Acral Melanoma Research Articles

The Roles of Vitamin D Receptor (VDR) and CD8+ T-Lymphocytes in Acral and Mucosal Melanoma Invasion Depth.

Acral and mucosal melanomas, the most common sun-shielded site melanoma subtypes in Asia and Indonesia, often yield poor prognoses. The invasion depth reflects their progressivity, and the pathogenesis is influenced by vitamin D receptor (VDR) status and CD8+ T-Lymphocyte amount. This study aims to determine the association between the invasion depth of acral and mucosal melanomas with their VDR and CD8+ immunoexpression. A cross-sectional observational study was conducted on 60 formalin-fixed paraffin-embedded (FPPE) samples, with equal representation in acral and mucosal melanoma groups from 2017 to 2021. The samples were assessed for the invasion depth and immunoexpression of VDR and CD8+. A chi-square test with an alternative Exact-Fisher analysis was used to determine the association between the variables in both subtype groups. An association between VDR and CD8+ immunoexpression and invasion depth in acral melanoma (p value = 0.0001 and 0.009, respectively) was observed, while only VDR immunoexpression was associated with the invasion depth in mucosal melanoma (p-value =0.004). Interestingly, no association was found between CD8+ immunoexpression and the invasion depth in mucosal melanoma (p = 0.640). The role of VDR and CD8+ T-lymphocytes are inversely associated with melanoma depth in acral melanoma, while only VDR is associated with melanoma depth in mucosal melanoma.

Single-cell profiling of acral melanoma infiltrating lymphocytes reveals a suppressive tumor microenvironment.

Acral lentiginous melanoma (ALM) is the most common melanoma subtype in non-Caucasians. Despite advances in cancer immunotherapy, current immune checkpoint inhibitors remain unsatisfactory for ALM. Hence, we conducted comprehensive immune profiling using single-cell phenotyping with reactivity screening of the T cell receptors of tumor-infiltrating T lymphocytes (TILs) in ALM. Compared with cutaneous melanoma, ALM showed a lower frequency of tumor-reactive CD8 clusters and an enrichment of regulatory T cells with direct tumor recognition ability, suggesting a suppressive immune microenvironment in ALM. Tumor-reactive CD8 TILs showed heterogeneous expression of coinhibitory molecules, including KLRC1 (NKG2A), in subpopulations with therapeutic implications. Overall, our study provides a foundation for enhancing the efficacy of immunotherapy in ALM.

Plantar acral melanoma: epidemiological, clinical, dermoscopic and histopathological features. A Brazilian cohort

BackgroundAcral melanomas (AM) are rare and approximately two-thirds of them occur on the soles of the feet beeing more prevalent in black and Asian individuals. Data on this subtype of melanoma are scarce in the Brazilian population. ObjectivesTo describe and correlate the epidemiological, clinical, dermoscopic, and histopathological features of AM a. MethodsSingle-center, retrospective and cross-sectional study, evaluating data from a 15-year period. ResultsA total of 48 cases were included. Mean age was 62.54 years, with a predominance of women (62.5%). The percentage of amelanotic melanomas was higher among lighter skin patients (20% × 7.7%). Polychromia was the most prevalent finding (94.4%). The parallel ridge pattern (PRP) had a prevalence of 78% and a serrated pattern was associated with lower Breslow thickness (p = 0.041). Ulceration present on histopathological (p = 0.013) or dermoscopic (p = 0.047) evaluation was associated with greater Breslow thickness. Study limitationsRetrospective study with loss of data. ConclusionAmelanotic tumors were more prevalent in ligther phototypes (20% × 7.7%). Polychromia was the most prevalent finding (94.4%) and ulceration observed on clinical or histopathological evaluation was associated with higher Breslow thickness (p = 0.013 and 0.047).

Evaluation of Heterogeneity in the Coding Region of BRAF, MAP2K1, and MAP2K2 Genes in Primary and Metastatic Melanomas.

