{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:34:49Z","timestamp":1760060089119,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Conventional melanoma is exceedingly rare in the pediatric population, particularly among prepubescent children, and its diagnosis and management necessitate a multidisciplinary approach. The objective of this present report is to delineate the diagnostic pathway and therapeutic management of a 4-year-old girl with conventional melanoma, with particular focus on the molecular context. A pigmented lesion located on the auricle was surgically excised, and subsequent histopathological and immunohistochemical analyses confirmed the diagnosis of malignant melanoma (pT3b). Radiologic investigations revealed no evidence of metastatic disease, and comprehensive genetic testing utilizing next-generation sequencing (NGS) identified no pathogenic variants in the germline genes examined, nor in the BRAF, NRAS, KRAS, and TP53 genes within the excised lesion. The patient remains in good general health. This case report adds to the limited body of literature on melanoma in pediatric patients and underscores the importance of thorough diagnostic evaluation in this age group.<\/jats:p>","DOI":"10.3390\/genes16080937","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T10:58:26Z","timestamp":1754564306000},"page":"937","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gene Mutation-Negative Malignant Melanoma in a Prepubertal Patient: A Clinical and Molecular Case Report"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2736-5524","authenticated-orcid":false,"given":"Adrian","family":"Gu\u017aniczak","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Poznan University of Medical Sciences, Fredry 10 Street, 61-701 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4714-6501","authenticated-orcid":false,"given":"Patrycja","family":"Sosnowska-Sienkiewicz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Medical University of Warsaw, \u017bwirki i Wigury 63A Street, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaros\u0142aw","family":"Szyd\u0142owski","sequence":"additional","affiliation":[{"name":"Department of Pediatric Otolaryngology, Poznan University of Medical Sciences, 27\/33 Szpitalna Street, 60-572 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawe\u0142","family":"Kurzawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, Poznan University of Medical Sciences, Przybyszewskiego 49 Street, 60-355 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2332-2750","authenticated-orcid":false,"given":"Danuta","family":"Januszkiewicz-Lewandowska","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, 27\/33 Szpitalna Street, 60-572 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/S0140-6736(23)00821-8","article-title":"Cutaneous Melanoma","volume":"402","author":"Long","year":"2023","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.ejca.2022.03.008","article-title":"European Consensus-Based Interdisciplinary Guideline for Melanoma. Part 1: Diagnostics: Update 2022","volume":"170","author":"Garbe","year":"2022","journal-title":"Eur. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1200\/JCO.23.01367","article-title":"Survival Trends Among Adolescents and Young Adults Diagnosed With Cancer in the United States: Comparisons With Children and Older Adults","volume":"42","author":"Keegan","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_4","first-page":"12","article-title":"Cancer Statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA A Cancer J. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1200\/JCO.2006.08.8310","article-title":"Melanoma in Children and Teenagers: An Analysis of Patients from the National Cancer Data Base","volume":"25","author":"Lange","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1111\/jdv.19220","article-title":"Melanoma in Children: A Systematic Review and Individual Patient Meta-Analysis","volume":"37","author":"Pampena","year":"2023","journal-title":"J. Eur. Acad. Dermatol. Venereol. JEADV"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.jaad.2012.12.953","article-title":"Pediatric Melanoma: Results of a Large Cohort Study and Proposal for Modified ABCD Detection Criteria for Children","volume":"68","author":"Cordoro","year":"2013","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Teixido, C., Castillo, P., Martinez-Vila, C., Arance, A., and Alos, L. (2021). Molecular Markers and Targets in Melanoma. Cells, 10.","DOI":"10.3390\/cells10092320"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ferrara, G., and Argenziano, G. (2021). The WHO 2018 Classification of Cutaneous Melanocytic Neoplasms: Suggestions From Routine Practice. