Adjuvant treatment with anti-PD-1 in acral melanoma: A nationwide study.

Previous studies demonstrated limited efficacy of immune checkpoint inhibitors in unresectable acral melanoma (AM); it remains unclear how this translates to the adjuvant setting. This study investigates clinical outcomes of acral compared to cutaneous melanoma (CM) patients treated with adjuvant anti-PD-1 after complete resection. All stages III-IV AM and CM patients receiving adjuvant anti-PD-1 after complete resection between 2018 and 2022 were included from the prospective nationwide Dutch Melanoma Treatment Registry. We analyzed recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). A multivariable Cox regression analysis of RFS was performed to adjust for potential confounders. We included 1958 (86 AM and 1872 CM) patients. At baseline, AM patients more frequently had KIT mutations, higher disease stages, and Eastern Cooperative Oncology Group Performance Status, and fewer BRAF and NRAS mutations. Median RFS was 14.8 months (95% confidence interval [CI]: 11.5-29.3) in AM and 37.4 months (95% CI: 34.6 to not reached) in CM (p = .002). After correcting for potential confounders, AM remained associated with a higher risk of recurrence (HRadj 1.53; 95% CI: 1.07-2.17; p = .019). Two-year DMFS tended to be worse for AM than for CM: 64.5% versus 79.7% (p = .050). Two-year OS was significantly lower in AM (71.5% vs. 84.3%; p = .027). The results of this study suggest a poorer outcome of adjuvant-treated AM compared to CM. Studies assessing the added value of adjuvant treatment in AM are needed. Future research should investigate alternative treatment strategies to improve outcomes of high-risk AM.

Prognostic and Predictive Significance of Ki67 in Primary Non-metastatic or Recurrent Acral Melanoma: Evidence from a Multicenter Retrospective Study.

BACKGROUND: The purpose of this work was to investigate the prognostic significance of Ki67 in acral melanoma (AM). PATIENTS AND METHODS: Ki67 values in primary lesions (pKi67) of 481 patients with primary non-metastatic AM (primary cohort) from three tertiary hospitals and in recurrent lesions (rKi67) of 97 patients (recurrent cohort) were recorded. The associations of p/rKi67 with clinicopathological features and prognosis were analyzed. RESULTS: In the primary cohort, high pKi67 group tended to have more ulceration, pT4, lymph node metastasis (LNM), nodal macrometastases, and recurrence (all P < 0.05). Logistic regression analysis revealed that pKi67 was significantly associated with pT4 and LNM (P = 0.004 and 0.027, respectively). Furthermore, both 5-year overall survival (OS) and recurrence-free survival (RFS) rates in high pKi67 group were significantly worse than those in moderate and low pKi67 groups (OS 47.8% versus 55.7 versus 76.8%, P = 0.002; RFS: 27.1 versus 42.8 versus 61.8%, P < 0.001). Similarly, in the recurrent cohort, the 5-year survival after recurrence (SAR) rates in high rKi67 group was significantly worse than those in moderate and low rKi67 groups (31.7 versus 47.4 versus 75%; P = 0.026). Stratified analysis also indicated a significant survival difference among pKi67 groups within various subgroups. Most importantly, multivariate Cox analysis demonstrated that pKi67 could be independently associated with OS and RFS, as well as rKi67 for SAR (all P < 0.05). CONCLUSIONS: A high Ki67 value was significantly associated with adverse pathological and prognostic features in both primary and recurrent AM cohorts. Ki67 should be routinely evaluated to guide risk stratification and prognostic prediction.

Baseline Serum neutrophil-to-lymphocyte ratio in acral melanoma compared with nonacral melanoma and its prognostic significance.

