Endometriosis beyond the Pelvis: A Case Series of Cutaneous Endometriosis and Literature Review

Introduction: Cutaneous endometriosis is an uncommon but well-known skin disorder that represents about 0.5% to 1% of all endometriosis. The objective of this case series is to report clinical presentation, diagnosis, and management of various forms of cutaneous endometriosis. Material and Methods: It was an observational, retrospective and descriptive review of cases presenting with cutaneous endometriosis among Cameroonian women managed at the gynaecological outpatient department of Yaounde Gynaeco-Obstetric and Pediatric Hospital. All the following parameters were analysed: age, parity, previous pelvic surgery, presenting symptoms and duration, associated symptoms, localizations, imaging, size of the lesion, other localization of endometriosis, management and histopathological results. Results: we reported 4 cases of cutaneous endometriosis, with 3 umbilical endometriosis and 1 abdominal scar endometriosis. Patient age ranged from 28 to 39 years with an average of 33 years. All patients described infertility (two primary and two secondary) and two had a history of abdominal surgery. All patients presented local cyclical signs such as pain, swelling, color change and bleeding. The duration of symptoms varied from 2 to 3 years and the size of lesions ranged from 2 to 3.5 cm for umbilical lesions and was 9 cm for abdominal scar endometriosis. In all cases, no imaging was required for the diagnosis, which was suspected on the basis of patient’s history and the cyclical nature of local signs, followed by wide surgical excision and confirmation on histopathology. Conclusion: Cutaneaous endometriosis is a rare benign condition. Umbilical endometriosis seems to be the main cutaneous localization and can be described as primary or secondary. Even if its diagnosis must be confirmed by histopathology, it should be considered in patient with cutaneous cyclic signs such as pain, swelling or bleeding with or without history of abdominal surgery.

Clinical Study on the Effectiveness of Xian Fang Huo Ming Yin for Treating Cutaneous Infections and Promoting Wound Healing in Patients with Perianal Abscess

Objective:To explore the effect of the Xian Fang Huo Ming Yin(XFHM)for treating cutaneous infections and promoting wound healing in patients with perianal abscesses.Methods:Sixty-one patients with perianal abscesses who were admitted to our hospital(Xinghua City People’s Hospital)from May 2022 to May 2023 were selected and randomly divided into two groups,a control group(30 cases)and a study group(31 cases).Both groups received surgical treatment.The control group received conventional treatment and warm water fumigation,sitz bath,and surgical dressing change after surgery,while the research group received XFHM based on the control group.XFHM was taken orally and replaced with warm water for fumigation and sitz bathing.Both groups received treatment for 4 weeks but discontinued sitz bathing after 2 weeks.Various clinical indicators between the two groups were compared.Results:The total clinical effective rate and wound recovery rate of the study group were higher than that of the control group.There were differences in the wound pain scores,surrounding tissue edema,and wound secretions at different time points.Both groups experienced wound pain.The scores of wound pain,surrounding tissue edema,and wound secretions of the study group were lower than those of the control group,7 and 14 days after surgery.The serum interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α)levels,and pH values of the study group were lower than those of the control group 10 days after surgery(P<0.05).Conclusion:The application of XFHM for treating cutaneous infections and promoting wound healing in patients with perianal abscesses improved the treatment outcome,alleviated clinical symptoms,and promoted healing.

Anti-leishmanial,immunomodulatory and anti-oxidative activity of quercetin against cutaneous leishmaniasis caused by Leishmania major

Objective:To evaluate the in vitro and in vivo efficacy of quercetin and its immunomodulatory and anti-oxidative activity against Leishmania major(L.major).Methods:L.major promastigotes and amastigotes were incubated with different concentrations of quercetin to estimate EC_(50).For in vivo study,the base of tails of mice was infected with L.major.After developing ulcers in the inoculation site,mice were treated with 50 mg/kg quercetin orally for 28 consecutive days.The wound-healing potential of quercetin was evaluated by histopathological analysis of tissue sections stained by hematoxylin and eosin as well as Masson's trichrome.In addition,the levels of tumor necrosis factor-α,interleukin-6,malondialdehyde,and adiponectin,the ferric reducing ability of plasma,as well as superoxide dismutase and glutathione peroxidase activities were measured.Results:The EC_(50)values of quercetin against L.major promastigotes and intracellular amastigotes were 0.27 and 0.85μM,respectively.Histopathological analysis showed that fewer inflammatory cells,more fibroblasts,and more collagen deposition were observed in tissue sections of quercetin-treated mice.In addition,treatment with quercetin markedly increased glutathione peroxidase activity,the ferric reducing ability of plasma and adiponectin levels while decreasing malondialdehyde,interleukin-6,and tumor necrosis factor-αlevels.Conclusions:Quercetin shows anti-leishmanial activity,immunomodulatory,anti-oxidative,and anti-inflammatory effects.Therefore,it may be further explored as an effective drug in treating leishmaniasis.