The incidence of melanoma has been increasing in recent decades. BRAF mutations appear in 50%-70% of melanomas. The BRAF-targeted therapy increased the disease-free survival of patients with metastatic melanoma, but this response may be short, due to several resistance mechanisms, such as the presence of other subclones with mutations. Evaluation of mutations and heterogeneity in the coding region of the BRAF, MAP2K1, and MAP2K2 genes in primary and metastatic melanomas. Twenty-seven samples of primary and metastatic superficial spreading melanoma (SSM) and acral lentiginous melanoma (ALM) were analyzed for BRAF, MAP2K1, and MAP2K2 mutations using the next-generation sequencing technique. In ALM, the mutation rate found was 50% in the BRAF and MAP2K1 genes and 28.6% in MAP2K2. In the SSM, BRAF was mutated in 76.9%, MAP2K1 in 30.8%, and MAP2K2 in 23.2% of the cases. All samples were formed by distinct tumor subclones in the same lesion. Intertumoral heterogeneity was present between primary and metastatic lesions of ALM in BRAF, MAP2K1, and MAP2K2; the cases of SSM were heterogeneous for BRAF and MAP2K1. We sought to evaluate the mutations in the BRAF, MAP2K1, and MAP2K2 genes, revealing a heterogeneous mutation profile in samples of ALM and SSM.

Neoadjuvant oncolytic virus orienx010 and toripalimab in resectable acral melanoma: a phase Ib trial

Neoadjuvant PD-1 inhibitor is promising in cutaneous melanoma but remains unknown in acral melanoma (AM). This phase Ib trial study (Clinicaltrials.gov NCT04197882) assessed the efficacy and safety of the combination of neoadjuvant oncolytic virus orienX010 (ori) and anti-PD-1 toripalimab (tori) for resectable AM. Thirty patients of stage III/IV received neoadjuvant therapy of ori and tori for 12 weeks before surgery, followed by adjuvant treatment with tori for 1 year. Primary endpoints were radiographic and pathological response rates, with secondary endpoints of 1- and 2-year recurrence-free survival (RFS) rates, event-free survival (EFS) rates, and safety. Twenty-seven completed surgery and tori adjuvant treatment and median follow-up was 35.7 months. Radiographic and pathological response rates were 36.7% and 77.8%, with complete response rates of 3.3% and 14.8%, 1- and 2-year RFS rates of 85.2% and 81.5%, and 1- and 2-year EFS rates of 83% and 73%, respectively. Adverse events occurred in all patients, mainly grade 1–2. There was no correlation between PET/CT evaluation and pathological response or progression-free survival/overall survival. Patients with pathological response showed tumor beds with high tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs). Cytokines and chemokines analysis showed the combination therapy significantly increases the secretion of proinflammatory cytokines and chemokines in both responders and non-responders. Therefore, neoadjuvant ori and tori demonstrated promising antitumor activity with high response rates and high 2-year RFS/EFS for AM with acceptable tolerability.

First-Line Nivolumab Plus Relatlimab Versus Nivolumab Plus Ipilimumab in Advanced Melanoma: An Indirect Treatment Comparison Using RELATIVITY-047 and CheckMate 067 Trial Data.

Nivolumab plus relatlimab and nivolumab plus ipilimumab have been approved for advanced melanoma on the basis of the phase II/III RELATIVITY-047 and phase III CheckMate 067 trials, respectively. As no head-to-head trial comparing these regimens exists, an indirect treatment comparison was conducted using patient-level data from each trial. Inverse probability of treatment weighting (IPTW) adjusted for baseline characteristic differences. Minimum follow-ups (RELATIVITY-047, 33 months; CheckMate 067, 36 months) were selected to best align assessments. Outcomes included progression-free survival (PFS), confirmed objective response rate (cORR), and melanoma-specific survival (MSS) per investigator; overall survival (OS); and treatment-related adverse events (TRAEs). A Cox regression model compared PFS, OS, and MSS. A logistic regression model compared cORRs. Subgroup analyses were exploratory. After IPTW, key baseline characteristics were balanced for nivolumab plus relatlimab (n = 339) and nivolumab plus ipilimumab (n = 297). Nivolumab plus relatlimab demonstrated similar PFS (hazard ratio [HR], 1.08 [95% CI, 0.88 to 1.33]), cORR (odds ratio, 0.91 [95% CI, 0.73 to 1.14]), OS (HR, 0.94 [95% CI, 0.75 to 1.19]), and MSS (HR, 0.86 [95% CI, 0.67 to 1.12]) to nivolumab plus ipilimumab. Subgroup comparisons showed larger numerical differences favoring nivolumab plus ipilimumab with acral melanoma, BRAF-mutant melanoma, and lactate dehydrogenase >2 × upper limit of normal, but were limited by small samples. Nivolumab plus relatlimab was associated with fewer grade 3-4 TRAEs (23% v 61%) and any-grade TRAEs leading to discontinuation (17% v 41%). Nivolumab plus relatlimab demonstrated similar efficacy to nivolumab plus ipilimumab in the overall population, including most-but not all-subgroups, and improved safety in patients with untreated advanced melanoma. Results should be interpreted with caution.

