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.

Bilateral Blistering Rash Following Gastric Bypass Procedure and Mushroom Soup Diet: Hepatitis C Virus-Seronegative Necrolytic Acral Erythema.

Necrolytic acral erythema (NAE) is an uncommon cutaneous disorder characterized by a symmetric acral distribution of erythematous plaques with underlying epidermal necrosis. While typically presenting in the context of hepatitis C virus (HCV) infection, NAE can also present secondary to nutritional deficiency or systemic disease. We present a case of NAE in a 66-year-old patient with no history of HCV infection status post gastric bypass who had a three-month history of eating only mushroom soup. The patient underwent a punch biopsy and was tested for a variety of nutritional deficiencies. Biopsy demonstrated partial necrosis of the upper epidermis, with subjacent re-epithelialization, squamatization, and vacuolopathy of the basal epidermis. He was treated with zinc replacement therapy after initial trials of tacrolimus and clobetasol were unsuccessful. At follow-up, he had significant improvement of the lesions. This case provides an example of an atypical presentation of NAE in the absence of HCV infection that presented as a complication of gastric bypass-associated nutritional deficiency.

Assessing the Efficacy of the Spectrum-Aided Vision Enhancer (SAVE) to Detect Acral Lentiginous Melanoma, Melanoma In Situ, Nodular Melanoma, and Superficial Spreading Melanoma.

Skin cancer is the predominant form of cancer worldwide, including 75% of all cancer cases. This study aims to evaluate the effectiveness of the spectrum-aided visual enhancer (SAVE) in detecting skin cancer. This paper presents the development of a novel algorithm for snapshot hyperspectral conversion, capable of converting RGB images into hyperspectral images (HSI). The integration of band selection with HSI has facilitated the identification of a set of narrow band images (NBI) from the RGB images. This study utilizes various iterations of the You Only Look Once (YOLO) machine learning (ML) framework to assess the precision, recall, and mean average precision in the detection of skin cancer. YOLO is commonly preferred in medical diagnostics due to its real-time processing speed and accuracy, which are essential for delivering effective and efficient patient care. The precision, recall, and mean average precision (mAP) of the SAVE images show a notable enhancement in comparison to the RGB images. This work has the potential to greatly enhance the efficiency of skin cancer detection, as well as improve early detection rates and diagnostic accuracy. Consequently, it may lead to a reduction in both morbidity and mortality rates.

Acral Metastasis to the Hand as the Primary Presentation of Malignancy.

Metastatic hand tumors are uncommon but important to include in the differential diagnosis for hand masses. In this study, we report the case of a patient presenting initially with hand pain and swelling with no other pertinent medical history except for an extensive smoking history. Subsequent mass biopsy and work-up revealed metastatic lung cancer. Acral metastases to the hand as the first manifestation of a primary tumor are a rare but debilitating condition with a poor prognosis. Hand surgeons must remain aware of the potential for metastatic hand tumors in patients without known malignancy and advocate for the prompt initiation of multidisciplinary care and treatment to maximize patient outcomes.

Three-Year Analysis of Adjuvant Therapy in Postoperative Melanoma including Acral and Mucosal Subtypes.

BACKGROUND: Adjuvant therapy has improved the clinical prognosis for postoperative melanoma patients. However, the long-term efficacy of this therapy on the melanoma acral and mucosal subtypes has not been fully evaluated in previous trials. This study assessed the 3-year recurrence-free survival and overall survival of patients with melanoma, including the acral and mucosal subtypes, treated with anti-PD-1 antibody (Ab) or with the combination of the BRAF and MEK inhibitors dabrafenib and trametinib. METHODS: We retrospectively analyzed both the 3-year time to relapse (TTR) and overall survival (OS) of 120 patients treated with anti-PD-1 antibody (Ab), or with the combination of dabrafenib and trametinib. RESULTS: The overall median TTR was 18.4 months, with a range of 0.69 to 36 months. The 3-year TTR of the acral and mucosal types was 28.1% and 38.5%, respectively. Baseline tumor thickness (TT) and acral type were associated with the TTR in subgroup analysis. Moreover, we classified 104 acral and non-acral cutaneous patients into the anti-PD-1 Abs or dabrafenib plus trametinib combined therapies cohort in multiple analyses. The acral subtype and TT were detected as important prognostic factors. In the 3-year OS, only tumor ulceration was associated with the OS in both univariate and multiple analyses. There was no significant difference in baseline or treatment-related factors of the mucosal type (p > 0.05). CONCLUSION: This study suggests that adjuvant therapy is more effective with non-acral cutaneous melanoma than either the acral or mucosal types at the 3-year TTR endpoint.