BACKGROUND: Acral lentiginous melanoma (ALM), a cutaneous melanoma subtype, exhibits a poorer prognosis than nonacral cutaneous melanoma (NACM). The neutrophil-to-lymphocyte ratio (NLR) is emerging as a prognostic indicator across diverse cancers. OBJECTIVE: We explored the baseline NLR disparities between ALM and NACM, and the NLR's prognostic significance in patients with ALM. METHODS: We reviewed records of patients with ALM and NACM diagnosed between 1997 and 2022, analyzing medical data. RESULTS: Among 327 and 159 patients with ALM and NACM, respectively, baseline NLR varied based on distinct clinicopathologic factors between ALM and NACM. In stage 3 to 4 melanomas, the median NLR for ALM (2.18; IQR, 1.70-3.08) significantly surpassed NACM (1.74; IQR, 1.33-2.53) (P = .029). In patients with ALM, high NLR (hazard ratio, 1.64; 95% CI, 1.02-2.66; P = .043) was independently correlated with poor progression-free survival when adjusting for ulceration, Breslow thickness of ≥2 mm, and nodal invasion. LIMITATIONS: Single-center, retrospective design. CONCLUSION: Advanced-stage ALM exhibited a significantly higher baseline NLR compared with that of NACM. Evaluating baseline NLR could provide valuable prognostic insights for patients with ALM.

Establishment of a CD8+ T cells-related prognostic risk model for acral melanoma based on single-cell and bulk RNA sequencing.

BACKGROUND: CD8+ T cells have been recognized as crucial factors in the prognosis of melanoma. However, there is currently a lack of gene markers that accurately describe their characteristics and functions in acral melanoma (AM), which hinders the development of personalized medicine. METHODS: Firstly, we explored the composition differences of immune cells in AM using single-cell RNA sequencing (scRNA-seq) data and comprehensively characterized the immune microenvironment of AM in terms of composition, developmental differentiation, function, and cell communication. Subsequently, we constructed and validated a prognostic risk scoring model based on differentially expressed genes (DEGs) of CD8+ T cells using the TCGA-SKCM cohort through Lasso-Cox method. Lastly, immunofluorescence staining was performed to validate the expression of four genes (ISG20, CCL4, LPAR6, DDIT3) in AM and healthy skin tissues as included in the prognostic model. RESULTS: The scRNA-seq data revealed that memory CD8+ T cells accounted for the highest proportion in the immune microenvironment of AM, reaching 70.5%. Cell-cell communication analysis showed extensive communication relationships among effector CD8+ T cells. Subsequently, we constructed a prognostic scoring model based on DEGs derived from CD8+ T cell sources. Four CD8+ T cell-related genes were included in the construction and validation of the prognostic model. Additionally, immunofluorescence results demonstrated that ISG20 and CCL4 were downregulated, while LPAR6 and DDIT3 were upregulated in AM tissues compared to normal skin tissues. CONCLUSION: Identifying biomarkers based on the expression levels of CD8+ T cell-related genes may be an effective approach for establishing prognostic models in AM patients. The independently prognostic risk evaluation model we constructed provides new insights and theoretical support for immunotherapy in AM.

Clinical practice consensus for the diagnosis and management of melanoma in Taiwan.

Melanoma is rare in Taiwan. Asian melanoma is distinct from Western melanoma because acral and mucosal melanoma accounts for the majority of melanoma cases, leading to distinct tumor behaviors and genetic profiling. With consideration of the clinical guidelines in Western countries, Taiwanese experts developed a local clinical practice consensus guideline. This consensus includes diagnosis, staging, and surgical and systemic treatment, based only on clinical evidence, local epidemiology, and available resources evaluated by experts in Taiwan. This consensus emphasizes the importance of surgical management, particularly for sentinel lymph node biopsies. In addition, molecular testing for BRAF is mandatory for patients before systemic treatment. Furthermore, immunotherapy and targeted therapy are prioritized for systemic treatment. This consensus aimed to assist clinicians in Taiwan in diagnosing and treating patients according to available evidence.

PRAME Updated: Diagnostic, Prognostic, and Therapeutic Role in Skin Cancer.

Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the field of skin cancer diagnostics and therapeutics. As a nuclear receptor and transcriptional regulator, PRAME plays a critical role in inhibiting retinoic acid signalling, which is essential for cell differentiation and proliferation. Its aberrant overexpression in various malignancies, particularly cutaneous melanoma, is associated with more aggressive tumour phenotypes, positioning PRAME as both a diagnostic and prognostic marker. In melanoma, PRAME is typically highly expressed, in contrast to its weak or absent expression in benign nevi, thereby improving the accuracy of differential diagnoses. The diagnostic value of PRAME extends to various lesions. It is significantly expressed in uveal melanoma, correlating to an increased risk of metastasis. In acral melanomas, especially those with histopathological ambiguity, PRAME helps to improve diagnostic accuracy. However, its expression in spitzoid and ungual melanocytic lesions is inconsistent and requires a comprehensive approach for an accurate assessment. In soft tissue sarcomas, PRAME may be particularly helpful in differentiating melanoma from clear cell sarcoma, an important distinction due to their similar histological appearance but different treatment approaches and prognosis, or in detecting dedifferentiated and undifferentiated melanomas. In non-melanoma skin cancers such as basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, the variable expression of PRAME can lead to diagnostic complexity. Despite these challenges, the potential of PRAME as a therapeutic target in melanoma is significant. Emerging immunotherapies, including T-cell-based therapies and vaccines targeting PRAME, are being investigated to exploit its cancer-specific expression. Ongoing research into the molecular role and mechanism of action of PRAME in skin cancer continues to open new avenues in both diagnostics and therapeutics, with the potential to transform the management of melanoma and related skin cancers.

Prognostic value of genetic aberrations and tumor immune microenvironment in primary acral melanoma.

BACKGROUND: Acral melanoma (AM) is the most common subtype in Chinese melanoma patients with a very poor prognosis. However, our understanding of the disease pathogenesis and molecular landscape is limited by the few studies that have been conducted. Here, we profiled the clinical characteristics, mutational landscapes and tumor immune microenvironment of AM patients to gain insights into disease characteristics and potential treatment strategies. METHODS: A total of 90 AM patients were enrolled and their tissue samples were subjected to next-generation sequencing and multiplexed immunohistochemistry tests. Kaplan-Meier curves and log-rank tests were used to analyze the prognostic potential of various genetic aberrations and immune cell compositions in AM. RESULTS: The median disease-free survival was 21.3 months and estimated median overall survival (OS) was 60 months. More advanced stages, older ages and thickness of greater than 4 mm were associated with worse prognosis in AM patients (HR = 2.57, 95% CI 1.25-5.29, p = 0.01; HR = 2.77, 95% CI 1.22-6.28, p = 0.02; HR = 3.43, 95% CI 1.51-7.82, p < 0.01, respectively), while patients who received post-surgical treatments had better survival (HR = 0.36, 95% CI 0.17-0.76, p = 0.01). The most frequently altered genes included BRAF (14.5%), KIT (16.9%), NRAS (12%), NF1 (10.8%), APC (7.2%), and ARID2 (6%). Copy number variations (CNV) were commonly found in CCND1 (19.3%), CDK4 (19.3%), MDM2 (14.5%) and FGF19 (12%). CDK4 amplifications was independently associated with shorter OS in AM patients (HR = 3.61, 95% CI 1.38-9.46, p = 0.01). CD8 + T cells (p < 0.001) and M1 macrophages (p = 0.05) were more highly enriched in the invasive margin than in the tumor center. Patients with higher levels of M1 macrophage infiltration in the invasive margin derived markedly longer OS (HR = 0.43, 95% CI 0.20-0.95, p = 0.03). Interestingly, in CDK4-amplified patients, there tended to be a low level of M1 macrophage infiltration in the invasive margin (p = 0.06), which likely explains the poor prognosis in such patients. CONCLUSIONS: Our study provided a comprehensive portrait of the clinicopathological features, genetic aberrations and tumor microenvironment profiles in AM patients and identified candidate prognostic factors, which may facilitate development of additional therapeutic options and better inform clinical management of AM patients. Based on these prognostic factors, further studies should focus on enhancing the infiltration of M1 macrophages, especially in CDK4-amplified AM patients.

