{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T20:21:00Z","timestamp":1789330860892,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Most patients with high-risk melanomas develop metastasis within the first few years after diagnosis. However, late recurrence of melanoma is seen in patients that metastasize more than 10 years after the primary diagnosis; a metastasis after 15 years is considered an ultra-late recurrence. It is critical to better understand the clinical and biological characteristics of this subset of melanoma patients in order to offer an individual treatment plan and prevent metastasis. Methods: We retrospectively analyzed melanoma patients with recurrence \u226510 years after a primary diagnosis documented between 1993 and 2012 at the skin cancer center of the University Medical Center Leipzig, Germany. We conducted a comprehensive review of the literature and compared the results with our data. Available archived primary melanoma tissue was investigated with a seven-marker immunohistochemical signature (immunoprint\u00ae) previously validated to reliably identify high-risk patients within stages IB-III. Results: Out of 36 analyzed patients, a third metastasized ultra-late (\u226515 years). The mean age at initial diagnosis was 51 years, with women being diagnosed comparatively younger than men. The largest proportion of patients with late recurrence had primary melanomas located on the trunk. The immunoprint\u00ae signature of the available primary melanomas allowed the accurate prediction of a high risk. However, it is difficult to draw a definitive conclusion from the small number of cases that could be analyzed with immunoprint\u00ae (n = 2) in this study. Apart from the primary tumor characteristics, the laboratory values at time of metastasis, comorbidities and outcome are also shown. Conclusion: Late and ultra-late recurrent melanomas seem not to differ from melanomas in general, apart from a distinctly higher proportion of lower leg localizations in ultra-late recurrent melanomas. The immunoprint\u00ae signature may help to identify high-risk primary tumors at the time of initial diagnosis. However, apart from the risk profile of the primary tumor, it seems that individual immune surveillance can control residual tumor cells for more than a decade. Advanced age and increasing comorbidities may contribute to a disturbed immunological balance.<\/jats:p>","DOI":"10.3390\/jcm11072026","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T06:01:34Z","timestamp":1649138494000},"page":"2026","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Risk Stratification and Clinical Characteristics of Patients with Late Recurrence of Melanoma (&gt;10 Years)"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2850-2526","authenticated-orcid":false,"given":"Robin","family":"Reschke","sequence":"first","affiliation":[{"name":"Department of Dermatology, Allergology and Venereology, University Medical Center, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Dumann","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Allergology and Venereology, University Medical Center, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6488-1917","authenticated-orcid":false,"given":"Mirjana","family":"Ziemer","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Allergology and Venereology, University Medical Center, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.clindermatol.2008.09.001","article-title":"Melanoma epidemiology and trends","volume":"27","author":"Garbe","year":"2009","journal-title":"Clin. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1097\/CMR.0000000000000489","article-title":"Stage-specific incidence trends of melanoma in an English region, 1996\u20132015, Longitudinal analyses of population-based data","volume":"30","author":"Herbert","year":"2018","journal-title":"Melanoma Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3109\/2000656X.2010.550472","article-title":"Recurrence of cutaneous malignant melanoma after more than 20 years","volume":"45","author":"Bredgaard","year":"2011","journal-title":"J. Plast. Surg. Hand Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jamcollsurg.2013.03.007","article-title":"Late recurrence in melanoma: Clinical implications of lost dormancy","volume":"217","author":"Faries","year":"2013","journal-title":"J. Am. Coll. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/S0007-1226(89)90111-2","article-title":"The incidence of late recurrence (greater than 10 years); an analysis of 536 consecutive cases of cutaneous melanoma","volume":"42","author":"Callaway","year":"1989","journal-title":"Br. J. Plast. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/nrc3793","article-title":"Mechanisms of disseminated cancer cell dormancy: An awakening field","volume":"14","author":"Sosa","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/pcmr.12432","article-title":"Immunogenic, cellular, and angiogenic drivers of tumor dormancy\u2014A melanoma view","volume":"29","author":"Senft","year":"2016","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/nature15726","article-title":"Oxidative stress inhibits distant metastasis by human melanoma cells","volume":"527","author":"Piskounova","year":"2015","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.2147\/OTT.S156421","article-title":"Impact of smoking on efficacy of PD-1\/PD-L1 inhibitors in non-small cell lung cancer patients: A meta-analysis","volume":"11","author":"Li","year":"2018","journal-title":"OncoTargets Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1742-1241.2004.00340.x","article-title":"Effects of cigarette smoking on the antioxidant defence in young healthy male volunteers","volume":"59","author":"Charalabopoulos","year":"2005","journal-title":"Int. J. Clin. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2217\/mmt.15.4","article-title":"Understanding melanoma stem cells","volume":"2","author":"Nguyen","year":"2015","journal-title":"Melanoma Manag."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Reschke, R., Gussek, P., and Ziemer, M. (2021). Identifying High-Risk Tumors within AJCC Stage IB-III Melanomas Using a Seven-Marker Immunohistochemical Signature. Cancers, 13.","DOI":"10.3390\/cancers13122902"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Meyer, S., Fuchs, T.J., Bosserhoff, A.K., Hofst\u00e4dter, F., Pauer, A., Roth, V., Buhmann, J.M., Moll, I., Anagnostou, N., and Brandner, J.M. (2012). A seven-marker signature and clinical outcome in malignant melanoma: A large-scale tissue-microarray study with two independent patient cohorts. