{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:38:10Z","timestamp":1760150290544,"version":"build-2065373602"},"reference-count":103,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T00:00:00Z","timestamp":1698019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"S\u00e3o Paulo Research Foundation","award":["FAPESP 2014\/50943-1"],"award-info":[{"award-number":["FAPESP 2014\/50943-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Multiple primary melanoma (MPM) is a diagnostic challenge even with ancillary imaging technologies available to dermatologists. In selected patients\u2019 phenotypes, the use of imaging approaches can help better understand lesion characteristics, and aid in early diagnosis and management. Methods: Under a 5-year prospective single-center follow-up, 58 s primary melanomas (SPMs) were diagnosed in two first-degree relatives, with fair skin color, red hair, green eyes, and personal history of one previous melanoma each. Patients\u2019 behavior and descriptive demographic data were collected from medical records. The information on the first two primary melanomas (PMs) were retrieved from pathology reports. The characteristics of 60 melanomas were collected from medical records, video dermoscopy software, and pathology reports. Reflectance confocal microscopy (RCM) was performed prior to excision of 22 randomly selected melanomas. Results: From February 2018 to May 2023, two patients underwent a pooled total of 214 excisional biopsies of suspect lesions, resulting in a combined benign versus malignant treatment ratio (NNT) of 2.0:1.0. The number of moles excised for each melanoma diagnosed (NNE) was 1.7:1.0 and 6.9:1.0 for the female and male patient respectively. The in-situ melanoma\/invasive melanoma ratio (IIR) demonstrated a higher proportion of in-situ melanomas for both patients. From June 2018 to May 2023, a total of 58 SPMs were detected by the combination of total body skin exam (TBSE), total body skin photography (TBSP), digital dermoscopy (DD), and sequential digital dermoscopy imaging (SDDI) via comparative approach. The younger patient had her PM one month prior to the second and third cutaneous melanomas (CMs), characterizing a case of synchronous primary CM. The male older relative had a total of 7 nonsynchronous melanomas. Conclusions: This CM cohort is composed of 83.3% in-situ melanoma and 16.7% invasive melanoma. Both patients had a higher percentage of SPM with clinical nevus-like morphology (84.5%), global dermoscopic pattern of asymmetric multiple component (60.3%) and located on the lower limbs (46.6%). When RCM was performed prior to excision, 81% of SPM had features suggestive of malignancy. As well, invasive melanomas were more frequent in the lower limbs (40%). In the multivariate model, for the two high-risk patients studied, the chance of a not associated with nevus (\u201cde novo\u201d) invasive SPM diagnosis is 25 times greater than the chance of a diagnosis of a nevus-associated invasive SPM.<\/jats:p>","DOI":"10.3390\/life13102102","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T05:54:35Z","timestamp":1698040475000},"page":"2102","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiple Primary Melanoma: A Five-Year Prospective Single-Center Follow-Up Study of Two MC1R R\/R Genotype Carriers"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4340-158X","authenticated-orcid":false,"given":"Ana Maria Fagundes","family":"Sortino","sequence":"first","affiliation":[{"name":"Cl\u00ednica Dermatol\u00f3gica Dermatis, Rua Joaquim Floriano 466, Itaim Bibi, S\u00e3o Paulo 04534-002, SP, Brazil"},{"name":"Hospital S\u00edrio-Liban\u00eas, Rua Dona Adma Jafet 115, Bela Vista, S\u00e3o Paulo 01308-050, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca Costa","family":"Soares de S\u00e1","sequence":"additional","affiliation":[{"name":"AC Camargo Cancer Center, Rua Pires da Mota 1.167, Aclima\u00e7\u00e3o, S\u00e3o Paulo 01529-001, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7050-3346","authenticated-orcid":false,"given":"Marcos Alberto","family":"Martins","sequence":"additional","affiliation":[{"name":"Centro Universit\u00e1rio Sa\u00fade ABC, Surgery Department, Avenida Lauro Gomes 2000, Vila Sacadura Cabral, Santo Andr\u00e9 09060-870, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Bertolli","sequence":"additional","affiliation":[{"name":"Hospital S\u00edrio-Liban\u00eas, Rua Dona Adma Jafet 115, Bela Vista, S\u00e3o Paulo 01308-050, SP, Brazil"},{"name":"A Benefic\u00eancia Portuguesa de S\u00e3o Paulo\u2013BP Mirante, Rua Martiniano de Carvalho 965, Bela Vista, S\u00e3o Paulo 01323-001, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafaela Brito","family":"de Paula","sequence":"additional","affiliation":[{"name":"AC Camargo Cancer Center, Rua