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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., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

Cold atmospheric plasma (CAP) may have applications in treating various types of malignant tumors. This study assessed the anticancer effects of CAP using melanoma and colon cancer cell lines. CAP treatment significantly reduced the in vitro viability of melanoma and colon cancer cell lines and had a negligible effect on the viability of normal human melanocytes. Additionally, CAP and epidermal growth factor receptor (EGFR) inhibitor had an additive anticancer effect in a CAP-resistant melanoma cell line. Reactive oxygen and nitrogen species known to be generated by CAP enhanced the anticancer effects of CAP and EGFR inhibitors. The in vivo anticancer activities of CAP were evaluated by testing its effects against syngeneic tumors induced in mice by melanoma and colon cancer cells. CAP treatment reduced tumor volume and weight in both cancer models, with the extent of tumor reduction dependent on the duration and number of CAP treatments. Histologic examination also revealed the tumoricidal effects of CAP in both tumor models. In conclusion, CAP inhibits the growth of mouse melanoma and colon cancer cell lines in vitro and shows tumoricidal effects against mouse models of melanoma and colon cancer in vivo.

Competing Interests: Conflicts of interest None disclosed.

The diagnostic role of preferentially expressed antigen in melanoma (PRAME) immunohistochemistry has not been thoroughly evaluated for acral melanocytic tumors. The objective of this study was to evaluate the utility of this modality for the diagnosis of acral melanocytic tumors compared with other potential markers. Melanocytic tumors were classified as either acral nevi, challenging melanocytic tumors (superficial atypical melanocytic proliferation of uncertain significance (SAMPUS)-favor benign (SAMPUS-FB), SAMPUS-favor malignant (SAMPUS-FM)) or acral melanomas. A total of 106 acral melanocytic tumors including acral nevi (n = 32), SAMPUS-FB (n = 17), SAMPUS-FM (n = 20), and acral melanomas (n = 37) were included. Diagnostic power, assessed using an area under the receiver operating characteristic curve (AUC) for distinguishing acral melanomas and acral nevi, was highest for PRAME (AUC = 0.997), followed by c-Myc (AUC = 0.755), cyclin D1 (AUC = 0.652), and c-Kit (AUC = 0.573). At a PRAME expression level ≥30% as a positive test for acral melanoma, the sensitivity and specificity of this marker for discriminating acral melanoma from acral nevus were 100% and 96.9%, respectively. PRAME immunohistochemistry also discriminated SAMPUS-FM from SAMPUS-FB with a sensitivity and specificity of 90.0% and 76.5%, respectively. In conclusion, PRAME immunohistochemistry can be used effectively to distinguish between various spectra of acral melanocytic neoplasms., (© 2022 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Background: Distinguishing benign lesion from early malignancy in melanocytic lesions of the nail unit still remains a diagnostic challenge, both clinically and histopathologically. While several immunohistochemistry (IHC) stainings have been suggested to help discriminate benign subungual melanocytic proliferation (SMP) and subungual melanoma in situ (MIS), the diagnostic utility of IHC staining for cyclin D1 and PRAME has not been thoroughly investigated in melanocytic lesions of nail unit., Methods: This retrospective study included cases of benign SMP and subungual MIS confirmed by biopsy at Asan Medical Center from January 2016 to December 2020. Cases of melanocytic activation without proliferation and melanoma where dermal invasion was identified were excluded. Cyclin D1 and PRAME expression was assessed by counting proportion of melanocytes with nuclear positivity under 200x magnification., Results: A total of 14 patients with benign SMP and 13 patients with subungual MIS were included in this study. 11 patients with benign SMP (71.4%) and 5 patients with subungual MIS (38.5%) showed > 60% nuclear immunostaining for cyclin D1, respectively. While 13 patients with benign SMP (92.9%) showed totally negative staining for PRAME, 10 patients with subungual MIS (76.9%) exhibited > 50% nuclear immunostaining for PRAME. Using the cutoff of 10%, PRAME exhibited good overall discrimination between benign SMP and subungual MIS (AUC = 0.849, 95% CI = 0.659-0.957)., Conclusions: This study suggests that PRAME IHC staining as a reliable discriminator in distinguishing subungual MIS from benign SMP., (© 2022. The Author(s).)