Cutaneous anthrax associated with facial palsy:A case report

Rationale:Anthrax is a zoonotic disease caused by spores of Gram-positive Bacillus anthracis,commonly affects mammals and in rare cases birds.Human infection occurs accidentally through direct or indirect exposure to animal or their products.Patient concerns:A 63-year-old man was referred to our hospital with flu-like symptoms and severe swelling and redness on the face,the roof of the mouth,and nostrils.He had a history of direct contact with a slaughtered mutton two days ago.He declared controlled diabetes,hypertension,hypertriglyceridemia,and heart failure.Lungs were normal in lung high resolution CT,but multiple lymphadenopathies were seen in the mediastinum.Bilateral axillary lymphadenopathy with a maximum sad of 23 mm and pleural effusion on the right side was observed.CT scan of the nose and sinuses showed an increased density of polyps in the left maxillary sinus.Slides were prepared from the patient's lesions and examined under a light microscope.Bacillus shape with Streptococcus bacteria was seen.Diagnosis:Anthrax co-infection with herpes systemic virus and Streptococcus pyogenes.Interventions:Multidrug therapy started with appropriate antibiotics.Outcomes:The symptoms of the patient gradually disappeared.The patient was discharged without any complications.Lessons:Cutaneous anthrax in endemic areas in patients with skin presentations and a history of contact with infected animals or products should be considered a differential diagnosis.This is more important in mixed infections where the main cause of the problem may be hidden.

Therapeutic response and safety of different treatments for cutaneous leishmaniasis in patients: A retrospective cross-sectional study

Objective:To analyze the therapeutic response and safety of different treatments for cutaneous leishmaniasis,received by patients in the Program for the Study and Control of Tropical Diseases-PECET-Medellín-Colombia.Methods:This is a retrospective cross-sectional study of patients attended at PECET Research Center during 2016-2021.Relevant information regarding sociodemographic characteristics,history of leishmaniasis,characterization of current infection,treatment received,follow-up of therapeutic response and safety was collected from the medical records.Data were analyzed with Pearson's Chi-square association tests and Mann-Whitney U test using statistical software.Results:A total of 486 clinical records of patients were analyzed,and 356 received treatment.Eight different therapeutic alternatives(systemic,local and in combination)were analyzed.The therapeutic response of the different alternatives used(except thermotherapy)was higher than 50%.Most frequent adverse events were myalgias,arthralgias and headache,and vesicles for systemic and local treatment,respectively.Conclusions:Safety profile and performance of local therapeutic alternatives and combined schemes for the treatment of uncomplicated cutaneous leishmaniasis are an interesting option for the management of the disease.

Characterization of prognosis and immune infiltration by a novel glutamine metabolism-related model in cutaneous melanoma

Glutamine metabolism(GM)plays an important role in tumor growth and proliferation.Skin cutaneous melanoma(SKCM)is a glutamine-dependent cancer.However,the molecular characteristics and action mechanism of GM on SKCM remain unclear.Therefore,we aimed to explore the effects of GM-related genes on survival,clinicopathological characteristics,and the tumor microenvironment in SKCM.In this study,682 SKCM samples were obtained from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.Consensus clustering was used to classify SKCM samples into distinct subtypes based on 41 GM-related genes.Differences in survival,immune infiltration,clinical characteristics,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways as well as differentially expressed genes(DEGs)between subgroups were evaluated.A prognostic model was constructed according to prognostic DEGs.Differential analyses in survival,immune infiltration,tumor microenvironment(TME),tumor mutation burden(TMB),stemness,and drug sensitivity between risk groups were conducted.We identified two distinct GM-related subtypes on SKCM and found that GM-related gene alterations were associated with survival probability,clinical features,biological function,and immune infiltration.Then a risk model based on six DEGs(IL18,SEMA6A,PAEP,TNFRSF17,AIM2,and CXCL10)was constructed and validated for predicting overall survival in SKCM patients.The results showed that the risk score was negatively correlated with CD8+T cells,activated CD4+memory T cells,M1 macrophages,andγδT cells.The group with a low-risk score was accompanied by a better survival rate with higher TME scores and lower stemness index.Moreover,the group with high-and low-risk score had a significant difference with the sensitivity of 75 drugs(p<0.001).Overall,distinct subtypes in SKCM patients based on GM-related genes were identified and the risk model was constructed,which might contribute to prognosis prediction,guide clinical therapy,and develop novel therapeutic strategies.

