whole genome sequencing elucidates etiological differences in MCPyV-negative Merkel cell carcinoma","volume":"263","author":"Stephan","year":"2024","journal-title":"Pathol. Res. Pract."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Laikova, K.V., Oberemok, V.V., Krasnodubets, A.M., Gal\u2019chinsky, N.V., Useinov, R.Z., Novikov, I.A., Temirova, Z.Z., Gorlov, M.V., Shved, N.A., and Kumeiko, V.V. (2019). Advances in the Understanding of Skin Cancer: Ultraviolet Radiation, Mutations, and Antisense Oligonucleotides as Anticancer Drugs. Molecules, 24.","DOI":"10.3390\/molecules24081516"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Shalata, W., Edri, H.T.F., Sarel, I., Ievko, A., Turaieva, S., Tairov, T., Berezhnov, I., Fenig, S., Fenig, E., and Ziv-Baran, T. (2025). Is the Addition of Chemotherapy to Adjuvant Radiation in Merkel Cell Cancer Beneficial? Real-World Data with Long-Term Follow-Up. Cancers, 17.","DOI":"10.3390\/cancers17060945"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Yakobson, A., Brenner, R., Edri, H.T.F., Ievko, A., Turaieva, S., Tairov, T., Berezhnov, I., Fenig, S., Fenig, E., and Ziv-Baran, T. (2026). Sun-Exposed vs. Non-Sun-Exposed Areas: Epidemiology and Pathogenesis of Non-Metastatic Merkel Cell Carcinoma. Diagnostics, 16.","DOI":"10.3389\/fimmu.2025.1691000"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zwijnenburg, E.M., Lubeek, S.F.K., Werner, J.E.M., Amir, A.L., Weijs, W.L.J., Takes, R.P., Pegge, S.A.H., van Herpen, C.M.L., Adema, G.J., and Kaanders, J.H.A.M. (2021). Merkel Cell Carcinoma: New Trends. Cancers, 13.","DOI":"10.3390\/cancers13071614"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.jaad.2025.12.043","article-title":"Survival trends, prognostic factors, and drivers of metastases in patients with metastatic Merkel cell carcinoma: A Surveillance, Epidemiology, and End Results program-based analysis","volume":"94","author":"Joshi","year":"2026","journal-title":"J. Am. Acad. Dermatol."}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/2\/193\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:19:21Z","timestamp":1776068361000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/2\/193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,11]]},"references-count":32,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["medsci14020193"],"URL":"https:\/\/doi.org\/10.3390\/medsci14020193","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,11]]}}}