Journal of Clinical and Aesthetic Dermatology • Hot Topics in Melanoma November 2025 • MEETING HIGHLIGHTS

The European Academy of Dermatology and Venereology held its 2025 Annual Meeting from September 17–20, 2025, in Paris, France. The conference gave researchers, physicians, and members of industry the opportunity to share and learn about the latest research in cutaneous oncology, including melanoma. The event included speaker presentations on various clinical topics in melanoma, as well as posters reporting the latest data on melanoma screening, biomarkers, and treatment options. Summaries of key abstracts from the meeting are included here.

How deep to cut? An international questionnaire characterizing clinicians’ approaches to wide local excision deep surgical margins in melanoma. An international questionnaire was developed to characterize clinicians’ approaches to deep surgical margins in wide local excision (WLE) for melanoma management, given observed variations in practice and differing international guidelines. The survey was circulated internationally, with 288 responses received from 25 countries across four continents. The United Kingdom (22.2%), Sweden (14.2%), and New Zealand (13.9%) were the top responding countries. Most respondents were consultant specialists (77.4%) and worked primarily in dermatology (89.6%). Fifty-one percent of respondents were Mohs micrographic surgeons, with 46.9% performing more than 20 WLEs annually. Among respondents, 73.3 percent believed depth of WLE does affect melanoma prognosis. For trunk and extremity melanomas, 75 percent would not always aim to reach fascia regardless of melanoma depth. For invasive melanoma over deep subcutis, 56.9 percent responded that they would excise to the same depth as lateral margins, rather than to fascia. Regarding fully excised early melanomas (Stage IA), 72.6 percent believed a subsequent WLE should be performed. Specific scenarios revealed varying practices. For example, for melanoma in situ on the abdomen, 50 percent would excise to deep fat and 15.4 percent to fascia, while for a 4.5mm Breslow ulcerated melanoma, 63.2 percent would excise to fascia. The results demonstrated significant heterogeneity in melanoma WLE depth management.

Germline predisposition in early onset melanoma: a study of a Greek patient cohort. The authors of this study sought to assess the heritable component of early-onset melanoma. In this retrospective study, they investigated germline predisposition in 45 Greek patients diagnosed with melanoma before the age of 30 years using whole-exome sequencing to identify rare variants (minor allele frequency <1%) and MC1R gene polymorphisms. Pathogenic or likely pathogenic (P/LP) germline variants in the melanoma-associated genes CDKN2A and MBD4 or other cancer-predisposing genes (MUTYH and XRCC4) were identified in 13 percent of patients. Heterozygous pathogenic variants in EPHB2, PNKP, ERCC6, and UVSSA were observed in nine percent of patients, though their association with cancer remains uncertain. Rare variants of uncertain significance (VUS) affecting CDKN2A, MITF, POT1, TERF2IP, and ACD were found in 18 percent of patients. Missense ACD VUS were statistically overrepresented in this cohort compared to gnomAD, and two MC1R polymorphisms were more frequent compared to previously reported frequencies in unselected melanoma populations. Given the 13 to 25 percent prevalence of P/LP variants and 18 percent prevalence of relevant VUS, the authors advocated for germline testing, genetic counseling, and periodic reassessment of VUS in patients with early-onset melanoma in order to assist in risk stratification and preventive interventions.

Clinical and epidemiological features associated with Breslow thickness, multiplicity, and early-onset in cutaneous melanoma. This cross-sectional study at a national tertiary melanoma referral center analyzed 145 patients to evaluate associations between clinical features and Breslow thickness, number of melanomas, and age at first diagnosis. Among patients, 31.7 percent had in situ melanomas, 51.7 percent had thin melanomas (<1.0mm), and 16.6 percent had thick melanomas (≥1.0mm), with most patients being female (64.1%), phototype II to III (82.1%), and over 50 years of age (60.8%). Multiple melanomas occurred in 28.3% of patients and were significantly associated with male sex (p=0.015), more than 100 nevi (p=0.001), atypical nevi (p=0.001), other skin cancers (p=0.001), and fewer freckles (p=0.028), while early-onset melanoma (18.6%, diagnosed before age 40 years) was associated with blonde or red hair (p<0.001), more than 100 nevi (p=0.002), atypical nevi (p<0.001), freckles (p=0.006), intermittent sun exposure (p=0.014), lower smoking rates (p=0.014), and higher cumulative risk (p=0.001). Regular sunscreen use was significantly associated with lower odds of thick versus thin melanoma (odds ratio [OR]: 0.14; 95% confidence interval [CI]: 0.03–0.70, p=0.017), with 95.8 percent of patients with thick melanoma reporting never using sunscreen. The results showed statistically significant associations between clinical features and Breslow thickness, multiple melanomas, and early-onset melanoma, and supported the role of photoprotection in clinical risk assessment.

