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3.
Clinicoecon Outcomes Res ; 12: 91-105, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104021

RESUMO

Aim: To identify the most common therapeutic options for the treatment of early-stage mycosis fungoides in Spain, quantify their associated healthcare resource use and costs. Methods: After reviewing the literature, a panel of 6 Spanish clinical dermatologists validated the treatments and healthcare resource use through a structured questionnaire. Individual responses were collected, analyzed and presented into a face-to-face meeting in order to reach a consensus. Cost categories considered were: drug acquisition and administration, photo/radiotherapy session and maintenance, clinical follow-up visits and laboratory tests. Costs were expressed in euros from 2018. The Spanish National Health System perspective was considered, taking into account direct health costs and time horizons of 1, 3 and 6 months. Results: Costs for the skin-directed treatments (SDT) assessed at 1, 3 and 6 months, were: Topical carmustine [€6,593.36, €19,780.09 and €27,592.78]; Phototherapy with psoralens and ultraviolet A light (PUVA) [€1,098.68, €2,999.99 and €3,187.60]; Narrow-band ultraviolet B phototherapy [€1,657.47, €4,842.10 and €4,842.10]; Total skin electron beam therapy (TSEBT) [€6,796.45, €7,913.34 and €7,913.34]. Cost for topical corticosteroids, being considered an adjuvant option, were €17.16, €51.49 and €102.97. Costs for the assessed systemic treatments alone or in combination with SDT at 1, 3 and 6 months, were: Systemic retinoids [€2,026.03, €5,206.63 and €7,426.42]; Systemic retinoids + PUVA phototherapy [€3,066.50, €8,271.26 and €10,046.58]; Interferon alfa + PUVA phototherapy [€1,541.09, €5,167.57 and €6,404.55]. Conclusion: According to the Spanish clinical practice, phototherapies in monotherapy were the treatments with the lowest associated costs regardless of the time horizon considered. TSEBT turned out as the treatment with the highest associated costs when considering 1 month. However, while considering 3 and 6 months the treatment with the highest associated costs was topical carmustine. The results of this analysis may provide critical information to measure the disease burden, to detect unmet medical needs and to advocate towards better treatments for this rare disease.

4.
PLoS One ; 14(1): e0210070, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30650110

RESUMO

BACKGROUND: Human papillomavirus (HPV) is the cause of a fraction of head and neck squamous cell carcinoma. Although this relation is well-known, it is still not clear the role of HPV in premalignant oral lesions such as oral lichen planus (OLP) and dysplasia. We aimed to evaluate the HPV-DNA prevalence and type distribution in a set of oral biopsies obtained from patients diagnosed with OLP and dysplasia, as well as the role of HPV in these lesions. METHODS: A retrospective cohort of all premalignant oral lesions consecutively diagnosed from March 30th 1995 to May 21st 2014 at Hospital of Bellvitge and Odontological University Hospital of Bellvitge was identified and classified in four groups: OLP (groups 1 and 2) and dysplasias (groups 3 and 4) that progressed or not to invasive cancer during follow-up. A random selection targeting 25 cases was aimed to be performed for each group. All selected cases were subjected to pathological evaluation, DNA quality control and HPV-DNA detection. HPV-DNA positive samples were further subject to p16INK4a analysis. RESULTS: A total of 83 cases yielded a valid HPV-DNA result. From those, 7 and 34 cases were OLP that progressed or not to invasive cancer during follow-up, whereas 24 and 18 cases were displasias that progressed or not to invasive cancer during follow-up, respectively. HPV-DNA was detected in 4 samples (3 dysplastic lesions and 1 OLP). Two samples were HPV16 positive (2%), 1 sample HPV18 positive (1%) and 1 sample (1%) was HPV indeterminate. Two out of four HPV-DNA positive cases had high p16INK4a expression and none of the HPV positive cases progressed to invasive cancer during long-term follow-up. CONCLUSIONS: We found a low HPV-DNA attributable fraction in premalignant lesions of the oral cavity, suggesting that HPV is unlikely to play a significant role in oral carcinogenesis in our setting.


