RESUMO
Mutations in two genes encoding cell cycle regulatory proteins have been shown to cause familial cutaneous malignant melanoma (CMM). About 20% of melanoma-prone families bear a point mutation in the CDKN2A locus at 9p21, which encodes two unrelated proteins, p16(INK4a) and p14(ARF). Rare mutations in CDK4 have also been linked to the disease. Although the CDKN2A gene has been shown to be the major melanoma predisposing gene, there remains a significant proportion of melanoma kindreds linked to 9p21 in which germline mutations of CDKN2A have not been identified through direct exon sequencing. The purpose of this study was to assess the contribution of large rearrangements in CDKN2A to the disease in melanoma-prone families using multiplex ligation-dependent probe amplification. We examined 214 patients from independent pedigrees with at least two CMM cases. All had been tested for CDKN2A and CDK4 point mutation, and 47 were found positive. Among the remaining 167 negative patients, one carried a novel genomic deletion of CDKN2A exon 2. Overall, genomic deletions represented 2.1% of total mutations in this series (1 of 48), confirming that they explain a very small proportion of CMM susceptibility. In addition, we excluded a new gene on 9p21, KLHL9, as being a major CMM gene.
Assuntos
Genes p16 , Melanoma/genética , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Proteínas de Transporte/genética , Cromossomos Humanos Par 9 , Inibidor p16 de Quinase Dependente de Ciclina/genética , Éxons , Feminino , Deleção de Genes , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , Mutação Puntual , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína Supressora de Tumor p14ARF/genéticaRESUMO
Metastatic melanoma treatment remains disappointing, and a combined approach by chemotherapy and immunotherapy might increase the response rates through a synergistic action. Accordingly, a clinical trial using oral temozolomide (TMZ) and subcutaneous PEG-interferon alpha-2b (PEG) in patients with metastatic melanoma was designed to determine the maximal tolerated dosage of both drugs and the antitumoral response. A multicenter, prospective, phase I/II study was conducted in 31 metastatic melanoma patients, without cerebral metastasis. Dose escalation was performed according to the modified continual reassessment method scale and resulted in four cohorts of patients: TMZ 150 mg/m2 5 days/week each 4 weeks and PEG 0.5 microg/kg/week - TMZ 150 mg/m2 5 days/week and PEG 1.0 microg/kg/week - TMZ 200 mg/m2 5 days/week and PEG 0.5 microg/kg/week - TMZ 200 mg/m2 5 days/week and PEG 1.0 microg/kg/week. Patients received a maximum of six cycles. Thirty-three patients were enrolled in this study: one in the first dose level, one in the second one, 18 in the third one and 11 in the fourth one. At level 4, four of 11 patients experienced dose-limiting toxicity and four nondose-limiting toxicity; toxicity was mainly hematologic (grade IV thrombocytopenia). An objective response was observed in five patients (two complete response and three partial response) receiving level 3 or 4 of treatment. The disease remained stable in three patients, and six of 31 patients were alive 24 months after enrollment. The association of oral TMZ with subcutaneous PEG in metastatic melanoma displayed an unacceptable hematological toxicity with the dosages of 200 mg/m2 5 days/week and 1 microg/week, respectively. At a lower level, this treatment was effective and deserves further investigations to define its indications in metastatic melanoma patients.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Dacarbazina/análogos & derivados , Interferon-alfa/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Administração Oral , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/imunologia , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/imunologia , Dacarbazina/uso terapêutico , Feminino , Humanos , Injeções Subcutâneas , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Interferon-alfa/imunologia , Masculino , Melanoma/imunologia , Pessoa de Meia-Idade , Polietilenoglicóis , Proteínas Recombinantes , Neoplasias Cutâneas/imunologia , TemozolomidaRESUMO
OBJECTIVES: To describe clinicopathologic features and to identify prognostic factors in a large series of primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL LT), as defined in the recent World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas. DESIGN: Retrospective multicenter study from the French Study Group on Cutaneous Lymphomas. SETTING: Nineteen departments of dermatology in 10 regions of France. PATIENTS: Sixty patients with a PCLBCL LT included in the registry of the French Study Group on Cutaneous Lymphomas. MAIN OUTCOME MEASURES: Age, sex, outcome, therapy, B symptoms, cutaneous extent, number of lesions, location (leg vs nonleg), serum lactate dehydrogenase level, and MUM-1 and Bcl-2 expression were recorded. Disease-specific survival was used as the main end point. Prognostic factors were identified using a Cox proportional hazards model. RESULTS: Primary cutaneous diffuse large B-cell lymphoma, leg type is characterized by a predilection for the leg (72%), a high proportion of Bcl-2 expression (85%), an advanced age at onset (mean age, 76 years), and frequent relapses and extracutaneous dissemination. The overall 5-year disease-specific survival rate was 41%. Location on the leg and multiple skin lesions were predictive of death in multivariate analysis. Although no variable related to therapy was significantly associated with survival, patients recently treated with combinations of anthracycline-containing chemotherapies and rituximab had a more favorable short-term outcome. CONCLUSIONS: Primary cutaneous diffuse large B-cell lymphoma, leg type is a distinct entity with a poor prognosis, particularly in patients with multiple tumors on the legs. Despite the advanced age of many patients, the prognosis could be improved with combinations of anthracycline-containing chemotherapies and rituximab.
