Objective:Acral melanoma(AM),a unique subtype prevalent in China,develops on the palms,soles,and nail beds.Despite its distinct clinical and pathological features compared to cutaneous melanoma(CM),the molecular basis...Objective:Acral melanoma(AM),a unique subtype prevalent in China,develops on the palms,soles,and nail beds.Despite its distinct clinical and pathological features compared to cutaneous melanoma(CM),the molecular basis underlying these differences remains poorly understood.This study aims to perform a comprehensive comparative transcriptomic analysis of AM and CM at the single-cell level to uncover key molecular distinctions.Methods:We analyzed single-cell RNA sequencing(scRNA-seq)data from 39 AM patients and 18 CM cases.Single-cell transcriptomic profiling was used to compare tumor cell subpopulations and microenvironmental differences.Bioinformatics tools were employed for cell clustering,differential gene expression analysis,cell-cell communication network inferences,and survival analysis.Results:AM exhibited a significantly higher proportion of MPZ^(+)melanoma cells,a subpopulation with Schwann cell-like properties associated with poor prognosis.These MPZ^(+)melanoma cells established extensive communication networks with AM-specific immune and stromal components,prompting an immunosuppressive microenvironment and enhancing angiogenic potential.Survival analysis further indicated that the presence of MPZ^(+)melanoma cells is closely linked to worse clinical outcomes in AM patients.Conclusions:This study provides novel insights into the molecular distinctions between AM and CM,highlighting the critical role of MPZ^(+)melanoma cells in AM progression.These findings enhance our understanding of AM pathophysiology and may contribute to the development of more targeted therapeutic strategies.展开更多
Introduction:Acral melanoma(AM)is the predominant subtype of cutaneous melanoma in Asian populations,characterized by more aggressive clinical features and limited neoadjuvant therapy response.Centrosomal protein 55 k...Introduction:Acral melanoma(AM)is the predominant subtype of cutaneous melanoma in Asian populations,characterized by more aggressive clinical features and limited neoadjuvant therapy response.Centrosomal protein 55 kDa(CEP55)has been implicated in the pathogenesis of various malignancies,but its role in AM remains undefined.Methods:CEP55 expression in melanoma tissues and cell lines was analyzed by RT-qPCR,Western blotting,and immunohistochemistry(IHC).Databases(GEPIA,Sangerbox,Kaplan-Meier plotter,and TIMER)were used to analyze the expression of CEP55 and its correlation with clinical data of melanoma patients.Functional assays were conducted in vitro and in vivo.RNA sequencing(RNA-seq)and rescue experiments were used to explore underlying mechanisms.Tissue microarrays were used to verify the relationship between CEP55 and immune checkpoints.Results:CEP55 overexpression is associated with Breslow thickness and TNM stage in melanoma tissues and cell lines.CEP55 knockdown inhibited melanoma cell proliferation,migration,and invasion.And CEP55 activated mitogen-activated protein kinase(MAPK)signaling,leading to BRAF inhibitor resistance.Besides,CEP55 overexpression was associated with more favorable responses to immunotherapy in melanoma patients.Conclusions:CEP55 plays a critical role in AM progression and immunotherapy.Targeting CEP55 may be a promising therapeutic strategy for AM.展开更多
Acral melanoma(AM)is the most common histologic subtype of melanoma in dark-skinned patients and is associated with a worse prognosis and a high mortality rate,largely due to the inconspicuous nature of early-stage le...Acral melanoma(AM)is the most common histologic subtype of melanoma in dark-skinned patients and is associated with a worse prognosis and a high mortality rate,largely due to the inconspicuous nature of early-stage lesions,which can lead to late diagnosis.Because of the overlapping clinical and histopathological features of AM with other forms of cutaneous melanomas,early detection of AM requires a multidisciplinary approach that integrates various diagnostic modalities,including clinical examination,dermoscopy,histopathology,molecular testing,radiological imaging,and blood tests.While surgery is the preferred method of treatment for AM,other therapeutic options may be employed based on the stage and underlying etiology of the disease.Immune checkpoint inhibitors,molecular targeted therapy,radiotherapy,chemotherapy,and oncolytic virotherapy represent promising advanced treatment options for AM.In this review,we provide an overview of the latest advancements in diagnostic and therapeutic methods for AM,highlighting the importance of early detection and the prompt,individualized management of this challenging disease.展开更多