Cyclin-Dependent Kinase Inhibitors in the Rare Subtypes of Melanoma Therapy.

Melanoma occurs in various forms and body areas, not only in the cutis, but also in mucous membranes and the uvea. Rarer subtypes of that cancer differ in genomic aberrations, which cause their minor sensibility to regular cutaneous melanoma therapies. Therefore, it is essential to discover new strategies for treating rare forms of melanoma. In recent years, interest in applying CDK inhibitors (CDKIs) in cancer therapy has grown, as they are able to arrest the cell cycle and inhibit cell proliferation. Current studies highlight selective CDK4/6 inhibitors, like palbociclib or abemaciclib, as a very promising therapeutic option, since they were accepted by the FDA for advanced breast cancer treatment. However, cells of every subtype of melanoma do not react to CDKIs the same way, which is partly because of the genetic differences between them. Herein, we discuss the past and current research relevant to targeting various CDKs in mucosal, uveal and acral melanomas. We also briefly describe the issue of amelanotic and desmoplastic types of melanoma and the need to do more research to discover cell cycle dysregulations, which cause the growth of the mentioned forms of cancer.

Characteristics of melanoma in Mexicans seen at "La Raza" National Medical Center

Melanoma is the third most common type of skin cancer in Mexico and represents 75% of skin cancer deaths. Dermoscopy is a diagnostic tool that increases early detection of melanoma compared to naked eye examination. The aim of this study was to describe the clinical, dermoscopic and histological characteristics of patients with a confirmed diagnosis of cutaneous melanoma treated at the "La Raza" National Medical Center. A retrospective, descriptive and cross-sectional study was carried out from March 1998 to December 2013, with 187 histologically confirmed cases, considering: sex, age, skin phototype, history, topography of the lesion, dermoscopic pattern, metastasis at the time of diagnosis and histological subtype, Breslow index and Clark index, using the chi-square test as a non-parametric statistical method to analyze the data obtained. Most patients had skin phototype III and the most affected location was the lower limb. Clinically, acral lentiginous melanomas and nodular melanomas were the most observed. The most common dermoscopic finding was the multicomponent pattern. Clinically and histologically, the most frequent subtype associated with metastasis was nodular melanoma. Acral lentiginous melanoma was more common among patients without metastasis. Unfortunately, melanoma is still diagnosed in advanced stages in Mexico; for its early recognition, training in the use of dermoscopy and greater awareness about melanoma in the Mexican population must be encouraged.

Nevus-associated acral melanoma has lower risk of recurrence and mortality than de novo acral melanoma: A multicenter, retrospective analysis of 482 patients

BackgroundIt is unknown whether acral melanomas (AM) associated with pre-existing nevi have similar risk to other acral melanomas. ObjectiveTo compare risk of recurrence and death between AM associated with pre-existing nevi and de novo AM. MethodsWe conducted a multicenter retrospective cohort study involving patients diagnosed with AM between February 2011 and November 2022. Results164 patients (34.0%) had nevus-associated acral melanoma (NAAM). NAAM has lower risk of recurrence (HR 0.69, 95% CI 0.52–0.91, P = 0.008) and mortality (HR 0.53, 95% CI 0.37–0.76, P < 0.001) than de novo acral melanoma (DNAM). The five-year recurrence-free survival (RFS) was 55.1% for NAAM compared to 42.3% for DNAM. The five-year overall survival (OS) was 75.1% for NAAM and 63.2% for DNAM. Multivariate analyses identified Breslow thickness, nevus association, and sentinel node status as independent predictors of RFS. Age, Breslow thickness, nevus association, lymphovascular invasion, ulceration, and sentinel node status were independent predictors of OS. LimitationsThe study's limitations included its retrospective design and missing data. ConclusionPatients with nevus-associated AM had significantly better RFS and OS compared to those with de novo AM. Nevus association was an independent prognostic factor for both RFS and OS.

Genetic Characteristics of Cutaneous, Acral, and Mucosal Melanoma in Japan.