Assuntos
Líquen Plano Bucal/patologia , Boca/patologia , Infecções por Papillomavirus/patologia , Lesões Pré-Cancerosas/patologia , Idoso , Carcinogênese , DNA Viral/análise , DNA Viral/genética , Feminino , Humanos , Líquen Plano Bucal/virologia , Masculino , Pessoa de Meia-Idade , Boca/virologia , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/virologia , Papillomaviridae/classificação , Papillomaviridae/genética , Papillomaviridae/fisiologia , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas/virologia , Estudos Retrospectivos , Espanha
5.
J Cutan Pathol ; 46(3): 182-189, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30511443

RESUMO

BACKGROUND: Primary cutaneous follicular center-cell lymphoma (PCFCL) is one of the most common types of cutaneous B-cell lymphoma. Differences in immunohistochemical expression of BCL2 and CD10 antigens along with the presence of t(14:18) translocation in neoplastic cells have been postulated as relevant clues in differentiating PCFCL from cutaneous lesions secondary to a systemic follicular lymphoma (SCFL). The aim of this study is to evaluate the significance and usefulness of these parameters in a large series of patients. METHODS: Patients with PCFCL and SCFL diagnosed at three university hospitals in Barcelona, from 2000 to 2015 were reviewed. Clinical, histopathological, immunophenotypical, genetic, and outcome parameters were analyzed. RESULTS: Eighty-one cases (59 PCFCL and 22 SCFL) were included. There were no significant differences between PCFCL and SCFL cases regarding clinical presentation, site of involvement, or predominant type of skin lesions. Most patients in both groups showed positivity for BCL2 and CD10, but strong expression of BCL2 and CD10 was associated with SCFL cases. Although more frequent in SCFL, a small proportion of PCFCL cases also showed the t(14:18) on FISH analysis. CONCLUSION: The intensity of BCL2 expression was found to be the single most valuable clue in differentiating PCFCL from SCFL cases on histopathological grounds.


Assuntos
Biomarcadores Tumorais/análise , Linfoma Folicular/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 18/genética , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neprilisina/análise , Neprilisina/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Translocação Genética/genética , Adulto Jovem
6.
JAMA Dermatol ; 154(12): 1424-1431, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30422238

RESUMO

Importance: Hypertriglyceridemia is the most frequent and limiting adverse effect of bexarotene therapy in cutaneous T-cell lymphoma (CTCL). Despite standard prophylactic measures, there is a wide variability in the severity of this complication, which could be associated with both genetic and environmental factors. Objectives: To analyze the association between genetic polymorphisms of apolipoprotein genes APOA5, APOC3, and APOE and the severity of hypertriglyceridemia during bexarotene therapy and to optimize patient selection for bexarotene therapy based on adverse effect profile. Design, Setting, and Participants: This case series study was conducted in 12 university referral hospitals in Spain from September 17, 2014, to February 6, 2015. One hundred twenty-five patients with a confirmed diagnosis of CTCL who had received bexarotene therapy for at least 3 months were enrolled. Nine patients were excluded owing to missing analytic triglyceride level data, leaving a study group of 116 patients. Data on demographic and cardiovascular risk factor were collected, and a complete blood analysis, including lipid profile and genetic analysis from a saliva sample, was performed. Main Outcomes and Measures: Primary outcomes were the maximal triglyceride levels reported in association with the minor alleles of the polymorphisms studied. Results: Among 116 patients, the mean (SD) age was 61.2 (14.7) years, 69 (59.5%) were men, and 85 (73.2%) had mycosis fungoides, the most prevalent form of CTCL. During bexarotene therapy, 96 patients (82.7%) experienced hypertriglyceridemia, which was severe or extreme in 8 of these patients (8.3%). Patients who carried minor alleles of the polymorphisms did not show significant differences in baseline triglyceride concentrations. After bexarotene treatment, carriers of at least 1 of the 2 minor alleles of APOA5 c.-1131T>C and APOC3 c.*40C>G showed lower levels of triglycerides than noncarriers (mean [SD], 241.59 [169.91] vs 330.97 [169.03] mg/dL, respectively; P = .02). Conclusions and Relevance: These results indicate that the screening of APOA5 and APOC3 genotypes may be useful to estimate changes in triglyceride concentrations during bexarotene treatment in patients with CTCL and also to identify the best candidates for bexarotene therapy based on the expected adverse effect profile.