Assuntos
Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Perna (Membro) , Linfoma de Células B/diagnóstico , Linfoma de Células B/mortalidade , Linfoma de Células B/terapia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapiaRESUMO
Cowden syndrome (CS) is a rare autosomal dominant genodermatosis, characterized by multiple hamartomas, particularly of the skin, associated with high frequencies of breast, thyroid, and genitourinary malignancies. Although Lhermitte-Duclos disease (LDD) or dysplastic gangliocytoma of the cerebellum, a slowly progressive unilateral tumor, is a major criterion of CS, its frequency in patients with CS is unknown. Other cerebral abnormalities, especially meningioma and vascular malformations, have also been described, albeit rarely, in these patients. The aim of the current study was to use cerebral magnetic resonance imaging (MRI) to evaluate LDD frequency and to investigate other brain abnormalities in CS patients recruited by dermatologists. A multicenter study was conducted in 8 hospital dermatology departments between January 2000 and December 2003. Twenty patients with CS were included; specific cerebral MRI abnormalities were found in 35% (7/20) of them. Cerebral MRI revealed LDD in 3 patients, a meningioma in 1, and numerous vascular malformations in 6 patients. Five patients had venous angiomas (3 associated with LDD) and 2 patients had cavernous angiomas (1 associated with LDD and a venous angioma). The discovery of asymptomatic LDD in 3 patients and a cavernous angioma in another prompted us to perform neurologic examinations regularly and MRI to estimate the size and the extension of the tumor, and to assess the need for surgery. CS similarities with Bannayan-Riley-Ruvalcaba (BRR) are discussed because some patients could also have the BRR phenotype (for example, genital lentigines, macrocephaly, multiple lipomas) and because BRR seems to have more central nervous system vascular anomalies. Because CS signs can involve numerous systems, all physicians who might encounter this disease should be aware of its neurologic manifestations. Our findings confirm the contribution of brain MRI to detecting asymptomatic LDD, vascular malformations, and meningiomas in patients with CS.
Assuntos
Encéfalo/patologia , Síndrome do Hamartoma Múltiplo/patologia , Imageamento por Ressonância Magnética , Adolescente , Adulto , Idoso , Angioma Venoso do Sistema Nervoso Central/complicações , Angioma Venoso do Sistema Nervoso Central/patologia , Neoplasias Cerebelares/complicações , Neoplasias Cerebelares/patologia , Criança , Feminino , Ganglioneuroma/complicações , Ganglioneuroma/patologia , Síndrome do Hamartoma Múltiplo/complicações , Síndrome do Hamartoma Múltiplo/genética , Hemangioma/complicações , Hemangioma/patologia , Humanos , Masculino , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/patologia , Meningioma/complicações , Meningioma/patologia , Pessoa de Meia-Idade , Mutação , PTEN Fosfo-Hidrolase , Monoéster Fosfórico Hidrolases/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
Blastic natural killer (NK) cell lymphoma (also termed CD4+CD56+ hematodermic neoplasm) is a recently described entity, with the first case reported in 1994. It was suggested initially that the disease originates from NK cells. Since 1994, single cases and a few small series have been published. In this review, data from the literature and a series of 30 cases from the French and Dutch study groups on cutaneous lymphomas are discussed. The major clinical, histopathologic, and phenotypic aspects of the disease and diagnostic criteria and data suggesting a plasmacytoid dendritic cell origin for the tumor cells are provided.
