RESUMO
Morphea and lichen sclerosis et atrophicus (LSA) are two distinct immune-mediated diseases with a dominant presentation of dermal fibrosis and sclerosis. The two diseases have many similar clinical and histological features and tend to co-occur. Both diseases are thought to result from a derailment of the normal response to environmental triggers. Positive family history is more common in LSA than morphea but individuals with morphea have a higher frequency of concomitant and familial autoimmunity. These findings hint at the involvement of inheritance in susceptibility to LSA and morphea and thus provide a rationale for exploring the disease genetics. This chapter contains a comprehensive review of the pathogenesis of the two diseases and their known genetic associations including HLA class I and II genes.
Assuntos
Hereditariedade , Líquen Escleroso e Atrófico , Esclerodermia Localizada , Humanos , Imunogenética , Padrões de Herança , Líquen Escleroso e Atrófico/complicações , Líquen Escleroso e Atrófico/genética , Líquen Escleroso e Atrófico/patologia , Esclerodermia Localizada/complicações , Esclerodermia Localizada/genética , Esclerodermia Localizada/patologiaRESUMO
BACKGROUND: Studies concerning pediatric lichen sclerosus are limited, and, to date, there have been no studies comparing the course of lichen sclerosus in boys and girls. We sought to examine all publications on boys and girls with lichen sclerosus and assess and compare epidemiology, symptoms and signs, genetic background, risk factors, treatment, and prognosis. METHODS: A systematic search was performed in the Embase, Medline, Cochrane, and Web of Science databases. Inclusion criteria were information on children ages 0-18 years and a clinical or histologic diagnosis of lichen sclerosus. Literature from 1985 to 2021 was reviewed. RESULTS: A total of 1780 articles were retrieved from the search, of which 90 articles were eligible for inclusion. Boys and girls present similarly on many aspects; nonetheless, treatment and follow-up are approached differently. CONCLUSIONS: Though the clinical approach is often different, lichen sclerosus in boys and girls demonstrates many similarities. More research is needed, especially on follow-up, to gain a better understanding of the course of lichen sclerosus and establish an advanced management plan for children.
Assuntos
Líquen Escleroso e Atrófico , Adolescente , Criança , Pré-Escolar , Feminino , Patrimônio Genético , Humanos , Lactente , Recém-Nascido , Líquen Escleroso e Atrófico/diagnóstico , Líquen Escleroso e Atrófico/epidemiologia , Líquen Escleroso e Atrófico/genética , Masculino , Prognóstico , Fatores de RiscoRESUMO
PURPOSE: To assess the expression of selected cytokines in penile lichen sclerosus (PLS) and associate them with the occurrence of micro-incontinence (MI) in different stages of PLS. METHODS: The skin biopsies from 49 PLS affected, and 13 from nonlesional foreskins (healthy control adult males undergoing circumcision due to phimosis caused by short frenulum) were obtained. All specimens were used for RNA extraction and RT-qPCR. Quantitative assessment of the gene expression of interleukin 1-A (IL-1A), interleukin 1-B (IL-1B), interleukin 1 receptor antagonist (IL-1RN), interleukin 6 (IL-6), transforming growth factor ß1 (TGF-ß1), and interferon-gamma (INF-γ) was performed. To determinate the presence of MI, the patients were asked about voiding patterns, especially leaking tiny drops of urine from the urethral meatus after urination. RESULTS: IL-1A, IL-6, and INF-γ mRNA levels were approximately 150, 16, and 59 times higher in PLS than in control samples, respectively. The highest IL-1A mRNA levels were observed in early PLS (n = 13), INF-γ in moderate PLS (n = 32), while IL-6 in severe PLS (n = 4). MI was noted in 45 PLS patients vs. 0 in control (p < 0.0001). IL-1A and IL-6 vs control ratios were concentration (ca.) 400 and 30 times higher, respectively, in MI PLS samples than in PLS without MI. CONCLUSION: Occlusion and irritating urine effect are associated with the clinical progression of penile LS with increased mRNA expression of IL-1A, INF-γ, and IL-6 pro-inflammatory cytokines in the foreskin.