Inflammatory cutaneous metastases originating from gastric cancer: A case report

BACKGROUND Cutaneous metastasis with gastric cancer(GC)origin is extremely rare and associated with poor prognosis.Nodular type is the most common type,while other forms are extremely rare.CASE SUMMARY This study describes severe skin redness,swelling,pain,and fever in a 65-year-old man diagnosed with GC,whose left chest wall,left upper limb,and left back were mainly affected.Firstly,the patient was diagnosed with“lymphangitis”and treated to promote lymphatic return.However,the symptoms were constantly deteriorating,and skin thickening and scattered small nodules gradually appeared.Finally,the skin biopsy confirmed cutaneous metastases,and the patient died 7 d later.CONCLUSION Our case highlights that cutaneous metastasis should be considered when skin lesions appear in patients with GC.

Transcriptome sequencing analysis of ursolic acid-mediated proliferation suppression on cutaneous T-cell lymphoma cells

Background:Ursolic acid is a triterpenoid compound found in natural plants that exhibits antiproliferative effects in various cancer cells.Our study is the first to demonstrate the strong inhibitory effects of ursolic acid on the proliferation of cutaneous T-cell lymphoma(CTCL)cells.We aimed to further investigate the underlying mechanism of the proliferation inhibition induced by ursolic acid in CTCL cells using transcriptome sequencing.Methods:Cell counting kit-8 assays were used to observe the effects of six traditional medicine monomers on the proliferation of CTCL cells.Transcriptome sequencing was used to identify differentially expressed genes after ursolic acid treatment.Bioinformatics analysis was performed to determine the potential mechanism.Real-time quantitative PCR and western blotting analyses were performed to confirm the sequencing results and verify the possible mechanisms of ursolic acid-mediated proliferation inhibition in CTCL cells.Results:Ursolic acid exhibited the strongest inhibitory effect on the proliferation of CTCL cells among the six traditional medicine monomers.Transcriptome sequencing analysis showed that 2,466 genes were significantly altered.Combined with Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis and protein-protein interaction network analysis,the interaction of various pathways and signaling molecules,such as tumor necrosis factor-α,NLR family pyrin domain containing 1,c-Jun N-terminal kinase,and melanoma differentiation-associated gene 5,accounted for the anti-tumor effects of ursolic acid in CTCL cells.Conclusion:Ursolic acid significantly inhibited the proliferation of CTCL cells,and our study laid a theoretical foundation for the future treatment of CTCL using ursolic acid.

Thioredoxin domain-containing protein 9 protects cells against UV-B-provoked apoptosis via NF-κB/p65 activation in cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma(cSCC),a type of non-melanoma skin cancer(NMSC),is the most common malignancy worldwide.Thioredoxin(TXN)domain-containing protein 9(TXNDC9)is a member of the TXN family that is important in cell differentiation.However,the biological function of this protein in cancer,particularly cSCC,is still unknown.In the present study,our experiments revealed the protective effects of TXNDC9 on UV-B-irritated cSCC cells.The initial findings showed that TXNDC9 is significantly upregulated in cSCC tissue and cells compared to normal skin tissue and keratinocytes.UV-B radiation robustly induces the expression of TXNDC9,and UV-B-induced cSCC cell death is boosted by TXNDC9 deficiency.Moreover,cSCC cells lacking TXNDC9 displayed attenuated activation of the NF-κB pathway.Additional studies by inhibiting TXNDC9 confirmed this finding,as TXNDC9 deficiency attenuated UV-B radiation-induced translocation of NF-κB p65 from the cytoplasm to the nucleus of cSCC.In conclusion,our work demonstrates the biological roles of TXNDC9 in cSCC progression and may provide a novel therapeutic target to treat cSCC in the future.