Assuntos
Antígenos de Neoplasias/metabolismo , Antígenos CD4/metabolismo , Antígeno CD56/metabolismo , Células Matadoras Naturais/patologia , Linfoma não Hodgkin/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Criança , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Feminino , Humanos , Células Matadoras Naturais/metabolismo , Linfoma não Hodgkin/metabolismo , Masculino , Pessoa de Meia-Idade , Plasmócitos/metabolismo , Plasmócitos/patologia , Neoplasias Cutâneas/metabolismoRESUMO
OBJECTIVE: To determine if a therapeutic regimen of twice-weekly applications of mechlorethamine hydrochloride and betamethasone dipropionate cream is effective in the treatment of early-stage mycosis fungoides while increasing cutaneous tolerance. DESIGN: Prospective nonrandomized study conducted from November 1999 to November 2002. SETTING: Eleven university or hospital dermatology departments in France. PATIENTS: Sixty-four consecutive patients with newly diagnosed early-stage mycosis fungoides (stage IA, n = 33; stage IB, n = 26; stage IIA, n = 5). INTERVENTIONS: Patients were treated with twice-weekly applications of a 0.02% aqueous solution of mechlorethamine followed by an application of betamethasone cream during a 6-month period. MAIN OUTCOME MEASURES: The primary end point was the rate of complete response during the treatment. Secondary end points were mean delay to achieve complete response, rate of severe cutaneous reactions of intolerance, and rate of relapse after achieving complete response. RESULTS: Thirty-seven patients (58%) had a complete response after a mean +/- SD treatment duration of 3.6 +/- 2.5 months: 20 (61%) of 33 patients with stage IA disease, 15 (58%) of 26 patients with stage IB disease, and 2 (40%) of 5 patients with stage IIA disease. Eighteen patients (28%) developed severe cutaneous reactions of intolerance that necessitated treatment discontinuation. Relapse was observed in 17 patients (46%) after a mean +/- SD time of 7.7 +/- 6.5 months. CONCLUSIONS: A regimen of twice-weekly applications of mechlorethamine and betamethasone cream is an effective treatment for early-stage mycosis fungoides. The decreased frequency of applications provides an advantage to the patient by being easy to use with limited adverse effects.
Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Beclometasona/administração & dosagem , Glucocorticoides/administração & dosagem , Mecloretamina/administração & dosagem , Micose Fungoide/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Administração Tópica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/efeitos adversos , Beclometasona/efeitos adversos , Criança , Esquema de Medicação , Quimioterapia Combinada , Feminino , Glucocorticoides/efeitos adversos , Humanos , Masculino , Mecloretamina/efeitos adversos , Pessoa de Meia-Idade , Micose Fungoide/patologia , Neoplasias Cutâneas/patologiaRESUMO
This study was undertaken to determine the prognostic value of bone marrow histopathologic and molecular analyses in 53 patients with mycosis fungoides and 7 with Sézary syndrome. Bone marrow was involved in only 1 patient with Sézary syndrome, clinical stage IVA, before bone marrow biopsy. An ambiguous T-cell infiltrate was observed in 8 patients but was not associated with disease progression. The bone marrow specimen was normal in 51 patients. Monoclonality was detected in the skin specimen in 44 cases; an identical T-cell clone in the blood specimen was found in 21 of them and, in 16 of the 21 patients, in bone marrow specimens without histologic correlation. Multivariate analysis confirmed that clinical stage and detection by polymerase chain reaction of an identical T-cell clone in skin and blood specimens had an independent prognostic value. No further prognostic value was observed for the presence of a T-cell clone in bone marrow specimens. Our data do not support the need for bone marrow examination in patients with mycosis fungoides/Sézary syndrome.
