Melanoma-like features in pediatric longitudinal melanonychia: A systematic review and meta-analysis.

BACKGROUND: Pediatric longitudinal melanonychia (LM) can exhibit atypical features that mimic red-flag signs for subungual melanoma in adults and lead to diagnostic uncertainty. Nail biopsy may be unnecessary if clinical inspection and dermoscopy suggest a benign nature. METHODS: We searched PubMed and Embase from inception to February 2023 for studies of any design reporting either the number or proportion of clinical and dermoscopic features in at least five children (≤18 years) with LM. Non-English articles, reviews, and abstracts were excluded. We performed a systematic review and meta-analysis to collate all existing data. RESULTS: A total of 1218 articles were screened and 24 studies with 1391 pediatric patients were included. Nevus was the most common diagnosis (86.3%). The most prevalent sites were fingernails (76.2%) and first digits (45.4%). Pooled proportions of common features were: dark-color bands (69.8%), multi-colored bands (47.6%), broad bandwidth (41.1%), pseudo-Hutchinson sign (41.0%), irregular patterns (38.1%), Hutchinson sign (23.7%), dots and globules (22.5%), nail dystrophy (18.2%), and triangular sign (10.9%). Outcomes included progression (widening or darkening, 29.9%), stability (23.3%), and spontaneous regression (narrowing or fading, 19.9%). Only eight cases of subungual melanoma in situ were reported, and no invasive melanomas were identified. CONCLUSION: Although atypical characteristics are common in pediatric LM, the probability of malignant transformation is exceedingly low. Appropriate evaluation and management of pediatric LM includes careful clinical and dermoscopic inspection with attention to benign features followed by long-term interval follow-up.

Acral lentiginous melanoma incidence by sex, race, ethnicity, and stage in the United States, 2010-2019.

INTRODUCTION: Acral lentiginous melanoma (ALM) is a rare type of melanoma associated with delayed diagnosis and poor survival rates. This study examines ALM incidence rates in comparison to all other melanoma types. METHODS: We used data from the Centers for Disease Control and Prevention's National Program of Cancer Registries and the National Cancer Institute's Surveillance, Epidemiology, and End Results Program, which together cover 99% of the US population. We calculated age-adjusted rates and rate ratios for ALM and all other malignant melanomas by sex, race and ethnicity, stage, and year of diagnosis (2010-2019). RESULTS: ALM incidence rates were significantly lower among non-Hispanic Black persons (1.8 per 1,000,000); non-Hispanic Asian/Pacific Islander (API) persons (1.7 per 1,000,000); and Hispanic Black, American Indian/Alaska Native (AI/AN), and API persons (1.5 per 1,000,000) compared to non-Hispanic White persons (2.3 per 1,000,000). Rates were significantly higher among Hispanic White persons (2.8 per 1,000,000) compared to non-Hispanic White persons. For all other melanoma types, incidence rates were significantly higher among non-Hispanic White persons compared to persons in each of the other racial and ethnic categories. The percentage of melanomas that were ALM ranged from 0.8% among non-Hispanic White persons to 19.1% among Hispanic Black, AI/AN, and API persons. CONCLUSION: These findings suggest that awareness of the potential for ALM in patients of all races and ethnicities could be balanced with an understanding of the rarity of the disease and the potential for the development of other melanoma types in racial and ethnic minority groups.

Melanoma in skin of color: Part II. Racial disparities, role of UV, and interventions for earlier detection.

Despite a higher incidence of melanoma among White individuals, melanoma-specific survival is worse among individuals with skin of color. Racial disparities in survival are multifactorial. Decreased skin cancer education focused on people with skin of color, lower rates of screening, increased socioeconomic barriers, higher proportions of more aggressive subtypes, and underrepresentation in research and professional education contribute to delays in diagnosis and treatment. Although high, intermittent UV exposure during childhood has been established as a significant modifiable risk factor for melanoma in individuals with lighter skin phototypes, there are limited data on UV exposure and melanoma risk in people with darker skin phototypes. The second article of this continuing medical education series will examine factors contributing to racial disparities in melanoma-specific survival, discuss the role of UV radiation, and address the need for further research and targeted educational interventions for melanoma in individuals with skin of color.

Melanoma in skin of color: Part I. Epidemiology and clinical presentation.

