{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T15:03:02Z","timestamp":1784818982494,"version":"3.55.0"},"reference-count":30,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T00:00:00Z","timestamp":1769817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Introduction: Mucosal melanomas are rare, and vulvar melanoma is typically diagnosed at an advanced stage with aggressive behavior and poor prognosis. The clitoral region adds challenges due to its functional importance and lack of a dedicated staging system, requiring individualized management. This review evaluates current evidence on prognosis with emphasis on clitoral involvement and highlights diagnostic and therapeutic challenges, underscoring the need for personalized strategies and prospective multicentre studies. Materials and Methods: A systematic review, registered in PROSPERO (CRD420251151187), was conducted per PRISMA guidelines across PubMed, Scopus, Embase, and Web of Science, including English-language case reports and series of primary clitoral melanoma published until August 2025, with no historical limits. Results: 15 cases from 10 studies were identified. The mean patient age was 60 years, with most tumors presenting at advanced stages (median Breslow thickness of 8 mm, frequent ulceration). Immunohistochemical markers and gene mutations are rarely investigated in reported cases. All patients underwent surgery, with variable lymph node assessment; adjuvant therapy was rarely used. Recurrence occurred in nearly one-third of cases, sometimes more than 10 years after initial treatment. Conclusions: Primary clitoral melanoma is extremely rare and often diagnosed late, underscoring the need for heightened clinical awareness. Wide local excision with organ preservation is preferred, and bilateral sentinel lymph-node biopsy can improve staging. The absence of a dedicated staging system and limited systemic evidence highlight the need for standardized protocols. Emerging molecular and immunologic approaches are promising, but prospective multicentre studies are essential to guide management.<\/jats:p>","DOI":"10.3390\/jpm16020070","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T16:12:37Z","timestamp":1770048757000},"page":"70","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Primary Clitoral Melanoma: Personalized Therapeutic Strategies Informed by Clinical Evidence and Systematic Review"],"prefix":"10.3390","volume":"16","author":[{"given":"Anna","family":"Pitsillidi","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Rheinland Klinikum Neuss, Preu\u00dfenstrasse 84, 41464 Neuss, Germany"},{"name":"Department of Obstetrics and Gynaecology, University of Witten Herdecke, 58448 Witten, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8701-4004","authenticated-orcid":false,"given":"Laura","family":"Vona","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Institute of Obstetrics and Gynaecology, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9266-3896","authenticated-orcid":false,"given":"Guglielmo","family":"Stabile","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Institute of Obstetrics and Gynaecology, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnter","family":"Noe\u0301","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Rheinland Klinikum Neuss, Preu\u00dfenstrasse 84, 41464 Neuss, Germany"},{"name":"Department of Obstetrics and Gynaecology, University of Witten Herdecke, 58448 Witten, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1007\/s11912-019-0843-x","article-title":"Primary Melanoma: From History to Actual Debates","volume":"21","author":"Testori","year":"2019","journal-title":"Curr. Oncol. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/978-3-319-22539-5_13","article-title":"Mucosal Melanoma: Epidemiology, Biology and Treatment","volume":"167","author":"Spencer","year":"2016","journal-title":"Cancer Treat. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"117","DOI":"10.6004\/jnccn.2024.0013","article-title":"Vulvar Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology","volume":"22","author":"Yashar","year":"2024","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s11912-012-0244-x","article-title":"Mucosal Melanoma: Pathogenesis, Clinical Behavior, and Management","volume":"14","author":"Postow","year":"2012","journal-title":"Curr. Oncol. Rep."},{"key":"ref_5","first-page":"739","article-title":"Primary Mucosal Melanomas: A Comprehensive Review","volume":"5","author":"Mihajlovic","year":"2012","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1002\/(SICI)1097-0142(19991001)86:7<1273::AID-CNCR24>3.0.CO;2-Z","article-title":"Malignant Melanoma of the Vulva in a Nationwide, 25-Year Study of 219 Swedish Females: Clinical Observations and Histopathologic Features","volume":"86","author":"Nilsson","year":"1999","journal-title":"Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1245\/s10434-014-4215-3","article-title":"Melanoma of the Vulva and Vagina: Principles of Staging and Their Relevance to Management Based on a Clinicopathologic Analysis of 85 Cases","volume":"22","author":"Seifried","year":"2015","journal-title":"Ann. Surg. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/j.jaad.2014.08.019","article-title":"Vulvar Nevi, Melanosis, and Melanoma: An Epidemiologic, Clinical, and Histopathologic Review","volume":"71","author":"Murzaku","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_9","first-page":"4017","article-title":"Primary Malignant Melanomas of the Female Lower Genital Tract: Clinicopathological Characteristics and Management","volume":"10","author":"Wang","year":"2020","journal-title":"Am. J. Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1111\/j.1365-4632.2007.03123.x","article-title":"Melanoma Clitoridis","volume":"46","author":"Ettler","year":"2007","journal-title":"Int. J. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1158\/1078-0432.CCR-16-2126","article-title":"Tumor Thickness and Mitotic Rate Robustly Predict Melanoma-Specific Survival in Patients with Primary Vulvar Melanoma: A Retrospective Review of 100 Cases","volume":"23","author":"Nagarajan","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_12","first-page":"89","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"10","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/s40792-024-02058-7","article-title":"Robot-Assisted Laparoscopic Hepatectomy for Liver Metastasis from Clitoral Malignant Melanoma: A Case Report","volume":"10","author":"Iwasaki","year":"2024","journal-title":"Surg. Case Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100875","DOI":"10.1016\/j.gore.2021.100875","article-title":"Imiquimod treatment of vulvar melanoma in situ invading the urethra","volume":"38","author":"Fuchs","year":"2021","journal-title":"Gynecol. Oncol. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1111\/pde.15296","article-title":"Primary vulvar melanoma in an adolescent patient","volume":"40","author":"Li","year":"2023","journal-title":"Pediatr. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4264","DOI":"10.3390\/curroncol28060362","article-title":"Management of Clitoral Melanoma Presenting as an Exophytic Clitoral Mass: A Case Report and Review of the Literature","volume":"28","author":"Chmielowski","year":"2021","journal-title":"Curr. Oncol."},{"key":"ref_17","first-page":"e4530","article-title":"Stage Two Malignant Melanoma of the Clitoris: A Case Report","volume":"11","author":"White","year":"2019","journal-title":"Cureus"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1111\/1346-8138.12921","article-title":"Malignant Melanoma on Female Clitoris with Bidirectional Upper and Lower Lymphatic Flow","volume":"42","author":"Takahashi","year":"2015","journal-title":"J. Dermatol."},{"key":"ref_19","first-page":"182","article-title":"Malignant Melanoma of the Vulva: Report of Six Cases and Review of the Literature","volume":"20","author":"Piura","year":"1999","journal-title":"Eur. J. Gynaecol. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1177\/030089167005600604","article-title":"Malignant Melanoma of the Vulva","volume":"56","author":"Cascinelli","year":"1970","journal-title":"Tumori J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S0002-9378(16)35702-7","article-title":"Malignant Melanoma of the Vulva","volume":"84","author":"Janovski","year":"1962","journal-title":"Am J Obstet Gynecol"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S1470-2045(08)70254-7","article-title":"Management of Primary Melanoma of the Female Urogenital Tract","volume":"9","author":"Piura","year":"2008","journal-title":"Lancet Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1097\/COC.0b013e3182868e82","article-title":"Rare Presentations of Primary Melanoma and Special Populations","volume":"37","author":"Kottschade","year":"2014","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1097\/01.AOG.0000271209.67461.91","article-title":"Vulvar Melanoma","volume":"110","author":"Sugiyama","year":"2007","journal-title":"Obstet. Gynecol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ygyno.2005.05.031","article-title":"Reconstructive Surgery Following Resection of Primary Vulvar Cancers","volume":"99","author":"Weikel","year":"2005","journal-title":"Gynecol. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ygyno.2013.10.037","article-title":"Modified Gluteal Fold Advancement V-Y Flap for Vulvar Reconstruction after Surgery for Vulvar Malignancies","volume":"132","author":"Bracchi","year":"2014","journal-title":"Gynecol. Oncol."},{"key":"ref_27","unstructured":"Rambhia, P.H., Scott, J.F., Vyas, R., and Gerstenblith, M.R. (2018). Genitourinary Melanoma, NCBI."},{"key":"ref_28","first-page":"e425-30","article-title":"Comparative Study between Two Different Staging Systems (AJCC TNM VS BALLANTYNE\u2019S) for Mucosal Melanomas of the Head & Neck","volume":"21","author":"Peteuil","year":"2016","journal-title":"Med. Oral. Patol. Oral. Cir. Bucal"},{"key":"ref_29","first-page":"219","article-title":"Amelanotic Vulvar Melanoma: Case Report and Review of the Literature","volume":"49","author":"Baderca","year":"2008","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1080\/14737140.2018.1489246","article-title":"The Eighth Edition American Joint Committee on Cancer (AJCC) Melanoma Staging System: Implications for Melanoma Treatment and Care","volume":"18","author":"Keung","year":"2018","journal-title":"Expert. Rev. Anticancer Ther."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/2\/70\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T16:20:13Z","timestamp":1770049213000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/2\/70"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,31]]},"references-count":30,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jpm16020070"],"URL":"https:\/\/doi.org\/10.3390\/jpm16020070","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,31]]}}}