Prediction of nonsentinel lymph node metastasis in acral melanoma with positive sentinel lymph nodes.

BACKGROUND: Metastasis in a nonsentinel lymph node (non-SLN) is an unfavorable independent prognostic factor in cutaneous melanoma (CM). Recent data did suggest potential value of completion lymph node dissection (CLND) in CM patients with non-SLN metastasis. Prediction of non-SLN metastasis assists clinicians in deciding on adjuvant therapy without CLND. We analyzed risk factors and developed a prediction model for non-SLN status in acral melanoma (AM). METHODS: This retrospective study enrolled 656 cases of melanoma who underwent sentinel lymph node biopsy at Fudan University Shanghai Cancer Center from 2009 to 2017. We identified 81 SLN + AM patients who underwent CLND. Clinicopathologic data, including SLN tumor burden and non-SLN status were examined with Cox and Logistics regression models. RESULTS: Ulceration, Clark level, number of deposits in the SLN (NumDep) and maximum size of deposits (MaxSize) are independent risk factors associated with non-SLN metastases. We developed a scoring system that combines ulceration, the cutoff values of Clark level V, MaxSize of 2 mm, and NumDep of 5 to predict non-SLN metastasis with an efficiency of 85.2% and 100% positive predictive value in the high-rank group (scores of 17-24). CONCLUSIONS: A scoring system that included ulceration, Clark level, MaxSize, and NumDep is reliable and effective for predicting non-SLN metastasis in SLN-positive AM.

Telomerase reverse transcriptase immunohistochemical expression is sensitive but not specific for TERT gene amplification in acral melanoma.

BACKGROUND: TERT gene amplification (TGA) is a mechanism of telomerase reverse transcriptase (TERT) upregulation frequently utilized by acral melanomas (AMs). Currently, the utility of TERT immunohistochemistry (IHC) to predict TGA status in AMs is poorly documented. METHODS: AMs (26 primary and 3 metastatic) and non-acral cutaneous melanomas (6 primary) were subjected to immunohistochemical analysis using anti-TERT antibody to demonstrate protein expression and fluorescence in situ hybridization (FISH) to assess genomic copy number alteration. The relationship between TERT immunoreactivity and TGA confirmed by FISH was assessed using logistic regression. RESULTS: TERT expression was seen in 50% (13/26) of primary and 100% (3/3) of metastatic AMs and 50% (3/6) of primary non-acral cutaneous melanomas. TGA was found in 15% (4/26) and 67% (2/3) of primary and metastatic AMs and 17% (1/6) of non-acral cutaneous melanomas. The intensity of TERT immunoreactivity correlated with TGA (p = 0.04) and a higher TERT copy number-to-control ratio in AMs, with a correlation coefficient of 0.41 (p = 0.03). The sensitivity and specificity of TERT immunoreactivity for predicting TGA in AMs were 100% and 57%, with corresponding positive and negative predictive values of 38% and 100%, respectively. CONCLUSIONS: The clinical utility of TERT IHC to predict TGA status in AMs appears to be limited given its low specificity and positive predictive value.

Compound clear cell sarcoma with EWSR1::CREM fusion.

Cutaneous clear cell sarcomas may be confused with melanomas as a result of overlapping histopathology and immunohistochemical staining. We report a case of a 41-year-old woman with a purported history of acral melanoma of the great toe. Twenty-one months after excision of the primary tumor, the patient developed a groin mass, diagnosed as metastatic melanoma on excision. Five months later, a biopsy of a lung mass was reported as metastatic melanoma. The patient was referred to our institution for treatment, which prompted molecular testing on the groin metastasis by targeted next-generation sequencing. Molecular testing results revealed TP53 and TERT promoter mutations and the absence of BRAF, KRAS, and KIT mutations; it also revealed an EWSR1::CREM fusion that was confirmed by Archer FusionPlex. The alleged acral melanoma was re-reviewed, showing an invasive amelanotic spindle cell neoplasm in the dermis with neoplastic nests at the dermal-epidermal junction; the tumor cells expressed markers of melanocytic differentiation but were negative for PRAME and BRAF immunohistochemical staining. Molecular testing of the toe and lung metastasis revealed the same EWSR1::CREM fusion. In light of the molecular findings, the diagnosis was revised to a primary acral compound clear cell sarcoma with EWSR1::CREM fusion.

