{"title":"Fusion Gene Detection in Driver Mutation-Negative Melanomas Using RNA-Based Anchored Multiplex Polymerase Chain Reaction","authors":"Tokimasa Hida, Masashi Idogawa, Sayuri Sato, Yukiko Kiniwa, Junji Kato, Kohei Horimoto, Shintaro Sugita, Shoichiro Tange, Masae Okura, Ryuhei Okuyama, Takashi Tokino, Hisashi Uhara","doi":"10.1111/pcmr.70056","DOIUrl":"https://doi.org/10.1111/pcmr.70056","url":null,"abstract":"<div>\u0000 \u0000 <p>Advanced melanoma is typically treated with immune checkpoint inhibitors (ICIs) and targeted therapies. However, their efficacy is limited in acral and mucosal melanomas, which are more prevalent in non-White populations and often exhibit low tumor mutational burden and lack <i>BRAF</i> mutations. Fusion genes, widely used as therapeutic targets in other cancers, may represent alternative targets in these melanoma subtypes. This study aimed to detect fusion genes in Japanese melanomas lacking major driver mutations (<i>BRAF</i>, <i>RAS</i>, <i>NF1</i>, or <i>KIT</i>) using a custom RNA-based anchored multiplex polymerase chain reaction (AMP) panel. RNA extracted from 14 tumors, primarily formalin-fixed paraffin-embedded specimens, was analyzed using a custom Archer FUSIONPlex panel. Libraries were successfully generated in 80% of cases, and two in-frame fusions—<i>MAD1L1</i>::<i>BRAF</i> and <i>CIC</i>::<i>MEGF8</i>—were identified (17%). <i>MAD1L1</i>::<i>BRAF</i> retained the BRAF kinase domain and may be targetable by MEK inhibitors. <i>CIC</i>::<i>MEGF8</i>, a novel fusion in melanoma, may result in transcriptional dysregulation through <i>CIC</i> loss of function. This Method paper outlines the AMP workflow, including troubleshooting strategies and quality control criteria, and demonstrates its applicability to clinical samples. Our findings support the utility of RNA-based fusion detection in driver-negative melanomas and the potential of fusion genes as actionable targets.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Noninvasive Assessment of Melasma Pathological Features: Side-By-Side Comparison of Two-Photon Microscopy and Reflectance Confocal Microscopy","authors":"Xiaoli Ning, Jungang Yang, Hongfei Ouyang, Lingfan Jiang, Jiahui Han, Ziyuan Tian, Jingkai Xu, Yujun Sheng, Xianbo Zuo, Yong Cui","doi":"10.1111/pcmr.70057","DOIUrl":"https://doi.org/10.1111/pcmr.70057","url":null,"abstract":"<div>\u0000 \u0000 <p>Melasma, a refractory hyperpigmentation disorder, requires noninvasive tools for accurate pathological assessment. This study compared two-photon microscopy (TPM) and reflectance confocal microscopy (RCM) for the in vivo characterization of melasma pathology. In this cross-sectional study, TPM and RCM features and imaging clarity were evaluated in 130 melasma patients. Spearman correlation analyses were performed between TPM-quantified epidermal melanin, the melanin index (MI), and the individual typology angle (ITA). Features were also compared between active and stable disease stages. TPM and RCM showed substantial agreement in detecting increased epidermal melanin (κ = 0.651), activated melanocytes at the dermal-epidermal junction (DEJ) (κ = 0.711), and flattened rete ridges (κ = 0.691) (all <i>p</i> < 0.001). TPM excelled in visualizing intracellular melanin distribution, pendulous melanocytes under the DEJ, and solar elastosis, while RCM better identified activated melanocytes at the DEJ. TPM-quantified epidermal melanin content correlated positively with MI and negatively with ITA. RCM-detected dermal inflammatory cells were more prevalent in active than in stable melasma. In conclusion, TPM and RCM synergistically capture critical melasma features, with TPM assessing disease severity via epidermal melanin quantification, whereas RCM reflects disease activity by detecting inflammatory cells. This provides clinicians with tailored imaging tools for precision management.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer Berkman, Ellie J. Maas, E. DeBortoli, Clare A. Primiero, H. Peter Soyer, Aideen McInerney-Leo