Assuntos
Líquen Escleroso e Atrófico , Fimose , Adulto , Citocinas/genética , Prepúcio do Pênis/patologia , Expressão Gênica , Humanos , Líquen Escleroso e Atrófico/complicações , Líquen Escleroso e Atrófico/genética , Masculino , Fimose/complicaçõesRESUMO
Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory dermatosis of unknown etiology involving the genital and/or extragenital area, showing histopathologically a characteristic homogeneization and sclerosis of the superficial collagen with variably dense lymphoid infiltrates. Intraepidermal lymphocytes may be observed, and in some cases may pose differential diagnostic problems with mycosis fungoides (MF). We studied the histopathologic features of 121 cases of LSA with dense lymphoid infiltrates (genital: 94; male:female: 93:1; age range: 2 to 87 y; median age: 11 y; extragenital: 27; male:female: 0.1:1; age range: 11 to 79 y; median age: 59 y), to better characterize the intraepidermal lymphoid infiltrate and to compare genital with extragenital cases. Epidermotropic lymphocytes mimicking the histopathologic features of MF were present in 93.6% of the genital specimens but none of the extragenital cases. Interestingly, typical features of LSA were mssing in 39.4% of genital LSA, and in a further 25.5% were present only focally. Immunohistochemical analyses showed a predominance of CD8+ T-lymphocytes within the epidermis. Molecular studies of the T-cell receptor genes revealed a monoclonal population of T-lymphocytes in nearly half of the cases. Our study shows that MF-like histopathologic features are extremely common in genital LSA but are never encountered in extragenital cases. A diagnosis of MF in the genital area should be made only upon compelling features, keeping in mind the frequent pseudolymphomatous aspects of LSA.
Assuntos
Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Masculinos/patologia , Líquen Escleroso e Atrófico/patologia , Micose Fungoide/patologia , Neoplasias Cutâneas/patologia , Pele/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Pré-Escolar , Diagnóstico Diferencial , Europa (Continente) , Feminino , Genes Codificadores dos Receptores de Linfócitos T , Neoplasias dos Genitais Femininos/genética , Neoplasias dos Genitais Femininos/imunologia , Neoplasias dos Genitais Masculinos/genética , Neoplasias dos Genitais Masculinos/imunologia , Humanos , Líquen Escleroso e Atrófico/genética , Líquen Escleroso e Atrófico/imunologia , Masculino , Pessoa de Meia-Idade , Micose Fungoide/genética , Micose Fungoide/imunologia , Valor Preditivo dos Testes , Pele/imunologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia , Linfócitos T/imunologia , Adulto JovemRESUMO
PURPOSE: To better understand the pathophysiology of lichen sclerosus (LS) urethral stricture disease (USD), we aimed to investigate expression profiles of microRNAs (miRNAs) in tissue samples from men undergoing urethroplasty. METHODS: Urethral stricture tissue was collected from 2005-2020. Histologic features diagnostic of LS were the basis of pathologic evaluation. Foci of areas diagnostic for LS or non-LS strictures were chosen for RNA evaluation. In an initial screening analysis, 13 LS urethral strictures and 13 non-LS strictures were profiled via miRNA RT-qPCR arrays for 752 unique miRNA. A validation analysis of 23 additional samples (9 LS and 14 non-LS) was performed for 15 miRNAs. Statistical analyses were performed using SPSS v25. Gene Ontology (GO) analysis was performed using DIANA-mirPath v. 3.0. RESULTS: In the screening analysis 143 miRNAs were detected for all samples. 27 were differentially expressed between the groups (false discovery p-value <0.01). 15 of these miRNAs individually demonstrated an area under the curve (AUC)>0.90 for distinguishing between between LS and non-LS strictures. 11-fold upregulation of MiR-155-5p specifically was found in LS vs. non-LS strictures (p<0.001, AUC = 1.0). In the validation analysis, 13 of the 15 miRNAs tested were confirmed to have differential expression (false discovery p-value <0.10). CONCLUSIONS: To our knowledge this is the first study evaluating miRNA expression profiles in LS and non-LS USD. We identified several miRNAs that are differentially expressed in USD caused by LS vs other etiologies, which could potentially serve as biomarkers of LS USD. The top eight differentially expressed miRNAs have been linked to immune response processes as well as involvement in wound healing, primarily angiogenesis and fibrosis.