Pires da Mota 1.167, Aclima\u00e7\u00e3o, S\u00e3o Paulo 01529-001, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clovis Ant\u00f4nio","family":"Lopes Pinto","sequence":"additional","affiliation":[{"name":"AC Camargo Cancer Center, Rua Pires da Mota 1.167, Aclima\u00e7\u00e3o, S\u00e3o Paulo 01529-001, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waldec Jorge","family":"David Filho","sequence":"additional","affiliation":[{"name":"Hospital Alem\u00e3o Oswaldo-Cruz, Rua Treze de Maio 1815, Bela Vista, S\u00e3o Paulo 01323-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana Casagrande","family":"Tavoloni Braga","sequence":"additional","affiliation":[{"name":"AC Camargo Cancer Center, Rua Pires da Mota 1.167, Aclima\u00e7\u00e3o, S\u00e3o Paulo 01529-001, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8968-4506","authenticated-orcid":false,"given":"Jo\u00e3o Pedreira","family":"Duprat Neto","sequence":"additional","affiliation":[{"name":"AC Camargo Cancer Center, Rua Pires da Mota 1.167, Aclima\u00e7\u00e3o, S\u00e3o Paulo 01529-001, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirce Maria","family":"Carraro","sequence":"additional","affiliation":[{"name":"AC Camargo Cancer Center, Rua Pires da Mota 1.167, Aclima\u00e7\u00e3o, S\u00e3o Paulo 01529-001, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8172-2483","authenticated-orcid":false,"given":"Maria Paula","family":"Curado","sequence":"additional","affiliation":[{"name":"AC Camargo Cancer Center, Rua Pires da Mota 1.167, Aclima\u00e7\u00e3o, S\u00e3o Paulo 01529-001, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1001\/jamadermatol.2019.1134","article-title":"Comparison of Survival Between Patients with Single vs Multiple Primary Cutaneous Melanomas","volume":"155","author":"Witkamp","year":"2019","journal-title":"JAMA Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1111\/jdv.18467","article-title":"Synchronous primary cutaneous melanomas: A descriptive study of their clinical features, histology, genetic background of the patients and clinical outcomes","volume":"36","author":"Podlipnik","year":"2022","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e2022182","DOI":"10.5826\/dpc.1204a182","article-title":"Indications for Digital Monitoring of Patients with Multiple Nevi: Recommendations from the International Dermoscopy Society","volume":"12","author":"Russo","year":"2022","journal-title":"Dermatol. Pract. Concept."},{"key":"ref_4","unstructured":"Elder, D.E., Massi, D., Scolyer, R.A., and Willemze, R. (2018). WHO Classification of Skin Tumours, WHO. [4th ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1111\/jdv.18453","article-title":"A review of nevus-associated melanoma: What is the evidence?","volume":"36","author":"Dessinioti","year":"2022","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1001\/jamadermatol.2014.514","article-title":"Detection of primary melanoma in individuals at extreme high risk: A prospective 5-year follow-up study","volume":"150","author":"Moloney","year":"2014","journal-title":"JAMA Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1111\/bjd.17767","article-title":"Surveillance for familial melanoma: Recommendations from a national centre of expertise","volume":"181","author":"Halk","year":"2019","journal-title":"Br. J. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/jdv.15194","article-title":"Incidence and characteristics of thick second primary melanomas: A study of the German Central Malignant Melanoma Registry","volume":"33","author":"Gassenmaier","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zocchi, L., Lontano, A., Merli, M., Dika, E., Nagore, E., Quaglino, P., Puig, S., and Ribeiro, S. (2021). Familial Melanoma and Susceptibility Genes: A Review of the Most Common Clinical and Dermoscopic Phenotypic Aspect, Associated Malignancies and Practical Tips for Management. J. Clin. Med., 10.","DOI":"10.3390\/jcm10163760"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e44","DOI":"10.1111\/bjd.15855","article-title":"Clinicopathological characteristics and prognosis of patients with multiple primary melanomas","volume":"178","author":"Adler","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e59","DOI":"10.1111\/jdv.18526","article-title":"Synchronous melanoma: A multi-centre case series","volume":"37","author":"Wolinska","year":"2023","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1111\/exd.12168","article-title":"CDKN2A and MC1R variants influence dermoscopic and confocal features of benign melanocytic lesions in multiple melanoma patients","volume":"22","author":"Bassoli","year":"2013","journal-title":"Exp. Dermatol."