Acral and mucosal melanomas are more prevalent in Asians than in Caucasians, unlike cutaneous melanomas, which are predominant in Caucasians. Recent studies have suggested that non-Caucasian cutaneous melanomas responded less to immune checkpoint inhibitors, highlighting the need for genetic profiling across ethnicities. This study aimed to elucidate the genetic characteristics of Japanese melanomas, which is an under-researched topic. Single-nucleotide variants, indels, and copy number alterations in 104 Japanese melanoma patients (37 cutaneous, 52 acral, and 15 mucosal) were analyzed using custom panel sequencing. Driver events were detected in 94% of the cases. Among cutaneous melanoma cases, 76% had BRAF mutations, and 8% had NRAS mutations. In acral melanoma, BRAF (9%), NRAS (17%), KRAS (8%), KIT (19%), and NF1 (7%) mutations were detected. Major driver mutations in mucosal melanoma were detected in NRAS, KRAS, NF1, PTEN, GNAQ, and KIT. The median tumor mutational burden across all melanoma types was 4.6 mutations/Mb, with no significant difference between the cutaneous and acral/mucosal types. Of the 21 patients with both primary and metastatic lesions, 11 showed distinct mutations in each. Potentially actionable mutations were detected in 58 patients in addition to BRAF V600E/K mutations in 31. This study highlights distinct genetic abnormalities and actionable alterations in Japanese melanoma patients. This suggests a lower tumor mutational burden in East Asian cutaneous melanoma, which may affect the efficacy of immune checkpoint inhibitors. The heterogeneity of driver mutations across and within individuals highlights the need for personalized treatment approaches.

Impact on Survival with Immunotherapy and Evaluation of Biomarkers in Peruvian Patients with Advanced Melanoma.

Advanced malignant melanoma is a very aggressive disease, historically with poor prognosis before the new advances with immunotherapy and targeted therapies that have changed the standard of care, especially in cutaneous melanoma. Peru has aggressive features such as higher rates of acral lentiginous melanoma (ALM) subtype with historically shorter survival. This study describes Peruvian patients with advanced melanoma treated with immunotherapy (nivolumab) in two oncological institutions (public and private), including the discussion of the impact on overall survival (OS) divided by subtype (with incidence in ALM histology) and potential biomarkers that could be related to prognosis. We found that immunotherapy is safe, and improves progression-free survival (PFS), OS and objective response rate (ORR) in our patients, with lower benefit in ALM histology. No prognostic blood inflammatory biomarkers were detected. There is very limited data of Peruvian patients with metastatic melanoma treated with immunotherapy, especially the outcomes in ALM histology. Our goal is to share an example of the impact of immunotherapy in a Latin American (LATAM) population considered as an unsatisfied group with an enormous need of novel treatments and biomarkers.

MicroRNA Quantification as an Accurate and Cost-Effective Method to Diagnose Acral Melanoma

MicroRNA Quantification as an Accurate and Cost-Effective Method to Diagnose Acral Melanoma

Combined PD-1 and CTLA-4 Blockade in an International Cohort of Patients with Acral Lentiginous Melanoma.

Combination immune checkpoint blockade targeting PD-1 and CTLA-4 leads to high response rates and improved survival in advanced cutaneous melanoma (CM). Less is known about the efficacy of this combination in acral lentiginous melanoma (ALM). To determine the efficacy of combination immune checkpoint blockade targeting PD-1 and CTLA-4 in a real-world, diverse population of ALM. This multi-institutional retrospective study analyzed patients with histologically confirmed ALM treated with the combination of PD-1 and CTLA-4 inhibitors between 2010-2022. The primary objective of the study was objective response rate (ORR) per RECIST criteria. The secondary objectives were progression-free survival (PFS) and overall survival (OS). In total, 109 patients with advanced ALM treated with combined PD-1 and CTLA-4 blockade in any line of treatment were included. The majority of patients had stage IV disease (n=81, 74.2%). The ORR for the entire cohort was 18.3% (95% CI 11.6-26.9%), with 9 (8.3%) complete responses (CR) and 11 (10.1%) partial responses (PR). An additional 22 patients (20.2%) had stable disease (SD), and the disease control rate (DCR) was 38.5%. The median PFS was 4.2 months [95% CI 3.25-5.62], while the median OS was 17 months [95% CI 12.4%-23.1%]. A total of 95 patients (87.2%) had a treatment-related adverse event, with 40.4% (n=44/109) experiencing at least one grade 3 or 4 toxicity. Elevated LDH (p=.04), 2+ lines of prior therapy (p=.03), and Asian race/ethnicity (p=.04) were associated with worse OS, while Hispanic/Latino race/ethnicity was associated with better OS (p=.02). Combination of PD-1 and CTLA-4 blockade is less effective for ALM, as compared to CM, despite similar toxicity. Asian patients, in particular, appear to derive lower benefit from this regimen. Novel treatment approaches are needed for this rare melanoma subtype.