Assuntos
Líquen Escleroso e Atrófico/genética , MicroRNAs/genética , Estreitamento Uretral/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Perfilação da Expressão Gênica , Marcadores Genéticos/genética , Humanos , Inflamação/patologia , Líquen Escleroso e Atrófico/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Uretra/patologia , Uretra/cirurgia , Estreitamento Uretral/patologia , Procedimentos Cirúrgicos Urológicos MasculinosRESUMO
Lichen sclerosus (LS) is a chronic inflammatory skin disorder with unknown pathogenesis. The aberrant expression of microRNAs (miRNAs) is considered to exert a crucial role in LS. We used the next-generation sequencing technology (RNASeq) for miRNA profiling and Ingenuity Pathway Analysis (IPA) for molecular network analysis. We performed qRT-PCR, miRNA transfection and Matrigel assays for functional studies. We identified a total of 170 differentially expressed miRNAs between female LS and matched adjacent normal tissue using RNASeq, with 119 upregulated and 51 downregulated. Bioinformatics analysis revealed molecular networks that may shed light on the pathogenesis of LS. We verified the expression of a set of miRNAs that are related to autoimmunity, such as upregulated miR-326, miR-142-5p, miR-155 and downregulated miR-664a-3p and miR-181a-3p in LS tissue compared to the matched adjacent normal tissue. The differentially expressed miRNAs were also verified in blood samples from LS patients compared to healthy female volunteers. Functional studies demonstrated that a forced expression of miR-142-5p in human dermal fibroblast PCS-201-010 cells resulted in decreased cell proliferation and migration. These findings suggest that differentially expressed miRNAs may play an important role in LS pathogenesis; therefore, they could serve as biomarkers for LS management.
Assuntos
Biomarcadores/análise , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Líquen Escleroso e Atrófico/patologia , MicroRNAs/genética , Pele/metabolismo , Biologia Computacional , Feminino , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Líquen Escleroso e Atrófico/genéticaRESUMO
BACKGROUND: Lichen sclerosus (LS) is an acquired inflammatory mucocutaneous disease affecting the anogenital area, characterized histologically by hyalinosis and thickened vessel walls in the dermis. The presence of serum autoantibodies against extracellular matrix protein 1 (ECM1) in LS patients may suggest its involvement in disease pathogenesis. OBJECTIVE: To examine if reduced ECM1 production by dermal fibroblasts contributes to the pathogenic features of LS. METHODS: Gene expression in ECM1 knockdown human dermal fibroblasts was analyzed by cDNA microarray. Functional enrichment for genes involved in cellular functions was conducted. Protein expression was analyzed by ELISA and confocal laser scanning microscopy using LS skin. RESULTS: Microarray analysis identified 3035 differentially expressed genes in ECM1 knockdown cells, wherein 1471 were upregulated genes related exclusively to cell adhesion, proliferation, apoptosis, intracellular signaling, and extracellular matrix organization. Further narrowing with criteria specific for localization and function of ECM1 identified 48 upregulated genes identified to have structural, fibrogenic, and carcinogenic properties. Of these, laminin-332 and collagen-IV displayed altered immunolabeling within the basement membrane zone (BMZ) and dermal vessels in LS skin, similar to that of collagen-VII, which exhibited unchanged transcription levels in ECM1-knockdown fibroblasts. Collagen-VII bound to recombinant ECM1 in a solid-phase immunoassay and colocalized with ECM1 in the skin BMZ. Further, ECM1-knockdown fibroblasts exhibited a marked delay in cell migration and gel contraction. CONCLUSION: In the absence of ECM1 expression in fibroblasts there is selective dysregulation and disassembly of structural and extracellular matrix molecules, which may result in microstructural abnormalities reminiscent of LS.
Assuntos
Proteínas da Matriz Extracelular/deficiência , Regulação da Expressão Gênica/imunologia , Líquen Escleroso e Atrófico/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Cultivadas , Matriz Extracelular/imunologia , Matriz Extracelular/patologia , Proteínas da Matriz Extracelular/genética , Feminino , Fibroblastos/citologia , Fibroblastos/imunologia , Fibroblastos/patologia , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Líquen Escleroso e Atrófico/imunologia , Líquen Escleroso e Atrófico/patologia , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Cultura Primária de Células , Interferência de RNA , Pele/citologia , Pele/imunologia , Pele/patologiaRESUMO
BACKGROUND/AIM: Differentiated vulvar intraepithelial neoplasia (dVIN) and lichen sclerosus (LS) can give rise to vulvar squamous cell carcinoma (VSCC), but genetic evidence is currently still limited. We aimed to determine genetic abnormalities in VSCC and backtrack these abnormalities in the dVIN and LS lesions. MATERIALS AND METHODS: DNA from VSCC and patient-matched dVIN and LS samples of twelve patients was collected. High-resolution genome-wide copy number analysis was performed and subsequently, we sequenced TP53. RESULTS: Copy number alterations were identified in all VSCC samples. One dVIN lesion presented with three copy number alterations that were preserved in the paired VSCC sample. Targeted sequencing of TP53 identified mutations in five VSCCs. All five mutations were traced back in the dVIN (n=5) or the LS (n=1) with frequencies ranging from 3-19%. CONCLUSION: Our data provide genetic evidence for a clonal relationship between VSCC and dVIN or LS.
