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1.
Clin Dermatol ; 42(1): 38-45, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37866411

RESUMO

A choroidal nevus is a common intraocular tumor in the United States, found in approximately 5% of Caucasian adults. The three main risks of melanocytic choroidal nevus include vision loss from a subfoveal nevus, development of subretinal fluid, and transformation of nevus into melanoma, a malignant counterpart. We explore clinical risk factors that predict benign melanocytic choroidal nevus transformation into a malignant choroidal melanoma. Based on a large analysis of 2,355 cases that were monitored longitudinally using multimodal imaging, the most recent list of clinical features includes tumor Thickness greater than 2 mm on ultrasonography, subretinal Fluid on optical coherence tomography, Symptomatic vision loss 20/50 or worse, Orange pigment on fundus autofluorescence, Melanoma hollow on ultrasonography, and DIaMeter greater than 5 mm on fundus photography. These factors are remembered with a mnemonic of the capital letters TFSOM-DIM for "To Find Small Ocular Melanoma Doing Imaging." Analysis of these factors demonstrated a Kaplan-Meier mean five-year risk of 1% with no risk factors, 11% with any one factor, 22% with any two factors, 34% with any three factors, 51% with any four factors, and 55% with any five factors. There was no patient with six risk factors. Of those with combinations of four risk factors, six of 15 combinations yielded a 70%-100% rate of transformation; of those with combinations of five risk factors, two of five combinations yielded a 70%-100% rate of transformation. Choroidal nevus carries a risk for evolving into melanoma, and understanding of clinical and imaging features predictive of this outcome is highly important.


Assuntos
Neoplasias da Coroide , Melanoma , Nevo Pigmentado , Nevo , Neoplasias Cutâneas , Adulto , Humanos , Melanoma/etiologia , Melanoma/patologia , Nevo Pigmentado/diagnóstico por imagem , Nevo Pigmentado/patologia , Neoplasias da Coroide/diagnóstico por imagem , Neoplasias da Coroide/patologia , Nevo/diagnóstico por imagem , Fatores de Risco , Neoplasias Cutâneas/etiologia , Estudos Retrospectivos
2.
Clin Dermatol ; 42(1): 62-70, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37865279

RESUMO

Primary uveal melanoma is rare and affects approximately 8,000 persons per year worldwide. This malignancy can involve the iris, ciliary body, and choroid. Of these three structures, the iris is the least commonly affected site, representing only 4% of all uveal melanomas. Iris melanoma can arise from iris melanocytic nevus, iris melanocytosis, or de novo. In a longitudinal study of 1,611 patients with iris nevus, transformation into melanoma, using Kaplan-Meier estimates, was found in 2.6% by five years and in 4.1% by 10 years. The factors that predicted growth of iris melanocytic nevus into melanoma are denoted by a letter (ABCDEF) guide: A for age ≤40 years old at presentation (hazard ratio [HR] = 3, P = .01), B for blood (hyphema) (HR = 9, P < .0004), C for clock hour of tumor inferiorly (tumor location) (HR = 9, P = .03), D for diffuse flat tumor configuration (HR = 14, P = .02), E for ectropion uveae (HR = 4, P = .002), and F for feathery ill-defined margins (HR = 3, P = .02). At diagnosis, iris melanoma has a mean cross-sectional diameter of 5.5 mm and thickness of 2.1 mm, often with tumor seeding (28%) and secondary glaucoma (35%). We provide a comprehensive review of iris nevus and melanoma to explore relevant demographic and clinical data, risk factors for tumor growth, management, and prognosis, with the hope that clinicians will be more comfortable in understanding this rare malignant condition.