Background: There are limited data regarding the difference in progression pattern between acral melanoma and nonacral melanoma., Aims: The objectives of this study were to compare the progression pattern between acral and nonacral melanoma and evaluate its impact on clinical outcomes., Methods: Clinical and histopathological features, survival outcomes and prognostic factors of 492 patients with acral melanoma or nonacral melanoma were retrospectively evaluated using the Asan Medical Center database., Results: The male-to-female ratio and the mean age was 1:0.92 and 60.2 years for acral melanoma (n = 249), and 1:0.85 and 58.4 years for nonacral melanoma (n = 243), respectively. The demographic difference was not significant. Although prediagnosis duration was longer and the advanced stage was more common in acral melanoma than that in nonacral melanoma, the vertical growth phase was more common in nonacral melanoma than that in acral melanoma, whereas, the horizontal diameter is longer in acral melanoma than that in nonacral melanoma. Dissemination to lymph nodes was more common in acral melanoma than that in nonacral melanoma. Lymph node involvement was associated with deeper Breslow thickness in nonacral melanoma but not in acral melanoma. The degree of correlation of prediagnosis duration with horizontal diameter was remarkable in acral melanoma, but with Breslow thickness in nonacral melanoma. Overall survival was worse in acral melanoma than that in nonacral melanoma. The prognostic value of Breslow thickness was more remarkable in nonacral melanoma than that in acral melanoma., Limitations: This study is a retrospective, single-center design., Conclusion: Acral melanoma has a longer radial growth phase compared with nonacral melanoma. However, acral melanoma is commonly associated with lymph node dissemination which contributed to worse survival in acral melanoma than nonacral melanoma.

Immune checkpoint blockade therapy can induce immune-related toxicity, but cutaneous lymphoma development has not been reported. A 56-year-old woman presented with two well-demarcated erythematous macules on the right sole and vitiligo on her extremities. Her facial melanoma had been treated with combination therapy (ipilimumab and pembrolizumab), followed by pembrolizumab monotherapy, a year prior. Microscopy revealed small-to-medium-sized lymphocytes permeating along with the basal epidermal layer. These were immuno-positive for CD2, CD3, and CD5, and showed complete CD7 loss; CD30, TCR-beta F1, and PD-1 were also detected. They exclusively expressed CD8, not CD4, and had a Ki-67 labeling index of 30-40%. Epstein-Barr virus in-situ hybridization was negative. Clonal T-cell receptor beta and gamma chain gene rearrangements were detected. Hence, the lesions were diagnosed as mycosis fungoides. This is the first report of mycosis fungoides development after anti-melanoma immunotherapy. The patient is currently on steroid ointments and phototherapy.

Background: Although cutaneous melanoma has been widely evaluated, data elucidating the clinical features and prognostic factors of cutaneous metastatic melanoma are limited., Objective: To determine and compare the clinicoprognostic features of cutaneous metastasis in acral and nonacral melanoma., Methods: The Asan Medical Center database was reviewed for cases of cutaneous metastatic melanoma that had been confirmed by skin biopsy between January 1996 and December 2017., Results: Cutaneous metastasis occurred in 12.4% (61 of 492 cases) of our cohort. The frequency of cutaneous metastasis was higher in nonacral melanoma than that in acral melanoma. The mean duration between the initial diagnosis of a primary tumor and cutaneous dissemination was 19.8 months. Cutaneous metastasis developed earlier during the disease course in acral melanoma than that in nonacral melanoma. Cutaneous metastasis was more disseminated, involving multiple anatomy sites in nonacral melanoma than that in acral melanoma. In-transit metastasis was significantly more common in acral melanoma than that in nonacral melanoma. The disease stage at the time of cutaneous metastasis was not significantly different between acral and nonaral melanoma. In-transit metastasis was commonly associated with visceral involvement in acral melanoma but not in nonacral melanoma. The extent and multiplicity of cutaneous metastasis were dependent on the status of other viscera during the cutaneous metastasis. No significant difference in survival during the cutaneous metastasis was observed between acral and nonacral melanoma., Conclusion: Clinicoprognostic features of cutaneous metastasis were different between acral and nonacral melanoma., (© 2020 the International Society of Dermatology.)