Assuntos
Carcinoma in Situ/genética , Carcinoma de Células Escamosas/genética , Líquen Escleroso e Atrófico/genética , Neoplasias Vulvares/diagnóstico por imagem , Neoplasias Vulvares/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-IdadeAssuntos
Doenças dos Genitais Masculinos/genética , Proteínas de Filamentos Intermediários/genética , Líquen Escleroso e Atrófico/genética , Mutação com Perda de Função , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Proteínas Filagrinas , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Lichen sclerosus (LS) is an inflammatory dermatosis with a predilection for anogenital skin. Developing lesions lead to vulvar pain and sexual dysfunction, with a significant loss of structural anatomical architecture, sclerosis, and increased risk of malignancy. Onset may occur at any age in both sexes, but typically affects more females than males, presenting in a bimodal fashion among pre-pubertal children and middle-aged adults. A definitive cure remains elusive as the exact pathogenesis of LS remains unknown. A general review of LS, histologic challenges, along with amounting support for LS as an autoimmune disease with preference for a Th1 immune response against a genetic background is summarized. In addition to the classically referenced ECM1 (extracellular matrix protein 1), a following discussion of other immune and genetic targets more recently implicated as causative or accelerant agents of disease, particularly miR-155, downstream targets of ECM1, galectin-7, p53, and epigenetic modifications to CDKN2A, are addressed from the viewpoint of their involvement in three different, but interconnected aspects of LS pathology. Collectively, these emerging targets serve not only as inherently potential therapeutic targets for treatment, but may also provide further insight into this debilitating and cryptic disease.
Assuntos
Líquen Escleroso e Atrófico/genética , Líquen Escleroso e Atrófico/imunologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Colágeno Tipo V/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Progressão da Doença , Epigênese Genética , Proteínas da Matriz Extracelular/metabolismo , Galectinas/metabolismo , Humanos , Sistema Imunitário , Incidência , Líquen Escleroso e Atrófico/patologia , MicroRNAs/metabolismo , Estresse Oxidativo , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: Limited data are available on risk factors associated with lichen sclerosus and no data are available on gender differences in genital lichen sclerosus (GLS). OBJECTIVE: This multicentre study aimed at identifying potential risk factors for GLS, through data collection from a large, mixed-sex sample of patients comparing gender-related differences in relation to data from the general population. METHODS: This was a cross-sectional study on 729 subjects (53.8% females, 46.2% males) affected with GLS, consecutively observed within a network of 15 Italian dermatology units. The following information was collected: demographic data, anthropometric measures, comorbidities, family history of LS, clinical features and symptoms related to GLS. RESULTS: Overweight and obesity, blood hypertension, hypothyroidism and an educational attainment equal or above upper secondary school level were more frequent among the study patients than among the general Italian population. Moreover, a family history of GLS was reported more frequently than expected among GLS patients. These factors were similar in males and females. The disease tended to occur later in females than in males. CONCLUSIONS: Our findings suggest that metabolic factors, and possibly a sedentary lifestyle, may play a role in GLS pathogenesis in genetically predisposed patients, and that risk profile is similar in males and females despite some difference in the onset of symptoms.