Assuntos
Neoplasias da Íris , Melanoma , Nevo Pigmentado , Neoplasias Cutâneas , Neoplasias Uveais , Humanos , Adulto , Melanoma/epidemiologia , Melanoma/terapia , Melanoma/diagnóstico , Estudos Longitudinais , Neoplasias da Íris/terapia , Neoplasias da Íris/patologia , Neoplasias Uveais/epidemiologia , Neoplasias Uveais/terapia , Neoplasias Uveais/patologia , Iris/patologia , Neoplasias Cutâneas/patologia
5.
Retin Cases Brief Rep ; 13(3): 202-206, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-28541267

RESUMO

PURPOSE: Birt-Hogg-Dubé Syndrome (BHDS) is a rare autosomal dominant condition that can predispose patients to numerous cutaneous fibrofolliculomas and other cutaneous lesions, pulmonary cysts with spontaneous pneumothorax, and multifocal renal tumors and cancer. The genetic mutations responsible for BHDS are related to tumor suppression and the mammalian target of rapamycin (mTOR) pathway. Previous reports of the ocular findings in BHDS include eyelid fibrofolliculomas, "flecked chorioretinopathy," and one report of choroidal melanoma. We report a patient with BHDS who presented with choroidal melanoma, sector melanocytosis, and retinal pigment epithelial microdetachments. METHODS: Observational case report. RESULTS: A 38-year-old man with BHDS manifesting with facial fibrofolliculomas/tricodiscomas and pulmonary cysts with previous pneumothorax of both lungs was noted to have a large choroidal nevus, managed with observation elsewhere. On referral 1 year later, photopsia and visual field defect were noted, and the patient was discovered to have subtle patchy sector ocular melanocytosis of the iris and choroid with choroidal melanoma and dependent subretinal fluid. The melanoma measured 14 mm in basal dimension and 6.8 mm in thickness. In addition, pinpoint retinal pigment epithelial microdetachments were observed in both eyes at the equator and confirmed on optical coherence tomography. Custom-fit plaque radiotherapy was provided for tumor control. CONCLUSION: The BHDS can be associated with tumors of the skin and kidney. In this case, we noted ocular melanocytosis, malignant choroidal melanoma, and bilateral pinpoint retinal pigment epithelial detachments.


Assuntos
Síndrome de Birt-Hogg-Dubé/patologia , Neoplasias da Coroide/patologia , Melanócitos/patologia , Descolamento Retiniano/patologia , Adulto , Humanos , Masculino , Epitélio Pigmentado da Retina/patologia
6.
J Invest Dermatol ; 139(2): 300-307, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30291846

RESUMO

Activation of the hedgehog pathway is causative of virtually all sporadic and Gorlin syndrome-related basal cell carcinomas (BCCs), with loss of function of Ptc1 being the most common genomic lesion. Sporadic BCCs also overexpress Dsg2, a desmosomal cadherin normally found in the basal layer. Using a mouse model of Gorlin syndrome (Ptc1+/lacZ mice), we found that overexpressing Dsg2 in the basal layer (K14-Dsg2/Ptc1+/lacZ mice) or the superficial epidermis (Inv-Dsg2/Ptc1+/lacZ mice) resulted in increased spontaneous BCC formation at 3 and 6 months, respectively. The tumors did not show loss of heterozygosity of Ptc1, despite high levels of Gli1 and phosphorylated Stat3. A panel of sporadic human BCCs showed increased staining of both Dsg2 and phosphorylated Stat3 in all nine samples. Overexpression of Dsg2 in ASZ001 cells, a Ptc1-/- BCC cell line, induced Stat3 phosphorylation and further increased Gli1 levels, in both an autocrine and paracrine manner. Three different Stat3 inhibitors reduced viability and Gli1 expression in ASZ001 cells but not in HaCaT cells. Conversely, stimulation of Stat3 in ASZ001 cells with IL-6 increased Gli1 expression. Our results indicate that Dsg2 enhances canonical hedgehog signaling downstream of Ptc1 to promote BCC development through the activation of phosphorylated Stat3 and regulation of Gli1 expression.