An infant with acral peeling of skin: A curious case of congenital syphilis.

Congenital syphilis (CS) is a vertically transmitted infection caused by the spirochete Treponema pallidum. It is seen rarely due to proper antenatal screening. Signs and symptoms appear within the first 2 years of life in early CS and after 2 years in late CS. Failure to diagnose and treat CS in its early stages can result in higher morbidity and mortality. Skin manifestations can guide toward the diagnosis of CS at an early stage. Here, we report a 2-day-old neonate who presented with acral peeling of skin along with respiratory distress and hepatosplenomegaly. Clinical suspicion of CS was made and subsequently confirmed by a positive venereal disease research laboratory test in both mother and child. The child was treated with aqueous crystalline penicillin G as per the CDC guidelines.

Clinical Characteristics and Special Considerations in the Management of Rare Melanoma Subtypes.

Rare histologic subtypes of melanoma, including acral, mucosal, uveal, and desmoplastic melanomas, only make up 5% of all diagnosed melanomas and are often underrepresented in large, randomized trials. Recent advancements in systemic therapy have shown marked improvement in pathologic response rates, improving progression-free and overall survival among cutaneous melanoma patients, but there are limited data to demonstrate improved survival among rarer subtypes of melanoma. Acral melanoma has a poor response to immunotherapy and is associated with worse survival. Mucosal melanoma has a large variability in its presentation, a poor prognosis, and a low mutational burden. Uveal melanoma is associated with a high rate of liver metastasis; recent adoption of infusion and perfusion therapies has demonstrated improved survival among these patients. Desmoplastic melanoma, a high-risk cutaneous melanoma, is associated with high locoregional recurrence rates and mutational burden, suggesting this melanoma may have enhanced response to immunotherapy. While these variants of melanoma represent distinct disease entities, this review highlights the clinicopathologic characteristics and treatment recommendations for each of these rare melanomas and highlights the utility of modern therapies for each of them.

Acral persistent papular mucinosis: a rare child case report and literature review.

Background: Acral persistent papular mucinosis (APPM) is a rare idiopathic subtype of localized lichen myxedematosus. To date, there have been less than 41 APPM cases reported worldwide, however, almost all patients were older than 18 years of age. A 7-year-old child was first reported in this paper. Case Description: A 7-year-old boy was admitted to our hospital with a solitary skin-colored papule on the radial side of the middle segment of his right index finger. The patient wanted to know the exact diagnosis and remove it because the flexion movement of the middle segment had been affected. Thus, a surgery was performed. Histopathological examination of a biopsy specimen obtained from the papule on the radial side of the middle segment of his right index finger showed a focal and well-circumscribed deposit of mucin in the papillary and middermis. The deposit never extended deeply into the reticular dermis. Mucin spared a subepidermal area in the papillary dermis. Alcian blue stains can highlight the mucin. The papule was histologically diagnosed as an APPM and excised surgically. The wound gradually healed after the operation, and no obvious recurrence, scar or other discomfort was observed during follow-up so far. Conclusions: To the best of our knowledge, this is the rare case of a child APPM presenting as a solitary papule affecting the flexion movement of the middle segment. Since it is a rare disease, we report this case to contribute to future research on the diagnosis and pathogenesis of APPM.

Expanding the landscape of oncogenic drivers and treatment options in acral and mucosal melanomas by targeted genomic profiling.

Despite advancements in treating cutaneous melanoma, patients with acral and mucosal (A/M) melanomas still have limited therapeutic options and poor prognoses. We analyzed 156 melanomas (101 cutaneous, 28 acral, and 27 mucosal) using the Foundation One cancer-gene specific clinical testing platform and identified new, potentially targetable genomic alterations (GAs) in specific anatomic sites of A/M melanomas. Using novel pre-clinical models of A/M melanoma, we demonstrate that several GAs and corresponding oncogenic pathways associated with cutaneous melanomas are similarly targetable in A/M melanomas. Other alterations, including MYC and CRKL amplifications, were unique to A/M melanomas and susceptible to indirect targeting using the BRD4 inhibitor JQ1 or Src/ABL inhibitor dasatinib, respectively. We further identified new, actionable A/M-specific alterations, including an inactivating NF2 fusion in a mucosal melanoma responsive to dasatinib in vivo. Our study highlights new molecular differences between cutaneous and A/M melanomas, and across different anatomic sites within A/M, which may change clinical testing and treatment paradigms for these rare melanomas.