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.675296"},{"key":"ref_10","first-page":"646","article-title":"Paediatric Melanoma: Clinical Update, Genetic Basis, and Advances in Diagnosis. Lancet Child Adolesc","volume":"3","author":"Merkel","year":"2019","journal-title":"Health"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e26792","DOI":"10.1002\/pbc.26792","article-title":"Pathology and Genomics of Pediatric Melanoma: A Critical Reexamination and New Insights","volume":"65","author":"Bahrami","year":"2018","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/jid.2014.425","article-title":"The Genomic Landscape of Childhood and Adolescent Melanoma","volume":"135","author":"Lu","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1002\/jso.27953","article-title":"A Review of Melanoma Subtypes: Genetic and Treatment Considerations","volume":"131","author":"Druskovich","year":"2025","journal-title":"J. Surg. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.soc.2020.11.005","article-title":"Pediatric Melanoma-Diagnosis, Management, and Anticipated Outcomes","volume":"30","author":"Aldrink","year":"2021","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1111\/pde.14672","article-title":"THE Demographics and Trends in Pediatric Melanoma in the United States: An Analysis of the National Cancer Database","volume":"38","author":"Yousif","year":"2021","journal-title":"Pediatr. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1111\/jdv.14299","article-title":"Paediatric Melanoma","volume":"31","author":"Stefanaki","year":"2017","journal-title":"J. Eur. Acad. Dermatol. Venereol. JEADV"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"205-viii","DOI":"10.1016\/j.det.2008.12.002","article-title":"Melanoma Epidemiology and Public Health","volume":"27","author":"Berwick","year":"2009","journal-title":"Dermatol. Clin."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/j.1365-4632.2010.04381.x","article-title":"Defining the Patient at High Risk for Melanoma","volume":"49","author":"Psaty","year":"2010","journal-title":"Int. J. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1158\/1055-9965.EPI-14-1062","article-title":"Development and Validation of a Melanoma Risk Score Based on Pooled Data from 16 Case-Control Studies","volume":"24","author":"Davies","year":"2015","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/jmedgenet-2015-103150","article-title":"Melanoma Genetics","volume":"53","author":"Read","year":"2016","journal-title":"J. Med. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e13214","DOI":"10.1111\/pcmr.13214","article-title":"Novel Variants in Medium and Low Penetrance Predisposing Genes in a Hungarian Malignant Melanoma Cohort With Increased Risk","volume":"38","author":"Bokor","year":"2025","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Fiasconaro, C.A., Carbone, A., Giordano, S., Cavallo, F., Fava, P., Pasini, B., Yakymiv, Y., Marchisio, S., Quaglino, P., and Ribero, S. (2025). Germline Non-CDKN2A Variants in Melanoma and Associated Hereditary Cancer Syndromes. Diseases, 13.","DOI":"10.3390\/diseases13060180"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3825","DOI":"10.1002\/cncr.33750","article-title":"A Prospective, Comprehensive Registry That Integrates the Molecular Analysis of Pediatric and Adolescent Melanocytic Lesions","volume":"127","author":"Pappo","year":"2021","journal-title":"Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1158\/2159-8290.CD-16-1237","article-title":"Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1)","volume":"7","author":"Drilon","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/pde.14935","article-title":"Genomic Comparison of Malignant Melanoma and Atypical Spitz Tumor in the Pediatric Population","volume":"39","author":"Church","year":"2022","journal-title":"Pediatr. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"290","DOI":"10.6004\/jnccn.2024.0036","article-title":"NCCN Guidelines\u00ae Insights: Melanoma: Cutaneous, Version 2.2024","volume":"22","author":"Swetter","year":"2024","journal-title":"J. Natl. Compr. Cancer Netw. JNCCN"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.annonc.2024.11.006","article-title":"Cutaneous Melanoma: ESMO Clinical Practice Guideline for Diagnosis, Treatment and Follow-Up","volume":"36","author":"Amaral","year":"2025","journal-title":"Ann. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1002\/ijc.31791","article-title":"Whole Genome Sequencing of Melanomas in Adolescent and Young Adults Reveals Distinct Mutation Landscapes and the Potential Role of Germline Variants in Disease Susceptibility","volume":"144","author":"Wilmott","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1080\/14737159.2020.1738221","article-title":"Evolution of Approaches to Identify Melanoma Missing Heritability","volume":"20","author":"Dalmasso","year":"2020","journal-title":"Expert. Rev. Mol. Diagn."