There have been limited studies comparing the clinical significance of lymphatic invasion in melanoma according to tumour site. The objective of this study was to evaluate the impact of lymphatic invasion on the clinicoprognostic features of acral and non-acral melanoma. Clinical and histopathological features and survival outcomes of 532 patients with acral melanoma or non-acral melanoma in the database of the Asan Medical Center, Korea, were retrospectively evaluated according to the presence of lymphatic invasion. Lymphatic invasion was significantly more common in acral melanoma than non-acral melanoma. In acral melanoma, lymphatic invasion was significantly associated with a higher frequency of lymph node involvement and advanced stages, but not associated with Breslow thickness or visceral dissemination. By contrast, lymphatic invasion in non-acral melanoma was significantly associated with a higher rate of visceral involvement, deeper Breslow thickness, as well as a higher rate of lymph node involvement and advanced stages. When acral melanoma and non-acral melanoma both with lymphatic invasion were compared, Breslow thickness was significantly shallower and vertical growth phase was significantly less common in acral melanoma. Meanwhile, visceral involvement was significantly more frequent in non-acral melanoma than acral melanoma. In conclusion, lymphatic invasion was more common in acral melanoma than non-acral melanoma and occurred in acral melanoma cases with relatively thin Breslow thickness, suggesting acral melanoma is lymphotropic., (Copyright © 2020 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

V-domain Ig suppressor of T-cell activation (VISTA), which mediates immune evasion in cancer, is mainly expressed on hematopoietic cells and myeloid cells in the tumor. We evaluated correlations among the expression of VISTA, the myeloid-derived suppressor cell marker CD33, and programmed death-1 (PD-1), and determined their relationships with clinicopathological characteristics and disease outcomes in melanoma. Diagnostic tissue from 136 cases of melanoma was evaluated by immunohistochemistry for CD33, VISTA, and PD-1 expression. Dual immunofluorescence using CD33 and VISTA antibodies was performed. VISTA expression positively correlated with CD33 expression in melanoma tissue. Dual immunofluorescence staining revealed that VISTA was expressed by CD33-positive myeloid cells. PD-1 expression correlated with CD33 and VISTA expression. CD33 and VISTA expression were significantly associated with negative prognostic factors, including a deeper Breslow thickness and an advanced stage of disease. High expression of either CD33 or VISTA was associated with worse survival. Positivity for both VISTA and PD-1 predicted worse survival. Multivariate analysis showed that both CD33 and VISTA expression were independent prognostic factors in cutaneous melanoma. VISTA and CD33 expression are independent unfavourable prognostic factors in melanoma, which suggests their potential as therapeutic targets.

Background: Lymphocyte-activating gene 3 (LAG-3) and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (TIGIT) domains are emerging checkpoint proteins., Objective: We evaluated LAG-3 and TIGIT protein expression patterns, correlated these patterns with programmed cell death 1 (PD-1) protein expression, and determined their effects on clinicopathologic characteristics and biologic responses in melanoma., Methods: Diagnostic tissue from 124 patients with melanoma were evaluated for LAG-3, TIGIT, and PD-1 expression by immunohistochemistry. Clinicopathologic features and survival were analyzed according to the expression of LAG-3, TIGIT, and PD-1., Results: LAG-3 and TIGIT expression on tumor-infiltrating lymphocytes were significantly correlated with that of PD-1 and was also significantly associated with negative prognostic factors: deeper Breslow thickness, lymph node involvement, and advanced stage of disease. However, PD-1 expression was not associated with clinicopathologic variables of prognostic significance. High expression of either LAG-3 or TIGIT was associated with worse survival. Subgroup analysis on the basis of Breslow thickness showed that both LAG-3 and TIGIT have prognostic significance regardless of tumor thickness. High expression of PD-1 was not predictive of survival., Limitations: Retrospective study in a single institution and possibility of type 1 error., Conclusion: Expression of LAG-3 and TIGIT represents an independent unfavorable prognostic factor in cutaneous melanoma., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Several studies have examined the correlation between nestin expression and the degree of tumor invasion in cutaneous melanoma. However, no information has been reported on nestin in primary mucosal melanoma of the head and neck. The present study examined the expression and prognostic significance of nestin in patients with primary mucosal melanoma of the oral cavity. Nestin expression was examined immunohistochemically in 39 patients (six oral melanoma in-situ cases and 33 invasive oral melanoma cases) and analyzed for association with disease progression. Age, sex, anatomic site, stage, level of invasion, regional lymph node metastasis, surgical margin involvement, and treatment modality were also analyzed. In the 33 invasive melanoma cases, invasion depth correlated significantly with prognosis in univariate and multivariate analyses. High-intensity nestin staining was observed in 14 of the 33 cases and a high proportion of nestin-positive cells was observed in 16 cases. In stage III oral melanoma cases, nestin expression was not significantly associated with disease progression. However, in stage IV cases, both the intensity and the proportion of nestin expression were significantly associated with disease progression (P=0.022 and 0.005, respectively). In all 33 invasive cases, multivariate analyses showed that both the intensity and the proportion of nestin were significantly associated with a poor prognosis (P=0.014 and 0.009; hazard ratio, 3.59 and 4.05; 95% confidence interval, 1.29-9.98 and 1.42-11.56, respectively). In conclusion, nestin can be a valuable prognostic indicator in the advanced-stage (stage IV) cases of oral mucosal melanoma.