Ultrasonographic identification of lateral femoral cutaneous nerve anatomical variation in persistent meralgia paresthetica:A case report

BACKGROUND Meralgia paresthetica(MP)is an entrapment mononeuropathy of the lateral femoral cutaneous nerve(LFCN).Although structural abnormalities in nerve tissues can be confirmed using ultrasonography,this is not routinely performed.CASE SUMMARY Herein,we present the case of a 52-year-old woman who developed MP after laparoscopic gynecological surgery.The patient was referred to our clinic from an obstetrics and gynecology clinic with symptoms of numbness and a tingling sensation in the left anterolateral thigh,which developed after surgery performed 5 mo earlier.Tests were performed to assess the disease status and determine the underlying causes.Ultrasonographic examination revealed an anatomical variation,where the left LFCN was entrapped within the inguinal ligament.This case suggests that performing ultrasonographic examination before and after surgery in the lithotomy position could help prevent MP.CONCLUSION This case demonstrates the value of ultrasonography in detecting anatomical variation and diagnosing persistent MP.Ultrasonography should be considered an adjunct to electromyography for optimal MP management.Further,this case would help other clinicians determine patient prognosis and decide on targeted treatment strategies.

Primary cutaneous anaplastic large cell lymphoma with overexpressed Ki-67 transitioning into systemic anaplastic large cell lymphoma:A case report

BACKGROUND Primary cutaneous anaplastic large cell lymphoma(PC-ALCL)differs from systemic anaplastic large cell lymphoma(sALCL)in cell biological behavior,clinical features,treatment,and outcome.PC-ALCL has been reported to rarely transition into sALCL,but the underlying mechanism is not clear.Here we report such a case with certain characteristics that shed light on this.CASE SUMMARY Herein,we report a 43-year-old male with symptoms of a skin nodule and histologically confirmed PC-ALCL with high expression of Ki-67.After three months of observation,two skin nodules re-appeared with muscle layer involvement and was histologically confirmed as sALCL.Seventeen months after receiving six cycles of CHOP regimen,the patient had pain in the chest and back,cough,shortness of breath,and night sweats.This was confirmed as relapse of sALCL by immunohistochemistry and several organs,such as the lung were involved as shown by positron emission tomography/computed tomography.After four cycles of DICE plus chidamide regimens followed by auto-hematopoietic stem cell transplantation(ASCT),complete remission(CR)duration was achieved for twelve months while the patient was on maintenance with chidamide(20 mg)pills.CONCLUSION This case had significantly high expression of Ki-67 when diagnosed as PC-ALCL initially and then transitioned into sALCL,which is rare.Auto-ASCT combined with demethylation drugs effectively maintained CR and prolonged progression free survival.

Primary Cutaneous Apocrine Carcinoma of the Neck Involving the Parotid Gland: A Case Report and Review of the Literature

Introduction: Primary cutaneous apocrine carcinoma (PCAC) is a rare skin malignant tumor that originates from areas with a high concentration of apocrine glands. The incidence of PCAC in the neck is relatively low. The age of onset in PCAC ranges from 5 to 70 years old. Clinically, PCAC typically shows up as painless nodules or lumps. In immunohistochemistry, positive expression of CK-7, GCDFP-15, AR, and myoepithelial markers are helpful in the diagnosis of PCAC. This case report pertains to a 59-year-old male of Asian descent. Five years ago, a painless mass was discovered behind his right ear, which grew slowly. This patient was identified as PCAC based on clinical symptoms, pathology, immunohistochemistry, and imaging characteristics. PCAC involved the parotid gland in this case;it is easy to be misdiagnosed as a primary malignant tumor of the parotid gland on imaging. Furthermore, a thorough set of clinical, imaging, pathological, and immunohistochemical examinations must be performed to make a diagnosis because it is challenging to differentiate PCAC from metastatic breast carcinoma. Conclusion: A well-developed multidisciplinary examination is essential because PCAC can be challenging to diagnose and differentiate.