Reconstruction of plantar surgical defects with synthetic dermal matrix and split-thickness skin grafts: A case series and functional podiatry outcomes.

Reconstruction of surgical defects after wide local excision of acral melanoma on the sole should allow patients to walk and bear weight. Moreover, certain options such as local transposition flaps can compromise follow-up. We present a case series of surgical defects on weight-bearing areas of the sole reconstructed using a synthetic dermal matrix and a split-thickness skin graft. This approach prevents surrounding tissue displacement and results in good functional outcomes assessed by baropodometry and computer-based podoscopy.

Combined tumour of aberrant cytokeratin expressing acral lentiginous melanoma and poroma: Diagnostic challenge.

Combined tumours are uncommon and therefore these tumours may pose a diagnostic challenge. In the current case report, it is aimed to present the clinicopathological features of a combined tumour including melanoma with aberrant cytokeratin expression and poroma.

Recurrence rate and survival implications of surgical margins in patients with acral melanoma. Is a wide margin necessary?

INTRODUCTION: Appropriate size of resection margins in acral melanoma is not clearly established. OBJECTIVE: To investigate whether narrow-margin excision is appropriate for thick acral melanoma. METHODS: Three-hundred and six patients with acral melanoma were examined. Factors associated with recurrence and survival were analyzed according to surgical margin size (1 to 2 cm and > 2 cm). RESULTS: Out of 306 patients, 183 were women (59.8%). Median Breslow thickness was 6 mm; 224 cases (73.2%) were ulcerated, 154 patients (50.3%) had clinical stage III disease, while 137 were at stage II (44.8%) and 15 at stage IV (4.9%). All cases had negative margins, with a median of 31.5 mm. A Breslow thickness of 7 mm (p = 0.001) and clinical stage III (p = 0.031) were associated with recurrence; the factors associated with survival were Breslow index (p = 0.047), ulceration (p = 0.003), advanced clinical stage (p < 0.001), and use of adjuvant therapy (p = 0.003). CONCLUSION: A resection margin of 1 to 2 cm did not affect tumor recurrence or survival in patients with acral melanoma.

INTRODUCCIÓN: La extensión apropiada de los márgenes de resección en el melanoma acral no está claramente establecida. OBJETIVO: Investigar si la escisión con margen estrecho es adecuada en el melanoma acral grueso. MÉTODOS: Se estudiaron 306 pacientes con melanoma acral. Conforme a la extensión del margen quirúrgico (de 1 a 2 cm y > 2 cm), se analizaron los factores asociados a la recurrencia y la supervivencia. RESULTADOS: De 306 pacientes, 183 fueron mujeres (59.8 %). La mediana del grosor de Breslow fue 6 mm; 224 casos (73.2 %) fueron de tipo ulcerados, 154 pacientes (50.3 %) tenían enfermedad en estadio clínico III, 137 en II (44.8 %) y 15 en IV (4.9 %). Todos los casos presentaron margen negativo, con una mediana de 31.5 mm. Un grosor de Breslow de 7 mm (p = 0.001) y la etapa clínica III (p = 0.031) se asociaron a recurrencia; los factores asociados a la supervivencia fueron el índice de Breslow (p = 0.047), la ulceración (p = 0.003), la etapa clínica avanzada (p < 0.001) y el uso de adyuvancia (p = 0.003). CONCLUSIÓN: Un margen de resección de 1 a 2 cm no afectó la recurrencia tumoral ni la supervivencia en los pacientes con melanoma acral.