{"title":"Germline CDKN2A Variant Cascade Testing Across Four Generations Reveals Familial Melanoma–Breast Cancer Genotype–Phenotype Correlation","authors":"Jennifer Berkman, Ellie J. Maas, E. DeBortoli, Clare A. Primiero, H. Peter Soyer, Aideen McInerney-Leo","doi":"10.1111/pcmr.70055","DOIUrl":"https://doi.org/10.1111/pcmr.70055","url":null,"abstract":"<p>This study reports co-segregation of a pathogenic <i>CDKN2A</i> variant with both melanoma and breast cancer in a four-generation pedigree. Eighteen individuals were test positive (<i>n</i> = 10), obligate (<i>n</i> = 5) or assumed carriers (<i>n</i> = 3) of the <i>CDKN2A</i> variant. Eleven of these had multiple melanomas, with initial diagnoses from teens to fifties. Six of thirteen female carriers had breast cancer (<i>n</i> = 5 test positive, <i>n</i> = 1 assumed carrier), with diagnoses ranging from thirties to sixties. Additional cancer diagnoses included pancreatic, and head and neck cancers. This study illustrates a possible genotype–phenotype association between a pathogenic <i>CDKN2A</i> variant and the co-occurrence of melanoma and breast cancer in a hereditary context.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gennie L. Parkman, Xiaonan Xu, Sheri L. Holmen, Florian A. Karreth
{"title":"The Roles of PTEN in Melanoma Suppression","authors":"Gennie L. Parkman, Xiaonan Xu, Sheri L. Holmen, Florian A. Karreth","doi":"10.1111/pcmr.70054","DOIUrl":"https://doi.org/10.1111/pcmr.70054","url":null,"abstract":"<p>Since its discovery more than a quarter century ago, PTEN has emerged as one of the most potent tumor suppressors and its loss of function is common to numerous cancer types including glioblastoma, prostate cancer, small cell lung cancer, and melanoma. PTEN is a lipid and protein phosphatase that contributes to various cellular processes, primarily by regulating key signaling pathways. Extensive research over the past two decades has uncovered many aspects of PTEN regulation and function and highlighted the role of PTEN in tumor suppression. PTEN loss-of-function is associated with the progression of a substantial portion of melanoma cases, and while its role in melanoma suppression is often ascribed to its inhibition of the PI3K/AKT signaling pathway, recent studies may hint at a more complex role for PTEN in melanoma. In this review, we provide an overview of how PTEN suppresses melanomagenesis.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muyi Yang, Suzanne Egyhazi Brage, Jan Lapins, Vitali Grozman, Fernanda Costa Svedman, Veronica Höiom, Hildur Helgadottir
{"title":"Germline MC1R Variant Status and Efficacy of Immune Checkpoint Inhibitors in Patients With Advanced Melanoma","authors":"Muyi Yang, Suzanne Egyhazi Brage, Jan Lapins, Vitali Grozman, Fernanda Costa Svedman, Veronica Höiom, Hildur Helgadottir","doi":"10.1111/pcmr.70050","DOIUrl":"https://doi.org/10.1111/pcmr.70050","url":null,"abstract":"<p>The melanocortin-1-receptor (MC1R<i>)</i> has a key role in melanocyte pigmentation regulation. Certain <i>MC1R</i> germline genetic variants (<i>R</i> alleles) result in deficient melanin production and are associated with red hair, freckling, UV sensitivity, and melanoma susceptibility. We aimed to address whether inherited polymorphisms in <i>MC1R</i> impact the efficacy of immune checkpoint inhibitors (ICI) in patients with metastatic melanoma. Patients with advanced melanoma undergoing ICI treatment were genotyped for <i>MC1R</i> variants. The patients were grouped by their germline <i>MC1R R</i> variants (≥ 1 or 0) and followed for treatment response, progression-free survival (PFS) and overall survival (OS). Of the 103 patients included, 39 (37.9%) had at least one <i>MC1R R</i> allele (<i>MC1R</i>-R-carriers), whereas 64 patients did not harbor any <i>R</i> allele (<i>MC1R</i>-R-non-carriers). The hazard ratio (HR) for PFS in <i>MC1R</i>-R-carriers was 0.60, (95% CI 0.37–0.98, <i>p</i> = 0.043). The HR for OS was 0.63 (95% CI 0.37–1.08, <i>p</i> = 0.091). While <i>MC1R</i> is closely associated with melanoma susceptibility, its impact on ICI efficacy has not been explored previously. <i>MC1R</i>-R-carriers with metastatic melanoma had improved PFS when treated with ICIs. If validated in larger cohorts, <i>MC1R</i> genotyping may serve as a factor helping to predict response to ICIs in melanoma patients.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rapid Diagnosis and Subtyping of Hermansky-Pudlak Syndrome With Flow Cytometry Analysis","authors":"Yingzi Zhang, Teng Liu, Qingsong Yang, Qiaorong Huang, Jiayi Ai, Yefeng Yuan, Wei Li, Aihua Wei","doi":"10.1111/pcmr.70048","DOIUrl":"https://doi.org/10.1111/pcmr.70048","url":null,"abstract":"<div>\u0000 \u0000 <p>The diagnostic approaches for Hermansky-Pudlak Syndrome (HPS) include genetic sequencing, immunoblotting, electron microscopy (EM), and flow cytometry with mepacrine staining. However, these methods are often impractical for routine clinical use due to high cost, technical complexity, and limited availability. In this study, we evaluated dense granules (DGs) function in HPS mouse models using flow cytometry with mepacrine and FluoZin-3 staining. We then developed a standardized, practical flow cytometry-based protocol and validated it in patients with HPS and oculocutaneous albinism (OCA), which were confirmed by whole-mount EM. In HPS mouse models (BLOC-1, BLOC-2, BLOC-3, and AP-3 deficient mutants), mepacrine uptake was consistently reduced. FluoZin-3 fluorescence showed subtype-specific zinc dysregulation, with elevated levels in BLOC-1, BLOC-2, and AP-3 mutants but decreased levels in the BLOC-3 mutant. In contrast, the OCA-6 mouse mutant showed no significant changes in either mepacrine or FluoZin-3 uptake. Similar patterns were observed in HPS and non-syndromic OCA patients. Our findings indicate that the protocol can enable the precise diagnosis and preliminary subtype classification of HPS, while also facilitating differential diagnosis between HPS and OCA. This method offers a rapid, clinically accessible alternative to conventional diagnostic techniques and may also be applicable to other storage pool disorders with DG defects.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Treatment of Acquired Dermal Macular Hyperpigmentation With Oral Isotretinoin: A Multi-Institutional Retrospective Study of 121 Cases","authors":"Zhongyi Xu, Yuecen Ding, Chengfeng Zhang, Davinder Parsad, Michelle Rodrigues, Muthu Sendhil Kumaran, Nawaf Almutairi, Iltefat Hamzavi, Jharna Amin, Houda Hammami Ghorbel, Leihong Xiang, Thierry Passeron","doi":"10.1111/pcmr.70052","DOIUrl":"https://doi.org/10.1111/pcmr.70052","url":null,"abstract":"<div>\u0000 \u0000 <p>The term acquired dermal macular hyperpigmentation (ADMH) was introduced to unify Riehl's melanosis (RM), lichen planus pigmentosus (LPP), and related entities. These are cosmetically distressing pigmentary disorders that pose therapeutic challenges. To investigate the efficacy and safety of oral isotretinoin in treating ADMH, we conducted a muticenter retrospective study of patients with ADMH treated with oral isotretinoin between 2014 and 2024. Patients from Australia, China, Europe, India, Middle East, North America, and North Africa were included. Patients lost to follow-up before two visits were excluded. The response was graded by a 5-point Investigator's Global Assessment (IGA) scale. A total of 121 patients were included. Most