Assuntos
Hipertensão/epidemiologia , Hipotireoidismo/epidemiologia , Líquen Escleroso e Atrófico/epidemiologia , Obesidade/epidemiologia , Doenças do Pênis/epidemiologia , Líquen Escleroso Vulvar/epidemiologia , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Criança , Comorbidade , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Escolaridade , Feminino , Humanos , Itália/epidemiologia , Líquen Escleroso e Atrófico/genética , Masculino , Pessoa de Meia-Idade , Doenças do Pênis/genética , Fatores de Risco , Comportamento Sedentário , Fatores Sexuais , Líquen Escleroso Vulvar/genética , Adulto JovemRESUMO
IMPORTANCE: The molecular mechanism leading to the development of vulvar squamous cell carcinoma (VSCC) from vulvar lichen sclerosus (VLS) is unknown. OBJECTIVE: To assess the possible involvement of the IRF6 tumor-suppressor gene in the development of VSCC from VLS. DESIGN: In laboratories at the University of Ferrara, Ferrara, Italy, IRF6 gene expression and promoter methylation were investigated in paraffin-embedded VSCC and adjacent vulvar intraepithelial neoplasia (VIN) and VLS specimens, in cancer-free VLS (cfVLS) specimens, and in healthy skin specimens by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) analysis and by sequencing of PCR-amplified bisulfite-treated DNA. Methylation-induced dysregulation was assessed by expression of p63, the IRF6-transactivator gene. MAIN OUTCOMES AND MEASURES: IRF6 expression, correlation with promoter methylation and p63 expression, and association with development of VSCC from VLS. RESULTS: Specimens from 60 participating women (1 specimen from each) were analyzed for the study (mean [SD] age, 66.3 [12.1] years): 20 paraffin-embedded specimens of VSCC (patient age, 75.3 [8.3] years) with adjacent VLS lesions, in 5 of which VIN preneoplastic tissue was also present (patient age, 64.3 [15.3] years); 20 cfVLS specimens (patient age, 62.1 [11.4] years) obtained from diagnostic biopsies; and 20 normal skin specimens from noncancer surgical patients (patient age, 61.4 [9.1] years). IRF6 messenger RNA was found to be reduced 4.5-, 2.9-, 6.6-, and 2.2-fold in VLS, VIN, VSCC, and cfVLS specimens, respectively, compared with controls, although p63 was still expressed in all specimens. IRF6 promoter was hypermethylated in 9 (45%) of 20 VLS specimens, 1 (20%) of 5 VIN specimens, 16 (80%) of 20 VSCC specimens, 2 (10%) of 20 cfVLS specimens, and 0 normal skin specimens. CONCLUSIONS AND RELEVANCE: IRF6 dysregulation may be involved in the development of VSCC from VLS. Methylation of the IRF6 promoter may be a marker of cancer risk in patients with VLS.
Assuntos
Carcinoma in Situ/genética , Carcinoma de Células Escamosas/genética , Transformação Celular Neoplásica/genética , Metilação de DNA , Fatores Reguladores de Interferon/genética , Líquen Escleroso e Atrófico/genética , RNA Mensageiro/análise , Neoplasias Vulvares/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Feminino , Expressão Gênica , Humanos , Líquen Escleroso e Atrófico/patologia , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Pele/química , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Neoplasias Vulvares/patologiaRESUMO
We describe a rare case of a 28 year-old male patient presenting with pruritus and increased sensitivity of the prepuce accompanied by erythematous confluent papules, unilateral nevus flammeus (NF) along almost the whole length of the right lower limb and two dysplastic nevi (DN), one located on the mid back and the other on the medial border of the right fifth toe, the latter coinciding with the NF. A biopsy of the prepuce revealed lichen sclerosus et atrophicus (LSA). Mental health assessment revealed anxiety disorder and predisposition to panic attacks. Several clinical, paraclinical and histopathological examinations were undertaken to evaluate potential underlying factors for such unusual combination of findings. Both dysplastic nevi were surgically removed. A topical calcineurin inhibitor treatment of the LSA was prescribed. For the first time in medical literature, we report an extremely rare association of NF, DN (including DN over NF) and LSA, and we are focusing our discussion on a potentially common genetic background which could explain this unusual combination of different diseases, which could in turn be caused by different mutations in common genes and/or different genes with close location in the genome.
Assuntos
Síndrome do Nevo Displásico/complicações , Líquen Escleroso e Atrófico/complicações , Mancha Vinho do Porto/complicações , Adulto , Síndrome do Nevo Displásico/genética , Humanos , Líquen Escleroso e Atrófico/genética , Masculino , Mutação , Mancha Vinho do Porto/genéticaRESUMO
Mycosis fungoides (MF) simulates a variety of dermatologic disorders histopathologically and clinically, well deserving the designation of a great mimicker. Interstitial MF is a rare, but well-recognized histopathological variant resembling the interstitial form of granuloma annulare or the inflammatory phase of morphea. From a clinical standpoint, MF can have a wide array of manifestations, including an anecdotal presentation with lesions clinically suggestive of lichen sclerosus (LS). We herein report a 25-year-old man with a history of patch-stage MF who later developed widespread LS-like lesions histopathologically consistent with interstitial MF. In some biopsies, additional features resembling LS were discerned. We think that our case might represent a unique variant of interstitial MF presenting with LS-like lesions. The diagnostic challenge arising from this uncommon presentation is discussed together with review of the literature.
