Journal of Clinical and Aesthetic Dermatology • Hot Topics in Melanoma November 2025 • JOURNAL WATCH

In the digital edition, click the PMID after each summary to access the article/abstract.

Patterns of failure in cutaneous head and neck melanoma following negative sentinel lymph node biopsy: a retrospective cohort study

Summary. In this retrospective cohort study, researchers evaluated the risk of recurrence in patients with cutaneous head and neck melanoma and negative sentinel lymph node biopsy (SLNB). Among 167 patients, 78 (46.7%) had a Breslow thickness greater than 2mm. Pathological ulceration was significantly more prevalent in patients with Breslow thickness greater than 2mm, compared to those with a Breslow thickness of 2mm or smaller. Forty-nine patients (29.3%) experienced melanoma recurrence. Multivariable analysis identified Breslow thickness greater than 2mm as a significant predictor of distant recurrence (p=0.02). Furthermore, pathological ulceration was significantly associated with time to distant recurrence (p=0.01).

Do cortisol and psychological distress levels impact the effectiveness of immunotherapy in patients with metastasized melanoma? A pilot study

Hinnen C, Tijssens F, von Haeseler E, et al. Melanoma Res. 2025;35(3):204–207.

Summary. Researchers evaluated the relationship between chronic stress and immunotherapy response in patients with metastatic melanoma. At three- and six-months post-immunotherapy initiation, progressive disease (PD) occurred in 12 (57%) and 13 (62%) patients, respectively. At six months, cortisol levels were significantly increased in patients with stable disease (SD)/ partial response (PR) compared to those with PD. Baseline Center for Epidemiological Studies Depression Scale (CES-D) scores were increased in patients with PD compared to those with SD/PR.

NeoACTIVATE Arm C: Phase II trial of neoadjuvant atezolizumab and tiragolumab for high-risk operable Stage III melanoma

Summary. This trial assessed the efficacy of neoadjuvant atezolizumab and tiragolumab in immune checkpoint inhibitor–naïve patients with Stage III melanoma. Twenty-seven of 34 patients (79.4%) completed all four cycles, and 30 underwent therapeutic lymph node dissection per protocol. The major pathologic response (MPR) rate was 47.1 percent, with 38.2 percent of patients achieving pathologic complete response. At median 19.9-month follow-up, 12-month event-free survival (EFS) and overall survival (OS) rates were 72.0 and 92.9 percent, respectively. At a median postoperative follow-up of 16.1 months, the 12-month recurrence-free survival (RFS) rate was 73.3 percent, and 12-month distant metastasis–free survival (DMFS) rate was 86.0 percent. During neoadjuvant therapy, at least one grade 3 or higher adverse event (AE) occurred in 14.7 percent of patients.

Annese T, Coltrini D, Belleri M, et al. Pathol Res Pract. 2025;275:156188. Epub ahead of print.

Summary. Comparing cutaneous malignant melanoma and normal skin, researchers observed that TMED10 expression was significantly increased in melanoma samples, and high TMED10 expression was associated with increased Clark level and poor survival outcomes. BRAFV600E-mutated tumors had significantly increased TMED10 expression. TMED10 positively correlated with TMED2, TMED8, HSP90AA1, and HSP90B1, and further analysis suggested that TMED10 was involved in endoplasmic reticulum–Golgi trafficking. Analysis of human tumor samples (n=60) showed that TMED10 protein expression was increased in tumors with higher Breslow thickness. Infiltrating lymphocytes in T3 and T4 melanoma had reduced TMED10 expression compared to benign lesions and T1 and T2 melanoma.

Sexual dysfunction in melanoma survivors: a cross-sectional study on prevalence and associated factors

Muñoz-Barba D, Sánchez-Díaz M, Molina- Leyva A, et al. J Clin Med. 2025;14(14):4891

Summary. Among 75 patients with cutaneous melanoma, 22 (29.3%) reported a negative impact of melanoma on sexual health, most frequently due to reduced sexual desire (n=12, 54.5%) and treatment-related physical discomfort (n=4, 18.2%). Mean numeric rating scale (NRS) score for sexual dysfunction was 2.25. A total of 41.3 percent of female patients met the threshold for sexual dysfunction as per the Female Sexual Function Index (FSFI; score ≤19), and factors associated with sexual dysfunction included older age, older age at diagnosis, single marital status, shorter disease duration, presence of visible surgical scars, and higher depression scores on the Hospital Anxiety and Depression Scale (HADS). Among male patients, 68.9 percent met the threshold for sexual dysfunction as per the International Index of Erectile Function (IIEF; score ≤21), and increased anxiety, higher depression scores on HADS, and lower Dermatology Quality of Life Index (DLQI) scores were associated with lower IIEF scores.