Assuntos
Apolipoproteína A-V/genética , Apolipoproteína C-III/genética , Bexaroteno/uso terapêutico , Hipertrigliceridemia/etiologia , Linfoma Cutâneo de Células T/tratamento farmacológico , Polimorfismo Genético , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Apolipoproteína A-V/metabolismo , Apolipoproteína C-III/metabolismo , DNA/genética , Feminino , Seguimentos , Genótipo , Humanos , Hipertrigliceridemia/genética , Hipertrigliceridemia/metabolismo , Linfoma Cutâneo de Células T/complicações , Linfoma Cutâneo de Células T/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença
7.
Eur J Dermatol ; 28(1): 64-70, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29400283

RESUMO

BACKGROUND: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is an aggressive lymphoma with a very low incidence in western populations. OBJECTIVE: To review the clinicopathological features and outcome of a multicentre series of ENKTL in Spain. MATERIALS & METHODS: A multicentre retrospective study was performed based on cases of ENKTL, collected from 1995 to 2004, from 12 dermatology departments included in the Spanish Lymphoma Study Group. The clinical, histopathological, and evolutive features of all these cases were reviewed. RESULTS: Eighteen patients (three male, 15 female) with median age of 67 years were included in the study. The onset of lesions occurred in the nasal region in 11 patients and on the skin outside this region in the remaining cases. The observed lesions were clinically heterogeneous, corresponding to papules, plaques, and nodules, with or without ulceration. All patients except four received different polychemotherapy regimens, either alone (n = 11) or in combination with radiotherapy (n = 4). After a variable follow-up period (1-36 months), only two patients remained alive. One patient was recently diagnosed (four months ago) with ENKTL in the nasal region and the other presented with skin-limited disease. The median overall survival was 9.5 months. CONCLUSIONS: The results of this retrospective survey confirm that ENKTL is a rare subtype of lymphoma in the Spanish population. All patients showed an aggressive clinical course and poor prognosis, regardless of the initial clinical presentation. Prospective data on larger series of patients treated homogenously are needed to establish the best treatment modality.


Assuntos
Linfoma Extranodal de Células T-NK/patologia , Neoplasias Nasais/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunofenotipagem , Linfoma Extranodal de Células T-NK/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias Nasais/terapia , Neoplasias Cutâneas/terapia , Espanha , Inquéritos e Questionários , Resultado do Tratamento
8.
Eur J Dermatol ; 27(3): 286-294, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28468739

RESUMO

EORTC 21081 was a randomized phase III study of observation alone versus lenalidomide maintenance (25 mg po for 21 days) after debulking therapy in patients with advanced-stage cutaneous T-cell lymphomas (CTCLs). The aim was to investigate whether maintenance treatment with lenalidomide prolonged response after debulking in patients who had not been previously treated with intravenous chemotherapy. A total of 26 centres from 10 different European countries registered 30 patients with advanced CTCL. Twenty-one patients were randomized (20% of the 105 patients initially deemed necessary for the study; the study was terminated early following withdrawal of funding support from Celgene). Of 30 registered patients, nine failed to be randomized, 12 were randomized to observation alone, and nine to lenalidomide maintenance. Median progression-free survival was 5.3 months (95% CI: 1.87-22.54) in the maintenance lenalidomide group and two months (95% CI: 0.92-7.82) in the observation alone group. Although statistical comparison in the study was severely underpowered and would not be meaningful, this study provides useful information, revealing rapid disease progression within four weeks in a third of patients, highlighting the need for maintenance therapy.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Linfoma Cutâneo de Células T/tratamento farmacológico , Linfoma Cutâneo de Células T/cirurgia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/cirurgia , Talidomida/análogos & derivados , Idoso , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Lenalidomida , Linfoma Cutâneo de Células T/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Cutâneas/patologia , Talidomida/uso terapêutico
9.
Croat Med J ; 57(3): 247-54, 2016 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-27374826