Although there is a higher incidence of melanoma among non-Hispanic White individuals, melanoma is diagnosed at more advanced stages and associated with worse survival rates among individuals with skin of color (SOC). The proportions of melanoma subtypes differ across racial groups, with acral lentiginous melanoma and mucosal melanoma representing higher proportions of melanoma diagnoses in individuals with SOC compared to White individuals. The recognition of distinct differences in anatomic locations and dermatoscopic patterns may facilitate the appropriate differentiation of physiologic from pathologic pigmentation. The first article of this continuing medical education series will focus on the epidemiology and clinical presentation of melanoma in individuals with SOC, with the aim of improving early diagnoses and clinical outcomes.

Developing skin cancer education materials for darker skin populations: crowdsourced design, message targeting, and acral lentiginous melanoma.

Despite decreased susceptibility, darker skin individuals who develop melanoma have worse survival. This disparity in melanoma mortality is the largest for any cancer, and partly driven by a lack of patient education materials targeted to darker skin populations in whom acral lentiginous melanoma (ALM) is the most common subtype. To address this communication disparity, the current study reports a multi-phase design process that leverages crowdsourcing and message testing to develop ALM-focused patient education materials for darker skin populations. Crowdsourced design was utilized to develop a pool of designs (phase 1), the pool was narrowed and thematically analyzed (phase 2), and select designs were evaluated via a message experiment (N = 1877). For darker skin populations, designs that depicted people enhanced knowledge of ALM through message memorability. The current study engages melanoma disparities by providing ALM patient education materials for darker skin populations vetted via a multi-phase process.

Anatomic mapping of acral melanocytic nevi and acral lentiginous melanomas among Taiwanese patients: A retrospective cohort study.

BACKGROUND: The early diagnosis of acral lentiginous melanoma (ALM) contributes to clinical outcomes since ALM can be mistaken for acral melanocytic nevus (AMN). ALM occurrence is reported to correlate with stress-bearing areas, which may assist in differential diagnoses. Our objective is to evaluate the distribution patterns of ALMs and AMNs on the palms and soles among Taiwanese patients. METHODS: A retrospective analysis was performed by reviewing the charts of 1400 patients diagnosed with benign and malignant pigmented lesions confirmed after excisional biopsy at our institution between 2000 and 2022 in Taiwan. Correlations between lesions and clinicopathological factors were analyzed. RESULTS: 309 AMNs and 177 ALMs were included. Mechanical stress was significantly associated with plantar ALMs (weight-bearing area: 92.65 %, arch: 7.35 %, P < 0.001). Significant differences in the distribution patterns were observed for plantar ALMs compared with all AMNs (P < 0.001) and non-atypical AMNs (P < 0.001), but were not observed between palmar AMNs and ALMs. CONCLUSION: Plantar ALMs were most commonly observed on the weight-bearing areas of the soles, distinct from the distribution of all AMNs and of non-atypical AMNs. The distribution features and anatomic mapping of ALMs may facilitate the early clinical diagnosis of ALM.

Survival differences in acral lentiginous melanoma according to socioeconomic status and race.

BACKGROUND: Relationships of socioeconomic status (SES) and race to survival in acral lentiginous melanoma (ALM) are poorly characterized. OBJECTIVE: To compare disease-specific survival in ALM across SES and race. METHODS: Retrospective cohort study using the Surveillance, Epidemiology, and End Results database, 2000 to 2016. RESULTS: We identified 2245 patients with a first ALM diagnosis. Five-year disease-specific survival was 77.8% (95% CI, 75.9%-79.9%). After adjustment, patients in the lowest and second-to-lowest SES quintile had 1.33 (95% CI, 0.90-1.96) and 1.42 (95% CI, 1.03-1.97) times the risk of death, respectively, compared to highest quintile patients. Hispanic White and Black patients had 1.48 (95% CI, 1.10-1.99) and 1.25 (95% CI, 0.88-1.79) times the risk of death, respectively, compared to non-Hispanic Whites. Hazard ratios for ALM-specific death decreased in Hispanic White and Black patients after adjusting for SES and American Joint Committee on Cancer stage at diagnosis. LIMITATIONS: Treatments could not be evaluated. SES was measured at the level of the census tract and does not account for individual level factors. CONCLUSION: Differences exist in ALM survival according to socioeconomic status and race. Differences in SES and American Joint Committee on Cancer stage at diagnosis contribute to survival disparities for Hispanic White and Black patients. Understanding factors driving survival disparities related to SES and race may improve ALM outcomes.

Appraisal of clinicopathological prognosticators in advanced acral lentiginous melanoma with characterization of PD-L1 and CD8/CD4 immunoprofiles.

