Skin diseases manifesting as agminated pigmented lesions have overlapping clinical manifestations. Therefore, accurate differentiation is challenging. The clinical characteristics, histopathological findings, and treatment response of patients diagnosed with partial unilateral lentiginosis, nevus spilus, or linear and whorled nevoid hypermelanosis were retrospectively analysed. Each disease demonstrated distinct demographic and clinical characteristics, and the responses to laser treatment varied. The median age at onset varied significantly among the groups: 0.1, 6.6, and 0.5 years in patients with nevus spilus, partial unilateral lentiginosis, and linear and whorled nevoid hypermelanosis, respectively. Regarding the locations of the skin lesions, partial unilateral lentiginosis occurred predominantly on the head and neck, while approximately half of nevus spilus and linear and whorled nevoid hypermelanosis were observed on the extremities. Although linear and whorled nevoid hypermelanosis and partial unilateral lentiginosis share a similar histological feature of basal hyperpigmentation, patients with linear and whorled nevoid hypermelanosis showed the best response to laser treatment, while patients with partial unilateral lentiginosis demonstrated a poor treatment response. The study\'s data may provide important clues for the differential diagnosis and clinical decision-making regarding the treatment of these agminated pigmented lesions.

OBJECTIVE: The distinction between the benign subungual melanocytic lesions and an early lesion of subungual melanoma (SUM) remains a diagnostic challenge. We evaluated the routine diagnostic utility of array Comparative Genomic Hybridization (aCGH) to detect whole-genome copy number variations (CNV) as well as targeted next-generation sequencing (NGS) in SUM.
RESULTS: This retrospective study included 20 cases of in situ SUM and 11 cases of invasive SUM. Analysis by aCGH detected common oncogene amplifications in all but one case of invasive SUM (n = 10) and in all cases of in situ SUM with a melanocyte count (MC) >45/mm (n = 4 true positive) and the average number of CNV was 8.5. Thirteen remaining cases of in situ SUM gave false negative results (n = 13), owing to a lack of sufficient melanocytes to analyse (median MC of 35.35; range: 10.16-39.5). Molecular analysis failed in four cases (three in situ SUM and one invasive SUM) due to insufficient amounts of DNA. Across the whole cohort, the sensitivity of aCGH was 52%, but when adjusting the cutoff to MC >45/mm, the sensitivity was 93%. Targeted NGS was less informative than aCGH analyses in our series of SUM.
CONCLUSIONS: To distinguish malignant from benign lesions, especially in situ SUM versus atypical lentiginous melanocytic proliferations, aCGH analysis should be performed when the MC is above 45 melanocytes per linear millimetre. This pangenomic method can detect oncogene amplifications, as well as a number of CNV >3, which strongly support the diagnosis of malignancy.

OBJECTIVE: Laser therapy has emerged as a widely favored treatment option for solar lentigines (SL). However, a significant challenge associated with this treatment, particularly among individuals with darker skin tones, is the notable risk of postinflammatory hyperpigmentation (PIH) induction. In response to these concerns, the authors conducted a prospective, self-controlled study to comprehensively evaluate the safety and effectiveness of 532-nm picosecond laser, both with and without a microlens array (MLA), for the management of SL in patients with Fitzpatrick skin types (FST) III-V.
METHODS: Twenty-seven patients with FST III-V and bilateral SL on the face underwent randomized treatment. One side of the face was treated with a 532-nm picosecond laser coupled with an MLA, utilizing the fractional pigment toning (FPT) technique, while the other side received treatment without the MLA, following the conventional technique (CT). The FPT technique utilized a 9-mm spot size with a fluence of 0.47 J/cm2 for two passes covering 40% of the area. In contrast, the CT used a 4.5-mm handpiece with fluence ranging from 0.3 to 0.7 J/cm2. Patients received a single treatment and were evaluated for pigment clearance, occurrence of PIH, and other adverse effects at 2 weeks, 1, 3, and 6 months posttreatment.
RESULTS: Twenty-seven participants completed the study protocol. Analysis of pigment clearance, measured via 3D photography, showed significant improvement from 2 weeks to 6 months posttreatment for both the FPT technique (p < 0.001) and CT (p = 0.004). PIH occurred in 64%, 80%, 96%, and 88% of cases on the CT side, compared to 8%, 32%, 36%, and 16% on the FPT technique side at 2 weeks, 1, 3, and 6 months posttreatment, respectively. The incidence of PIH was significantly lower on the FPT technique side compared to the CT side throughout the follow-up periods. Additionally, transient and mild hypopigmentation occurred in one participant (4%) on the FPT technique side and in five participants (20%) on the CT side. No other adverse effects were observed during the study.
CONCLUSIONS: The 532-nm picosecond laser emerges as a safe and efficacious treatment modality for SL in individuals with FST III-V. Particularly noteworthy is the efficacy of the FPT technique, which demonstrates comparable effectiveness while significantly reducing the incidence of PIH compared to the CT.

