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1.
J Am Acad Dermatol ; 90(2): 309-318, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37988042

RESUMO

BACKGROUND: Dermoscopic and reflectance confocal microscopy (RCM) correlations between morphologic groups of melanoma have not yet been described. OBJECTIVE: Describe and compare dermoscopic and RCM features of cutaneous melanomas with histopathological confirmation. METHODS: Single center, retrospective analysis of consecutive melanomas evaluated with RCM (2015-2019). Lesions were clinically classified as typical, nevus-like, amelanotic/nonmelanoma skin cancer (NMSC)-like, seborrheic keratosis (SK)-like and lentigo/lentigo maligna (LM)-like. Presence or absence of common facial and nonfacial melanoma dermoscopic and RCM patterns were recorded. Clusters were compared with typical lesions by multivariate logistic regression. RESULTS: Among 583 melanoma lesions, significant differences between clusters were evident (compared to typical lesions). Observation of dermoscopic features (>50% of lesions) in amelanotic/NMSC-like lesions consistently displayed 3 patterns (atypical network, atypical vascular pattern + regression structures), and nevus-like and SK-like lesions and lentigo/LM-like lesions consistently displayed 2 patterns (atypical network + regression structures, and nonevident follicles + heavy pigmentation intensity). Differences were less evident with RCM, as almost all lesions were consistent with melanoma diagnosis. LIMITATIONS: Small SK-like lesions sample, single RCM analyses (no reproduction of outcome). CONCLUSION: RCM has the potential to augment our ability to consistently and accurately diagnose melanoma independently of clinical and dermoscopic features.


Assuntos
Sarda Melanótica de Hutchinson , Ceratose Seborreica , Lentigo , Melanoma , Nevo Pigmentado , Nevo , Neoplasias Cutâneas , Humanos , Melanoma/patologia , Dermoscopia , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Sarda Melanótica de Hutchinson/patologia , Ceratose Seborreica/diagnóstico , Nevo/diagnóstico por imagem , Nevo Pigmentado/patologia , Lentigo/diagnóstico , Microscopia Confocal , Diagnóstico Diferencial
2.
J Am Acad Dermatol ; 90(5): 994-1001, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38296197

RESUMO

BACKGROUND: Basal cell carcinoma (BCC) is usually diagnosed by clinical and dermatoscopy examination, but diagnostic accuracy may be suboptimal. Reflectance confocal microscopy (RCM) imaging increases skin cancer diagnostic accuracy. OBJECTIVE: To evaluate additional benefit in diagnostic accuracy of handheld RCM in a prospective controlled clinical setting. METHODS: A prospective, multicenter study in 3 skin cancer reference centers in Italy enrolling consecutive lesions with clinical-dermatoscopic suspicion of BCC (ClinicalTrials.gov: NCT04789421). RESULTS: A total of 1005 lesions were included, of which 474 histopathologically confirmed versus 531 diagnosed by clinical-dermatoscopic-RCM correlation, confirmed with 2 years of follow-up. Specifically, 740 were confirmed BCCs. Sensitivity and specificity for dermatoscopy alone was 93.2% (95% CI, 91.2-94.9) and 51.7% (95% CI, 45.5-57.9); positive predictive value was 84.4 (95% CI, 81.7-86.8) and negative predictive value 73.3 (95% CI, 66.3-79.5). Adjunctive RCM reported higher rates: 97.8 (95% CI, 96.5-98.8) sensitivity and 86.8 (95% CI, 82.1-90.6) specificity, with positive predictive value of 95.4 (95% CI, 93.6-96.8) and negative predictive value 93.5 (95% CI, 89.7-96.2). LIMITATIONS: Study conducted in a single country. CONCLUSIONS: Adjunctive handheld RCM assessment of lesions clinically suspicious for BCC permits higher diagnostic accuracy with minimal false negative lesions.


Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Dermoscopia/métodos , Estudos Prospectivos , Carcinoma Basocelular/diagnóstico por imagem , Carcinoma Basocelular/patologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Sensibilidade e Especificidade , Microscopia Confocal/métodos
3.
Exp Dermatol ; 32(4): 348-358, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36394180

RESUMO

Few studies have combined high-resolution, non-invasive imaging, such as standardized clinical images, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), for age-related skin change characterization according to age groups. This study aimed to correlate clinical manifestations of ageing with skin cytoarchitectural background observed with high-resolution, non-invasive imaging according to age-related skin pattern distribution. A set of 140 non-pathological facial skin images were retrospectively retrieved from a research database. Subjects, aged between 20 and 89, were divided into 7 age groups. Clinical features were explored with VISIA, including hyperpigmentation, skin texture, wrinkles, pores and red areas, quantified and expressed as automated absolute scores. Previously described RCM and OCT epidermal and dermal features associated with ageing were investigated. All features were assessed for distribution and correlation among age groups. Significant direct correlations between age and clinical features were proven for cutaneous hyperpigmentation, skin texture, wrinkles and red areas. As age advances, RCM epidermal irregular honeycomb and mottled pigmentation are more frequently observed and collagen is more frequently coarse, huddled and curled, while the epidermis in OCT is thickened and the dermal density is decreased with more disrupted collagen fibres. RCM and OCT feature changes correlate directly and indirectly as well as correlating directly and indirectly with standardized clinical images. Clinical manifestations of ageing correlate with skin cytoarchitectural background observed with RCM and OCT. In conclusion, complimentary information between standardized clinical images and high-resolution, non-invasive imaging will assist in the development of future studies dedicated to skin ageing assessment and treatment effectiveness.


Assuntos
Hiperpigmentação , Envelhecimento da Pele , Neoplasias Cutâneas , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Tomografia de Coerência Óptica/métodos , Estudos Retrospectivos , Pele/diagnóstico por imagem , Pele/patologia , Colágeno , Microscopia Confocal/métodos , Hiperpigmentação/diagnóstico por imagem , Neoplasias Cutâneas/patologia
4.
J Eur Acad Dermatol Venereol ; 37(9): 1718-1730, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37210653

RESUMO

Effective cancer screening detects early-stage tumours, leading to a lower incidence of late-stage disease over time. Dermoscopy is the gold standard for skin cancer diagnosis as diagnostic accuracy is improved compared to naked eye examinations. As melanoma dermoscopic features are often body site specific, awareness of common features according to their location is imperative for improved melanoma diagnostic accuracy. Several criteria have been identified according to the anatomical location of the melanoma. This review provides a comprehensive and contemporary review of dermoscopic melanoma criteria according to specific body sites, including frequently observed melanoma of the head/neck, trunk and limbs and special site melanomas, located on the nail, mucosal and acral region.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Dermoscopia , Melanoma/diagnóstico por imagem , Melanoma/patologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Extremidades/diagnóstico por imagem , Extremidades/patologia , Pele/patologia
5.
J Eur Acad Dermatol Venereol ; 37(11): 2293-2300, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37357442

RESUMO

INTRODUCTION: Dermoscopic predictors of lentigo maligna (LM) and lentigo maligna melanoma (LMM) have been recently reported, but these have not been reported in reflectance confocal microscopy (RCM). OBJECTIVES: (i) To validate dermoscopic predictors for LM/LMM, (ii) to identify RCM patterns in LM and LMM, and (iii) correlations between dermoscopic and RCM features in LM and LMM. MATERIALS AND METHODS: A retrospective, multicentre study of consecutive lesions with histologically proven LM or LMM subtypes of the head and face, with complete sets of dermoscopic and RCM images. RESULTS: A total of 180 lesions were included (n = 40 LMM). Previously reported differential dermoscopic features for LM subtypes were confirmed. Other features significantly associated with LMM diagnosis included irregular hyperpigmented areas, shiny white streaks, atypical vessels and light brown colour at dermoscopy and medusa head-like structures, dermal nests and nucleated cells within the papillae at RCM (p < 0.05). Correlations among LM lesions between dermoscopic and RCM features included brown to-grey dots and atypical cells (epidermis), grey colour and inflammation and obliterated follicles and medusa head-like structures. Among LMM lesions, significant correlations included obliterated follicles with folliculotropism, both irregular hyperpigmented areas and irregular blotches with widespread atypical cell distribution (epidermis), dermal nests and nucleated cells within the papillae (dermis). Irregular blotches were also associated with medusa head-like structures (dermal epidermal junction [DEJ]). CONCLUSIONS: Dermoscopic and RCM features can assist in the in vivo identification of LM and LMM and many are correlated. RCM three-dimensional analysis of skin layers allows the identification of invasive components in the DEJ and dermis.