BACKGROUND Necrolytic acral erythema(NAE) is a rare dermatological disorder,which is associated with hepatitis C virus(HCV) infection or zinc deficiency.It is characterized by erythematous or violaceous lesions occurr...BACKGROUND Necrolytic acral erythema(NAE) is a rare dermatological disorder,which is associated with hepatitis C virus(HCV) infection or zinc deficiency.It is characterized by erythematous or violaceous lesions occurring primarily in the lower extremities.The treatment includes systemic steroids and oral zinc supplementation.We report a case of NAE in a 66-year-old human immunodeficiency virus(HIV)/HCV co-infected woman with NAE.NAE is rarely reported in co-infected patients and the exact mechanisms of pathogenesis are still unclear.CASE SUMMARY A 66-year-old HIV/HCV co-infected female patient presented with painless,nonpruritic rash of extremities for one week and underwent extensive work-up for possible rheumatologic disorders including vasculitis and cryoglobulinemia.Punch skin biopsies of right and left thigh revealed thickened parakeratotic stratum corneum most consistent with NAE.Patient was started on prednisone and zinc supplementation with resolution of the lesions and improvement of rash.CONCLUSION Clinicians should maintain high clinical suspicion for early recognition of NAE in patients with rash and HCV.展开更多
Acral melanoma(AM)is a rare and lethal type of skin cancer.It can be diagnosed by expert dermatologists,using dermoscopic imaging.It is challenging for dermatologists to diagnose melanoma because of the very minor dif...Acral melanoma(AM)is a rare and lethal type of skin cancer.It can be diagnosed by expert dermatologists,using dermoscopic imaging.It is challenging for dermatologists to diagnose melanoma because of the very minor differences between melanoma and non-melanoma cancers.Most of the research on skin cancer diagnosis is related to the binary classification of lesions into melanoma and non-melanoma.However,to date,limited research has been conducted on the classification of melanoma subtypes.The current study investigated the effectiveness of dermoscopy and deep learning in classifying melanoma subtypes,such as,AM.In this study,we present a novel deep learning model,developed to classify skin cancer.We utilized a dermoscopic image dataset from the Yonsei University Health System South Korea for the classification of skin lesions.Various image processing and data augmentation techniques have been applied to develop a robust automated system for AM detection.Our custombuilt model is a seven-layered deep convolutional network that was trained from scratch.Additionally,transfer learning was utilized to compare the performance of our model,where AlexNet and ResNet-18 were modified,fine-tuned,and trained on the same dataset.We achieved improved results from our proposed model with an accuracy of more than 90%for AM and benign nevus,respectively.Additionally,using the transfer learning approach,we achieved an average accuracy of nearly 97%,which is comparable to that of state-of-the-art methods.From our analysis and results,we found that our model performed well and was able to effectively classify skin cancer.Our results show that the proposed system can be used by dermatologists in the clinical decision-making process for the early diagnosis of AM.展开更多