Confocal microscopy in patients with melanoma. Is the miss worth the risk? Literature review regarding diagnostic accuracy in melanoma detection. This literature review examined diagnostic accuracy of confocal microscopy in melanoma detection by searching Medline, PubMed, Scopus, Informit Health, and Cochrane Library databases using keywords including “confocal microscopy,” “melanoma,” “pigmented lesion,” “false negative,” and “diagnostic accuracy.” A total of 45 articles were identified and reviewed. Studies demonstrated that sensitivity of the testing modality and early diagnosis were key to reducing melanoma mortality, and while specificity was desirable, it did not impact melanoma mortality. Confocal microscopy is used to support the decision to excise, enroll in monitoring, or confirm a benign diagnosis, but false negative diagnoses can lead to progression, metastasis, and increased mortality if melanoma lesions are not excised. The authors concluded that thorough history with clinical examination aided by dermoscopy with excision of concerning lesions is, and likely should remain, the gold standard for melanoma management, and before confocal microscopy can be used outside of trials, it must demonstrate at least equivalent sensitivity to usual medical care and ideally show an overall benefit in terms of morbidity, mortality, and cost.

Emotional distress in patients with melanoma across three assessment time points. This study examined the relationship between emotional state and quality of life in 55 patients with melanoma, including 23 women and 32 men, at three assessment time points: (1) at the beginning of hospitalization prior to re-excision and sentinel lymph node biopsy (SLNB), (2) during hospitalization following the surgical procedure, and (3) at a follow-up outpatient visit after receiving histopathological results. The most common melanoma subtype was superficial spreading melanoma (n=35), followed by nodular melanoma (n=19), with one case of acral lentiginous melanoma. Patients reported higher levels of emotional distress at the first and third assessment points when compared to the second assessment point. In addition, a statistically significant difference in quality of life was observed between the first and third assessment points, with lower quality of life at these time points compared to the second assessment point, indicating a possible clinical and psychosocial benefit from treatment. The authors concluded that these findings contribute to better understanding of the psychological needs of patients with melanoma throughout treatment and could serve as a foundation for developing guidelines to improve psychosocial support, healthcare delivery, and overall quality of life.

Clinically inspired dual-stage AI framework for resource-efficient melanoma diagnosis: integrating clinical and histopathological imaging. The authors of this study developed a novel two-stage artificial intelligence (AI) framework for melanoma diagnosis that mimics clinical practice by combining clinical image triage with histopathological verification to improve diagnostic accuracy while minimizing resource consumption. The authors created a paired dataset linking clinical images with corresponding histopathological slides and employed two cascaded classifiers: a clinical image classifier optimized to reduce false negatives during initial screening, followed by a high-precision histopathological classifier for definitive diagnosis, implemented using VGGNet and Vision Transformer architectures. The dual-stage framework achieved 99.80-percent accuracy, significantly outperforming single-modality approaches, with the clinical classifier demonstrating robust sensitivity and effectively prioritizing cases for histopathological analysis while reducing unnecessary resource expenditure. The authors believe this clinically inspired two-stage AI strategy aligns with real-world medical practice while providing a balance between accuracy and practicality. By synergizing clinical and histopathological data, their method has the potential for use in underserved regions with limited diagnostic infrastructure.

The effect of stress-related amygdala metabolic activity on tumor aggressiveness in melanoma. This retrospective study of 61 patients who underwent ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) for staging of pathologically proven melanoma between 2021 and 2024 evaluated the impact of amygdala metabolic activity (AmygA), a surrogate imaging biomarker of chronic stress, on distant metastasis and recurrence. AmygA was calculated as the ratio of maximum standardized uptake value (SUVmax) of the amygdala to mean standardized uptake value (SUVmean) of the temporal lobe, and SUVmax of spleen and bone marrow were assessed to evaluate systemic inflammation. Patients with melanoma with distant metastasis had significantly higher levels of AmygA and spleen SUVmax than those without distant metastasis (p<0.0001 and p=0.0298, respectively), and both AmygA (p=0.0001) and spleen SUVmax (p=0.0306) were significant predictors of distant metastasis, with AmygA remaining significant (p=0.0004) in multivariate Cox regression analysis. Patients with elevated AmygA and distant metastasis were more likely to experience recurrence (both p<0.0001), with optimal AmygA cutoff values of 1.133 for distant metastasis and 1.097 for recurrence, and AmygA demonstrated weak to moderate correlation with spleen SUVmax (r=0.349, p=0.006) and bone marrow SUVmax (r=0.493, p=0.002). Metabolic activity of the amygdala on ¹⁸F-FDG PET/CT is suggested to be associated with tumor aggressiveness in melanoma, with elevated AmygA potentially indicating higher risk of distant metastasis and recurrence.