OBJECTIVE: Acral lentiginous melanoma is the most common subtype of cutaneous melanoma in Asian countries. This study aims to clarify the associations between certain histologic and immunohistochemical parameters, and identify their prognostic values. METHODS: We assessed several histologic features and conducted immunohistochemical study of programmed cell death ligand 1 (clone 22C3) and CD8/CD4 in 61 Taiwanese patients with Stage III/IV, non-BRAF acral lentiginous melanomas. RESULTS: A total of 41 males and 20 females were included, with a median age of 74 years. The majority of tumors occurred at nonungual locations (86.9%), with 'foot' being the most frequently affected site (85.2%). Positive programmed cell death ligand 1 staining (combined positive score ≥ 10) was significantly associated with the status of tumor-infiltrating lymphocytes (P = 0.036). Lack of skin ulceration was linked to the immunoexpression of CD8/CD4-high (P = 0.004). A superior clinical outcome was found in the tumor-infiltrating lymphocytes-present group (P = 0.011), and among which, CD8/CD4-high was significantly correlated with better survival (P < 0.001). Combined survival analysis revealed that the PD-L1(-) TIL(+) CD8/CD4-high subgroup was associated with favorable prognosis, and cases with PD-L1(+) TIL(-) showed the worst disease specific survival (P < 0.001). In the univariate analysis, lymphovascular invasion (P = 0.002), skin ulceration (P = 0.002), tumor-infiltrating lymphocytes (P = 0.015) and CD8/CD4 status (P < 0.001) were significant prognostic factors. At the multivariate level, the statuses of CD8/CD4-low (P < 0.001) and lymphovascular invasion (P = 0.014) represented the independent poor prognosticators. CONCLUSION: For advanced, non-BRAF acral lentiginous melanomas, comprehensive assessments of these microscopic traits, along with CD8/CD4 and PD-L1 immunoprofiles, may help guide the clinicians and patients through treatment decisions.

Adjuvant nivolumab therapy may not improve disease-free survival in resected acral lentiginous melanoma patients: A retrospective case series.

Adjuvant nivolumab therapy has been reported to improve the survival of melanoma patients. Acral lentiginous melanoma (ALM) has been reported to be less likely to respond to immune checkpoint inhibitors (ICIs) than other subtypes. However, the efficacy of adjuvant nivolumab therapy for ALM patients remains uncertain due to the low number of cases. In this single-center retrospective case series, we analyzed the clinical data of patients with resected stage III/IV ALM who were referred to our department between April 1, 2004 and March 31, 2022. The analyzed clinical data included age, sex, TNM stage, treatments, adverse events and disease-free survival (DFS). Enrolled patients were divided into a nivolumab group and a non-ICI group according to the adjuvant therapy they received. In total, 27 patients were included. The nivolumab and non-ICI groups had 5 and 22 patients, respectively. There were no significant differences in patient characteristics between the two groups. There were no serious treatment-related adverse events in the non-ICI group, but one patient in the nivolumab group developed type 1 diabetes. In the survival analysis, the DFS for the nivolumab group did not exceed that of the non-ICI group in postoperative adjuvant therapy for ALM patients. Given that adjuvant nivolumab therapy sometimes results in serious adverse effects, the administration of the therapy may need to be carefully considered, especially for ALM patients.

Characteristics of Acral Lentiginous Melanoma According to Location in Stress- or Non-Stress-Bearing Areas: A Retrospective Study of 95 Patients. / Características del melanoma lentiginoso acral según su relación con la presión. Estudio retrospectivo de 95 pacientes.

BACKGROUND AND OBJECTIVE: Acral lentiginous melanoma (ALM) arises in areas that are not generally exposed to UV radiation. Chronic trauma has been hypothesized to play a role in the development of this tumor. The aim of this study was to analyze the association between the presence and characteristics of ALM and location in stress- and non-stress-bearing areas. MATERIAL AND METHODS: Observational, descriptive analysis. For 95 patients with ALM evaluated at Fundación Clínica Vida in Medellin, Colombia between January 2016 and August 2020 we collected demographic, histologic and clinical variables and assigned the patients to 2 groups depending on whether their tumor was located in a stress-bearing area or not. RESULTS: Ninety-five patients (36 men and 59 women) with a median age of 59 years were studied. ALMs were more common in stress-bearing areas than in non-stress-bearing areas (58 [61%] vs. 17 [17.8%]). A history of direct trauma at the site of the tumor was reported in 18.9% of the cases (p = .025) and was most common in patients with nail lesions. Invasive ALMs in stress-bearing areas had a greater Breslow thickness (p = .006) and higher ulceration rates than those in non-stress-bearing areas (p = .018). CONCLUSIONS: ALM on both the feet and hands is more common in stress-bearing areas. Our findings support the hypothesis that mechanical stress may have a pathogenic role in ALM.