Assuntos
Líquen Escleroso e Atrófico/patologia , Micose Fungoide/patologia , Neoplasias Cutâneas/patologia , Pele/patologia , Adulto , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Líquen Escleroso e Atrófico/genética , Líquen Escleroso e Atrófico/metabolismo , Masculino , Micose Fungoide/química , Micose Fungoide/genética , Micose Fungoide/terapia , Valor Preditivo dos Testes , Pele/química , Neoplasias Cutâneas/química , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapiaRESUMO
Mycosis fungoides is the most common primary cutaneous lymphoma; however, it remains a significant diagnostic challenge, in part because of the overlap with several inflammatory dermatoses. Despite advances in immunohistochemistry and molecular diagnostics, false-positive, false-negative, and indeterminate diagnoses are not uncommon. In most cases, the overall balance of morphologic, immunophenotypic, and genetic features must be considered carefully because there are few sensitive and specific clues to the diagnosis. Moreover, an appropriate clinical presentation is essential to the diagnosis and helps to favor or exclude inflammatory/reactive processes. Herein, we discuss 3 important inflammatory dermatoses that may closely simulate mycosis fungoides, and we review the use of ancillary studies in these challenging cases.
Assuntos
Líquen Escleroso e Atrófico/diagnóstico , Pele/patologia , Adulto , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/imunologia , Dermatite Alérgica de Contato/patologia , Diagnóstico Diferencial , Toxidermias/diagnóstico , Toxidermias/imunologia , Toxidermias/patologia , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T , Humanos , Líquen Escleroso e Atrófico/genética , Líquen Escleroso e Atrófico/patologia , Líquen Escleroso e Atrófico/fisiopatologia , Masculino , Micose Fungoide/diagnóstico , Micose Fungoide/imunologia , Micose Fungoide/patologia , Fimose/etiologia , Prognóstico , Pseudolinfoma/induzido quimicamente , Pseudolinfoma/diagnóstico , Pseudolinfoma/imunologia , Pseudolinfoma/patologia , Pele/imunologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Etiology of lichen sclerosus (LiS) and localized scleroderma (LoS) is uncertain and probably multifactorial. CASE: We describe a case of female monozygotic twins who presented co-existence of LiS and LoS. Skin lesions typical for LoS occurred in both patients, at the age of 10. One sister was diagnosed with linear LoS of the lower limb affecting deeper situated subcutaneous tissue and muscles. The other sister was diagnosed with guttate LoS of the trunk, with slow progression of the skin lesions. In both sisters vulvar LiS developed at the age of 19. CONCLUSIONS: Co-existence of LiS and LoS in monozygotic twins indicates the possible genetic contribution to the pathogenesis of these diseases and the close relationship between them.
Assuntos
Doenças em Gêmeos , Líquen Escleroso e Atrófico/genética , Esclerodermia Localizada/genética , Gêmeos Monozigóticos , Feminino , Humanos , Líquen Escleroso e Atrófico/complicações , Esclerodermia Localizada/complicações , Irmãos , Adulto JovemRESUMO
AIMS: Lichen sclerosus (LS) is a chronic inflammatory disease of the genital skin of unknown aetiology. The role of LS in penile squamous cell carcinogenesis is not well characterized. HPV has been implicated in both, as have epigenetic changes. The presence of HPV and hypermethylation of the MGMT, p16, RASSF1, RASSF2, TSLC1 and TSP1 genes were studied in penile LS; MGMT, RASSF2 and TSLC1 hypermethylation in penile cancer and TSLC1 hypermethylation in vulvar LS and cancer extends previous results reported by our group. METHODS AND RESULTS: Thirty-seven HPV genotypes and hypermethylation were evaluated by PCR/reverse-line-blot and methylation-specific PCR respectively, in 27 preputial LS, 24 penile SCC, 30 vulvar SCC, 21 vulvar LS and 22 normal skin cases. HPV66 was present in 3.7% of penile LS cases, and p16 and RASSF2 hypermethylation were more frequent in penile cancer than in penile LS. p16, RASSF1, RASSF2 and TSP1 hypermethylation were similar in penile and vulvar LS. CONCLUSIONS: Gene hypermethylation is a common event in penile LS, and occurs approximately as frequently as in vulvar LS. Certain genes can be hypermethylated as an early or late event in LS or cancer, respectively. This suggests a possible sequential role for these alterations in the transition from benign to malignant lesions.