BACKGROUND Acral persistent papular mucinosis(APPM)is a rare idiopathic subtype of localized lichen myxedematosus.To date,there have been 40 APPM cases reported worldwide;however,only 7 cases have been reported in the...BACKGROUND Acral persistent papular mucinosis(APPM)is a rare idiopathic subtype of localized lichen myxedematosus.To date,there have been 40 APPM cases reported worldwide;however,only 7 cases have been reported in the Korean literature.CASE SUMMARY A 70-year-old man was referred to our hospital with a solitary pinkish nodule on the dorsum of his right hand.Despite the absence of symptoms,the patient wanted to know the exact diagnosis;thus,a biopsy was performed.Histopathological examination of a biopsy specimen obtained from the nodule on the dorsum of his hand revealed orthokeratotic hyperkeratosis with patchy parakeratosis,prominent hypergranulosis,and diffuse dissecting mucinous deposition between collagen bundles,along with some bland-looking spindle cells throughout the dermis.The nodule was histologically diagnosed as an APPM,and an intralesional triamcinolone injection(2.5 mg/mL)was started every 2 wk.After three sessions of treatment,the patient showed marked improvements.CONCLUSION To the best of our knowledge,this is the first case of a Korean APPM presenting as a solitary nodule that showed a marked response to triamcinolone intralesional injection.Since it is a rare disease,we report this case to contribute to future research on the pathogenesis and treatment of APPM.展开更多
Superficial acral fibromyxoma (SAF) is a tumor that occurs on the distal phalanges of the digits. As it does not spontaneously regress and is often associated with pain, the primary treatment is surgical resection. It...Superficial acral fibromyxoma (SAF) is a tumor that occurs on the distal phalanges of the digits. As it does not spontaneously regress and is often associated with pain, the primary treatment is surgical resection. It is often associated with the nail component of the affected digit, and thus cosmesis is an important goal of the operation. We herein describe a case of SAF on the distal phalanges of the fifth digit of the foot beneath the nail, which was successfully resected with the nail component kept intact. Moreover, although SAF is most commonly CD34-positive, the present case was CD34-negative except for endothelial cells within the tumor. While CD34-negative SAF has been previously reported, the current case further indicates that CD34-positivity is not essential for the diagnosis of SAF.展开更多
Purpose To construct an effective prognostic nomogram for patients with clinically localized Acral lentiginous mela-noma(ALM).Methods This retrospective study included ALM patients from the Surveillance,Epidemiology,a...Purpose To construct an effective prognostic nomogram for patients with clinically localized Acral lentiginous mela-noma(ALM).Methods This retrospective study included ALM patients from the Surveillance,Epidemiology,and End Results(SEER)database from 2004–2015.The 1686 cases were divided into the training and internal validation cohorts at a ratio of 7:3.The Cox regression analyses were performed to select risk factors for the nomogram.The performances of the nomogram were evaluated using the concordance index(C-index),area under receiver operating characteristic curve(AUC),and calibration plots,and validated in an external multicenter cohort.Results Age,gender,race,and stage were significantly associated with overall survival(OS),with a C-index of 0.727 and 0.722 in the training and internal validation groups,respectively.The AUC of 2-,4-,and 6 years were higher than or equal to 0.75.Age,gender,race,site,and stage were related to ALM patients’CSS which have better C-index of 0.791 and 0.774 in the training and internal validation set.The AUC of 2-,4-,and 6-were higher than or equal to 0.80.Both survival calibration curves of 2-,4,and 6-year OS and CSS brought out a good consistency.The external multicenter cohort authenticated the value of the nomogram of OS,with a C-index of 0.657 and an AUC of 0.67,0.72,and 0.65 at 2,4,and 6 years.Good consistency was also observed.Conclusion A prognostic nomogram was established and validated to help predict the survival of ALM patients and guide individualized treatment strategies.展开更多
Background To describe the cutaneous acral findings in a pediatric population noticed during this pandemic.Methods A retrospective descriptive study was performed collecting data on 36 patients under 14 years old,pres...Background To describe the cutaneous acral findings in a pediatric population noticed during this pandemic.Methods A retrospective descriptive study was performed collecting data on 36 patients under 14 years old,presenting suspicious acral skin manifestations for coronavirus disease 2019(COVID-19).Results Patients were mostly male(63.8%).The mean age was 11.11 years.66.67%of patients showed erythematous papules,and 44.44%purpuric macules.Feet were aifected in 97.22%of patients and hands in 5.55%.Lesions were asymptomatic in 50%of patients.30.55%of patients showed extracutaneous findings,preceding skin lesions in 12.62 days.Seven patients underwent specific severe acute coronavirus 2(SARS-CoV-2)testing;all of these patients tested negative.Conclusions The association between these symptoms and SARS-CoV-2 remains unclear.We recommend using these manifestations as a sign of SARS-CoV-2 infection in children.This could lead to the examination of asymptomatic and mildly symptomatic children so that contagions may be avoided.展开更多