RESUMO

AIM: To assess the toxicity, tolerance, steroid-sparing capacity, effectiveness, and response rate to imatinib and dasatinib for the treatment of severe sclerotic chronic graft-vs-host disease (scGVHD). METHODS: This retrospective study analyzed 8 consecutive patients with severe refractory scGVHD who received salvage therapy with imatinib. Patients intolerant and/or refractory to imatinib received dasatinib treatment. RESULTS: 7 patients discontinued imatinib treatment (1 achieved complete response, 5 were resistant and/or intolerant, and 1 developed grade IV neutropenia) and 1 patient achieved prolonged partial response, but died due to an infectious complication while on treatment. 5 patients started dasatinib treatment (3 achieved partial responses and discontinued dasatinib, 1 achieved a durable partial response, but died due to a consecutive rapid pulmonary cGVHD progression and 1 with stable disease discontinued treatment due to gastroenteric intolerance). The response rate (partial and/or complete responses) for severe scGVHD was 25% for imatinib and 60% for dasatinib. CONCLUSION: In our series, dasatinib was better tolerated, safer, steroid-sparing, and had a low incidence of infectious complications, which suggests that it may be a more effective therapeutic alternative for patients with refractory scGVHD than imatinib. Treatment of scGVHD with effective antifibrotic drugs such as TKI, which block the kinase fibrotic pathway, may be a safe and effective therapeutic option, but further studies are needed to confirm our findings.


Assuntos
Antineoplásicos/uso terapêutico , Dasatinibe/uso terapêutico , Doença Enxerto-Hospedeiro , Mesilato de Imatinib/uso terapêutico , Esclerose/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Dasatinibe/administração & dosagem , Feminino , Humanos , Mesilato de Imatinib/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Terapia de Salvação , Esclerose/complicações , Resultado do Tratamento
10.
J Invest Dermatol ; 136(7): 1490-1499, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27039262

RESUMO

Sézary syndrome is a leukemic form of cutaneous T-cell lymphoma with an aggressive clinical course. The genetic etiology of the disease is poorly understood, with chromosomal abnormalities and mutations in some genes being involved in the disease. The goal of our study was to understand the genetic basis of the disease by looking for driver gene mutations and fusion genes in 15 erythrodermic patients with circulating Sézary cells, 14 of them fulfilling the diagnostic criteria of Sézary syndrome. We have discovered genes that could be involved in the pathogenesis of Sézary syndrome. Some of the genes that are affected by somatic point mutations include ITPR1, ITPR2, DSC1, RIPK2, IL6, and RAG2, with some of them mutated in more than one patient. We observed several somatic copy number variations shared between patients, including deletions and duplications of large segments of chromosome 17. Genes with potential function in the T-cell receptor signaling pathway and tumorigenesis were disrupted in Sézary syndrome patients, for example, CBLB, RASA2, BCL7C, RAMP3, TBRG4, and DAD1. Furthermore, we discovered several fusion events of interest involving RASA2, NFKB2, BCR, FASN, ZEB1, TYK2, and SGMS1. Our work has implications for the development of potential therapeutic approaches for this aggressive disease.


Assuntos
Mutação , Síndrome de Sézary/genética , Neoplasias Cutâneas/genética , Idoso , Idoso de 80 Anos ou mais , Aberrações Cromossômicas , Variações do Número de Cópias de DNA , Feminino , Deleção de Genes , Duplicação Gênica , Humanos , Linfoma Cutâneo de Células T/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Análise de Sequência de RNA , Transdução de Sinais
11.
J Clin Oncol ; 33(32): 3766-73, 2015 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-26438120

RESUMO

PURPOSE: Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. PATIENTS AND METHODS: Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). RESULTS: Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). CONCLUSION: To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value, which, used together in a prognostic index, may be useful to stratify advanced-stage patients.