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038222"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Forget, P., Khalifa, C., Defour, J.P., Latinne, D., Van Pel, M.C., and De Kock, M. (2017). What is the normal value of the neutrophil-to-lymphocyte ratio?. BMC Res. Notes, 10.","DOI":"10.1186\/s13104-016-2335-5"},{"key":"ref_15","unstructured":"Gesellschaft der Epidemiologischen Krebsregister Deutschland (2022, March 15). Melanom Atlas. Available online: http:\/\/atlas.gekid.de\/CurrentVersion\/atlas.html."},{"key":"ref_16","first-page":"3081","article-title":"Primary Locations of Malignant Melanoma Lesions Depending on Patients\u2019 Gender and Age","volume":"18","author":"Salwowska","year":"2017","journal-title":"Asian Pac. J. Cancer Prev. APJCP"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1111\/j.1365-4362.1992.tb03980.x","article-title":"Lack of predictive factors in late recurrence of stage I melanoma","volume":"31","author":"Tahery","year":"1992","journal-title":"Int. J. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e11446","DOI":"10.1097\/MD.0000000000011446","article-title":"Prognostic value of neutrophil-to-lymphocyte ratio in melanoma: Evidence from a PRISMA-compliant meta-analysis","volume":"97","author":"Ding","year":"2018","journal-title":"Medicine"},{"key":"ref_19","first-page":"1311","article-title":"S100 beta is a more reliable tumor marker in peripheral blood for patients with newly occurred melanoma metastases compared with MIA, albumin and lactate-dehydrogenase","volume":"21","author":"Kaskel","year":"2001","journal-title":"Anticancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1111\/jdv.16106","article-title":"Late recurrence of melanoma after 10 years\u2014Is the course of the disease different from early recurrences?","volume":"34","author":"Sarac","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1002\/ijc.29281","article-title":"Risk factors related to late metastases in 1372 melanoma patients disease free more than 10 years","volume":"136","author":"Ribero","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1007\/s00268-010-0859-8","article-title":"Malignant melanoma of the skin: Long-term follow-up and time to first recurrence","volume":"35","author":"Hohnheiser","year":"2011","journal-title":"World J. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1111\/j.1468-3083.2009.03536.x","article-title":"Late recurrence (10 years or more) of malignant melanoma in south-east Germany (Saxony). A single-centre analysis of 1881 patients with a follow-up of 10 years or more","volume":"24","author":"Hansel","year":"2010","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1046\/j.1365-2133.2003.05097_8.x","article-title":"Late (10 years) recurrence of melanoma: The Scottish experience","volume":"148","author":"Leman","year":"2003","journal-title":"Br. J. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1067\/mjd.2000.107234","article-title":"Late metastases of cutaneous melanoma: An analysis of 31 patients","volume":"43","author":"Baumert","year":"2000","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s001050050588","article-title":"Melanomerstmetastasen nach 10 und mehr Jahren Erscheinungsfreiheit","volume":"48","author":"Peters","year":"1997","journal-title":"Hautarzt"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1002\/(SICI)1097-0142(19970615)79:12<2361::AID-CNCR10>3.0.CO;2-P","article-title":"Ultra-late recurrence (15 years or longer) of cutaneous melanoma","volume":"79","author":"Tsao","year":"1997","journal-title":"Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1097\/00000658-199008000-00010","article-title":"Late recurrence of malignant melanoma. Analysis of 168 patients","volume":"212","author":"Crowley","year":"1990","journal-title":"Ann. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1097\/00006534-199009000-00024","article-title":"Late recurrence of localized cutaneous melanoma: Its influence on follow-up policy","volume":"86","author":"McEwan","year":"1990","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1055\/s-2008-1066732","article-title":"Sp\u00e4te Metastasierung bei malignem Melanom der Haut","volume":"114","author":"Landthaler","year":"1989","journal-title":"Dtsch. Med. Wochenschr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/jso.2930420206","article-title":"Late recurrence of stage I malignant melanoma","volume":"42","author":"Gutman","year":"1989","journal-title":"J. Surg. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1001\/archsurg.1985.01390340053010","article-title":"Late relapse from cutaneous stage I malignant melanoma","volume":"120","author":"Shaw","year":"1985","journal-title":"Arch. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1001\/archsurg.1983.01390070012003","article-title":"Late recurrence of cutaneous melanoma","volume":"118","author":"Briele","year":"1983","journal-title":"Arch. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1001\/archderm.1983.01650320018009","article-title":"Effect of anatomical location on prognosis in patients with clinical stage I melanoma","volume":"119","author":"Rogers","year":"1983","journal-title":"Arch. Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Tas, F., and Erturk, K. (2021). Limb melanomas: Acral melanomas have worse survival. J. Dermatol. Treat., 1\u20138.","DOI":"10.1080\/09546634.2021.1877248"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/bjs.11946","article-title":"Predicting recurrence in patients with sentinel node-negative melanoma: Validation of the EORTC nomogram using population-based data","volume":"108","author":"Ahmed","year":"2021","journal-title":"Br. J. Surg."},{"key":"ref_37","first-page":"215","article-title":"Therapy understanding and health related quality of life in stage III\/IV melanoma patients treated with novel adjuvant therapies","volume":"19","author":"Reschke","year":"2021","journal-title":"J. Dtsch. Dermatol. Ges."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/7\/2026\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:49:55Z","timestamp":1760136595000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/7\/2026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,5]]},"references-count":37,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["jcm11072026"],"URL":"https:\/\/doi.org\/10.3390\/jcm11072026","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,5]]}}}