Intrathecal anti-PD-1 treatment in metastatic melanoma patients with leptomeningeal disease (LMD): real-world data and evidence.

Leptomeningeal disease (LMD) is a severe complication of melanoma with a very poor prognosis. Despite improved treatment strategies and prolonged survival, the incidence of LMD has increased over the past decade. This real-world study aims to evaluate the efficacy and safety of intrathecal anti-PD-1 treatment in melanoma patients with LMD. Melanoma patients with LMD diagnosed by magnetic resonance imaging (MRI) and/or cerebrospinal fluid (CSF) cytology were treated with intrathecal infusions of nivolumab 20mg once every 2 weeks (n = 5) or pembrolizumab 20mg once every 3 weeks (n = 3), alongside systemic therapy. Patients received a median of 5.5 treatment cycles (range 2-9). Efficacy and safety analyses were performed on all treated patients. From June 2022 to February 2023, eight patients were treated, including four with cutaneous melanoma, two with acral melanoma, and two with primary leptomeningeal melanoma. All patients exhibited linear or small nodular enhancement of the leptomeninges on MRI. Four patients had concurrent parenchymal brain metastases. Tumor cells were identified in six patients by CSF cytology, and two patients underwent leptomeningeal biopsy for pathological diagnosis. According to the RANO-LM criteria, five patients responded to treatment with symptom improvement and reduction or disappearance of linear enhancement on MRI, while three patients developed progressive disease. With a median follow-up of 20.7 weeks (range 8.1-45.3 weeks), the median OS and median intracranial progression-free survival (IPFS) for intrathecal anti-PD-1 treatment were 21.1 and 16.1 weeks, respectively. All treatment-related adverse events were grade 1-2, including headache (grade 1, n = 1; grade 2, n = 2) and low back pain (grade 1, n = 1). In this real-world study, intrathecal anti-PD-1 treatment demonstrated potential clinical benefits and was well tolerated in metastatic melanoma patients with LMD.

Validation of a Dermatoscopy-Based Algorithm for the Diagnosis of Acral Melanoma

Introduction: Diagnosis of acral melanocytic lesions can be challenging. The BRAAFF checklist was introduced as a tool to help differentiate between acral nevi and melanoma but has not been validated. Methods: We asked raters with varying expertise in dermatoscopy to diagnose dermatoscopic images of 533 acral nevi and 144 melanomas via an online platform with and without use of the BRAAFF checklist. From the ratings, we calculated sensitivity, specificity, and interrater agreement. Additionally, a new simplified version of the checklist was also tested. Results: We collected 6,880 ratings from 175 readers. The BRAAFF checklist achieved a sensitivity of 92.5% and a specificity of 65.0%, which was similar to diagnosis from pattern recognition (sensitivity 90.0%, specificity: 72.1%). Interrater agreement for the BRAAFF criteria ranged from fair to moderate, with lowest agreement for parallel ridge and fibrillar pattern (alpha = 0.31) and highest for asymmetry of colors and structures (alpha = 0.46). Agreement and diagnostic accuracy were higher for more experienced readers. A simplified version with only two criteria achieved similar sensitivity (95.0%) and lower specificity (60.0%) as the original BRAAFF checklist. Conclusion: The BRAAFF checklist is a useful tool for the diagnosis of melanocytic acral lesions with acceptable sensitivity and reasonable specificity but is not superior to pattern recognition. A simplified version of the checklist could be easier to use with equal sensitivity while exhibiting a modest reduction in specificity.

Unraveling the Obesity Paradox: Exploring the Impact of Body Weight on Cutaneous Melanoma Prognosis in Asian Population.

Obesity has been identified as a significant risk factor for various diseases, including certain cancers; however, its association with melanoma remains a subject of debate. Despite the increasing incidence of cutaneous melanoma in Taiwan, there has been limited research on its correlation with obesity. This study aims to investigate the relationship between obesity and the prognosis of cutaneous melanoma in Taiwan. Between January 1, 2000, and December 31, 2022, 201 patients were diagnosed with cutaneous melanoma at our hospital, with 61.69% of them diagnosed with acral melanoma. Data on body weight, height, tumor stages and prognosis were collected and analyzed. The result revealed that older age (≥ 65 years old), male, advanced Breslow thickness stage (T3 and T4) and tumor ulceration were identified as risk factors for worse overall survival in both cutaneous melanoma and acral melanoma. In the adjusted multivariable analysis, being overweight was considered a protective factor in both cutaneous and acral melanoma. Contrary to expectations, it was observed that melanoma patients with obesity exhibited better survival rates compared to those with normal or underweight status. Additionally, no significant differences were found between acral melanoma and non-acral melanoma subtypes regarding the impact of body weight on overall survival.

