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1.
PLoS One ; 14(5): e0214714, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31042723

RESUMO

Solar lentigo, benign lesions which mostly appear on chronically, sun-exposed surfaces, are associated with ageing. Patients are increasingly requesting a more uniform skin texture, especially for hands. Treatment options include dermoabrasion, intense pulsed light, cryotherapy, peelings, and laser therapy. Topical compounds can be employed, in alternative or associated with dermatologic procedures. The current study was designed to evaluate solar lentigo hyperpigmentation, skin architecture and clinician and patient assessments comparing a dermocosmetic lightening product (active) with a moisturizing product (control) according to clinical, digital and subjective analyses in 72 lesions over 12-month follow up period. Statistically significant differences were observed between the lesions treated with the active compared to the control in terms of papillary brightness (p = 0.03) and contrast (p = 0.03), and in the limitation of dermal-epidermal junction destructuring (p = 0.03) according to dermal-epidermal junction destructuring score at Reflectance Confocal Microscopy. Luminance (p = 0.04) and redness (p = 0.03) were improved at color analysis, and physician and patient evaluations favored the active in efficacy and patient satisfaction investigations. The dermocosmetic lightening product utilized in the current study proved to be more effective, according to clinical, digital and subjective analyses in reducing lesion hyperpigmentation, stabilizing the lesion skin architecture and increasing patient satisfaction compared to the control in a cohort of 36 subjects, over a 12-month period. Beside demonstrating the efficacy of this topical lightening product, we propose a "destructuring score", which improves the robustness of solar lentigo's evaluation, and can be used in future studies to standardize the quantitative comparisons of different treatment options.


Assuntos
Mãos/patologia , Lentigo/tratamento farmacológico , Preparações Clareadoras de Pele/administração & dosagem , Administração Tópica , Idoso , Feminino , Mãos/diagnóstico por imagem , Humanos , Itália , Lentigo/diagnóstico por imagem , Lentigo/patologia , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Satisfação do Paciente , Preparações Clareadoras de Pele/uso terapêutico , Resultado do Tratamento
2.
Hautarzt ; 70(7): 506-513, 2019 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-31076812

RESUMO

Solitary congenital or early apparent pigmented macules are usually without relevance; however, when multiple, extensive or in a patterned arrangement, they are not uncommonly the first sign of an underlying genetic syndrome. The present article gives an overview on the clinical significance of multiple café-au-lait macules, multiple lentigines and pigmentary mosaicism and discusses the differential diagnosis of associated syndromes. Early diagnosis with the essential contribution of the dermatologist is not only important for genetic counseling but can also contribute to avoidance of sometimes life-threatening complications.


Assuntos
Manchas Café com Leite , Hiperpigmentação , Lentigo , Anormalidades da Pele/genética , Manchas Café com Leite/diagnóstico , Manchas Café com Leite/genética , Diagnóstico Diferencial , Aconselhamento Genético , Doenças Genéticas Inatas , Humanos , Hiperpigmentação/diagnóstico , Hiperpigmentação/genética , Lentigo/genética , Lentigo/patologia , Mosaicismo , Síndrome
3.
J Surg Oncol ; 119(8): 1060-1069, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30883783

RESUMO

BACKGROUND: The prognostic benefit of sentinel lymph node biopsy (SLNB) and factors predictive of survival specifically in patients with acral lentiginous melanoma (ALM) are unknown. METHODS: The SEER database was queried for ALM cases that underwent SLNB from 1998 to 2013. Clinicopathological factors were correlated with SLN status, overall survival (OS), and melanoma-specific survival (MSS). RESULTS: Median age for the 753 ALM study patients was 65 years, and 48.2% were male. Median thickness was 2 mm with 38.1% of cases having ulceration. SLN metastases were detected in 194 of 753 cases (25.7%). Multivariable analysis showed that thickness, Clark level IV-V, and ulceration significantly predicted for SLN metastasis (P < 0.05). For patients with positive SLN, 5-year OS and MSS were significantly worse at 48.1% and 58.9%, respectively, compared with 78.7% and 88.5%, respectively, for patients with negative SLN (P < 0.0001). On multivariable analyses, older age, male gender, increasing thickness, ulceration, and a positive SLN significantly predicted for worse OS and MSS (all P < 0.05). CONCLUSION: This study confirms the important role of SLNB in ALM. SLN metastases are seen in 25.7% of ALM cases, providing significant prognostic information. In addition, thickness, ulceration status, and SLNB status significantly predict survival in patients with ALM.