patients (64.5%) were treated with a dose of 20 mg/d for an average of 8 months. Oral isotretinoin improved the severity of pigmentation in all RM and 85 (90.4%) LPP patients, with 17 (63.0%) RM and 31 (33.0%) LPP patients achieving marked improvement. RM patients responded better than LPP patients (<i>p</i> = 0.005). Patients with localized lesions (<i>p</i> = 0.0012), disease duration of less than 5 years (<i>p</i> = 0.046 for RM, <i>p</i> = 0.0272 for LPP), Fitzpatrick skin phototypes III-VI (<i>p</i> = 0.0081), or longer duration of treatment (<i>p</i> = 0.0178) responded better. Oral isotretinoin appears to be a promising treatment modality for ADMH.</p>\u0000 </div>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Martin Q. Rasmussen, Marie L. Bønnelykke-Behrndtz, Camilla Merrild, Ida Tvilling, Julie N. Christensen, Morten M. Nielsen, Jeanette B. Georgsen, Nina Naumann, Johann M. Gudbergsson, Anders Etzerodt, Jakob S. Pedersen, Russell W. Jenkins, Søren E. Degn, Søren K. Moestrup, Henrik Schmidt, Torben Steiniche, Mette Madsen
{"title":"LRP2 Expression in Melanoma Is Associated With a Transitory Cell State, Increased T Cell Infiltration, and Is Upregulated by IFNy Signaling","authors":"Martin Q. Rasmussen, Marie L. Bønnelykke-Behrndtz, Camilla Merrild, Ida Tvilling, Julie N. Christensen, Morten M. Nielsen, Jeanette B. Georgsen, Nina Naumann, Johann M. Gudbergsson, Anders Etzerodt, Jakob S. Pedersen, Russell W. Jenkins, Søren E. Degn, Søren K. Moestrup, Henrik Schmidt, Torben Steiniche, Mette Madsen","doi":"10.1111/pcmr.70053","DOIUrl":"https://doi.org/10.1111/pcmr.70053","url":null,"abstract":"<p>Low density lipoprotein receptor-related protein 2 (LRP2) is a 600 kilodalton multi-ligand endocytic membrane receptor expressed in several cell types during fetal development, including neuroepithelial cells, and in select absorptive epithelial cells in the adult. In epithelial cancers, LRP2 expression is associated with a differentiated tumor cell state and better prognosis. In previous work, we found that while LRP2 is not expressed in benign naevi, it is frequently acquired in melanoma. However, the molecular drivers of LRP2 expression in melanoma and characteristics of LRP2-expressing melanoma have yet to be described. Here, we show that LRP2 expression is related to a transitory melanoma cell state defined by co-expression of melanocyte lineage and neural crest transcriptional programs. Further, we reveal that melanoma LRP2 expression is increased in T cell-inflamed tumors and is directly upregulated through interferon-gamma signaling. Correlation of melanoma LRP2 expression with clinicopathological variables demonstrates that LRP2 expression is associated with low Breslow thickness and low clinical stage in primary melanomas. Taken together, the present study describes the characteristics of LRP2-expressing melanoma and reveals interferon-gamma signaling as a novel strong positive regulator of LRP2 expression in melanoma.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pauliina E Repo, Eveliina Jakkula, Juho Hiltunen, Heidi Putkuri, Aleksandra Staskiewicz-Tuikkanen, Reetta-Stiina Järvinen, Martin Täll, Virpi Raivio, Rana'a T Al-Jamal, Tero T Kivelä, Joni A Turunen
{"title":"Germline Cancer Susceptibility Variants in Patients With Uveal Melanoma.","authors":"Pauliina E Repo, Eveliina Jakkula, Juho Hiltunen, Heidi Putkuri, Aleksandra Staskiewicz-Tuikkanen, Reetta-Stiina Järvinen, Martin Täll, Virpi Raivio, Rana'a T Al-Jamal, Tero T Kivelä, Joni A Turunen","doi":"10.1111/pcmr.70041","DOIUrl":"10.1111/pcmr.70041","url":null,"abstract":"<p><p>Some patients with uveal melanoma (UM) show genetic cancer predisposition: ~2% harbor a pathogenic or likely pathogenic (P/LP) germline variant in BAP1 or, rarely, in 20 other cancer-associated genes. Up to 75% of patients