Trends by race and ethnicity in incidence and mortality of acral lentiginous melanoma: analysis of Surveillance, Epidemiology, and End Results 2000-2020.

Limited data describe the epidemiology and risk factors of acral lentiginous melanoma (ALM). In this retrospective analysis, we examined trends in incidence and mortality of ALM among racial and ethnic minoritized populations. We queried 22 Surveillance, Epidemiology, and End Results registries for cases of ALM among Hispanics, non-Hispanic Asians or Pacific Islanders (NHAPIs), non-Hispanic Blacks (NHBs), and non-Hispanic Whites (NHWs) from 2000 through 2020. Age-adjusted incidence and annual percentage changes (APCs) were estimated. Kaplan-Meier curves were stratified by race and ethnicity and compared with log-rank tests. Cox proportional hazard regression models were adjusted for age, sex, race, ethnicity, income, urban-rural residence, stage, and treatment. Of 4188 total cases of ALM with complete data, our study cohort was comprised of 792 (18.9%) Hispanics, 274 (6.5%) NHAPIs, 336 (8.0%) NHBs, and 2786 (66.5%) NHWs. The age-adjusted incidence of ALM increased by 2.48% (P < 0.0001) annually from 2000 to 2020, which was driven by rising rates among Hispanics (APC 2.34%, P = 0.001) and NHWs (APC 2.69%, P < 0.0001). Incidence remained stable among NHBs (APC 1.15%, P = 0.1) and NHAPIs (APC 1.12%, P = 0.4). From 2000 through 2020, 765 (18.3%) patients died from ALM. Compared to NHWs, Hispanics, NHAPIs, and NHBs had significantly increased ALM-specific mortality (all P < 0.0001). Unadjusted and adjusted cause-specific mortality modeling revealed significantly elevated risk of ALM-specific mortality among Hispanics (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.22-1.75; adjusted hazard ratio [aHR] 1.38, 95% CI 1.14-1.66), NHAPIs (HR 1.80, 95% CI 1.41-2.32; aHR 1.58, 95% CI 1.23-2.04), and NHBs (HR 1.98, 95% CI 1.59-2.47; aHR 2.19, 95% CI 1.74-2.76) (all P < 0.001). Our study finds rising incidence of ALM among Hispanics and NHWs along with elevated risk of ALM-specific mortality among racial and ethnic minoritized populations. Future strategies to mitigate health inequities in ALM are warranted.

Effective treatment of actinic keratosis on the hands with red light photodynamic therapy using BF-200 ALA.

BACKGROUND: Acral actinic keratosis (AK) lesions are considered difficult to treat, and published data for photodynamic therapy (PDT) on these lesions is limited. Thus, we evaluated sustained efficacy, safety, and satisfaction after PDT for AK on the hands. METHODS: We analysed subgroup data for treatment on the hands from a randomised, double-blind, intra-individual phase III study. All participants previously underwent up to two field-directed red light PDTs with 10 % 5-aminolevulinic acid nanoemulsion gel (BF-200 ALA). Assessments included pain during PDT, clearance and recurrence rates, and satisfaction. RESULTS: 24 participants treated on the hands were included; 21 participants were analysed. Complete clearance rates with BF-200 ALA were 90.9 % (lesion-based) and 76.2 % (per participant's side), both markedly higher than with vehicle. The lesion recurrence rate with BF-200 ALA was 29.0 %. Adverse events reflected the mode of action. Mean pain intensities were 4.8 ± 3.8 (BF-200 ALA) and 0.8 ± 2.1 (vehicle) on an 11-point numeric rating scale. Most participants (81.0 %) rated their satisfaction with BF-200 ALA as very good or good. CONCLUSION: This subgroup analysis indicates that PDT with BF-200 ALA provides a suitable treatment for AK lesions on the hands.

Pattern Analysis of Benign and Malignant Atypical Melanocytic Skin Lesions of Palms and Soles: Variations of Dermoscopic Features According to Anatomic Site and Personal Experience.