基金supported by the National Key Research and Development Project(No.2023YFC3404400)。
文摘Objective:Acral melanoma(AM),a unique subtype prevalent in China,develops on the palms,soles,and nail beds.Despite its distinct clinical and pathological features compared to cutaneous melanoma(CM),the molecular basis underlying these differences remains poorly understood.This study aims to perform a comprehensive comparative transcriptomic analysis of AM and CM at the single-cell level to uncover key molecular distinctions.Methods:We analyzed single-cell RNA sequencing(scRNA-seq)data from 39 AM patients and 18 CM cases.Single-cell transcriptomic profiling was used to compare tumor cell subpopulations and microenvironmental differences.Bioinformatics tools were employed for cell clustering,differential gene expression analysis,cell-cell communication network inferences,and survival analysis.Results:AM exhibited a significantly higher proportion of MPZ^(+)melanoma cells,a subpopulation with Schwann cell-like properties associated with poor prognosis.These MPZ^(+)melanoma cells established extensive communication networks with AM-specific immune and stromal components,prompting an immunosuppressive microenvironment and enhancing angiogenic potential.Survival analysis further indicated that the presence of MPZ^(+)melanoma cells is closely linked to worse clinical outcomes in AM patients.Conclusions:This study provides novel insights into the molecular distinctions between AM and CM,highlighting the critical role of MPZ^(+)melanoma cells in AM progression.These findings enhance our understanding of AM pathophysiology and may contribute to the development of more targeted therapeutic strategies.
基金supported by CAMS Innovation Fund for Medical Sciences(CIFMS)(2024-I2M-C&T-B-089)National Key Research and Development Program(2022YFC2504700,2022YFC2504701,2022YFC2504705)National Natural Science Foundation of China(NSFC81872216).
文摘Introduction:Acral melanoma(AM)is the predominant subtype of cutaneous melanoma in Asian populations,characterized by more aggressive clinical features and limited neoadjuvant therapy response.Centrosomal protein 55 kDa(CEP55)has been implicated in the pathogenesis of various malignancies,but its role in AM remains undefined.Methods:CEP55 expression in melanoma tissues and cell lines was analyzed by RT-qPCR,Western blotting,and immunohistochemistry(IHC).Databases(GEPIA,Sangerbox,Kaplan-Meier plotter,and TIMER)were used to analyze the expression of CEP55 and its correlation with clinical data of melanoma patients.Functional assays were conducted in vitro and in vivo.RNA sequencing(RNA-seq)and rescue experiments were used to explore underlying mechanisms.Tissue microarrays were used to verify the relationship between CEP55 and immune checkpoints.Results:CEP55 overexpression is associated with Breslow thickness and TNM stage in melanoma tissues and cell lines.CEP55 knockdown inhibited melanoma cell proliferation,migration,and invasion.And CEP55 activated mitogen-activated protein kinase(MAPK)signaling,leading to BRAF inhibitor resistance.Besides,CEP55 overexpression was associated with more favorable responses to immunotherapy in melanoma patients.Conclusions:CEP55 plays a critical role in AM progression and immunotherapy.Targeting CEP55 may be a promising therapeutic strategy for AM.
基金This work was supported by the Zhejiang Provincial Natural Science Foundation of China(No.LS21H060001)the Alibaba Youth Studio Project(No.ZJU-032)the Zhejiang Province Medical and Health Science and Technology Program(Nos.2022KY1455 and 2022RC136).The funding bodies had no role in the design of the study,in collection,analysis,and interpretation of data,or in drafting the manuscript.We thank Fatima ALALIWI and Ma LING for their invaluable support and encouragement.