Assuntos
Melanoma/mortalidade , Melanoma/patologia , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Linfonodo Sentinela/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Idoso , Feminino , Humanos , Lentigo/mortalidade , Lentigo/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Programa de SEER , Estados Unidos/epidemiologia
5.
Eur J Dermatol ; 29(1): 2-5, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30827948

RESUMO

The co-existence of papular nevus spilus (PNS) and ipsilateral extracutaneous abnormalities involving peripheral nerves of the skin or muscles was originally described as "speckled lentiginous nevus syndrome". To avoid confusion with macular nevus spilus, the condition was recently re-named "papular nevus spilus syndrome". In addition to 14 published cases, we identified six new cases via a search of the worldwide literature. New diagnostic criteria are suggested: (1) presence of a PNS; (2) presence of a neurological or skeletal abnormality which is usually ipsilateral to the nevus; and (3) absence of a nevus sebaceus. According to current knowledge, PNS syndrome is a rather rarely occurring, sporadic disorder that can be considered to be part of a spectrum of mosaic RASopathies, which includes isolated PNS, isolated nevus sebaceus, PNS syndrome, Schimmelpenning syndrome, and phacomatosis pigmentokeratotica.


Assuntos
Nevo Pigmentado/patologia , Neoplasias Cutâneas/patologia , Diagnóstico Diferencial , Humanos , Lentigo/patologia , Mosaicismo , Síndromes Neurocutâneas/genética , Síndromes Neurocutâneas/patologia , Nevo Pigmentado/classificação , Nevo Pigmentado/genética , Nevo Sebáceo de Jadassohn/genética , Nevo Sebáceo de Jadassohn/patologia , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/genética
7.
Clin Transl Oncol ; 21(9): 1127-1134, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30778854

RESUMO

PURPOSE: This study aims to evaluate the association between composition of tumor-infiltrating lymphocytes (TIL) and expression of p16 in acral lentiginous melanoma (ALM), and their impact on prognosis. MATERIALS AND METHODS: A cohort of 148 surgical pathology specimens of ALM was studied. TIL were evaluated by immunohistochemical detection of CD3 and CD8, along with CD20, CD4, CD68, and CD163 in a subset of 43 cases. p16 protein expression was also investigated in all the cases. RESULTS: The median age was 66 years, median Breslow thickness was 6.0 mm, grade III TIL was found in 28.4% and lymph nodes were involved in 54.2%. Breslow thickness (p < 0.001), stage I-II (p < 0.001), negative lymph nodes (p < 0.001) and < 10% p16 (p = 0.01) were associated with longer survival. Grade III of TIL was associated with thinner Breslow thickness (p = 0.008) and lower mitosis (p = 0.047). A higher density of CD3 TIL was associated with male gender (p = 0.008), thinner Breslow thickness (p = 0.047), negative lymph node (p = 0.031), early stage (p = 0.046), and p16 nuclear expression of > 10% (p = 0.045). Higher CD8 TIL was associated with > p16 (p = 0.03). Survival analysis found that longer survival had a trend to be associated with high TIL (p = 0.090). Levels of CD3+ and CD8+ cells were correlated with those of CD4+, CD20+, CD68+ and CD163+ immune cells. CONCLUSIONS: Higher levels of TIL tend to be associated with better overall survival in ALM. Loss of expression of p16 is associated with lower levels of CD3+ and CD8+ TIL, indicating a probable relationship between p16 and TIL immune response in ALM .


Assuntos
Biomarcadores Tumorais/análise , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Lentigo/patologia , Linfócitos do Interstício Tumoral/imunologia , Melanoma/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Lentigo/imunologia , Lentigo/metabolismo , Masculino , Melanoma/imunologia , Melanoma/metabolismo , Pessoa de Meia-Idade , Prognóstico , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/metabolismo , Taxa de Sobrevida
8.
Dermatol Online J ; 25(1)2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30710906

RESUMO

Development of lentigines in areas of resolving psoriatic plaques is a rare phenomenon that has been reported following various treatment modalities including phototherapy, topical therapies, and biologics. Although the exact mechanism is unknown, evidence suggests that the cause may be multifactorial, with factors such as skin type, sun exposure, inflammation, and immunologic cytokines all playing a potential role. Herein, we present the first reported case of a patient developing multiple lentigines following treatment of psoriasis with the IL-23 inhibitor guselkumab.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Lentigo/patologia , Psoríase/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados , Humanos , Masculino
11.
Clin Exp Dermatol ; 44(4): 418-421, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30280421

RESUMO

Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours arising in the gastrointestinal tract. Early detection, before metastasis occurs, is important as complete surgical excision achieves cure. Approximately 85% of GISTs are associated with mutations in the KIT gene, and although the majority of GISTs are sporadic, familial GISTs have been identified. Several families with multiple GIST tumours have also been described with various cutaneous findings including hyperpigmentation, multiple lentigines, vitiligo and urticaria pigmentosa. We discuss a 6-year-old boy who presented with an unusual pattern of hyperpigmentation in association with a family history of GIST. A causative KIT mutation was identified in DNA from the pigmented skin and from the resected GIST, and the patient was referred to the Paediatric Gastroenterology department for GIST screening. The term 'GIST cutaneous hyperpigmentation disease' has been suggested previously for the association of familial GIST with cutaneous hyperpigmentation caused by a germline KIT mutation.