Management of Acral and Mucosal Melanoma: Medical Oncology Perspective.

Acral and mucosal melanomas (MM) are rare subtypes of melanoma that are biologically and clinically distinct from cutaneous melanoma. Despite the progress in the treatment of cutaneous melanomas with the development of targeted and immune therapies, the therapeutic options for these less common subtypes remain limited. Difficulties in early diagnosis, the aggressive nature of the disease, and the frequently occult sites of origin have also contributed to the poor prognosis associated with acral and MM, with substantially worse long-term prognosis. The rarity of these subtypes has posed significant barriers to better understanding their biological features and investigating novel therapies. Consequently, establishing standardized treatment guidelines has been a challenge. In this review, we provide a brief overview of the current knowledge regarding acral and MM, focusing on their epidemiology, genetic backgrounds, and unique clinical characteristics. Further discussion centers around the management of primary and advanced disease and the role of emerging targeted and immune therapies for these subtypes, specifically focusing on issues relevant to medical oncologists.

Clinical features, molecular pathology, and immune microenvironmental characteristics of acral melanoma.

Acral melanoma (AM) has unique biology as an aggressive subtype of melanoma. It is a common subtype of melanoma in races with darker skin tones usually diagnosed at a later stage, thereby presenting a worse prognosis compared to cutaneous melanoma. The pathogenesis of acral melanoma differs from cutaneous melanoma, and trauma promotes its development. Compared to cutaneous melanomas, acral melanomas have a significantly lighter mutational burden with more copy number variants. Most acral melanomas are classified as triple wild-type. In contrast to cutaneous melanomas, acral melanomas have a suppressive immune microenvironment. Herein, we reviewed the clinical features, genetic variants, and immune microenvironmental characteristics of limbic melanomas to summarise their unique features.

Hyperplastic melanocytes with chromosomal aberrations in surrounding skin of subungual melanoma: fluorescence in situ hybridisation analysis using whole-slide digital imaging.

AIMS: Subungual melanoma (SUM) is increasingly being treated with conservative surgery. Consequently, the evaluation of the resection margins has increased in importance. However, in several cases it is difficult to distinguish the in-situ lesion of SUM from hyperplastic melanocytes in the surrounding skin. We examined whether PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry and fluorescence in situ hybridisation (FISH) labelling of CCND1 (11q13), RREB1 (6p25), MYB (6q23), and centromere 6 (CEP6) genes differentiated SUM from hyperplastic melanocytes. METHODS AND RESULTS: We reviewed specimens of 36 SUM cases and compared PRAME immunostains of invasive melanoma, melanoma in situ, and hyperplastic melanocytes. PRAME-positive cases accounted for 90.5% of invasive melanoma, 88.9% of in situ melanoma, and 59.4% of hyperplastic melanocyte specimens. While invasive and in situ melanomas in more than half of the examined cases were diffusely positive, this was found for only 9.4% of hyperplastic melanocyte cases. Four-coloured FISH using whole-slide digital imaging was used to analyse positive detection rates and changes in chromosomal aberrations. The FISH positive detection rate was 100% in invasive melanomas, 94.7% in melanomas in situ, and 66.7% in hyperplastic melanocytes. The number of RREB1 (6p25) signals per cell was significantly amplified following tumour progression. CONCLUSION: Hyperplastic melanocytes in the surrounding skin of SUM, considered morphologically non-neoplastic, showed chromosomal aberrations similar to those in melanoma. Such cells are also thought similar to the field cells of acral melanomas. Thus, whole-slide digital imaging is a technique that allows the evaluation of individual melanocyte lesions by FISH.

Prognostic impact of Breslow thickness in acral melanoma: A retrospective analysis.