BRAF and NRAS Mutations and the Association with Prognosis of Acral Lentiginous and Nodular Melanomas in Indonesia.

Melanomas are rare yet the most aggressive skin cancer among Asians. Clinical presentation, risk factors, and the underlying molecular mechanisms are strikingly different from cutaneous melanoma in Caucasians. Mutation patterns of BRAF and NRAS genes were examined from DNAs derived from primary melanoma tumor tissues (fresh tissues or formalin-fixed paraffin-embedded samples) using pyrosequencing. A total of 63 patients consisting of acral lentiginous melanoma (N=22, 34.9%) and nodular melanoma (N=41, 65.1%) were included in this study. Most patients were diagnosed at Stage III-IV (N=49, 77.8%), Breslow thickness more than 4 mm (N=51, 80.9%), presence of ulceration (N=35, 55.6%), diameter larger than 6 mm (N=61, 96.8%), regional node infiltration (N=41, 77.8%). BRAF and NRAS mutations were found in 28 (44.4%) and 8 (12.7%), respectively. BRAF and NRAS mutations were significantly associated with older melanoma patients (OR = 6.075, 95%CI = 2.013-18.333 dan OR = 13.263, 95%CI = 1.518-115.901, respectively). BRAF mutations were associated with lower overall survival (Median survivals were 16.5 vs 31.4 months, Log-rank test P=0.001). NRAS mutations were not significantly associated with lower overall survival. In this study, melanoma patients are largely diagnosed at the late stages with ulceration and involvement of regional lymph nodes. BRAF mutations are associated with lower survival of cutaneous melanoma patients.

Acral lentiginous melanoma in situ on the palm with a diffuse parallel furrow pattern

Acral lentiginous melanoma in situ on the palm with a diffuse parallel furrow pattern

From genes to populations: developing precision medicine for acral lentiginous melanoma through in silico and epidemiological studies

Acral Lentiginous Melanoma (ALM) is a rare and aggressive form of melanoma that predominantly affects individuals with darker skin tones, posing significant challenges in both diagnosis and treatment. The growing demand for more personalized and effective treatments has led to the exploration of innovative approaches to tackle these challenges. This study integrates in silico drug design with comprehensive statistical analysis to identify and validate therapeutic targets specific to ALM. Key genes such as PLD1, CDKN2A, KIT, TERT, and NRAS were identified using advanced bioinformatics tools like DisGeNET, PANTHER DB, Network Analyst, and STRING DB. In parallel, a detailed demographic analysis involving 248 patients was conducted using SPSS, shedding light on factors influencing knowledge and awareness of ALM within affected populations. The findings from this dual approach emphasize the critical need for tailored therapeutic strategies that account for both genetic factors and patient demographics. The projected increase in ALM cases and the associated need for targeted therapies underscore the importance of continuing research into specialized treatments that can address the unique characteristics of this melanoma subtype. By advancing our understanding of ALM’s genetic profile and epidemiology, this study lays the foundation for the development of precision medicine solutions that could significantly improve patient outcomes and overall management of this aggressive disease.

A Narrative Review of the Evolution of Diagnostic Techniques and Treatment Strategies for Acral Lentiginous Melanoma.

Acral melanoma (AM) is a subtype of cutaneous melanoma located on the palms, soles, and nails. The pathogenesis of AM involves mechanical stimulation and characteristic tumor-promoting mutations, such as those in the KIT proto-oncogene. Dermoscopy is useful for diagnosing AM, which is characterized by parallel ridge patterns and irregular diffuse pigmentation. Although histopathological confirmation is the gold standard for diagnosing AM, lesions showing minimal histopathological changes should be considered early-stage AM if they clinically resemble it. Recently, immunohistochemical staining of preferentially expressed antigen in melanoma has been recognized as a useful method to distinguish benign from malignant melanocytic tumors. Research reveals that AM is associated with an immunosuppressive microenvironment characterized by increased numbers of M2 macrophages and regulatory T cells, alongside a decreased number of tumor-infiltrating lymphocytes. Mohs micrographic surgery or digit-sparing wide local excision has been explored to improve quality of life and replace wide local excision or proximal amputation. AM has a worse prognosis than other subtypes, even in the early stages, indicating its inherent aggressiveness.