},{"key":"ref_13","first-page":"509","article-title":"Early detection of cutaneous melanoma by sequential digital dermatoscopy (SDD)","volume":"11","author":"Kraus","year":"2013","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1111\/bjd.21274","article-title":"CONCORD Working Group. Does the morphology of cutaneous melanoma help to explain the international differences in survival? Results from 1578482 adults diagnosed during 2000\u20132014 in 59 countries (CONCORD-3)","volume":"187","author":"Stiller","year":"2022","journal-title":"Br. J. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1071\/HC10268","article-title":"Digital monitoring by whole body photography and sequential digital dermoscopy detects thinner melanomas","volume":"2","author":"Rademaker","year":"2010","journal-title":"J. Prim. Health Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.jaad.2019.05.101","article-title":"Improvement of diagnostic confidence and management of equivocal skin lesions by integration of reflectance confocal microscopy in daily practice: Prospective study in 2 referral skin cancer centers","volume":"83","author":"Manubens","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_17","first-page":"673","article-title":"Genetic risk factors in melanoma etiopathogenesis and the role of genetic counseling: A concise review","volume":"22","author":"Serman","year":"2022","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.abd.2020.10.005","article-title":"Total body mapping in the follow-up of melanocytic lesions: Recommendations of the Brazilian Society of Dermatology","volume":"96","author":"Barcaui","year":"2021","journal-title":"An. Bras. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1016\/j.jaad.2011.04.008","article-title":"Benefits of total body photography and digital dermatoscopy (\u201ctwo-step method of digital follow-up\u201d) in the early diagnosis of melanoma in patients at high risk for melanoma","volume":"67","author":"Salerni","year":"2012","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jaad.2010.12.039","article-title":"Total body skin examination for skin cancer screening in patients with focused symptoms","volume":"66","author":"Argenziano","year":"2012","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1001\/archderm.144.4.502","article-title":"Assessment of the optimal interval for and sensitivity of short-term sequential digital dermoscopy monitoring for the diagnosis of melanoma","volume":"144","author":"Altamura","year":"2008","journal-title":"Arch. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1001\/jamadermatol.2015.2680","article-title":"Total-Body Examination vs Lesion-Directed Skin Cancer Screening","volume":"152","author":"Hoorens","year":"2016","journal-title":"JAMA Dermatol."},{"key":"ref_23","first-page":"e2022174","article-title":"Dermoscopy and Reflectance Confocal Microscopy to Estimate Breslow Index and Mitotic Rate in Primary Melanoma","volume":"12","author":"Brito","year":"2022","journal-title":"Dermatol. Pract. Concept."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1111\/jdv.15784","article-title":"A comparative dermoscopic and reflectance confocal microscopy study of naevi and melanoma with negative pigment network","volume":"33","author":"Farnetani","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.abd.2021.10.010","article-title":"The skin through reflectance confocal microscopy\u2014Historical background, technical principles, and its correlation with histopathology","volume":"97","author":"Braghiroli","year":"2022","journal-title":"An. Bras. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/bjd.12781","article-title":"Hyporeflective pagetoid cells: A new clue for amelanotic melanoma diagnosis by reflectance confocal microscopy","volume":"171","author":"Losi","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e42","DOI":"10.1111\/j.1468-3083.2012.04465.x","article-title":"Reflectance confocal microscopy in the diagnosis of partially and completely amelanotic melanoma: Report on seven cases","volume":"27","author":"Maier","year":"2013","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s13671-018-0218-9","article-title":"Confocal Microscopy in Skin Cancer","volume":"7","author":"Laimer","year":"2018","journal-title":"Curr. Dermatol. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.jaad.2010.10.035","article-title":"De novo melanoma and melanoma arising from pre-existing nevus: In Vivo morphologic differences as evaluated by confocal microscopy","volume":"65","author":"Longo","year":"2011","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1200\/JGO.20.00005","article-title":"Demographic, Clinical, and Pathologic Features of Patients with Cutaneous Melanoma: Final Analysis of the Brazilian Melanoma Group Database","volume":"6","author":"Wainstein","year":"2020","journal-title":"JCO Glob. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1001\/jamadermatol.2017.2926","article-title":"Improvement of Genetic Testing for Cutaneous Melanoma in Countries with Low to Moderate Incidence: The Rule of 2 vs the Rule of 3","volume":"153","author":"Delaunay","year":"2017","journal-title":"JAMA Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/j.0909-725X.2005.00127.x","article-title":"Practical color calibration for dermoscopy, applied to a digital epiluminescence microscope","volume":"11","author":"Grana","year":"2005","journal-title":"Skin. Res. Technol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1684\/ejd.2017.3129","article-title":"Clinical assessment of skin phototypes: Watch your words!","volume":"27","author":"Trakatelli","year":"2017","journal-title":"Eur. J. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.jaad.2018.08.028","article-title":"Clinical spectrum of cutaneous melanoma morphology","volume":"80","author":"Klebanov","year":"2019","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"572","DOI":"10.5114\/ada.2020.94593","article-title":"Predictive value of global dermoscopic pattern in patients diagnosed with cutaneous melanoma","volume":"38","author":"Podolec","year":"2021","journal-title":"Postepy Dermatol. Allergol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1001\/jamadermatol.2021.2845","article-title":"Assessment of Diagnostic Accuracy of Dermoscopic Structures and Patterns Used in Melanoma Detection: A Systematic Review and Meta-analysis","volume":"157","author":"Williams","year":"2021","journal-title":"JAMA Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1111\/jdv.16679","article-title":"Dermoscopy comparative approach for early diagnosis in familial melanoma: Influence of MC1R genotype","volume":"35","author":"Longo","year":"2021","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1001\/jamadermatol.2019.4912","article-title":"Clinical and Dermoscopic Features Associated with Difficult-to-Recognize Variants of Cutaneous Melanoma: A Systematic Review","volume":"156","author":"Pampena","year":"2020","journal-title":"JAMA Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects","volume":"310","author":"Association","year":"2013","journal-title":"JAMA"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Pagliarello, C., Magi, S., Mazzoni, L., and Stanganelli, I. (2021). Proportion of Thick versus Thin Melanomas as a Benchmarking Tool. J. Clin. Med., 10.","DOI":"10.3390\/jcm10235545"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Fidalgo, F., Torrezan, G.T., de S\u00e1, B.C.S., Barros, B.D.F., Moredo, L.F., Valieris, R., de Souza, S.J., Duprat Neto, J.P., Krepischi, A.C.V., and Carraro, D.M. (2022). Family-based whole-exome sequencing identifies rare variants potentially related to cutaneous melanoma predisposition in Brazilian melanoma-prone families. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0262419"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1111\/jdv.16847","article-title":"The impact of anatomical location and sun exposure on the dermoscopic recognition of atypical nevi and early melanomas: Usefulness of an integrated clinical-dermoscopic method (iDScore)","volume":"35","author":"Tognetti","year":"2021","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1001\/jamadermatol.2020.5651","article-title":"Efficiency of Detecting New Primary Melanoma Among Individuals Treated in a High-risk Clinic for Skin Surveillance","volume":"157","author":"Guitera","year":"2021","journal-title":"JAMA Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/pcmr.12646","article-title":"Melanocortin 1 receptor (MC1R) polymorphisms\u2019 influence on size and dermoscopic features of nevi","volume":"31","author":"Vallone","year":"2018","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/j.1365-2133.2008.08826.x","article-title":"Dermoscopic features of melanomas associated with MC1R variants in Spanish CDKN2A mutation carriers","volume":"160","author":"Puig","year":"2009","journal-title":"Br. J. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1111\/bjd.17833","article-title":"High naevus count and MC1R red hair alleles contribute synergistically to increased melanoma risk","volume":"181","author":"Duffy","year":"2019","journal-title":"Br. J. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1111\/jdv.14675","article-title":"Reinterpreting dermoscopic pigment network with reflectance confocal microscopy for identification of melanoma-specific features","volume":"32","author":"Farnetani","year":"2018","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1111\/jdv.12411","article-title":"Dermoscopic features of cutaneous melanoma are associated with clinical characteristics of patients and tumours and with MC1R genotype","volume":"28","author":"Fargnoli","year":"2014","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Atak, M.F., Farabi, B., Navarrete-Dechent, C., Rubinstein, G., Rajadhyaksha, M., and Jain, M. (2023). Confocal Microscopy for Diagnosis and Management of Cutaneous Malignancies: Clinical Impacts and Innovation. Diagnostics, 13.","DOI":"10.3390\/diagnostics13050854"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/pcmr.12923","article-title":"Morphological evolution in melanoma in situ using revised pattern analysis","volume":"34","author":"Ramji","year":"2021","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1111\/jdv.16367","article-title":"Inverse association between the total naevus count and melanoma thickness","volume":"34","author":"Marghoob","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1097\/CMR.0000000000000511","article-title":"Melanoma signature in Brazil: Epidemiology, incidence, mortality, and trend lessons from a continental mixed population country in the past 15 years","volume":"28","author":"Buzaid","year":"2018","journal-title":"Melanoma Res."},{"key":"ref_53","unstructured":"Mendonc\u0327a e Silva, D.R., Curado, M.P., and Fregnani, J.H.T.G. (2023). Observat\u00f3rio do C\u00e2ncer, A.C. Camargo Cancer Center, Funda\u00e7\u00e3o Ant\u00f4nio Prudente. Available online: https:\/\/accamargo.org.br\/sites\/default\/files\/2023\/04\/observatorio_do_cancer_rhc_2000-2020.pdf."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1097\/CMR.0000000000000395","article-title":"Multiple primary melanoma: A single centre retrospective review","volume":"27","author":"Menzies","year":"2017","journal-title":"Melanoma Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1002\/cncr.33307","article-title":"Indoor tanning exposure in association with multiple primary melanoma","volume":"127","author":"Karapetyan","year":"2021","journal-title":"Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1111\/bjd.18524","article-title":"A risk prediction model for the development of subsequent primary melanoma in a population-based cohort","volume":"182","author":"Cust","year":"2020","journal-title":"Br. J. Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1111\/ijd.14918","article-title":"Digital dermoscopic changes during follow-up of de-novo and nevus-associated melanoma: A cohort study","volume":"59","author":"Pampena","year":"2020","journal-title":"Int. J. Dermatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/j.jaad.2017.06.149","article-title":"A meta-analysis of nevus-associated melanoma: Prevalence and practical implications","volume":"77","author":"Pampena","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/srt.12770","article-title":"Nevus-associated melanoma: An observational retrospective study of 22 patients evaluated with dermoscopy and reflectance confocal microscopy","volume":"26","year":"2020","journal-title":"Skin. Res. Technol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/ajd.13171","article-title":"Cutaneous melanoma associated with naevi prevalence: A 15-year cross-sectional retrospective study","volume":"61","author":"Scalvenzi","year":"2020","journal-title":"Australas. J. Dermatol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Dessinioti, C., Befon, A., and Stratigos, A.J. (2023). The Association of Nevus-Associated Melanoma with Common or Dysplastic Melanocytic Nevus: A Systematic Review and Meta-Analysis. Cancers, 15.","DOI":"10.3390\/cancers15030856"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/bjd.19819","article-title":"A multicentre study of naevus-associated melanoma vs. de novo melanoma, tumour thickness and body site differences","volume":"185","author":"Dessinioti","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1001\/jamadermatol.2015.3775","article-title":"Association of Patient Risk Factors and Frequency of Nevus-Associated Cutaneous Melanomas","volume":"152","author":"Haenssle","year":"2016","journal-title":"JAMA Dermatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1111\/ijd.13977","article-title":"Recognition of early melanoma: A monocentric dermoscopy follow-up study comparing de novo melanoma with nevus-associated melanoma","volume":"57","author":"Boehncke","year":"2018","journal-title":"Int. J. Dermatol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1111\/jdv.17133","article-title":"The differences in clinical and dermoscopic features between in situ and invasive nevus-associated melanomas and de novo melanomas","volume":"35","author":"Reiter","year":"2021","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1001\/jamadermatol.2019.1514","article-title":"Evaluation of the Number-Needed-to-Biopsy Metric for the Diagnosis of Cutaneous Melanoma: A Systematic Review and Meta-analysis","volume":"155","author":"Nelson","year":"2019","journal-title":"JAMA Dermatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.jaad.2019.12.063","article-title":"Meta-analysis of number needed to treat for diagnosis of melanoma by clinical setting","volume":"82","author":"Petty","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.jaad.2022.11.044","article-title":"Risk of melanoma and nonmelanoma skin cancer with immunosuppressants, part I: Calcineurin inhibitors, thiopurines, IMDH inhibitors, mTOR inhibitors, and corticosteroids","volume":"88","author":"Kreher","year":"2023","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/jso.27111","article-title":"Anatomical location of melanoma: A gender-specific analysis","volume":"127","author":"Bainvoll","year":"2023","journal-title":"J. Surg. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.jaad.2023.02.016","article-title":"A retrospective study of small-diameter invasive melanomas: Metastasis at diagnosis and 9-year follow-up","volume":"89","author":"Dessinioti","year":"2023","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1111\/ijd.16710","article-title":"Dermoscopic predictors of melanoma in small diameter melanocytic lesions (mini-melanoma): A retrospective multicentric study of 269 cases","volume":"62","author":"Nazzaro","year":"2023","journal-title":"Int. J. Dermatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1001\/jamadermatol.2014.1348","article-title":"Genes, Environment, and Melanoma (GEM) Study Group. Comparison of clinicopathologic features and survival of histopathologically amelanotic and pigmented melanomas: A population-based study","volume":"150","author":"Thomas","year":"2014","journal-title":"JAMA Dermatol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1093\/jnci\/djq363","article-title":"Melanoma Genetics Consortium. Association of MC1R variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: A GenoMEL study","volume":"102","author":"Demenais","year":"2010","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1111\/bjd.21707","article-title":"Common genetic variants associated with melanoma risk or naevus count in patients with wildtype MC1R melanoma","volume":"187","author":"Combalia","year":"2022","journal-title":"Br. J. Dermatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.jaad.2015.04.029","article-title":"Dysplastic nevus: Fact and fiction","volume":"73","author":"Rosendahl","year":"2015","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1111\/jdv.18470","article-title":"The long-term evolution of melanocytic nevi among high-risk adults","volume":"36","author":"Reiter","year":"2022","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e292","DOI":"10.1111\/ajd.13039","article-title":"Melanoma risk stratification of individuals with a high-risk naevus phenotype\u2014A pilot study","volume":"60","author":"Rishpon","year":"2019","journal-title":"Australas. J. Dermatol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1111\/jdv.15707","article-title":"The prevalent dermoscopic criterion to distinguish between benign and suspicious pink tumours","volume":"33","author":"Russo","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1001\/archderm.144.9.1207","article-title":"Dermoscopy and the diagnostic challenge of amelanotic and hypomelanotic melanoma","volume":"144","author":"Stoecker","year":"2008","journal-title":"Arch. Dermatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"77","DOI":"10.5826\/dpc.0401a13","article-title":"Dermatoscopic features of cutaneous non-facial non-acral lentiginous growth pattern melanomas","volume":"4","author":"Keir","year":"2014","journal-title":"Dermatol. Pract. Concept."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1007\/s11864-018-0573-6","article-title":"Dermatoscopy of Neoplastic Skin Lesions: Recent Advances, Updates, and Revisions","volume":"19","author":"Weber","year":"2018","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.jaad.2009.11.698","article-title":"How to diagnose nonpigmented skin tumors: A review of vascular structures seen with dermoscopy: Part I. Melanocytic skin tumors","volume":"63","author":"Zalaudek","year":"2010","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1001\/jamadermatol.2017.6447","article-title":"Accuracy of Dermoscopic Criteria for the Diagnosis of Melanoma in Situ","volume":"154","author":"Lallas","year":"2018","journal-title":"JAMA Dermatol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.jaad.2015.02.1117","article-title":"Clinical and dermoscopic characteristics of melanomas on nonfacial chronically sun-damaged skin","volume":"72","author":"Jaimes","year":"2015","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_85","first-page":"380","article-title":"Dermoscopy: A Review of the Structures That Facilitate Melanoma Detection","volume":"119","author":"Marghoob","year":"2019","journal-title":"J. Am. Osteopath. Assoc."