Assuntos
Sarda Melanótica de Hutchinson , Hiperpigmentação , Neoplasias Cutâneas , Humanos , Sarda Melanótica de Hutchinson/diagnóstico , Neoplasias Cutâneas/patologia , Dermoscopia/métodos , Estudos Retrospectivos , Diferenciação Celular , Microscopia Confocal/métodos
6.
Medicina (Kaunas) ; 60(1)2023 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-38256291

RESUMO

Introduction: Basal cell carcinoma (BCC) represents around 80% of all malignant skin cancers worldwide, constituting a substantial burden on healthcare systems. Due to excellent clearance rates (around 95%), surgery is the current gold-standard treatment. However, surgery is not always possible or preferred by patients. Numerous non-surgical therapies, sometimes combined, have been associated with promising tumor free survival rates (80-90%) in non-melanoma skin cancers (NMSCs). Most research has enrolled superficial basal cell carcinomas (sBCCs), with limited recent studies also involving low-risk nodular BCCs (nBCCs). Given lower efficacy rates compared to surgery, close monitoring during the follow-up period is essential for patients treated with non-surgical therapies. Monitoring with dermoscopy is constrained by low sensitivity rates. Reflectance confocal microscopy (RCM) is more sensitive in monitoring non-surgically treated NMSCs. Case presentation: A 41-year-old woman with a single nBCC relapse following photodynamic therapy (PDT) located on the dorsum of the nose presented to our center. Given the aesthetically sensitive location of the lesion and the patient's preference for a non-surgical approach, a combined treatment of CO2 laser and PDT was prescribed. A superpulsed CO2 laser (power: 0.5-3 W, frequency: 10 Hz, spot size 2 mm) with two PDT sessions (2 weeks apart) were conducted. At 6 weeks follow-up, monitoring performed with RCM revealed a reduction but not eradication of basaloid tumor islands. Another 2 sessions of PDT were recommended. At 3, 12 and 30 months of follow-up, the nasal dorsum area of the previous nBBC lesion was noted to be slightly hypopigmented (observed clinically), with a mild erythematous background (observed by dermoscopy). RCM evaluation confirmed the absence of RCM BCC criteria. The cosmetic outcome was very much improved. Conclusions: Combined CO2 laser and PDT for the treatment of a localized nBCC on the dorsum of the nose of a 41-year-old proved to offer tumor free survival at 30-month follow-up, as monitored with RCM. RCM is useful for the evaluation of non-surgical therapies as it has comparably higher sensitivity than dermoscopy and is especially useful in cases of suspected late recurrence. Further studies are needed to validate ongoing tumor free survival following this combined nonsurgical approach in the treatment of nBCC.


Assuntos
Carcinoma Basocelular , Lasers de Gás , Fotoquimioterapia , Neoplasias Cutâneas , Feminino , Humanos , Adulto , Dióxido de Carbono , Lasers de Gás/uso terapêutico , Carcinoma Basocelular/diagnóstico por imagem , Carcinoma Basocelular/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Microscopia Confocal
7.
Lancet ; 398(10305): 1065-1073, 2021 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-34469763

RESUMO

BACKGROUND: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. METHODS: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. FINDINGS: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86-1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91-1·32; p=0·21). INTERPRETATION: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. FUNDING: UK Medical Research Council and Health Technology Assessment Programme.


Assuntos
Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/estatística & dados numéricos , Stents/estatística & dados numéricos , Acidente Vascular Cerebral/mortalidade , Idoso , Feminino , Humanos , Masculino , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
8.
Exp Dermatol ; 31(7): 1048-1055, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35220636

RESUMO

Differential diagnosis of extrafacial flat pigmented lesions with dermoscopic reticular and/or homogeneous pattern is challenging. Dendritic cells upon reflectance confocal microscopy (RCM) still represent a pitfall. This study aims to determine the role of dendritic cells upon RCM in the epidermis and dermo-epidermal junction (DEJ), together with common RCM features for melanoma and nevi, in dermoscopically equivocal extrafacial flat pigmented lesions. A retrospective evaluation of RCM images of melanocytic extrafacial flat pigmented lesions with reticular and/or homogeneous dermoscopic pattern and with histopathological diagnosis, was performed. A multivariate model of RCM features was used to obtain a score of independent risk factors. A total of 698 lesions were included. Increasing patient age, epidermal dendritic cells, many dendritic cells in the DEJ (>30%) and many (>5/mm2 ) round atypical cells were independent risk factors for melanoma. Edged papillae and melanophages were indicative of nevus. A score based on these features was developed to assist in melanoma differential diagnosis. The RCM observation of abundant (>30%) dendritic cells in the DEJ is highly suggestive of malignity. This independent risk factor should also be considered for improved differential diagnosis of extrafacial melanoma.