Cutaneaous Myiasis: A Rare Tropical Disease in an 11-Year-Old Girl

Myiasis is the infestation of live human and vertebrate animals with maggots that feed on the host’s dead or living tissue, depending on the life cycle of the fly. It is a rare condition and often misdiagnosed. Tropical and subtropical regions of the world are commonly affected. The aim of this case report is to share this uncommon cutaneous condition with health workers and also remind them of its common symptoms and signs such that its diagnosis is not missed. An 11-year-old girl presented with a nine-day history of itchy rash involving mainly the trunk and upper arms which were found to be cutaneous Myiasis. Cutaneous Myiasis can cause miserly to the affected individual due to its symptoms, yet it can be prevented with good environmental and personal hygiene. Diagnosis and treatment are cheap and effective.

ALK-Rearranged Lung Adenocarcinoma Initially Presenting with Cutaneous Metastases: A Case Report

Only 1% - 12% of patients with lung cancer develop cutaneous metastases. While adenocarcinoma is incredibly common, it is rare for a cutaneous manifestation of the disease to be the initial presenting complaint. Skin manifestations can be difficult to identify and can appear to be deceptively benign, leading to delays in diagnosis and treatment. ALK+ lung cancer specifically has an increased frequency of distant lymph node involvement and lymphangitic carcinomatosis relative to typical EGFR+ lung cancer. Herein we report a case of ALK-rearranged lung adenocarcinoma that initially presented as cutaneous skin metastases to the neck. Such skin lesions should be identified early, and considered as a potential manifestation of an internal malignancy. Given the poor prognosis associated with cutaneous metastases, further diagnostic tests, such as imaging or biopsy, should be done with urgency.

Cardio-facio-cutaneous综合征2例报告并文献复习

目的探讨Cardio-facio-cutaneous综合征(CFC)的临床表型及基因变异特征。方法提取2例CFC患儿及其父母外周血DNA,采用靶向基因高通量测序技术检测变异基因,并运用Sanger测序进行验证。结果 2例患儿均为汉族女性,分别为13个月和7岁半,有内眦赘皮、鼻梁塌平、头发稀疏等相似的颅面部特征,均伴有生长发育迟缓及癫痫发作史。1例心电图有T波变化,P-R间期正常高限;另1例心电图正常。基因检测显示,2例患儿在MAP2K1基因3号外显子上各有一处杂合的错义变异,分别为c.383G>T,p.Gly128Val和c.389A>G,p.Tyr130Cys,且均为新生突变(de novo),均系文献报道过的CFC变异位点。结论 2例为国内首次报道CFC病例,且均为MAP2K1基因突变型。因既往报道CFC患儿大多合并心脏病变,2例患儿均继续随访心脏功能。

Plantar Cornu Cutaneum Associated with Cutaneous Myxoma

Cutaneous horns are rare in black patients probably as a result of the rarity of sun induced associated skin lesions. However reports of these lesions are filtering in from Africa. In this paper we report an unusual case on the sole of the foot in a native African from Nigeria. This is probably the first documentation of the lesion on the sole of the foot in the world literature.

Forecasting the number of zoonotic cutaneous leishmaniasis cases in south of Fars province, Iran using seasonal ARIMA time series method

Objective: To predict the trend of cutaneous leishmaniasis and assess the relationship between the disease trend and weather variables in south of Fars province using Seasonal Autoregressive Integrated Moving Average(SARIMA) model,Methods: The trend of cutaneous leishmaniasis was predicted using Mini tab software and SARIMA model,Besides,information about the disease and weather conditions was collected monthly based on time series design during January 2010 to March 2016,Moreover,various SARIMA models were assessed and the best one was selected,Then,the model's fitness was evaluated based on normality of the residuals' distribution,correspondence between the fitted and real amounts,and calculation of Akaike Information Criteria(AIC) and Bayesian Information Criteria(BIC),Results: The study results indicated that SARIMA model(4,1,4)(0,1,0)(12) in general and SARIMA model(4,1,4)(0,1,1)(12) in below and above 15 years age groups could appropriately predict the disease trend in the study area,Moreover,temperature with a three-month delay(lag3) increased the disease trend,rainfall with a four-month delay(lag4) decreased the disease trend,and rainfall with a nine-month delay(lag9) increased the disease trend,Conclusions: Based on the results,leishmaniasis follows a descending trend in the study area in case drought condition continues,SARIMA models can suitably measure the disease trend,and the disease follows a seasonal trend.