},{"key":"ref_86","first-page":"000533820","article-title":"Diagnostic accuracy of hyperpigmented microcircles in dermatoscopy of non-facial non-acral melanomas. A pilot retrospective study using a public image database","volume":"10","author":"Pietkiewicz","year":"2023","journal-title":"Dermatology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e307","DOI":"10.1111\/ajd.14087","article-title":"Reply to: \u2018Melanoma diagnosis at a specialist dermatology practice without the use of photographic surveillance\u2019","volume":"64","author":"Adler","year":"2023","journal-title":"Australas J. Dermatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S0140-6736(96)90873-9","article-title":"Melanoma","volume":"347","author":"Rivers","year":"1996","journal-title":"Lancet"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1001\/jamadermatol.2017.2330","article-title":"Genotypic and Phenotypic Features of BAP1 Cancer Syndrome: A Report of 8 New Families and Review of Cases in the Literature","volume":"153","author":"Haugh","year":"2017","journal-title":"JAMA Dermatol."},{"key":"ref_90","unstructured":"Soares de S\u00e1, B.C. (2023, June 05). Investiga\u00e7\u00e3o de Variantes Gen\u00e9ticas Germinativas nos Pacientes com Crit\u00e9rio Cl\u00ednico para Melanoma Heredit\u00e1rio em Acompanhamento no Ambulat\u00f3rio de Melanoma Familial do N\u00facleo de C\u00e2ncer de pele do A.C.Camargo Cancer Center: Associa\u00e7\u00e3o com Caracter\u00edsticas Cl\u00ednicas. Tese (Doutorado)-Funda\u00e7\u00e3o Ant\u00f4nio Prudente. Available online: https:\/\/accamargo.phlnet.com.br\/Doutorado\/2020\/BCSSa\/BCSSa.pdf."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"9818","DOI":"10.1158\/0008-5472.CAN-06-0494","article-title":"High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL","volume":"66","author":"Goldstein","year":"2006","journal-title":"Cancer Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s10555-017-9661-5","article-title":"Identification, genetic testing, and management of hereditary melanoma","volume":"36","author":"Leachman","year":"2017","journal-title":"Cancer Metastasis Rev."},{"key":"ref_93","unstructured":"(2023, July 30). Available online: https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/variation\/VCV001026654.6."},{"key":"ref_94","unstructured":"Giusti, F., Marini, F., and Brandi, M.L. (2005). GeneReviews, University of Washington."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_96","unstructured":"(2023, July 30). Available online: https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/variation\/VCV000650967.7."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ajhg.2016.06.015","article-title":"Exome Sequencing Identifies Biallelic MSH3 Germline Mutations as a Recessive Subtype of Colorectal Adenomatous Polyposis","volume":"99","author":"Adam","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Hu, H.H., Benfodda, M., Dumaz, N., Gazal, S., Descamps, V., Bourillon, A., Basset-Seguin, N., Riffault, A., Ezzedine, K., and Bagot, M. (2014). A large French case-control study emphasizes the role of rare Mc1R variants in melanoma risk. Biomed. Res. Int., 2014.","DOI":"10.1155\/2014\/925716"},{"key":"ref_99","first-page":"210","article-title":"Update in genetic susceptibility in melanoma","volume":"3","author":"Potrony","year":"2015","journal-title":"Ann. Transl. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.2147\/CLEP.S273566","article-title":"Effects of Exogenous Hormones and Reproductive Factors on Female Melanoma: A Meta-Analysis","volume":"12","author":"Sun","year":"2020","journal-title":"Clin. Epidemiol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Chiavarini, M., Naldini, G., Giacchetta, I., and Fabiani, R. (2022). Exogenous Hormone Factors in Relation to the Risk of Malignant Melanoma in Women: A Systematic Review and Meta-Analysis. Cancers, 14.","DOI":"10.3390\/cancers14133192"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e39","DOI":"10.1017\/S2045796023000525","article-title":"Population-based cohort study of oral contraceptive use and risk of depression","volume":"32","author":"Johansson","year":"2023","journal-title":"Epidemiol. Psychiatr. Sci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.bbi.2023.08.006","article-title":"The relationship of lifetime history of depression on the ovarian tumor immune microenvironment","volume":"114","author":"Hathaway","year":"2023","journal-title":"Brain Behav. Immun."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/10\/2102\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:10:13Z","timestamp":1760130613000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/10\/2102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,23]]},"references-count":103,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["life13102102"],"URL":"https:\/\/doi.org\/10.3390\/life13102102","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2023,10,23]]}}}