Background: The differential diagnosis of atypical melanocytic skin lesions localized on palms and soles represents a diagnostic challenge: indeed, this spectrum encompasses atypical nevi (AN) and early-stage melanomas (EN) displaying overlapping clinical and dermoscopic features. This often generates unnecessary excisions or delayed diagnosis. Investigations to date were mostly carried out in specific populations, focusing either on acrolentiginous melanomas or morphologically typical acquired nevi. Aims: To investigate the dermoscopic features of atypical melanocytic palmoplantar skin lesions (aMPPLs) as evaluated by variously skilled dermatologists and assess their concordance; to investigate the variations in dermoscopic appearance according to precise location on palms and soles; to detect the features with the strongest association with malignancy/benignity in each specific site. Methods: A dataset of 471 aMPPLs-excised in the suspect of malignancy-was collected from 10 European Centers, including a standardized dermoscopic picture (17×) and lesion/patient metadata. An anatomical classification into 17 subareas was considered, along with an anatomo-functional classification considering pressure/friction, (4 macroareas). A total of 156 participants (95 with less than 5 years of experience in dermoscopy and 61 with ≥than 5 years) from 17 countries performed a blinded tele-dermoscopic pattern analysis over 20 cases through a specifically realized web platform. Results: A total of 37,440 dermoscopic evaluations were obtained over 94 (20%) EM and 377 (80%) AN. The areas with the highest density of EM compared to AN were the heel (40.3% EM/aMPPLs) of the sole and the "fingers area" (33%EM/aMPPLs) of the palm, both characterized by intense/chronic traumatism/friction. Globally, the recognition rates of 12 dermoscopic patterns were non statistically different between 95 dermatology residents and 61 specialists: aMPPLs in the plantar arch appeared to be the most "difficult" to diagnose, the parallel ridge pattern was poorly recognized and irregular/regular fibrillar patterns often misinterpreted. Regarding the aMPPL of the "heel area", the parallel furrow pattern (p = 0.014) and lattice-like pattern (p = 0.001) significantly discriminated benign cases, while asymmetry of colors (p = 0.002) and regression structures (p = 0.025) malignant ones. In aMPPLs of the "plantar arch", the lattice-like pattern (p = 0.012) was significant for benignity and asymmetry of structures, asymmetry of colors, regression structures, or blue-white veil for malignancy. In palmar lesions, no data were significant in the discrimination between malignant and benign aMPPLs. Conclusions: This study highlights that (i) the pattern analysis of aMPPLs is challenging for both experienced and novice dermoscopists; (ii) the histological distribution varies according to the anatomo-functional classification; and (iii) different dermoscopic patterns are able to discriminate malignant from benign aMPPLs within specific plantar and palmar areas.

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.

A Case of Superficial Acral Fibromyxoma of the Index Finger.

Superficial acral fibromyxoma (SAFM) is a rare, slow-growing benign soft tissue tumor that is typically asymptomatic in nature and usually affects the acral regions of the hands and feet. The majority of these lesions are subungual. Excisional biopsy is the primary treatment modality. Despite the distinct clinical and histopathological features, misidentification of this slow-growing tumor persists. This case report contributes to the existing literature by delineating the clinicopathologic features, radiographic and MRI findings, and treatment strategies of SAFM.

A Misdiagnosed Case of Malignant Melanoma in an Infected Nail: A Case Report.

Subungual melanoma is associated with the highest mortality among all skin cancers and is strongly linked to acquired mutations caused by exposure to ultraviolet radiation in sunlight. The commonest sites of occurrence are the great toe and thumb. Diagnosis of melanoma often becomes a challenge as it is difficult to differentiate it from other pigmented disorders. A histopathological evaluation of the lesion with adequate nail matrix biopsy can address the diagnostic dilemma. Additionally, an early diagnosis of melanoma is critical as once detected early, it is often treatable. We present a case of a 72-year-old diabetic male patient with a pigmented lesion over the right great toe. In view of the patient's age and history of diabetes, the initial presentation was mistaken as onychomycosis which created a diagnostic dilemma. Hence, we present this case to shed light upon the fact that these lesions can mimic several other benign conditions like fungal melanonychia, lentigo, and subungual hemorrhage. To avoid misdiagnosis and subsequent delay in management, early clinical, dermoscopic, and very pertinently, histopathological and radiological co-relations are extremely important.

High prevalence of dermatophytosis of the feet in acral melanoma of the foot.