Acral Lentiginous Melanoma: A United States Multi-Center Substage Survival Analysis.

BACKGROUND: Acral lentiginous melanoma is associated with worse survival than other subtypes of melanoma. Understanding prognostic factors for survival and recurrence can help better inform follow-up care. OBJECTIVES: To analyze the clinicopathologic features, melanoma-specific survival, and recurrence-free survival by substage in a large, multi-institutional cohort of primary acral lentiginous melanoma patients. METHODS: Retrospective review of the United States Melanoma Consortium database, a multi-center prospectively collected database of acral lentiginous melanoma patients treated between January 2000 and December 2017. RESULTS: Of the 433 primary acral lentiginous melanoma patients identified (median [range] age: 66 [8-97] years; 53% female, 83% white), 66% presented with stage 0-2 disease and the median time of follow-up for the 392 patients included in the survival analysis was 32.5 months (range: 0-259). The 5-year melanoma-specific survivals by stage were 0 = 100%, I = 93.8%, II = 76.2%, III = 63.4%, IIIA = 80.8%, and IV = 0%. Thicker Breslow depth ((HR) = 1.13; 95% CI = 1.05-1.21; P < .001)) and positive nodal status ((HR) = 1.79; 95% CI = 1.00-3.22; P = .050)) were independent prognostic factors for melanoma-specific survival. Breslow depth ((HR = 1.13; 95% CI = 1.07-1.20; P < .001), and positive nodal status (HR = 2.12; 95% CI = 1.38-3.80; P = .001) were also prognostic factors for recurrence-free survival. CONCLUSION: In this cohort of patients, acral lentiginous melanoma was associated with poor outcomes even in early stage disease, consistent with prior reports. Stage IIB and IIC disease were associated with particularly low melanoma-specific and recurrence-free survival. This suggests that studies investigating adjuvant therapies in stage II patients may be especially valuable in acral lentiginous melanoma patients.

Acral Lentiginous Melanoma: Incidence and Survival in the United States, 2006-2015, an Analysis of the SEER Registry.

BACKGROUND: Acral lentiginous melanoma (ALM) is one of the four major subtypes in cutaneous malignant melanoma (CMM). We aimed to study the incidence and survival of ALM in the United States in recent 10 y and compare the survival between ALM and nonacral CMM. In the meantime, racial disparity and prognostic factors associated with survival were investigated. METHODS: All the cases of ALM registered in the Surveillance, Epidemiology, and End Results registry from 2006 to 2015 were retrieved, including non-Hispanic whites (NHW), black Americans (blacks), Asian/Pacific Islanders, and Hispanic whites. Age-adjusted incidence was calculated. Clinicopathologic data, including age, gender, race, geographic location, Breslow thickness, ulceration, pathologic staging, sentinel lymph node status, and surgical approach, were collected and analyzed. Melanoma-specific survival (MSS) was analyzed in patients with ALM and CMM. The Kaplan-Meier method was used to estimate the influence of clinicopathologic data on ALM MSS. Only cases with complete staging and active follow-up were included in prognostic factor analysis. RESULTS: A total of 1724 ALM and 87,442 nonacral CMM patients were included in the study. For ALM patients, the age-adjusted incidence rate was 2.0 per million person-years. The proportion of ALM among all melanoma subtypes was greatest in blacks (32.6%). The 5-y MSS rates of ALM were lower than CMM overall (80.6% versus 93.0%, P < 0.001, respectively). When controlled by stage, the difference was significant in patients diagnosed at stages I and III. ALM 5-y MSS rates were highest (84.3%) in NHW, intermediate in Asian/Pacific Islanders (76.6%), Hispanic white (72.0%), and lowest in blacks (66.9%). Blacks were elderly, male predominant, located in East and Middle American, and had thicker, more ulcerated, advanced disease as compared with NHWs. When controlled by stage, survival difference was significant between NHWs and blacks in stage I (P = 0.004) and stage III (P = 0.005) patients. Gender, race, sentinel lymph node status, and pathologic stage were identified as independent risk factors in multivariate analysis. CONCLUSIONS: The incidence of ALM has been steady in recent 10 y and more prevalent in aged people. ALM is associated with a worse prognosis than CMM. Black Americans have the worst prognosis, and survival difference is significant between NHW and blacks.

Acral lentiginous melanoma: Clinicopathologic and survival differences according to tumour location.