文摘Acral melanoma(AM)is the most common histologic subtype of melanoma in dark-skinned patients and is associated with a worse prognosis and a high mortality rate,largely due to the inconspicuous nature of early-stage lesions,which can lead to late diagnosis.Because of the overlapping clinical and histopathological features of AM with other forms of cutaneous melanomas,early detection of AM requires a multidisciplinary approach that integrates various diagnostic modalities,including clinical examination,dermoscopy,histopathology,molecular testing,radiological imaging,and blood tests.While surgery is the preferred method of treatment for AM,other therapeutic options may be employed based on the stage and underlying etiology of the disease.Immune checkpoint inhibitors,molecular targeted therapy,radiotherapy,chemotherapy,and oncolytic virotherapy represent promising advanced treatment options for AM.In this review,we provide an overview of the latest advancements in diagnostic and therapeutic methods for AM,highlighting the importance of early detection and the prompt,individualized management of this challenging disease.
文摘BACKGROUND Necrolytic acral erythema(NAE) is a rare dermatological disorder,which is associated with hepatitis C virus(HCV) infection or zinc deficiency.It is characterized by erythematous or violaceous lesions occurring primarily in the lower extremities.The treatment includes systemic steroids and oral zinc supplementation.We report a case of NAE in a 66-year-old human immunodeficiency virus(HIV)/HCV co-infected woman with NAE.NAE is rarely reported in co-infected patients and the exact mechanisms of pathogenesis are still unclear.CASE SUMMARY A 66-year-old HIV/HCV co-infected female patient presented with painless,nonpruritic rash of extremities for one week and underwent extensive work-up for possible rheumatologic disorders including vasculitis and cryoglobulinemia.Punch skin biopsies of right and left thigh revealed thickened parakeratotic stratum corneum most consistent with NAE.Patient was started on prednisone and zinc supplementation with resolution of the lesions and improvement of rash.CONCLUSION Clinicians should maintain high clinical suspicion for early recognition of NAE in patients with rash and HCV.
文摘Acral melanoma(AM)is a rare and lethal type of skin cancer.It can be diagnosed by expert dermatologists,using dermoscopic imaging.It is challenging for dermatologists to diagnose melanoma because of the very minor differences between melanoma and non-melanoma cancers.Most of the research on skin cancer diagnosis is related to the binary classification of lesions into melanoma and non-melanoma.However,to date,limited research has been conducted on the classification of melanoma subtypes.The current study investigated the effectiveness of dermoscopy and deep learning in classifying melanoma subtypes,such as,AM.In this study,we present a novel deep learning model,developed to classify skin cancer.We utilized a dermoscopic image dataset from the Yonsei University Health System South Korea for the classification of skin lesions.Various image processing and data augmentation techniques have been applied to develop a robust automated system for AM detection.Our custombuilt model is a seven-layered deep convolutional network that was trained from scratch.Additionally,transfer learning was utilized to compare the performance of our model,where AlexNet and ResNet-18 were modified,fine-tuned,and trained on the same dataset.We achieved improved results from our proposed model with an accuracy of more than 90%for AM and benign nevus,respectively.Additionally,using the transfer learning approach,we achieved an average accuracy of nearly 97%,which is comparable to that of state-of-the-art methods.From our analysis and results,we found that our model performed well and was able to effectively classify skin cancer.Our results show that the proposed system can be used by dermatologists in the clinical decision-making process for the early diagnosis of AM.