Assuntos
Tumores do Estroma Gastrointestinal/genética , Hiperpigmentação/genética , Proteínas Proto-Oncogênicas c-kit/genética , Criança , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/patologia , Mutação em Linhagem Germinativa/genética , Humanos , Hiperpigmentação/diagnóstico , Hiperpigmentação/patologia , Lentigo/patologia , Masculino , Programas de Rastreamento/normas , Mutação , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/patologia , Urticaria Pigmentosa/patologia , Vitiligo/patologia
15.
Theranostics ; 8(17): 4620-4632, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30279727

RESUMO

Cutaneous ageing is an important extrinsic process that modifies the pigmentary system. Because cellular senescence is a fundamental ageing mechanism, we examined the role of senescent cells in ageing pigmentation. Methods: Biopsies obtained from senile lentigo and perilesional normal skin were assayed for a marker of cellular senescence, p16INK4A. To determine the secretory phenotypes of senescent fibroblasts, we performed microarray, RNA sequencing and methylation array analyses in senile lentigo and senescent fibroblasts. To further investigate the impact of senescent cells on ageing-related pigmentation, an intervention that targeted senescent cells using radiofrequency was performed. Results:In vivo, senescent fibroblasts accumulated at the sites of age-related pigmentation. Phenotype switching of the cells resulted in the repression of stromal-derived factor 1 (SDF1) by promoter methylation. SDF1 induced melanocyte differentiation via stromal-epithelial interactions, ultimately driving skin pigmentation. Furthermore, the elimination of senescent fibroblasts from pigmented skin using radiofrequency was accompanied by skin lightening, rendering it a potential target for treatment. Conclusion: Aged pigmented skin contains an increasing proportion of senescent fibroblasts. Cells with phenotype switching exhibited a loss of SDF1, which stimulates the melanogenic process and thereby contributes to aging pigmentation. These data may promote the development of new therapeutic paradigms, such as a stroma-targeting therapy for pigmentary disorders.


Assuntos
Envelhecimento/patologia , Diferenciação Celular , Senescência Celular , Fibroblastos/patologia , Lentigo/patologia , Lentigo/fisiopatologia , Melanócitos/fisiologia , Biópsia , Comunicação Celular , Quimiocina CXCL12/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/genética , Regulação para Baixo , Células Epiteliais/fisiologia , Feminino , Perfilação da Expressão Gênica , Humanos , Lentigo/terapia , Análise em Microsséries , Pessoa de Meia-Idade , Pigmentação , Pigmentos Biológicos/metabolismo , Terapia por Radiofrequência/métodos , Análise de Sequência de RNA , Pele/patologia , Células Estromais/fisiologia
18.
J Invest Dermatol ; 138(8): 1825-1833, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29510193

RESUMO

Fibroblast-derived melanogenic paracrine mediators are known to play a role in melanogenesis. To investigate the effect of CCN1 (also called CYR61 or cysteine-rich 61) on melanogenesis, normal human epidermal melanocytes were treated with recombinant CCN1 protein. Our findings show that CCN1 activates melanogenesis through promoting melanosome maturation and up-regulation of MITF, TRP-1, and tyrosinase via the integrin α6ß1, p38 MAPK, and ERK signaling pathways. Furthermore, we found that UVB irradiation stimulates the secretion of CCN1 from normal human dermal fibroblasts, and CCN1 knockdown in fibroblasts attenuates melanogenesis in melanocyte-fibroblast co-culture system. Moreover, using immunohistochemistry and immunofluorescence staining, we discovered that CCN1 is overexpressed in the dermis of both solar lentigines and Riehl's melanosis lesions. These findings suggest that CCN1 is a fibroblast-derived melanogenic paracrine mediator that is secreted under UVB irradiation, and it may play an important role in the development of hyperpigmentation diseases such as Riehl's melanosis.