Background: Although nail apparatus melanoma has been widely evaluated, only limited data are available concerning its clinical features, which depend on its initial clinical morphology, broadly defined as a melanonychia or nonmelanonychia lesion., Objective: We sought to determine heterogeneity on the basis of the initial clinical morphology of nail apparatus melanoma., Methods: We searched the Asan Medical Center database for cases of nail apparatus melanoma that were confirmed by skin biopsy specimen. Patients were classified with either nail apparatus melanoma that began as melanonychia (group A) or nail apparatus melanoma that began as nonmelanonychia lesions (group B)., Results: We identified 49 patients with nail apparatus melanoma. Of these, 29 and 20 patients were included in groups A or B, respectively. The prediagnosis duration was significantly longer in group A. At the time of diagnosis, advanced stage and deeper Breslow thickness were noted in group B. The median overall survival period of the whole cohort was 93.0 months, and the 5-year overall survival was 67%. Patients in group A demonstrated better survival outcomes., Limitations: This study is a retrospective, single-center design., Conclusion: Nail apparatus melanoma demonstrates different clinical features and survival outcomes depending on whether the lesion begins as melanonychia or nonmelanonychia., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Nail apparatus melanoma (NAM) is a subtype of cutaneous melanoma occurring at nail units and belongs to the acral lentiginous melanoma subgroup. Due to its unique anatomical structure to protect the acral site, mechanical trauma may have a clinicoprognostic impact on NAM. Therefore, we investigated the clinicoprognostic and histopathological characteristics of NAM according to the presence of trauma history prior to melanoma development. Methods: Clinicopathological and follow-up data of patients with NAM according to trauma history were obtained. Results: We included 87 patients with NAM, 21.8% of whom had a previous trauma history. Trauma-related NAMs were more likely to involve the toenail (p = 0.040), include a high proportion of amelanotic melanomas (p = 0.038) as well as nail bed tumor (p = 0.013), and have a longer time interval between the onset of nail change and confirmed diagnosis (p = 0.012). Moreover, survival analysis revealed that trauma-related NAMs more frequently showed progression in general (p = 0.034) and nodal metastasis (p = 0.047) and had worse prognosis in terms of progression-free survival (p = 0.004). Conclusion: In conclusion, NAMs with previous trauma have unique clinicoprognostic characteristics. The specific clinicopathological features of NAMs according to trauma indicate that trauma may play a role in melanoma development. [ABSTRACT FROM AUTHOR]