BACKGROUND/OBJECTIVES: Acral lentiginous melanoma (ALM) is a melanoma subtype associated with atypical locations on the hands and feet and advanced disease at diagnosis. There is a limited understanding of whether the survival is similar for nail, non-nail, lower limb and upper limb ALM patients. We therefore explored clinicopathologic characteristics and melanoma-specific survival of ALM patients according to tumour location. METHODS: A prospectively collected cohort study was performed of all primary invasive cutaneous acral lentiginous melanomas with known thickness and tumour location reviewed at a tertiary referral centre over 21 years. RESULTS: A total of 101 ALM patients were reviewed from 1994 until 2016. The majority of cases (82/101) occurred on the feet. Hand ALMs were thicker and more likely to be ulcerated than feet ALMs (P = 0.05 and 0.02, respectively); however, survival was not statistically different between these two groups (univariate HR 0.48 P = 0.11, 95% CI, 0.20-1.17; multivariate HR 0.67 P = 0.40, 95% CI, 0.27-1.69, respectively). Non-nail ALM patients had longer survival when compared to nail ALM on univariate analysis (HR 0.40, 95% CI, 0.17 to 0.90) which was accounted for by Breslow thickness and ulceration (multivariate HR 0.56, 95% CI, 0.24 to 1.34). CONCLUSIONS: The reduced melanoma-specific survival in nail ALM patients was likely due to their greater thickness and ulceration. Although hand ALMs are thicker and more frequently ulcerated, this is likely due to the higher proportion of nail ALMs present in this location.

High density of M2-macrophages in acral lentiginous melanoma compared to superficial spreading melanoma.

AIMS: Acral lentiginous melanoma (ALM) is the most common type of melanoma in people with darker skin phototypes. There is some evidence that the aetiology, pathogenesis, risk factors and natural history of ALM differ from those of superficial spreading melanoma (SSM). ALM behaves more aggressively than SSM, but the biological explanation for these differences remains unknown. The presence of one subtype of macrophages, termed M2-macrophage (M2-M), has been found to be related to local progression, metastasis and poor prognosis in several neoplasms. The aim of this study was to compare the density of M2-Ms in ALMs versus SSMs, and to examine whether or not the density of M2-Ms is associated with histopathological features predictive of adverse prognosis in cutaneous melanoma (CM), as well as development of metastasis. METHODS AND RESULTS: Sixty-seven ALMs and 67 SSMs cases were analysed. The tumours were classified according to thickness, ulceration, mitosis and metastasis. M2-M quantity was evaluated using immunohistochemistry with anti-CD163 and anti-CD206 antibodies. M2-Ms were increased in ALM compared with SSM, and were related to the histopathological features predictive of adverse prognosis in CM, such as thickness > 1.0 mm, ulceration and mitotic activity, and the development of metastasis. CONCLUSIONS: Our study is the first, to our knowledge, to demonstrate the increased presence of M2-Ms in ALM compared with SSM. Our findings suggest that the increased M2-Ms in ALM are associated with the main histopathological features predictive of adverse prognosis in CM, as well as the presence of metastasis, and that these cells can be related to the aggressive behaviour seen in ALMs.

Acral Lentiginous Melanoma Is Associated with Certain Poor Prognostic Histopathological Factors but May Not be Correlated with Nodal Involvement, Recurrence, and a Worse Survival.

BACKGROUND/AIMS: Acral lentiginous melanoma (ALM) is a small subtype of melanoma affecting Caucasians far more often than other ethnic groups, such as blacks, Hispanics, and Asians. Only a few studies have yielded controversial results on ALM so far. The aim of this study was to define the histopathological and clinical expressions of ALM and to compare them with those of non-ALM in a large group of Turkish patients from a single referral institution. METHODS: One hundred two ALM patients were analyzed retrospectively. RESULTS: The median age of the patients was 58 years. The lower limbs (the thigh and leg as well as the foot) were predominantly affected (78%) and cases were mostly nonungual (89%). ALM were found more frequently in females (p = 0.04). They were ulcerated (p = 0.0001), they were associated with neurotropism (p = 0.0001), they lacked the BRAF mutation (p = 0.03), and they less often coexisted with a preceding melanocytic nevus (p = 0.0001). No correlations were found between ALM and either nodal involvement or distant metastasis. The recurrence-free survival and overall survival rates for ALM patients were similar to those of patients with other histopathologies. The 5-year recurrence-free survival and 5-year overall survival rates for ALM patients were 58.7 and 59%, respectively. CONCLUSION: Although ALM is associated with some aggressive histopathological factors, it may not correlated with nodal involvement, recurrence, or poor survival.