Association between fertility treatments and melanoma risk in infertile women: a systematic review and meta-analysis. This systematic review and meta-analysis searched PubMed, Web of Science, Cochrane Library, and Scopus to assess whether infertile women undergoing fertility treatments have higher melanoma incidence compared to untreated infertile women. A total of eight cohort studies were included in the study, reporting 11,061 melanoma cases with follow-up periods ranging from 8.8 to 21 years, and a random-effects model with 95-percent CIs was used to estimate pooled hazard ratios (HRs) and risk ratios (RRs). The pooled HR analysis demonstrated a modest increase in melanoma risk among women exposed to any fertility treatment when compared to untreated controls (HR: 1.16; 95% CI: 1.04–1.29; I2=12.9%; p=0.006), but subgroup analyses by treatment type showed no statistically significant associations for clomiphene (HR: 1.75; 95% CI: 0.93–3.33; p=0.085), assisted reproductive technology (HR: 1.10; 95% CI 0.81–1.36; p=0.371), or gonadotropins (HR: 1.03; 95% CI: 0.49–2.16). The pooled RR analysis across all fertility treatments also did not demonstrate statistical significance (RR: 1.45; 95% CI: 0.76–2.78; I2=84.7%; p=0.264). While the findings indicated a modest overall increase in melanoma risk, they also highlighted the need for cautious interpretation due to heterogeneity among studies and absence of statistically significant results in the subgroup analyses, with future large-scale prospective cohort studies needed to further clarify the association between fertility treatments and melanoma.

RESEARCH BITE—Hand and foot melanomas: does location define risk? A dual perspective

This retrospective study analyzed 80 cases of hand and foot melanomas (HFM) diagnosed between 2010 and 2024, including 46 nail unit melanomas and 34 cutaneous HFM, to evaluate whether anatomical site or histopathological subtype plays a more decisive role in disease progression. Variables analyzed included age at diagnosis, anatomical site, histopathological subtype, Breslow thickness, ulceration status, mitotic rate, sentinel lymph node involvement, and metastatic status, with comparisons made using student’s t-test for continuous variables and Chi-squared test for categorical variables. Nail unit melanomas exhibited significantly higher Breslow thickness at diagnosis (3.31mm vs. 2.00mm; p=0.0307) and greater metastatic rate (67.4% vs. 26.5%; p=0.00028) compared to cutaneous HFM. When melanomas were classified by histopathological subtype, no significant differences were observed in Breslow thickness (p=0.97) or metastatic rates (p=0.55), suggesting that anatomical localization is the primary determinant of aggressive behavior in HFM. The findings support the integration of anatomical site as a key factor in risk stratification and management strategies, with future research needed to focus on biological mechanisms underlying these differences to develop prognostic models and therapeutic interventions.

Source: Magnaterra E, Querzoli G, Venturi F, et al. Hand and foot melanomas: does location define risk? A dual perspective. Presented at EADV Congress 2025; 17–20 Sep 2025; Paris, France.

RESEARCH BITE—Rising melanoma mortality in Brazil: an epidemiological analysis from 2018 to 2023

This epidemiological study analyzed melanoma mortality data from the Brazilian health database DATASUS between 2018 and 2023. Brazil recorded 3,177 deaths from melanoma during this period, with prevalence among individuals aged 60 to 69 years (26%) and 70 to 79 years (19.9%), female individuals (57.5%), and White individuals (68%). The Southeast region accounted for 46 percent of deaths, followed by the South region (31.6%). Melanoma-related deaths showed a significant increase, rising from 501 in 2021 to 570 in 2022 (a 13% increase) and reaching 609 in 2023 (an additional 6% increase). The authors concluded that this increase in melanoma-related deaths highlights the need for targeted public health interventions and preventive strategies, especially in high-risk populations and regions.

Source: Ventura de Santana de Jesus AC, Putini Vieira AC. Rising melanoma mortality in Brazil: an epidemiological analysis from 2018 to 2023. Presented at EADV Congress 2025; 17–20 Sep 2025; Paris, France.