Assuntos
Carcinoma de Células Escamosas/genética , Metilação de DNA , Líquen Escleroso e Atrófico/genética , Neoplasias Penianas/genética , Neoplasias Vulvares/genética , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Feminino , Humanos , Líquen Escleroso e Atrófico/patologia , Líquen Escleroso e Atrófico/virologia , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Neoplasias Penianas/patologia , Neoplasias Penianas/virologia , Neoplasias Vulvares/patologia , Neoplasias Vulvares/virologiaRESUMO
PURPOSE: Lichen sclerosus is a potentially important factor in the ongoing debate concerning the pathology of persistent congenital phimosis. We assessed the molecular differences of congenital phimosis in boys with and without lichen sclerosus compared to age matched boys with fully retractable foreskins to gain more insight into the pathogenesis of fibrotic remodeling of the prepuce. MATERIALS AND METHODS: A total of 150 boys were circumcised in a prospective study between 2007 and 2009. Using target gene specific preamplification and quantitative real-time polymerase chain reaction based low density arrays, we measured the mRNA expression of 45 tissue remodeling associated genes in foreskins of boys with absolute phimosis and lichen sclerosus (8 patients) and those of an age matched group of boys with phimosis but no lichen sclerosus (8), as well as a control group with foreskins without delimitable changes (6). Complementary protein expression and inflammatory infiltrates were assessed by immunohistochemical analysis. RESULTS: Cellular composition, inflammatory infiltrate and microenvironment as seen in histologically proven lichen sclerosis differed significantly from the other groups. In particular, lichen sclerosis was characterized by over expression of bone morphogenetic protein 2 and its corresponding receptor, matrix metalloproteinases 1 and 9 and tissue inhibitor of metalloproteinases 1, cytokine chemokine ligands 5 (RANTES) and interleukin 4, and transforming growth factor-ß2 and its corresponding receptor. There were no major molecular differences between specimens from boys with congenital phimosis without signs of lichen sclerosis and controls. CONCLUSIONS: Distinct expression patterns of tissue remodeling associated genes are evident in boys with congenital phimosis and lichen sclerosis, while congenital phimosis without lichen sclerosis represents a physiological condition.
Assuntos
Perfilação da Expressão Gênica , Líquen Escleroso e Atrófico/complicações , Líquen Escleroso e Atrófico/genética , Fimose/congênito , Fimose/genética , Criança , Pré-Escolar , Prepúcio do Pênis/patologia , Humanos , Líquen Escleroso e Atrófico/patologia , Masculino , Fimose/complicações , Fimose/patologia , Estudos ProspectivosRESUMO
Male genital lichen sclerosus (MGLSc) has a bimodal distribution in boys and men. It is associated with squamous cell carcinoma (SCC). The pathogenesis of MGLSc is unknown. HPV and autoimmune mechanisms have been mooted. Anti extracellular matrix protein (ECM)1 antibodies have been identified in women with GLSc. The gene expression pattern of LSc is unknown. Using DNA microarrays we studied differences in gene expression in healthy and diseased prepuces obtained at circumcision in adult males with MGLSc (n = 4), paediatric LSc (n = 2) and normal healthy paediatric foreskin (n = 4). In adult samples 51 genes with significantly increased expression and 87 genes with significantly reduced expression were identified; paediatric samples revealed 190 genes with significantly increased expression and 148 genes with significantly reduced expression. Concordance of expression profiles between adult and paediatric samples indicates the same disease process. Functional analysis revealed increased expression in the adult and child MGSLc samples in the immune response/cellular defence gene ontology (GO) category and reduced expression in other categories including genes related to squamous cancer. No specific HPV, autoimmune or squamous carcinogenesis-associated gene expression patterns were found. ECM1 and CABLES1 expression were significantly reduced in paediatric and adult samples respectively.