Assuntos
Melanoma , Nevo , Neoplasias Cutâneas , Células Dendríticas , Dermoscopia/métodos , Diagnóstico Diferencial , Humanos , Melanoma/patologia , Microscopia Confocal/métodos , Nevo/diagnóstico , Estudos Retrospectivos , Neoplasias Cutâneas/patologia
9.
Exp Dermatol ; 31(7): 1076-1082, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35263469

RESUMO

Hidradenitis suppurativa (HS) is an inflammatory disease characterized by a recurrent-remission trend and clinical lesions that range from asymptomatic to inflamed, deep-seated nodules with scarring and suppuration. The aim of our study was to identify morphologic and vascular features of HS nodules by means of dynamic optical coherence tomography (D-OCT) and to define if they are correlated to patient endotype and risk of disease progression. A set of standardized clinical pictures and D-OCT images were acquired from 57 inflammatory nodules of 40 patients affected by HS. A set of 20 clinical and D-OCT images were acquired from 20 healthy volunteers as a control group. The comparison of D-OCT features among HS and control group was analysed. The correlation between HS patient endotype and D-OCT features of the lesions was calculated. D-OCT enabled to identify vascular and morphological aspects characterizing HS nodular inflammatory lesions. In addition, several D-OCT features were significantly different among distinct disease endotypes. The characterization of HS nodular inflammatory lesions through D-OCT, corresponding to blood vessel dilation and inflammatory associated hyper-vascularization, may have important clinical consequences in the assessment of HS risk of progression, therapeutic decisions and treatment efficacy monitoring.


Assuntos
Hidradenite Supurativa , Hidradenite Supurativa/diagnóstico por imagem , Hidradenite Supurativa/tratamento farmacológico , Humanos , Neovascularização Patológica , Tomografia de Coerência Óptica , Resultado do Tratamento
10.
Exp Dermatol ; 31(6): 890-898, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35102605

RESUMO

BACKGROUND: Basal cell carcinoma can simulate melanoma and specific dermoscopic criteria have not yet been defined in a large cohort. OBJECTIVE: To identify dermoscopic "trump" characteristics for differential diagnosis, identify cluster groups and assess the clinical impact of this study's findings. METHODS: Retrospective, multicentric comparative study of atypical, non-facial basal cell carcinoma (≥1 seven-point checklist criteria) and melanoma (with at least one BCC criteria) at dermoscopy. Observed dermoscopic features were used to develop a proposed score. Lesion clusters were defined with hierarchical analysis. Clinical impact was assessed with a blinded reader study following this study's results. RESULTS: A total of 146 basal cell carcinoma and 76 melanoma were included. Atypical vascular pattern was common to most lesions (74.5%). Twelve trump features were included in the proposed score (sensitivity 94.1% and specificity 79.5%). Cluster analysis identified 3 basal cell carcinoma and 3 melanoma clusters. Findings improved overall diagnostic accuracy and confidence (26.8% and 13.8%, respectively; p < 0.001). CONCLUSIONS: These findings support the notion that atypical vascular pattern should be considered a shared feature of both melanoma and atypical basal cell carcinoma. Our proposed score improves diagnostic accuracy and confidence. Absence of pigmented features was associated with lower diagnostic accuracy and confidence.


Assuntos
Carcinoma Basocelular , Melanoma , Neoplasias Cutâneas , Carcinoma Basocelular/diagnóstico por imagem , Carcinoma Basocelular/patologia , Dermoscopia/métodos , Diagnóstico Diferencial , Humanos , Melanoma/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias Cutâneas/patologia
11.
J Am Acad Dermatol ; 86(5): 1049-1057, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-33823198