Assuntos
Modelos Estatísticos , Micose Fungoide/mortalidade , Micose Fungoide/patologia , Síndrome de Sézary/mortalidade , Síndrome de Sézary/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Adulto , Fatores Etários , Idoso , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/sangue , L-Lactato Desidrogenase/metabolismo , Masculino , Pessoa de Meia-Idade , Micose Fungoide/metabolismo , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Síndrome de Sézary/metabolismo , Pele/enzimologia , Neoplasias Cutâneas/metabolismo , Taxa de Sobrevida
12.
J Invest Dermatol ; 135(12): 3144-3152, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26302069

RESUMO

Notch is a family of transmembrane receptors that participate in the regulation of cell differentiation, proliferation, and stemness. Notch pathway activation has also been found associated with different human cancers including primary cutaneous T-cell lymphomas (CTCL). The elucidation of the mechanisms driving Notch activation in these particular diseases has remained elusive. Here we studied the possibility that DNA methylation at Notch pathway gene promoters and/or deregulation of Notch-associated microRNAs contribute to activate Notch in mycosis fungoides (MF). By genome-wide DNA methylation analysis, we failed to detect any consistent methylation at the Notch1, the Notch-ligand Jagged1, or the Notch-target Hes1 gene promoters, but found a significant methylation of the Notch-related microRNAs, in particular miR-200c and miR-124. Downregulation of miR-200c is associated with overexpression of Jagged1, concomitant to Notch1 activation. CTCL cell lines were infected with lentiviral vector encoding for miR-200c and ectopic expression of miR-200c in CTCL lines resulted in Jagged1 protein downregulation associated with a reduction in the levels of active Notch1. Our study deciphers an epigenetic mechanism regulating the Notch pathway in (MF) that might contribute to the future design of more specific therapeutic strategies.


Assuntos
Epigênese Genética , Linfoma Cutâneo de Células T/genética , MicroRNAs/fisiologia , Micose Fungoide/genética , Receptor Notch1/fisiologia , Transdução de Sinais/fisiologia , Neoplasias Cutâneas/genética , Proteínas de Ligação ao Cálcio/fisiologia , Linhagem Celular Tumoral , Metilação de DNA , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Proteína Jagged-1 , Proteínas de Membrana/fisiologia , Estudos Retrospectivos , Proteínas Serrate-Jagged
13.
J Invest Dermatol ; 135(4): 1128-1137, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25405321

RESUMO

MicroRNAs usually regulate gene expression negatively, and aberrant expression has been involved in the development of several types of cancers. Microarray profiling of microRNA expression was performed to define a microRNA signature in a series of mycosis fungoides tumor stage (MFt, n=21) and CD30+ primary cutaneous anaplastic large cell lymphoma (CD30+ cALCL, n=11) samples in comparison with inflammatory dermatoses (ID, n=5). Supervised clustering confirmed a distinctive microRNA profile for cutaneous T-cell lymphoma (CTCL) with respect to ID. A 40 microRNA signature was found in MFt including upregulated onco-microRNAs (miR-146a, miR-142-3p/5p, miR-21, miR-181a/b, and miR-155) and downregulated tumor-suppressor microRNAs (miR-200ab/429 cluster, miR-10b, miR-193b, miR-141/200c, and miR-23b/27b). Regarding CD30+ cALCL, 39 differentially expressed microRNAs were identified. Particularly, overexpression of miR-155, miR-21, or miR-142-3p/5p and downregulation of the miR-141/200c clusters were observed. DNA methylation in microRNA gene promoters, as expression regulatory mechanism for deregulated microRNAs, was analyzed using Infinium 450K array and approximately one-third of the differentially expressed microRNAs showed significant DNA methylation differences. Two different microRNA methylation signatures for MFt and CD30+ cALCL were found. Correlation analysis showed an inverse relationship for microRNA promoter methylation and microRNA expression. These results reveal a subgroup-specific epigenetically regulated microRNA signatures for MFt and CD30+ cALCL patients.


Assuntos
Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Linfoma Cutâneo de Células T/genética , MicroRNAs/metabolismo , Adulto , Idoso , Linhagem Celular Tumoral , Análise por Conglomerados , Ilhas de CpG , Feminino , Perfilação da Expressão Gênica , Humanos , Antígeno Ki-1/metabolismo , Linfoma Cutâneo de Células T/metabolismo , Papulose Linfomatoide/genética , Papulose Linfomatoide/metabolismo , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/metabolismo , Masculino , Pessoa de Meia-Idade , Micose Fungoide/genética , Micose Fungoide/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Regiões Promotoras Genéticas , Estudos Retrospectivos , Adulto Jovem
14.
J Cutan Pathol ; 41(1): 51-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24151865