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1097\/01.cmr.0000131014.79262.bf","article-title":"Germline CDKN2A Mutations Are Rare in Child and Adolescent Cutaneous Melanoma","volume":"14","author":"Berg","year":"2004","journal-title":"Melanoma Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1001\/archderm.136.9.1118","article-title":"Low Prevalence of Germline CDKN2A and CDK4 Mutations in Patients with Early-Onset Melanoma","volume":"136","author":"Tsao","year":"2000","journal-title":"Arch. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/jdv.17735","article-title":"Melanoma in Children and Adolescents: Analysis of Susceptibility Genes in 123 Italian Patients","volume":"36","author":"Pellegrini","year":"2022","journal-title":"J. Eur. Acad. Dermatol. Venereol. JEADV"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e31705","DOI":"10.1097\/MD.0000000000031705","article-title":"BRCA2 Gene Mutation in Cancer","volume":"101","author":"Xie","year":"2022","journal-title":"Medicine"},{"key":"ref_34","first-page":"210","article-title":"Update in Genetic Susceptibility in Melanoma","volume":"3","author":"Potrony","year":"2015","journal-title":"Ann. Transl. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/nature16158","article-title":"Corrigendum: A SUMOylation-Defective MITF Germline Mutation Predisposes to Melanoma and Renal Carcinoma","volume":"531","author":"Bertolotto","year":"2016","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/humu.20476","article-title":"Comprehensive Evaluation of Allele Frequency Differences of MC1R Variants across Populations","volume":"28","author":"Gerstenblith","year":"2007","journal-title":"Hum. Mutat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/ijc.29018","article-title":"MC1R Variants Increased the Risk of Sporadic Cutaneous Melanoma in Darker-Pigmented Caucasians: A Pooled-Analysis from the M-SKIP Project","volume":"136","author":"Pasquali","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1016\/j.jid.2016.05.099","article-title":"Association of Melanocortin-1 Receptor Variants with Pigmentary Traits in Humans: A Pooled Analysis from the M-Skip Project","volume":"136","author":"Tagliabue","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"39","DOI":"10.2147\/PHMT.S115534","article-title":"Pediatric Melanoma: Incidence, Treatment, and Prognosis","volume":"8","author":"Saiyed","year":"2017","journal-title":"Pediatr. Health Med. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e2021161S","DOI":"10.5826\/dpc.11S1a161S","article-title":"Epidemiology and Risk Factors of Melanoma: A Review","volume":"11","author":"Conforti","year":"2021","journal-title":"Dermatol. Pract. Concept."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.jaad.2017.09.065","article-title":"Clinical and Dermoscopic Characterization of Pediatric and Adolescent Melanomas: Multicenter Study of 52 Cases","volume":"78","author":"Carrera","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"607","DOI":"10.2340\/00015555-1280","article-title":"Melanoma in a 5-Year-Old Child with a Giant Congenital Melanocytic Naevus","volume":"92","author":"Surrenti","year":"2012","journal-title":"Acta Derm. Venereol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"557","DOI":"10.2147\/CCID.S308725","article-title":"Giant Congenital Melanocytic Nevus in a Chinese Newborn","volume":"14","author":"Lin","year":"2021","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"142","DOI":"10.21276\/apjhs.2019.6.2.20","article-title":"Giant Congenital Melanocytic Nevus in Newborn: Case Report","volume":"6","author":"Bajaj","year":"2019","journal-title":"Asian Pac. J. Health Sci."},{"key":"ref_45","first-page":"473635","article-title":"Giant Congenital Melanocytic Naevus with Proliferative Nodules Mimicking Congenital Malignant Melanoma: A Case Report and Review of the Literature of Congenital Melanoma","volume":"2013","author":"Scalvenzi","year":"2013","journal-title":"Case Rep. Dermatol. Med."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/8\/937\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:24:56Z","timestamp":1760034296000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/8\/937"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,6]]},"references-count":45,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["genes16080937"],"URL":"https:\/\/doi.org\/10.3390\/genes16080937","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2025,8,6]]}}}