RESUMO

BACKGROUND: Digital dermoscopy follow up (DDF) is useful in improving the recognition of melanoma, catching early changes over time, although benign nevi can also show changes. Reflectance confocal microscopy (RCM) improves accuracy in diagnosing melanoma and decreases the number of unnecessary resections. OBJECTIVE: To evaluate dynamic dermoscopic and RCM changes during follow up of equivocal melanocytic lesions and assess the impact of adjunctive RCM to DDF for melanoma diagnosis. METHODS: A retrospective, multicenter study of extrafacial atypical melanocytic lesions excised during follow up was performed. Morphologic changes were evaluated, comparing dermoscopy and RCM baseline and follow-up images. RESULTS: One hundred thirty-seven atypical melanocytic lesions were studied, including 14 melanomas and 123 benign nevi. Significantly greater changes in DDF of atypical network, regression, atypical streaks, and asymmetrical growth as well as in dynamic RCM of atypical cells and dermal-epidermal junction disarray were noted in melanomas. With adjunctive dynamic RCM and major changes at DDF, sensitivity reached 100%, with 40.6% specificity. LIMITATIONS: Selected series of difficult to recognize lesions, with both DDF and dynamic RCM images. CONCLUSION: Adjunctive dynamic RCM improves early melanoma recognition sensitivity.


Assuntos
Melanoma , Nevo de Células Epitelioides e Fusiformes , Neoplasias Cutâneas , Dermoscopia/métodos , Diagnóstico Diferencial , Seguimentos , Humanos , Melanoma/diagnóstico por imagem , Melanoma/cirurgia , Microscopia Confocal/métodos , Nevo de Células Epitelioides e Fusiformes/diagnóstico , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgia
12.
Medicina (Kaunas) ; 58(10)2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36295604

RESUMO

Background and Objectives: Solid-organ transplant recipients (SOTRs) are notably considered at risk for developing cutaneous malignancies. However, most of the existing literature is focused on kidney transplant-related non-melanoma skin cancers (NMSCs). Conflicting data have been published so far on NMSC incidence among liver transplant recipients (LTRs), and whether LTRs really should be considered at lower risk remains controversial. The aim of the present study was to prospectively collect data on the incidence of cutaneous neoplasms in an LTR cohort. Materials and Methods: All LTRs transplanted at the Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit of Modena University Hospital from October 2015 to June 2021 underwent a post-transplant periodic skin check at the Dermatology Unit according to our institutional integrated care pathway. Data on the presence of cutaneous malignant and premalignant lesions were collected at every timepoint. Results: A total of 105 patients were enrolled in the present study. Nearly 15% of the patients developed cutaneous cancerous and/or precancerous lesions during the follow-up period. Almost half of the skin cancerous lesions were basal cell carcinomas. Actinic keratoses (AKs) were observed in six patients. Four patients developed in situ squamous cell carcinomas, and one patient was diagnosed with stage I malignant melanoma. Otherwise, well-established risk factors for the occurrence of skin tumors, such as skin phototype, cumulative sun exposure, and familial history of cutaneous neoplasms, seemed to have no direct impact on skin cancer occurrence in our cohort, as well as an immunosuppressive regimen and the occurrence of non-cutaneous neoplasms. Conclusions: Close dermatological follow-up is crucial for LTRs, and shared protocols of regular skin checks in this particular subset of patients are needed in transplant centers.


Assuntos
Carcinoma Basocelular , Ceratose Actínica , Transplante de Fígado , Dermatopatias , Neoplasias Cutâneas , Humanos , Transplante de Fígado/efeitos adversos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/etiologia , Ceratose Actínica/complicações , Imunossupressores/efeitos adversos , Dermatopatias/complicações , Incidência , Fatores de Risco , Fígado/patologia
13.
Mol Cell Neurosci ; 108: 103538, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32828963