The clinical characteristics and pathogenesis of acral melanoma of the foot (AMF) have not been sufficiently elucidated. Clinical or subclinical persistent inflammation of the feet is caused by dermatophytosis of the feet (DPF). Persistent inflammation is potentially associated with oncogenesis. Moreover, diabetes has been reported to be associated with the development of dermatophytosis and cancer. The present study aimed to elucidate the clinical association between DPF and AMF, with consideration of diabetes. The medical records of 114 Japanese patients were retrospectively examined and divided into an AMF group (n = 30) and a control group consisting of patients with foot diseases other than melanoma (n = 84). Microscopic DPF screening was performed on all patients who reported symptoms in the foot, with or without AMF. Patients underwent a microscopic test to detect the presence of dermatophytes, and the diagnosis of DPF was made based on a positive result. In the AMF group, 18 (60.0%) and eight (26.7%) patients had DPF and diabetes, respectively. Four patients (13.3%) had both DPF and diabetes. In the control group, 25 (29.8%) and 11 (13.1%) patients had DPF and diabetes, respectively. Five patients (6.0%) had both DPF and diabetes. Univariate analyses showed a significantly higher prevalence of DPF in the AMF group than in the control group (odds ratio, 3.540; p = 0.003, Pearson χ2 test). Furthermore, multivariate analyses of sex, body mass index, DPF, and diabetes revealed DPF as a significant factor associated with AMF (odds ratio, 4.285; p = 0.002, logistic regression analysis). The hyperkeratotic type of DPF was more frequently observed in patients with AMF than in control patients (odds ratio, 11.083; p < 0.001, Pearson χ2 test). In conclusion, the present study found a significantly higher prevalence of DPF, especially its hyperkeratotic type, in patients with AMF. DPF may be associated with AMF pathogenesis.

Study of Risk Factors for the Presence of Interdigital Nevi of the Feet. / Estudio de los factores de riesgo de la presencia de los nevus interdigitales de los pies.

BACKGROUND AND OBJECTIVES: No studies focused on counting the interdigital acquired melanocytic nevi (AMN) of the foot (IDNf) have ever been conducted. Therefore, our objective was to study the relationship between the presence of IDNf and the total number of AMN in the feet and the rest of the body, the racial phenotypic characteristics, and other risk factors for melanoma. MATERIAL AND METHODS: We conducted a cross-sectional observational study with 255 patients ≥18 years old who attended our Dermatology Unit from September 2020 through February 2021, and included all AMN ≥1mm from the feet and ≥2mm from the rest of the bod. The association between the variables was studied using univariate and multivariate logistic regression models. RESULTS: The presence of IDNf was significantly and independently associated with the presence of plantar AMN and body counts ≥50 AMN. However, no significant differences were observed regarding sex, age, personal history of melanoma, presence of nevi on the dorsum of the foot, history of sunburn or UV rays, or racial phenotypic characteristics. CONCLUSIONS: The presence of IDNf is associated with a higher count of plantar nevi and total AMN in the body, meaning that interdigital spaces of the foot-anatomical expansions of the sole and other possibly genetic causes-could be responsible for the number of AMN found in this location, as these regions are not photoexposed.

Integrative molecular and spatial analysis reveals evolutionary dynamics and tumor-immune interplay of in situ and invasive acral melanoma.

In acral melanoma (AM), progression from in situ (AMis) to invasive AM (iAM) leads to significantly reduced survival. However, evolutionary dynamics during this process remain elusive. Here, we report integrative molecular and spatial characterization of 147 AMs using genomics, bulk and single-cell transcriptomics, and spatial transcriptomics and proteomics. Vertical invasion from AMis to iAM displays an early and monoclonal seeding pattern. The subsequent regional expansion of iAM exhibits two distinct patterns, clonal expansion and subclonal diversification. Notably, molecular subtyping reveals an aggressive iAM subset featured with subclonal diversification, increased epithelial-mesenchymal transition (EMT), and spatial enrichment of APOE+/CD163+ macrophages. In vitro and ex vivo experiments further demonstrate that APOE+CD163+ macrophages promote tumor EMT via IGF1-IGF1R interaction. Adnexal involvement can predict AMis with higher invasive potential whereas APOE and CD163 serve as prognostic biomarkers for iAM. Altogether, our results provide implications for the early detection and treatment of AM.