Assuntos
Síndrome do Nevo Basocelular/patologia , Desmogleína 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Neoplasias Cutâneas/patologia , Animais , Síndrome do Nevo Basocelular/genética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Técnicas de Introdução de Genes , Proteínas Hedgehog/metabolismo , Humanos , Camundongos , Camundongos Transgênicos , Receptor Patched-1/genética , Fosforilação , Fator de Transcrição STAT3/antagonistas & inibidores , Pele/patologia , Neoplasias Cutâneas/genética , Proteína GLI1 em Dedos de Zinco/metabolismo
7.
J Invest Dermatol ; 138(11): 2470-2479, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29753032

RESUMO

In addition to playing a role in adhesion, desmoglein 2 (Dsg2) is an important regulator of growth and survival signaling pathways, cell proliferation, migration and invasion, and oncogenesis. Although low-level Dsg2 expression is observed in basal keratinocytes and is downregulated in nonhealing venous ulcers, overexpression has been observed in both melanomas and nonmelanoma malignancies. Here, we show that transgenic mice overexpressing Dsg2 in basal keratinocytes primed the activation of mitogenic pathways, but did not induce dramatic epidermal changes or susceptibility to chemical-induced tumor development. Interestingly, acceleration of full-thickness wound closure and increased wound-adjacent keratinocyte proliferation was observed in these mice. As epidermal cytokines and their receptors play critical roles in wound healing, Dsg2-induced secretome alterations were assessed with an antibody profiler array and revealed increased release and proteolytic processing of the urokinase-type plasminogen activator receptor. Dsg2 induced urokinase-type plasminogen activator receptor expression in the skin of transgenic compared with wild-type mice. Wounding further enhanced urokinase-type plasminogen activator receptor in both epidermis and dermis with a concomitant increase in the prohealing laminin-332, a major component of the basement membrane zone, in transgenic mice. This study demonstrates that Dsg2 induces epidermal activation of various signaling cascades and accelerates cutaneous wound healing, in part, through urokinase-type plasminogen activator receptor-related signaling cascades.


Assuntos
Desmogleína 2/metabolismo , Queratinócitos/fisiologia , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Pele/patologia , Cicatrização/genética , Animais , Moléculas de Adesão Celular/metabolismo , Proliferação de Células , Células Cultivadas , Desmogleína 2/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transdução de Sinais , Pele/metabolismo , Calinina
8.
Ophthalmic Plast Reconstr Surg ; 33(4): 233-236, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27811637

RESUMO

INTRODUCTION: Cutaneous horn of the eyelid is uncommon. The authors evaluate the features of benign, premalignant, and malignant tumors at the base of cutaneous horn of the eyelid. OBJECTIVE: To describe the clinical and histopathologic features of cutaneous horn of the eyelid. DESIGN: A retrospective analysis of 13 cases of cutaneous horn of the eyelid treated between 1994 and 2014 was performed. PARTICIPANTS: Thirteen patients participated in this study. MAIN OUTCOME MEASURES: Main outcome measures include clinical and histopathologic features and outcomes of cutaneous horn. RESULTS: The mean patient age was 54 years (median 64 years, range 9-91 years), and 6 patients (46%) were women. The cutaneous horn affected the upper (n = 5), lower (n = 6) eyelid, or was not indicated (n = 2). The mean height of the cutaneous horn was 7.6 mm (median 8mm, range 4-12 mm) and mean basal diameter was 3.8 mm (median 3mm, range 2-6 mm). The cutaneous horn was comprised of superficial layers of keratin with hyperkeratosis and parakeratosis overlying a solid tumor at the base in all cases. The tumor base included benign (n = 6, 46%), premalignant (n = 4, 31%), and malignant (n = 3, 23%) conditions. The benign basal lesions included seborrheic keratosis (n = 1), nevus sebaceous of Jadassohn (n = 1), pseudoepitheliomatous hyperplasia (n = 1), trichilemmoma (n = 1), and inverted follicular keratosis (n = 2). Premalignant basal lesions were actinic keratosis (n = 4), and malignant basal lesions included squamous cell carcinoma (n = 2) and sebaceous gland carcinoma (n = 1). CONCLUSIONS: The clinical significance of cutaneous horn of the eyelid lies not in the horn itself but the nature of the underlying base. Malignancy was found in 23% of patients.


Assuntos
Doenças Palpebrais/diagnóstico , Pálpebras/patologia , Ceratose/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
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