OBJECTIVE: Freckles and lentigines are common pigmented problems which not only cause substantial cosmetic morbidity but also create psychosocial concern. The available modalities for the treatment of pigmented lesions are often unsatisfactory for patients, require a long treatment period, and often cause skin irritation. With the advent of lasers, safe and effective treatment options for epidermal pigmentation have become more varied for different Fitzpatrick skin types. We aimed to evaluate the efficacy and safety of 577-nm yellow laser in the treatment of pigmented epidermal lesions.
METHODS: This study was carried out on 50 patients presented with pigmented epidermal lesions (25 presented with freckles and 25 presented with lentigines). Each patient received four treatment sessions with a 577-nm diode laser at 2-week intervals.
RESULTS: There was significant improvement in freckles and lentigines, as 23 out of 50 patients showed marked improvement, 11 patients showed moderate improvement, 10 patients showed mild improvement, and only six patients had no changes. Moreover, 23 patients were very satisfied, 18 patients were satisfied, and nine patients were not satisfied. As regards the safety of the 577-nm yellow laser, there was no significant adverse effect among patients except pain, erythema, and hyperpigmentation, which resolved within one month after treatment.
CONCLUSIONS: This study showed that the 577-nm yellow laser is an effective, safe, and well-tolerated device in the treatment of freckles and lentigines.

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Although the pathogenesis of solar lentigo (SL) involves chronic ultraviolet (UV) exposure, cellular senescence, and upregulated melanogenesis, underlying molecular-level mechanisms associated with SL remain unclear. The aim of this study was to investigate the gene regulatory mechanisms intimately linked to inflammation in SL. Skin samples from patients with SL with or without histological inflammatory features were obtained. RNA-seq data from the samples were analyzed via multiple analysis approaches, including exploration of core inflammatory gene alterations, identifying functional pathways at both transcription and protein levels, comparison of inflammatory module (gene clusters) activation levels, and analyzing correlations between modules. These analyses disclosed specific core genes implicated in oxidative stress, especially the upregulation of nuclear factor kappa B in the inflammatory SLs, while genes associated with protective mechanisms, such as SLC6A9, were highly expressed in the non-inflammatory SLs. For inflammatory modules, Extracellular Immunity and Mitochondrial Innate Immunity were exclusively upregulated in the inflammatory SL. Analysis of protein-protein interactions revealed the significance of CXCR3 upregulation in the pathogenesis of inflammatory SL. In conclusion, the upregulation of stress response-associated genes and inflammatory pathways in response to UV-induced oxidative stress implies their involvement in the pathogenesis of inflammatory SL.

BACKGROUND: Q-switched (QS) Nd: YAG laser is one of the treatment options for solar lentigines (SLs). However, the incidence of post-inflammatory hyperpigmentation (PIH) is a common complication, especially in dark-complexioned skin. Isobutylamido thiazolyl resorcinol (ITR) has been reported as a preventive modality for ultraviolet B (UVB)-induced hyperpigmentation.
OBJECTIVE: This study aims to evaluate the efficacy and safety of ITR for the prevention of laser-induced PIH.
METHODS: A randomized, evaluator-blinded study including 24 subjects with SLs was conducted. Three SLs of each patient were randomized into three groups, which were to apply ITR twice daily, once daily, and no application for 2 weeks. Thereafter, 532-nm QS Nd: YAG laser was performed. Incidence of laser-induced PIH, relative melanin index (RMI), mean luminance score (L*), hyperpigmentation score, and adverse events were recorded for 2 months post-laser.
RESULTS: The incidence of PIH at the 4th week after laser treatment was significantly lower in the ITR twice-daily group compared to the no-application group (20.83% vs. 50%, p = 0.028). There was no statistically significant difference in RMI, mean L*, and hyperpigmentation score between treatments at all visits. No serious adverse events were reported regarding ITR application and laser treatment.
CONCLUSIONS: Two-week application of ITR prior to QS: Nd YAG laser treatment may potentially reduce the incidence of PIH. A longer duration of application, including after the laser procedure, may be more beneficial for the prevention of laser-induced PIH.

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