RESUMO

Microglia are the resident innate immune cells of the central nervous system and exert functions of host defense and maintenance of normal tissue homeostasis, along with support of neuronal processes in the healthy brain. Chronic and dysregulated microglial cell activation has increasingly been linked to the status of neuroinflammation underlying many neurodegenerative diseases, including multiple sclerosis (MS). However, the stimulus (or stimuli) and mechanisms by which microglial activation is initiated and maintained MS are still debated. The purpose of our research was to investigate whether the endogenous mitochondrial (mt)-derived damage-associated molecular patterns (MTDs) mtDNA, N-formyl peptides and cardiolipin (CL) contribute to these phenomena. We characterized the effects of the abovementioned MTDs on microglia activation in vitro (i.e. using HMC3 cells) by evaluating the expression of gene coding for proteins involved in their binding and coupled to downstream signaling pathways, the up-regulation of markers of activation on the cell surface and the production of pro-inflammatory cytokines and reactive oxygen species. At the transcriptional level, significant variations in the mRNA relative expression of five of eleven selected genes were observed in response to stimulation. No changes in activation of antigenic profile or functional properties of HMC3 cells were observed; there was no up-regulation of HLA-DR expression or increased secretion of tumor necrosis factor-α and interleukin-6. However, after stimulation with mtDNA and CL, an increase in cellular oxidative stress, but not in the mt ROS O2-, compared to control cells, were observed. There were no effects on cell viability. Overall, our data suggest that MTDs could cause a failure in microglial activation toward a pro-inflammatory phenotype, possibly triggering an endogenous regulatory mechanism for the resolution of neuroinflammation. This could open a door for the development of drugs selectively targeting microglia and modulating its functionality to treat MS and/or other neurodegenerative conditions in which MTDs have a pathogenic relevance.


Assuntos
Microglia/metabolismo , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Cardiolipinas/metabolismo , Linhagem Celular , Antígenos HLA-DR/genética , Antígenos HLA-DR/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , Microglia/efeitos dos fármacos , Estresse Oxidativo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
14.
J Dtsch Dermatol Ges ; 19(2): 223-229, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33166059

RESUMO

BACKGROUND: Lentigo maligna (LM) and lentigo maligna-melanoma (LMM) are histotypes of melanoma arising in skin with cumulative solar radiation damage. The extension of atypical melanocytes to the hair follicle (folliculotropism) is a histopathological feature of LM/LMM. Its role has not been totally clarified, but it may be correlated to treatment response in LM or to progression in LMM. OBJECTIVE: This retrospective, multicentric study aims to identify dermatoscopic features associated with folliculotropism in LMs/LMMs. PATIENTS AND METHODS: We analyzed cases of head and neck LMs/LMMs diagnosed between 2005-2014 at Melanoma Units, University of Bologna/Modena/Florence/Siena (Italy), Nice (France): 25 LMs and 73 LMMs were included. RESULTS: Grey circles (44 %) indicated an isthmic/bulb level of involvement, which were completely absent in the infundibular LM lesions (P = 0.041). In the group of LMMs, light/dark brown pseudonetwork and light brown structureless areas were an indicator of diffuse distribution of malignant melanocytes in the follicular units (P < 0.001 and P = 0.001, respectively), while grey circles indicated focal or diffuse distribution (P < 0.001). CONCLUSIONS: A better understanding of the extension of malignant melanocytes is helpful, aiding clinicians in their decision to perform a radical excision or obtaining a biopsy in the most invasive area of the lesion, which includes potential folliculotropism.


Assuntos
Sarda Melanótica de Hutchinson , Melanoma , Neoplasias Cutâneas , Humanos , Itália , Estudos Retrospectivos
15.
Exp Dermatol ; 29(10): 945-952, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32748489

RESUMO

BACKGROUND: In vivo reflectance confocal microscopy (RCM) increases diagnostic accuracy for melanoma diagnosis when combined with dermoscopy. In patients with multiple atypical nevi, a comparative dermoscopic approach improves melanoma recognition and saves unnecessary excision. The performance of a comparative approach combining dermoscopy and RCM has not been yet investigated. OBJECTIVE: To validate a comparative dermoscopic + RCM approach according to melanoma diagnostic accuracy in patients with multiple atypical nevi. METHODS: Consecutive patients undergoing RCM examination for ≥3 atypical melanocytic lesions, assessed with a dermoscopic + RCM comparative approach in a real-life setting, from July 2012 to April 2018 at a single centre, were enrolled. Dermoscopic and dermoscopic + RCM morphologic approaches were retrospectively applied by evaluating revisited 7-point checklist, RCM and Delphi scores for each enrolled lesion. Comparative dermoscopic and dermoscopic + RCM approaches were subsequently used. For each approach, lesions were classified as non-suspicious (long-term follow-up) or suspicious (short-term follow-up or excision) and diagnostic accuracy for melanoma diagnosis was assessed. RESULTS: Diagnostic accuracy progressively increased comparing morphologic to comparative approaches, and comparing dermoscopic to dermoscopic + RCM approaches. The retrospective comparative dermoscopic + RCM approach revealed the largest area under the curve (0.84; 95%CI:0.79-0.89; P < .001) and the lowest number needed to excise (5.7). Furthermore, this approach had the highest specificity (67.6%) and sensitivity (100%) levels, which were similar to those verified in the real-life setting. The main study limitations are the retrospective design and high-risk patient inclusion only. CONCLUSIONS: Comparative dermoscopic + RCM approach increases melanoma diagnostic accuracy, reducing unnecessary excision without missing melanomas.