RESUMO

Primary cutaneous T-cell lymphomas (CTCL) comprise a heterogeneous group of neoplasms with diverse clinical behavior. Mycosis fungoides (MF) is the most common type of CTCL. Immunophenotypical shift during progression of the disease is a rare event and its significance is unknown. We present three primary CTCL cases that showed an immunophenotypical shift and poor prognosis. Conventional hematoxylin/eosin and immunohistochemical-stained sections were examined in all the cases. Molecular analysis for rearrangement of the T-cell receptor (TCR) gene was performed in two cases. One case was classified as MF, while the other two lacked epidermotropism, and were considered primary cutaneous peripheral T-cell lymphoma (PTCL), NOS. Two cases were CD3+/CD4+ and one case was CD3+/CD8+ at diagnosis. The first two patients suffered many relapses and eventually, new CTCL lesions with a CD3+/CD8+ phenotype were observed. Both cases revealed identical clonal TCR rearrangements on the initial and late lesions, supporting the interpretation of a single clonal proliferation with different phenotypes. The third case progressed with skin recurrences and pulmonary lesions with a predominant CD3+/CD4+/CD8- phenotype. All cases manifested poor prognosis and two patients died of lymphoma. Immunophenotypical shift between CD4 and CD8 in CTCL seems to be a rare phenomenon that may be associated with disease progression.


Assuntos
Antígenos CD4/imunologia , Antígenos CD8/imunologia , Linfoma Cutâneo de Células T/patologia , Neoplasias Cutâneas/patologia , Pele/patologia , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Imunofenotipagem , Linfoma Cutâneo de Células T/genética , Linfoma Cutâneo de Células T/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Pele/imunologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia
15.
J Am Acad Dermatol ; 69(3): 357-65, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23796549

RESUMO

BACKGROUND: Primary cutaneous marginal zone B-cell lymphomas are low-grade lymphomas running an indolent course. Skin relapses have been frequently reported but little information about disease-free survival (DFS) is available. OBJECTIVE: We sought to evaluate relapse rate and DFS in patients with primary cutaneous marginal zone B-cell lymphomas. METHODS: Clinical features, European Organization for Research and Treatment of Cancer/International Society for Cutaneous Lymphomas stage, light chain restriction, clonality, treatments, skin relapses, DFS, stage progression, extracutaneous disease, and outcome are analyzed in a series of 137 patients. RESULTS: Patients were classified as solitary lesion (T1) (n = 70; 51%), regional skin involvement (T2) (n = 40; 29%), and generalized skin lesions (T3) (n = 27; 20%). Surgical excision, local radiotherapy, or a combination were the initial treatment in 118 patients (86%). In 121 of 137 patients (88%) a complete remission was observed after initial treatment, including 99 of 106 patients (93%) with solitary or localized disease and 22 of 31 patients (71%) with multifocal lesions. Cutaneous relapses were observed in 53 patients (44%). Median DFS was 47 months. Patients with multifocal lesions or T3 disease showed higher relapse rate and shorter DFS. No significant differences were observed between surgery and radiotherapy, but surgery alone was associated with more recurrences at initial site. Overall survival at 5 and 10 years was 93%. Six patients (4%) developed extracutaneous disease during follow-up. LIMITATIONS: This was a case series retrospective study. CONCLUSION: Our results support long-term follow-up in patients with primary cutaneous marginal zone B-cell lymphomas. Disseminated skin lesions have higher relapse rate and shorter DFS suggesting further investigation on systemic therapies in such a group of patients.


Assuntos
Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/terapia , Recidiva Local de Neoplasia/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
16.
Artigo em Inglês | MEDLINE | ID: mdl-22668438

RESUMO

OBJECTIVES: The objective of this study was to analyze the clinical features of a series of patients with orofacial granulomatosis (OFG). STUDY DESIGN: Twenty patients diagnosed with OFG at Bellvitge Hospital (Barcelona, Spain) from 1985 to 2010 were included in the study. RESULTS: All of our patients (9 men and 11 women, median age 48.1 years) presented with labial swelling. Six patients presented with recurrent orofacial swelling, 12 with permanent swelling, and 2 with progressive swelling. Fissured tongue was observed in 9 cases, and 2 patients presented with recurrent episodes of peripheral facial paralysis. The median follow-up time was 65.1 months, ranging from 4 to 300 months. None of our patients developed sarcoidosis or Crohn disease. CONCLUSIONS: In the south of Europe, OFG does not appear to be as frequently associated with Crohn disease as in northern Europe. Although several treatments may achieve transient control of the orofacial swelling, there is no curative treatment for OFG and some patients may develop embarrassing lesions.