Cutaneous melanoma and occupational UV exposure: associations with anatomical site, histological subtype, and Breslow thickness

Summary. In this retrospective analysis, researchers assessed the relationship between occupational ultraviolet (UV) exposure and melanoma. Occupational UV exposure was reported in 246 of 1,417 (17.36%) patients with melanoma (mixed indoor/outdoor: 14.82%; outdoor: 2.54%). The prevalence of lentigo maligna was significantly increased in outdoor workers (13.89%) versus mixed (6.19%) and indoor (5.55%) workers (p=0.046). Compared to indoor workers, outdoor workers experienced significantly greater frequency of head and neck (p=0.015) and trunk (p=0.018) involvement and significantly lower frequency of limb involvement (p<0.001). Breslow thickness was significantly linked to occupational UV exposure as well (p=0.015); prevalence of Breslow thickness of 1mm or smaller was higher among those without occupational UV exposure compared to patients with occupational UV exposure (83% vs. 76%).

Summary. Analyzing data from the Surveillance, Epidemiology, and End Results (SEER) database, researchers found 53.1 percent of patients with stage IV cutaneous melanoma underwent surgical resection; the rate of resection was significantly higher in the pre-immunotherapy era (2004–2010) versus the postimmunotherapy era (2011–2020; 59.6% vs. 50.4%, p<0.0001). The annual rate of decline of all surgical resections was 0.97 percent in the postimmunotherapy era. In the pre-immunotherapy era, the rate of primary and distant resections was 35.7 and 31.8 percent, respectively; these rates significantly decreased to 27.7 and 28.5 percent, respectively, in the postimmunotherapy era (p<0.0001 and p=0.0005, respectively).

RESEARCH BITE—LRP2 expression in melanoma is associated with a transitory cell state, increased T-cell infiltration, and is upregulated by IFNγ signaling

In this study, researchers evaluated the role of low density lipoprotein receptor-related protein 2 (LRP2) in cutaneous melanoma. Analyzing cutaneous melanoma samples, researchers found that LRP2 gene expression was elevated in transitory melanoma cells, and further analysis confirmed that LRP2 protein expression was increased in was also elevated in transitory melanoma cells. Undifferentiated melanoma cells did not express LRP2 gene or protein, and neural crest-like melanoma cells showed no LRP2 gene expression and minimal LRP2 protein expression. There was a positive correlation between LRP2 expression and T-cell inflammation. In melanoma cell lines, interferon-gamma (IFNγ) stimulation led to increased expression of LRP2. Further analysis demonstrated that LRP2 expression was increased in tumors with Breslow thickness less than 1mm (vs. >2mm) and in stage I tumors (vs. stage II or III).

Source: Rasmussen MQ, Bønnelykke-Behrndtz ML, Merrild C, et al. LRP2 expression in melanoma is associated with a transitory cell state, increased T-cell infiltration, and is upregulated by IFNy signaling. Pigment Cell Melanoma Res. 2025;38(5):e70053

RESEARCH BITE—Intratumoral vidutolimod as monotherapy or in combination with pembrolizumab in patients with programmed cell death 1 blockade–resistant melanoma: final analysis from a Phase Ib study

In this Phase Ib trial, researchers assessed the safety and efficacy of vidutolimod with or without pembrolizumab in unresectable, metastatic melanoma resistant to programmed cell death 1 (PD-1) blockade. A total of 159 patients received vidutolimod plus pembrolizumab, split into two groups based on vidutolimod formulation (PS20-A, 0.005–0.01% polysorbate 20, n=98; PS20-B, 0.00167% polysorbate 20, n=61) and 40 patients received vidutolimod monotherapy. Best objective response rate (ORR) was highest in the PS20-A group (23.5%), followed by the monotherapy group (20.0%) and the PS20-B group (11.5%). In both combination and monotherapy groups, the most frequently reported treatment-emergent adverse events (TEAEs) were chills, pyrexia, and fatigue. Grade 3 or greater TEAEs occurred in 55.3 percent of patients who received combination therapy and 37.5 percent of those who received monotherapy.

Source: Milhem MM, Zakharia Y, Davar D, et al. Intratumoral vidutolimod as monotherapy or in combination with pembrolizumab in patients with programmed cell death 1 blockade–resistant melanoma: final analysis from a Phase 1b study. Cancer. 2025;131(15):e70022.