BACKGROUND: Evidence for the prognostic importance of tumor thickness in acral melanoma (AM) patients is limited. OBJECTIVE: The objective of the study was to determine the prognostic impact of Breslow thickness in AM. METHODS: This multicenter study enrolled patients diagnosed with localized AM between January 1, 2000 and December 31, 2017. Melanoma-specific survival (MSS) in different tumor thickness strata (T1-T4: ≤1, >1-2, >2-4, >4 mm, respectively) was estimated by the Kaplan-Meier method. Comparisons were performed by the log-rank test and multivariable Cox regression. RESULTS: A total of 853 patients with clinical N0 (cN0) AM were included in the analysis. The median follow-up time was 60.1 months. The median MSS in patients with T1-T4 disease was not reached, 111.0, 92.8, and 67.1 months, respectively. MSS differed significantly among cN0 patients with T1-T3 AM (log-rank P = .004, .012, <0.001 for T1 vs T2, T2 vs T3, and T1 vs T3, respectively); however, there was no significant difference between T3 and T4 AM (hazard ratio = 0.82, 95% CI, 0.62-1.09). Six-subgroup analyses confirmed that survival outcomes were similar between different subgroups with tumor thickness >2 mm. LIMITATIONS: The limitations were retrospective design and some missing variables. CONCLUSIONS: There was no association between tumor thickness and survival in AM patients with a Breslow thickness >2 mm.

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.

Advanced Acral Melanoma Therapies: Current Status and Future Directions.

OPINION STATEMENT: Melanoma is one of the deadliest malignancies. Its incidence has been significantly increasing in most countries in recent decades. Acral melanoma (AM), a peculiar subgroup of melanoma occurring on the palms, soles, and nails, is the main subtype of melanoma in people of color and is extremely rare in Caucasians. Although great progress has been made in melanoma treatment in recent years, patients with AM have shown limited benefit from current therapies and thus consequently have worse overall survival rates. Achieving durable therapeutic responses in this high-risk melanoma subtype represents one of the greatest challenges in the field. The frequency of BRAF mutations in AM is much lower than that in cutaneous melanoma, which prevents most AM patients from receiving treatment with BRAF inhibitors. However, AM has more frequent mutations such as KIT and CDK4/6, so targeted therapy may still improve the survival of some AM patients in the future. AM may be less susceptible to immune checkpoint inhibitors because of the poor immunogenicity. Therefore, how to enhance the immune response to the tumor cells may be the key to the application of immune checkpoint inhibitors in advanced AM. Anti-angiogenic drugs, albumin paclitaxel, or interferons are thought to enhance the effectiveness of immune checkpoint inhibitors. Combination therapies based on the backbone of PD-1 are more likely to provide greater clinical benefits. Understanding the molecular landscapes and immune microenvironment of AM will help optimize our combinatory strategies.

Differences by Anatomical Site of Non-Acral Lentiginous Melanomas of the Lower Limb.

BACKGROUND: Acral location of melanomas is associated with poor survival. It can be due, at least in part, to the fact that acral lentiginous melanoma, a distinct melanoma subtype, has a particular biological profile and a bad clinical behavior. However, since almost 50% of acral melanomas are not of acral lentiginous melanoma subtype, the worse clinical behavior could also be attributable to the intrinsic characteristics of the location. OBJECTIVE: This study aimed to investigate if melanomas of the lower limb excluding acral lentiginous melanoma differ by location. METHODS: This retrospective, observational study recruited patients from an oncology referral center in Spain. We included 285 patients with superficial spreading and nodular melanomas of the lower limb. We compare melanomas by site, clinical and pathological characteristics, and the differences by location of disease-free and melanoma-specific survival by the Kaplan-Meier method and Cox proportional hazard method. RESULTS: Patients with melanomas on the foot, compared to those on the rest of the limb, were older and reported having suffered less sunburns; the melanoma more frequently appeared in areas that had been rarely sun exposed, were more frequently of nodular type, presented thicker tumors, with more ulceration, less regression, and more advanced stage of the disease. Foot location increased the risk of relapse and decreased melanoma-specific survival. CONCLUSION: Melanoma development in foot is less related to sun exposure and is associated with pathological features that can account for the worse prognosis and poorer survival.