Assuntos
Granulomatose Orofacial/patologia , Adulto , Idoso , Doença Crônica , Doença de Crohn/complicações , Europa (Continente) , Feminino , Seguimentos , Granulomatose Orofacial/tratamento farmacológico , Granulomatose Orofacial/etiologia , Humanos , Doenças Labiais/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Espanha , Língua Fissurada/patologia , Adulto Jovem
17.
Biol Blood Marrow Transplant ; 18(2): 318-23, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22068151

RESUMO

Sclerotic chronic graft-versus-host disease (scGVHD) is a severe form of this disease that resembles systemic sclerosis and has limited and disappointing treatment options. Tyrosine kinase inhibitors (TKI) targeting up-regulated profibrotic pathways, such as imatinib mesylate, have been proposed as a potential therapeutic approach for patients with scGVHD. Dasatinib, a second-generation TKI with a well-established safety and efficacy profile in chronic myeloid leukemia patients, who are refractory or intolerant to imatinib, has also shown potent antifibrotic effects. We present here the first direct clinical evidence, from 3 patients treated in a small single-center series, suggesting that dasatinib can be a therapeutic option for patients with severe scGVHD resistant or intolerant to imatinib. All patients achieved partial response, with improvement in scGHVD target organs severity, joint mobility, lung impairment, and deep fibrotic lesions. This clinical response has remained stable or continued to improve after a median of 22 months (20-25) on dasatinib treatment, with very good tolerance. In addition, corticosteroids could be discontinued or significantly reduced in all patients. This clinical evidence suggests that dasatinib could be a safe and effective alternative for scGVHD patients refractory to corticosteroids and resistant or intolerant to imatinib. Based on these preliminary findings, and in order to address appropriate patient selection, time of intervention, and choice of drug, future larger studies should more formally establish the efficacy and safety of second-generation TKI for the treatment of scGVHD.


Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Piperazinas/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagem , Terapia de Salvação/métodos , Dermatopatias/tratamento farmacológico , Tiazóis/administração & dosagem , Adulto , Benzamidas , Transplante de Medula Óssea , Doença Crônica , Dasatinibe , Resistência a Medicamentos , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/fisiopatologia , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Masculino , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Esclerose , Dermatopatias/etiologia , Dermatopatias/patologia , Dermatopatias/fisiopatologia , Tiazóis/efeitos adversos , Transplante Homólogo
18.
J Am Acad Dermatol ; 66(4): 650-4, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21816504

RESUMO

BACKGROUND: Primary cutaneous diffuse large B-cell lymphoma (PCDLBCL), leg type can eventually disseminate to extracutaneous sites including testes. In addition, patients with testicular lymphoma can develop specific skin involvement. OBJECTIVE: We sought to describe similarities between PCDLBCL, leg type and testicular B-cell lymphoma affecting the skin. METHODS: We report two cases with typical clinicopathological and immunophenotypical features of leg type lymphoma occurring simultaneously with a testicular B-cell lymphoma. We also report an additional case of PCDLBCL, leg type with secondary testicular involvement. RESULTS: All cases presented with typical red tumors exclusively located on the legs. Histologically, all cases showed a diffuse nonepidermotropic infiltrate composed of large blastic cells mainly centroblastic type. Phenotype showed strong positivity for Bcl-2, MUM-1, and FOXP1. Epstein-Barr virus stains and CD30 were negative in the 3 cases. In all cases the testicular infiltration showed the same pathological and phenotypical changes to those observed in the skin. LIMITATIONS: This was a retrospective case series study. CONCLUSION: Skin involvement by testicular B-cell lymphomas and PCDLBCL, leg type are indistinguishable on the basis of pathologic and immunophenotypical features, therefore specific investigation and clinic correlation are needed.