文摘BACKGROUND Acral persistent papular mucinosis(APPM)is a rare idiopathic subtype of localized lichen myxedematosus.To date,there have been 40 APPM cases reported worldwide;however,only 7 cases have been reported in the Korean literature.CASE SUMMARY A 70-year-old man was referred to our hospital with a solitary pinkish nodule on the dorsum of his right hand.Despite the absence of symptoms,the patient wanted to know the exact diagnosis;thus,a biopsy was performed.Histopathological examination of a biopsy specimen obtained from the nodule on the dorsum of his hand revealed orthokeratotic hyperkeratosis with patchy parakeratosis,prominent hypergranulosis,and diffuse dissecting mucinous deposition between collagen bundles,along with some bland-looking spindle cells throughout the dermis.The nodule was histologically diagnosed as an APPM,and an intralesional triamcinolone injection(2.5 mg/mL)was started every 2 wk.After three sessions of treatment,the patient showed marked improvements.CONCLUSION To the best of our knowledge,this is the first case of a Korean APPM presenting as a solitary nodule that showed a marked response to triamcinolone intralesional injection.Since it is a rare disease,we report this case to contribute to future research on the pathogenesis and treatment of APPM.
文摘Superficial acral fibromyxoma (SAF) is a tumor that occurs on the distal phalanges of the digits. As it does not spontaneously regress and is often associated with pain, the primary treatment is surgical resection. It is often associated with the nail component of the affected digit, and thus cosmesis is an important goal of the operation. We herein describe a case of SAF on the distal phalanges of the fifth digit of the foot beneath the nail, which was successfully resected with the nail component kept intact. Moreover, although SAF is most commonly CD34-positive, the present case was CD34-negative except for endothelial cells within the tumor. While CD34-negative SAF has been previously reported, the current case further indicates that CD34-positivity is not essential for the diagnosis of SAF.
基金supported by the Shanghai Science and Technology Development Funds(19411951700 to Y.Chen)LinGang laboratory“Seeking Distinguished Young Scholars”project(LG-QS-202205-11 to W.Sun)the National Natural Science Foundation of China(81802636 to W.Sun).
文摘Purpose To construct an effective prognostic nomogram for patients with clinically localized Acral lentiginous mela-noma(ALM).Methods This retrospective study included ALM patients from the Surveillance,Epidemiology,and End Results(SEER)database from 2004–2015.The 1686 cases were divided into the training and internal validation cohorts at a ratio of 7:3.The Cox regression analyses were performed to select risk factors for the nomogram.The performances of the nomogram were evaluated using the concordance index(C-index),area under receiver operating characteristic curve(AUC),and calibration plots,and validated in an external multicenter cohort.Results Age,gender,race,and stage were significantly associated with overall survival(OS),with a C-index of 0.727 and 0.722 in the training and internal validation groups,respectively.The AUC of 2-,4-,and 6 years were higher than or equal to 0.75.Age,gender,race,site,and stage were related to ALM patients’CSS which have better C-index of 0.791 and 0.774 in the training and internal validation set.The AUC of 2-,4-,and 6-were higher than or equal to 0.80.Both survival calibration curves of 2-,4,and 6-year OS and CSS brought out a good consistency.The external multicenter cohort authenticated the value of the nomogram of OS,with a C-index of 0.657 and an AUC of 0.67,0.72,and 0.65 at 2,4,and 6 years.Good consistency was also observed.Conclusion A prognostic nomogram was established and validated to help predict the survival of ALM patients and guide individualized treatment strategies.
文摘Background To describe the cutaneous acral findings in a pediatric population noticed during this pandemic.Methods A retrospective descriptive study was performed collecting data on 36 patients under 14 years old,presenting suspicious acral skin manifestations for coronavirus disease 2019(COVID-19).Results Patients were mostly male(63.8%).The mean age was 11.11 years.66.67%of patients showed erythematous papules,and 44.44%purpuric macules.Feet were aifected in 97.22%of patients and hands in 5.55%.Lesions were asymptomatic in 50%of patients.30.55%of patients showed extracutaneous findings,preceding skin lesions in 12.62 days.Seven patients underwent specific severe acute coronavirus 2(SARS-CoV-2)testing;all of these patients tested negative.Conclusions The association between these symptoms and SARS-CoV-2 remains unclear.We recommend using these manifestations as a sign of SARS-CoV-2 infection in children.This could lead to the examination of asymptomatic and mildly symptomatic children so that contagions may be avoided.