Assuntos
Melanoma/diagnóstico por imagem , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Nevo/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Adulto , Área Sob a Curva , Dermoscopia , Feminino , Humanos , Microscopia Intravital , Masculino , Melanoma/patologia , Microscopia Confocal , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/patologia , Nevo/patologia , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Neoplasias Cutâneas/patologia
16.
Dermatol Ther ; 33(6): e14076, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32713163

RESUMO

Despite an increasing request for skin rejuvenation above the knee, very few treatment options have been reported in literature. To evaluate the efficacy and safety of 1:4 hyperdiluted calcium hydroxylapatite (CaHA) in the treatment of skin laxity and dimples of the skin above the knees. A retrospective evaluation of hyperdiluted CaHA treatment for skin laxity and dimples above the knee was performed. Efficacy was classified as blinded evaluation of pre (T0) and 3-month post-treatment (T1) photographs by three investigators according to the validated knee cellulite severity score (KCSS) and patient satisfaction. Safety was evaluated through pain scores and adverse events evaluation. A significant reduction of KCSS at T1, as compared to T0, mainly in subjects with lower KCSS at T0, was observed (P < .05). All blinded assessments resulted in a correct identification of T0 and T1 pictures and evaluations of all investigators were found to be consistent and reliable. All patients were satisfied. Only minor adverse events (swelling, erythema, bruising, and skin irregularities) were reported, lasting 2 to 3 weeks after treatment. Our preliminary results highlight the efficacy and safety of hyperdiluted CaHA in the treatment of skin laxity and cellulite above the knees.


Assuntos
Celulite , Técnicas Cosméticas , Envelhecimento da Pele , Cálcio , Técnicas Cosméticas/efeitos adversos , Durapatita , Humanos , Satisfação do Paciente , Projetos Piloto , Estudos Retrospectivos
17.
Skin Res Technol ; 26(6): 779-787, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32207198

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory disease. Recently, dupilumab was approved for moderate-to-severe AD. D-OCT is a noninvasive tool for the characterization of skin diseases. OBJECTIVE: To describe the changes observed with D-OCT in lesional and clinically healthy skin of patients with refractory severe AD under dupilumab treatment. METHODS: We analyzed AD lesions and healthy skin by D-OCT. Clinical scores of AD severity were assessed at baseline (T0) and after 1 and 3 months of treatment (T1, T2). Descriptive statistics, chi-square test, and t test were used to compare the analyzed parameters over time and between AD lesions and clinically healthy skin. RESULTS: At baseline, average EASI was 45.7. During the follow-up, EASI75 and EASI90 were achieved in 57% and 36% of patients at T1 and 100% and 86% of patients at T2, respectively. Lesional skin D-OCT parameters related to epidermal remodeling and inflammation evidenced a significant improvement after 1 month of treatment. In clinically healthy skin, D-OCT parameters improved significantly after 3 months of treatment, especially for collagen remodeling and inflammation. CONCLUSION: The study demonstrates that the clinical improvement of severe AD patients under dupilumab treatment is correlated with specific D-OCT changes of patients' lesional and clinically healthy skin.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Dermatite Atópica , Tomografia de Coerência Óptica , Dermatite Atópica/diagnóstico por imagem , Dermatite Atópica/tratamento farmacológico , Humanos , Resultado do Tratamento
18.
Exp Dermatol ; 28(11): 1321-1327, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31520496