with familial UM (FUM) lack genetic diagnosis, prompting a search beyond BAP1. We studied with exome sequencing blood samples from 106 patients with UM and higher-than-average risk of cancer (UM ≤ 45 years of age, bilateral or familial UM, or personal history of non-ocular cancer) and no P/LP variants in BAP1. Sixteen (15%; 95% confidence interval [CI] 9-23) patients carried at least one P/LP variant in dominant cancer genes (CHEK2, DDX41, FANCM, HOXB13, RAD50, SDHA, SDHB) and fifteen in recessive ones. Only CHEK2 and FANCM have previously been reported in patients with UM. Six patients (6%; 95% CI 2-12) carried multilocus P/LP variants. Their median age at diagnosis of UM was 51 (range, 22-69) years, 9 years less than the cohort median of 60 (range, 13-89). This suggests a role for co-occurring pathogenic variants and potentially multilocus inherited neoplasia allele syndrome (MINAS) in UM predisposition. None with FUM carried P/LP variants, warranting investigation of further genes, lower penetrance variants, and multi-gene heterozygosity in UM predisposition.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 5","pages":"e70041"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical Prognostic Factors Predicting Outcomes in Vitiligo: A Scoping Review.","authors":"Lipsa Kumari, Nikhil Mehta, Shivam Pandey, Vishal Gupta, Kanika Sahni, M Ramam, Somesh Gupta","doi":"10.1111/pcmr.70044","DOIUrl":"10.1111/pcmr.70044","url":null,"abstract":"<p><p>The progression of non-segmental vitiligo is highly unpredictable, exhibiting various phenotypes that can range from rapid progression to stability. Due to limited literature, we conducted a scoping review to identify factors influencing the outcomes of non-segmental vitiligo, focusing on disease progression, extent, and response to therapy. This review adhered to PRISMA-ScR guidelines and involved searching the PubMed and Google Scholar databases for studies published in English from January 1995 to December 2023. We included observational, retrospective, case-control, and cohort studies while excluding case reports, systematic reviews, meta-analyses, and studies on segmental vitiligo. Out of 922 records identified, 819 were screened, resulting in 792 exclusions based on titles or abstracts. Ultimately, 22 articles were selected for review after evaluating the full texts of 27 articles. Several factors were consistently linked to poorer prognoses in multiple studies: family history of vitiligo, mucosal involvement, Koebnerization, and the presence of adverse clinical markers. Age of onset yielded conflicting results regarding disease progression but showed general agreement concerning the extent of involvement. Specific lesions such as confetti-like lesions were also associated with progression in limited studies. Additionally, longer disease duration, leukotrichia, and mucosal involvement correlated with a greater body surface area affected by vitiligo, often resulting in poor repigmentation responses to medical treatments. Patients exhibiting poor prognostic markers-such as family history, mucosal lesions, or Koebnerization-should be advised to monitor for new lesions closely and consider early treatment initiation. Understanding the factors influencing the course of non-segmental vitiligo's course can guide clinicians in tailoring management strategies that reflect individual patient needs while considering the complexities associated with this condition. A prospective study with at least 1 year of follow-up is needed to comprehensively describe observed progression, along with well-defined predictors and outcome measures including temporal course patterns. Prospero Registration: CRD42023446544.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"38 5","pages":"e70044"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}