Assuntos
Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Neoplasias Cutâneas/patologia , Neoplasias Testiculares/secundário , Idoso , Humanos , Imunofenotipagem , Perna (Membro) , Linfoma de Células B/genética , Linfoma de Células B/imunologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/imunologia , Masculino , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia
19.
Cancer Genet ; 204(7): 405-9, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21872828

RESUMO

Chromosomal aberrations involving T-cell receptor (TCR) gene loci have been described in several T-cell malignancies. In primary cutaneous T-cell lymphomas (CTCL), the frequency of these aberrations has not yet been well established. We analyzed TCR gene loci (TCRAD, TCRB, and TCRG) status in CTCLs by fluorescence in situ hybridization (FISH). Twenty-five patients with CTCLs were included in the study: 13 Sézary syndromes (SS), six tumoral stage mycosis fungoides (MFt), and six primary cutaneous anaplastic large cell lymphomas CD30(+) (cALCL-CD30(+)). FISH was performed with three break-apart probes flanking TCRAD (14q11), TCRB (7q34), and TCRG (7p14) loci in each case. TCR gene chromosomal rearrangements were not detected in any of the analyzed cases. Gains of TCRB and TCRG genes were observed in 23% (3 of 13) of SS and 50% (3 of 6) of MFt, reflecting the presence of trisomy and/or tetrasomy of chromosome 7 already detected by conventional cytogenetics and array comparative genetic hybridization techniques. TCR loci rearrangements are not frequent in CTCLs; however, we cannot exclude a pathogenic role in these malignancies.


Assuntos
Genes Codificadores dos Receptores de Linfócitos T , Micose Fungoide/genética , Síndrome de Sézary/genética , Neoplasias Cutâneas/genética , Tetrassomia , Translocação Genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 7/genética , Feminino , Loci Gênicos , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Micose Fungoide/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T gama-delta/genética , Estudos Retrospectivos , Síndrome de Sézary/patologia , Neoplasias Cutâneas/patologia
20.
Histol Histopathol ; 26(2): 213-21, 2011 02.
Artigo em Inglês | MEDLINE | ID: mdl-21154235

RESUMO

FOXP1 protein is expressed in normal activated B cells and overexpressed in a subset of diffuse large B-cell lymphomas, including primary cutaneous large B-cell lymphomas (PCLBCL), leg type. High expression of FOXP1 has been associated to an unfavourable prognosis with independent survival significance. However, little is known regarding the mechanisms underlying the overexpression of FOXP1 in PCLBCL, leg type. Our aims were to analyze FOXP1 cytogenetic status and protein expression in a series of PCLBCL, leg type. Finally, we compared the observed results with those obtained in a group of patients with primary cutaneous follicle centre lymphoma (PCFCL). Fifteen patients with PCLBCL, leg type and nine patients with primary cutaneous follicle centre lymphoma (PCFCL) were included in the study. For each biopsy specimen, FOXP1 translocation and copy number changes were evaluated by fluorescence in situ hybridization (FISH) and protein expression by immunohistochemistry (IHC). Immunohistochemistry showed FOXP1 staining in 13 PCLBCL, leg type, whereas all PCFCL were negative. FISH analysis disclosed no translocations involving FOXP1 gene in any of the cases. However, FOXP1 gene gains (3 to 4 copies) were observed in 82% of samples of PCLBCL, leg type and in 37% of PCFCL. FOXP1 expression was independent from FOXP1 translocation. Our results confirm that overexpression of FOXP1 is present in a considerable proportion of PCLBCL, leg type and might indicate an unfavourable prognosis. Mechanisms not related to translocation seem to be responsible for this overexpression.


Assuntos
Fatores de Transcrição Forkhead/genética , Linfoma Difuso de Grandes Células B/genética , Proteínas Repressoras/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Aberrações Cromossômicas , Feminino , Fatores de Transcrição Forkhead/metabolismo , Dosagem de Genes , Duplicação Gênica , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Perna (Membro)/patologia , Linfoma Folicular/genética , Linfoma Folicular/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Repressoras/metabolismo , Estudos Retrospectivos , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
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