Background: There are limited data regarding the difference in progression pattern between acral melanoma and nonacral melanoma.Aims: The objectives of this study were to compare the progression pattern between acral and nonacral melanoma and evaluate its impact on clinical outcomes.Methods: Clinical and histopathological features, survival outcomes and prognostic factors of 492 patients with acral melanoma or nonacral melanoma were retrospectively evaluated using the Asan Medical Center database.Results: The male-to-female ratio and the mean age was 1:0.92 and 60.2 years for acral melanoma (n = 249), and 1:0.85 and 58.4 years for nonacral melanoma (n = 243), respectively. The demographic difference was not significant. Although prediagnosis duration was longer and the advanced stage was more common in acral melanoma than that in nonacral melanoma, the vertical growth phase was more common in nonacral melanoma than that in acral melanoma, whereas, the horizontal diameter is longer in acral melanoma than that in nonacral melanoma. Dissemination to lymph nodes was more common in acral melanoma than that in nonacral melanoma. Lymph node involvement was associated with deeper Breslow thickness in nonacral melanoma but not in acral melanoma. The degree of correlation of prediagnosis duration with horizontal diameter was remarkable in acral melanoma, but with Breslow thickness in nonacral melanoma. Overall survival was worse in acral melanoma than that in nonacral melanoma. The prognostic value of Breslow thickness was more remarkable in nonacral melanoma than that in acral melanoma.Limitations: This study is a retrospective, single-center design.Conclusion: Acral melanoma has a longer radial growth phase compared with nonacral melanoma. However, acral melanoma is commonly associated with lymph node dissemination which contributed to worse survival in acral melanoma than nonacral melanoma. [ABSTRACT FROM AUTHOR]

Microenvironment responsive nanomaterials are attractive for therapeutic applications with regional specificity. Here we report pH responsive gold nanoparticles which are designed to aggregate in acidic condition similar to cancer environment and returned to its original disassembled states in a physiological pH. The pH responsive behavior of the particles is derived by change of electrostatic interaction among the particles where attraction and repulsion play a major role in low and high pH of the environment, respectively. Since different electrostatic interaction behavior of the particles in varied pH is induced not by irreversible chemical change but by simple protonation differences, the pH responsive process of assembly and disassembly is totally reversible. The low pH specific aggregation of gold nanoparticles resulted in red shift of plasmonic absorption peak and showed higher photothermal efficacy in acidic pH than in normal physiological pH. The low pH specific photothermal effect with long wave laser irradiation was directly applied to cancer specific photothermal therapy and resulted higher therapeutic effect for melanoma cancer cells than non-pH responsive gold nanoparticles. [ABSTRACT FROM AUTHOR]

With the increasing incidence of skin cancer, many noninvasive technologies to detect its presence have been developed. This review focuses on reflectance confocal microscopy (RCM), optical coherence tomography (OCT), high-frequency ultrasound (HFUS), electrical impedance spectroscopy (EIS), pigmented lesion assay (PLA), and Raman spectroscopy (RS) and discusses the basic principle, clinical applications, advantages, and disadvantages of each technology. RCM provides high cellular resolution and has high sensitivity and specificity for the diagnosis of skin cancer. OCT provides lower resolution than RCM, although its evaluable depth is deeper than that of RCM. RCM and OCT may be useful in reducing the number of unnecessary biopsies, evaluating the tumor margin, and monitoring treatment response. HFUS can be mainly used to delineate tumor depths or margins and monitor the treatment response. EIS provides high sensitivity but low specificity for the diagnosis of skin malignancies. PLA, which is based on the genetic information of lesions, is applicable for the detection of melanoma with high sensitivity and moderate-to-high specificity. RS showed high accuracy for the diagnosis of skin cancer, although more clinical studies are required. Advances in these technologies for the diagnosis of skin cancer can lead to the realization of optimized and individualized treatments. [ABSTRACT FROM AUTHOR]

The association between tumor-associated macrophages (TAMs) and the expression of immune checkpoint molecules has not been well described in cutaneous melanoma. We evaluated the correlations between the expression of markers of TAMs, cluster of differentiation 163 (CD163), and immune checkpoint molecules, programmed cell death protein-1 (PD-1), and lymphocyte activating gene-3 (LAG-3). We also determined their relationships with the clinicopathological features and disease outcomes in melanoma. Diagnostic tissues collected from melanoma patients were evaluated using immunohistochemistry for CD163, PD-1, and LAG-3 expression. CD163 expression positively correlated with PD-1 and LAG-3 expression. High expression of both CD163 and PD-1 expressions was significantly associated with negative prognostic factors and worse prognosis than high expression of the single markers. High co-expression of CD163 and LAG-3 was associated with poor clinicopathological indexes of melanoma and worse survival compared to the high expression of the single markers. The expression of immune checkpoint molecules PD-1 and LAG-3 positively correlated with the M2-TAM density in melanoma tissue. Simultaneous high M2-TAM density and immune checkpoint molecules expression acted as independent poor prognostic factors in cutaneous melanoma. [ABSTRACT FROM AUTHOR]