Cutaneous leishmaniasis in Iran: Results from an epidemiological study in urban and rural provinces

Objective: To examine the prevalence and clinical manifestations of cutaneous leishmaniasis(CL) in Iran.Methods: This study was conducted in Iran between 2011 and 2013. Sampling, preparing, developing, and fixing of suspicious skin lesions were completed in healthcare centers in 31 Iranian provinces as well as in the Academic Reference Laboratory and the National Reference Laboratory. The information was then analyzed at the Ministry of Health's Information Management Center of Contagious Diseases.Results: Over a three-year period, the number of people identified with CL was 56 546.The highest incidence was reported in 2011(27.5 per 100 000). Wet CL accounted for 43.7% of cases while 43.3% resulted from sporotrichoid leishmaniasis. The results showed that there was a higher incidence of CL due to Leishmania major(50.2%) than to Leishmania tropica. The results of this study found that the highest incidence of CL had happened respectively in Ilam, Fars and, Khorasan Razavi Provinces between 2011 and 2013.Conclusions: Although the incidence of the disease is declining, CL is still a public health concern and disease control protocols need to be established. Therefore, further studies are needed to identify the vectors, reservoirs, and disease species as well as to develop appropriate disease control strategies.

Phlebotomus papatasi and Meriones libycus as the vector and reservoir host of cutaneous leishmaniasis in Qomrood District,Qom Province,central Iran

Objective:To determine the sand flies species responsible for most transmission of Leishmania major(L major) to human,as well as to determine the main reservoir hosts of the disease. Methods:Sand flies were collected using sticky papers and mounted in Puri’s medium for species identification.Rodents were trapped by live Sherman traps.Both sand flies and rodents were subjected to molecular methods for detection of leishmanial parasite.Results:Phlebotomus papatasi(P.papatasi) was the common species in outdoor and indoor resting places.Employing PCR technique only three specimens of 150 P.papatasi(2%) were found naturally infected by parasites with a band of 350 bp which is equal to the L major parasite.Forty six rodents were captured by Sherman traps and identified.Microscopic investigation on blood smear of the animals for amastigote parasites revealed 1(3.22%) infected Meriones libycus(M.libycus). Infection of this animal to L.major was confirmed by PCR against rDNA loci of the parasite. Conclusions:This is the first molecular report of parasite infection of both vector(P.papatasi) and reservoir(M.libycus) to L major in the region.The results indicated that P.papatasi was the primary vector of the disease and circulating the parasite between human and reservoirs and M. libycus was the most important host reservoir for maintenance of the parasite source in the area.

Bsm I(rs1544410) and Fok I(rs2228570) vitamin D receptor polymorphisms, smoking, and body mass index as risk factors of cutaneous malignant melanoma in northeast Italy

Objective:To investigate whether vitamin D receptor gene(VDR)Bsm I-rs1544410 and Fok I-rs2228570 polymorphisms,smoking duration,and body mass index(BMI)are risk factors for cutaneous melanoma,especially metastatic melanoma.Methods:We studied 120 cutaneous melanoma cases[68 stage I and II non-metastatic melanoma(NMet M)patients,plus 52Stage III and IV metastatic melanoma(Met M)patients],and 120 matching healthy controls from northeast Italy.VDR polymorphisms were measured by restriction fragment length polymorphism analysis.Absence or presence of Bsm I and Fok I restriction sites was denoted by"B"and"F"or by"b"and"f,"respectively.Results:VDR-Bsm I bb genotype was more frequent among Met M(32.7%)than among NMet M cases(13.2%),with odds ratio(OR)=3.18.Comparison of all melanoma patients vs healthy controls showed that the following biomarkers were at risk:≥20 years of smoking(OR=2.43);≥20 years of smoking combined with bb(OR=4.78),Bb+bb(OR=2.30),Ff(OR=3.04),and Ff+ff(OR=3.08);obesity(BMI>30Conclusions:Risk factors for cutaneous Met M include two VDR polymorphisms combined with smoking duration and obesity.Results suggest gene-environment implications in melanoma susceptibility and severity.Future studies in larger cohorts and in subjects with different genetic background are warranted to extend our findings.