Assuntos
Proteína Rica em Cisteína 61/metabolismo , Fibroblastos/metabolismo , Lentigo/patologia , Sistema de Sinalização das MAP Quinases , Melaninas/biossíntese , Melanócitos/metabolismo , Adulto , Células Cultivadas , Proteína Rica em Cisteína 61/genética , Derme/patologia , Derme/efeitos da radiação , Epiderme/metabolismo , Feminino , Fibroblastos/efeitos da radiação , Técnicas de Silenciamento de Genes , Humanos , Integrina alfa6beta1/metabolismo , Lentigo/etiologia , Masculino , Pessoa de Meia-Idade , Raios Ultravioleta , Regulação para Cima
19.
J Am Acad Dermatol ; 79(2): 327-336.e2, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29601937

RESUMO

BACKGROUND: Most subungual melanocytic lesions in children are benign, but some are difficult to classify due to prominent lentiginous growth and high-grade cytologic atypia. OBJECTIVE: To characterize the clinicopathologic features of these rare lesions. METHODS: Subungual atypical lentiginous melanocytic proliferations from patients <20 years of age were collected for clinical and histopathologic review. Fluorescence in situ hybridization (FISH) was performed when possible. RESULTS: Eleven patients aged 2-19 years had expanding or darkening longitudinal pigmented streak(s) with or without Hutchinson sign. Microscopically, all revealed predominantly single-cell growth, pagetoid scatter, and poor circumscription. Eight (73%) cases showed focal or poor nesting, and 3 (27%) demonstrated confluence. Nuclear enlargement, hyperchromasia, and angulation were present in 8 (73%) cases, 7 (64%) cases, and 6 (55%) cases, respectively. One of 4 cases tested by FISH was positive. Three lesions recurred locally without other adverse outcome. LIMITATIONS: Small sample size and short clinical follow-up. Two cases were examined in partial biopsies only. CONCLUSION: Some subungual melanocytic lesions in children and adolescents are histologically indistinguishable from adult subungual melanoma in situ. While the biologic potential remains elusive, FISH might aid in risk stratification. Awareness of this rare group of lesions is crucial for facilitating future investigation into its biologic behavior.


Assuntos
Lentigo/patologia , Melanócitos/patologia , Doenças da Unha/patologia , Adolescente , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Sarda Melanótica de Hutchinson/diagnóstico , Sarda Melanótica de Hutchinson/genética , Sarda Melanótica de Hutchinson/patologia , Sarda Melanótica de Hutchinson/cirurgia , Hibridização in Situ Fluorescente , Lentigo/diagnóstico , Lentigo/genética , Lentigo/cirurgia , Masculino , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patologia , Melanoma/cirurgia , Doenças da Unha/diagnóstico , Doenças da Unha/genética , Doenças da Unha/cirurgia , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Adulto Jovem
20.
J Invest Dermatol ; 138(7): 1529-1538, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29428356

RESUMO

We tested the use of a deep learning algorithm to classify the clinical images of 12 skin diseases-basal cell carcinoma, squamous cell carcinoma, intraepithelial carcinoma, actinic keratosis, seborrheic keratosis, malignant melanoma, melanocytic nevus, lentigo, pyogenic granuloma, hemangioma, dermatofibroma, and wart. The convolutional neural network (Microsoft ResNet-152 model; Microsoft Research Asia, Beijing, China) was fine-tuned with images from the training portion of the Asan dataset, MED-NODE dataset, and atlas site images (19,398 images in total). The trained model was validated with the testing portion of the Asan, Hallym and Edinburgh datasets. With the Asan dataset, the area under the curve for the diagnosis of basal cell carcinoma, squamous cell carcinoma, intraepithelial carcinoma, and melanoma was 0.96 ± 0.01, 0.83 ± 0.01, 0.82 ± 0.02, and 0.96 ± 0.00, respectively. With the Edinburgh dataset, the area under the curve for the corresponding diseases was 0.90 ± 0.01, 0.91 ± 0.01, 0.83 ± 0.01, and 0.88 ± 0.01, respectively. With the Hallym dataset, the sensitivity for basal cell carcinoma diagnosis was 87.1% ± 6.0%. The tested algorithm performance with 480 Asan and Edinburgh images was comparable to that of 16 dermatologists. To improve the performance of convolutional neural network, additional images with a broader range of ages and ethnicities should be collected.


Assuntos
Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Pele/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biópsia , Conjuntos de Dados como Assunto , Diagnóstico Diferencial , Reações Falso-Positivas , Feminino , Granuloma Piogênico/diagnóstico por imagem , Granuloma Piogênico/patologia , Humanos , Ceratose Actínica/diagnóstico por imagem , Ceratose Actínica/patologia , Ceratose Seborreica/diagnóstico por imagem , Ceratose Seborreica/patologia , Lentigo/diagnóstico por imagem , Lentigo/patologia , Masculino , Pessoa de Meia-Idade , Fotografação , Valor Preditivo dos Testes , Curva ROC , Pele/patologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Software , Verrugas/diagnóstico por imagem , Verrugas/patologia , Adulto Jovem
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