RESUMO

BACKGROUND: The melanocortin 1 receptor (MC1R) gene is one of the major determinants of skin pigmentation. It is a highly polymorphic gene and some of its polymorphisms have been related to specific skin phenotypes, increased risk of skin cancers and skin photoageing. Currently, its contribution to changes in dermal features in photo-exposed skin is unknown. OBJECTIVE: The main objective of this study is to evaluate the potential correlation between MC1R status and specific healthy photo-exposed skin characteristics. MATERIALS AND METHODS: Skin facial features were estimated by evaluation with standard digital photography with automated features count, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in 100 healthy women. Skin of the forearms was used as a control. RESULTS: The study found an association between RHC MC1R polymorphisms and dermal features in photo-exposed areas being represented by increased vessel density and pixel density in OCT (P = .025 and P = .001, respectively) and increased coarse collagen in RCM (P = .034), as compared to non-RHC subjects. To our knowledge this is previously unreported. Additionally, previously reported correlations between light hair colour and pigmented spots with MC1R RHC polymorphisms have been confirmed. CONCLUSIONS: Our results suggest the role of RHC MC1R variants in dermal variations of facial skin, as compared to non-RHC variants. To our knowledge this is previously unreported.


Assuntos
Receptor Tipo 1 de Melanocortina/genética , Envelhecimento da Pele/genética , Adulto , Feminino , Humanos , Microscopia Confocal , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia de Coerência Óptica
19.
Exp Dermatol ; 28(3): 254-260, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30636079

RESUMO

Cutaneous melanoma (CM) is one of the most prevalent skin cancers, which lacks both a prognostic marker and a specific and lasting treatment, due to the complexity of the disease and heterogeneity of patients. Reflectance confocal microscopy (RCM) in vivo analysis is a versatile approach offering immediate morphological information, enabling the identification of four primary cutaneous RCM CM types. Whether RCM CM types are associated with a specific protein and molecular genetic profiles at the tissue level remains unclear. The current pilot study was designed to identify potential correlations between RCM CM types and specific biological characteristics, combining immunohistochemistry (IHC) and molecular analyses. Eighty primary CMs evaluated at patient bedside with RCM (type 1 [19, 24%], type 2 [12, 15%], type 3 [7, 9%] and type 4 [42, 52%]) were retrospectively evaluated by IHC stains (CD271, CD20, CD31, cyclin D1), fluorescence in situ hybridization FISH for MYC gain and CDKN2A loss and molecular analysis for somatic mutations (BRAF, NRAS and KIT). RCM CM types correlated with markers of stemness property, density of intra-tumoral lymphocytic B infiltrate and cyclin D1 expression, while no significant association was found with blood vessel density nor molecular findings. RCM CM types show a different marker profile expression, suggestive of a progression and an increase in aggressiveness, according to RCM morphologies.


Assuntos
Melanoma/diagnóstico por imagem , Melanoma/genética , Microscopia Confocal/métodos , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Ciclina D1/metabolismo , Dermatologia , Feminino , GTP Fosfo-Hidrolases/genética , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mutação , Invasividade Neoplásica , Projetos Piloto , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-kit/genética , Estudos Retrospectivos , Melanoma Maligno Cutâneo
20.
BJU Int ; 124(3): 469-476, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30908852

RESUMO

OBJECTIVE: To report the first application of ex vivo fluorescence confocal microscopy (FCM) - a novel optical technology that is capable of providing fast microscopic imaging of unfixed tissue specimens- in the urological field assessing its diagnostic accuracy for non neoplastic and cancerous prostate tissue (prostatic adenocarcinoma) compared to the 'gold standard' histopathological diagnoses. PATIENTS AND METHODS: In all, 89 specimens from 13 patients with clinically localised prostate cancer were enrolled into the study. All patients underwent robot-assisted laparoscopic radical prostatectomy with fresh prostatic tissue biopsies taken at the end of each intervention using an 18-G biopsy punch. Specimens were randomly assigned to the three collaborating pathologists for evaluation. Intra- and inter-observer agreement was tested by the means of Cohen's κ. The diagnostic performance was evaluated on receiver operating characteristic curve analysis. RESULTS: The overall diagnostic agreement between FCM and histopathological diagnoses was substantial with a 91% correct diagnosis (κ = 0.75) and an area under the curve of 0.884 (95% confidence interval 0.840-0.920), 83.33% sensitivity, and 93.53% specificity. CONCLUSION: FCM seems to be a promising tool for enhanced specimens' reporting performance, given its simple application and very rapid microscopic image generation (<5 min/specimen). This technique may potentially be used for intraoperative pathological specimens' analysis.


Assuntos
Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Próstata , Prostatectomia/métodos , Neoplasias da Próstata , Idoso , Biópsia , Humanos , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/patologia , Próstata/cirurgia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Curva ROC , Procedimentos Cirúrgicos Robóticos/métodos
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