Assuntos
Células da Medula Óssea/patologia , Síndrome de Sézary/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Clonais , DNA de Neoplasias/análise , Eletroforese em Gel de Poliacrilamida , Feminino , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T/genética , Humanos , Masculino , Pessoa de Meia-Idade , Micose Fungoide/genética , Micose Fungoide/patologia , Reação em Cadeia da Polimerase , Prognóstico , Estudos Prospectivos , Síndrome de Sézary/genética , Neoplasias Cutâneas/genéticaRESUMO
Neurofibromatosis 1 (NF1) is a genetically transmitted disease occurring approximately once in 3000 live births and resulting from mutations of the NF1 gene that encodes a protein named neurofibromin, a negative regulator of the ras-dependent pathway. An excess of neoplasia especially tumours of neuroectodermal origin is classically observed. The occurrence of malignant melanoma in patients with NF1 has already been described in scattered clinical reports but little is known as to the characteristics of melanoma arising in NF1 patients. A multicentric retrospective study was conducted on a panel of French referring centres for a period of 13 years to identify patients with both melanoma and NF1. Patients with mucosal or ocular melanoma were excluded. The diagnosis of malignant melanoma was based on specific histology whereas NF1 was identified according to the criteria proposed by the NIH Consensus Conference. All patient fulfilling criteria for both melanoma and NF1 were investigated using a common procedure recording clinical and histological data along with prognostic factors for the two diseases. Eleven patients were identified with both diseases. The clinical pattern of NF1 was quite similar to the classical form of the disease, but some unusual features were present as regards to the melanoma: a sex-ratio of 10 women for one man and an average age lower than expected (median age=33 years) for melanoma occurrence. Among prognostic factors, median thickness was high compared to large series of melanoma in the literature (3.20 versus 1.5 mm). Another neoplasia occurred in three patients. An increase in melanoma incidence in patients with NF1 remains hypothetical but our small series of malignant melanoma arising in NF1 patients displays a large female preponderance, a higher thickness than expected and a frequent association with a second neoplasia. The peculiar female proneness for cancer whatever its localization and the risk of multiple neoplasias have already been reported in NF1 patients and could be true for malignant melanoma as well.
Assuntos
Melanoma/complicações , Neurofibromatose 1/complicações , Neoplasias Cutâneas/complicações , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Melanoma/diagnóstico , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neurofibromatose 1/diagnóstico , Estudos Retrospectivos , Distribuição por Sexo , Neoplasias Cutâneas/diagnósticoRESUMO
The early diagnosis of cutaneous melanoma alone is capable of significantly reducing the morbidity and mortality associated with this tumour. It is pertinent to all physicians who normally observe skin during the clinical examination; who must have a degree of suspicion for all recent or modified pigmented lesions, and should offer a cutaneous follow-up and advise decreased sun exposure in all patients with multiple naevi. The modification of a lesion, intensely black in colour, are the key elements which arouse suspicion of a melanoma and incite either its removal or a specialist opinion. The follow-up of the patient treated surgically for a melanoma is mainly clinical (skin, subcutaneous tissues, lymph node examination) but has to be consistent (more often on a trimesterly basis), systematic, and annual after 5 to 8 years, during the whole life of the patient with a high risk of a second melanoma. Equally, family members of a patient with a melanoma should also be systematically examined.
Assuntos
Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Diagnóstico Diferencial , Diagnóstico Precoce , Seguimentos , Humanos , Melanoma/genética , Melanoma/cirurgia , Nevo/diagnóstico , Educação de Pacientes como Assunto , Linhagem , Fatores de Risco , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/cirurgiaAssuntos
Dermatofibrossarcoma/genética , Proteínas de Fusão Oncogênica/genética , Adulto , Humanos , Masculino , OmbroAssuntos
Adenoma de Glândula Sudorípara/diagnóstico , Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias das Glândulas Sudoríparas/diagnóstico , Adenoma de Glândula Sudorípara/tratamento farmacológico , Adenoma de Glândula Sudorípara/patologia , Antimetabólitos Antineoplásicos/administração & dosagem , Axila , Capecitabina , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Diagnóstico Diferencial , Esquema de Medicação , Cotovelo , Feminino , Fluoruracila/análogos & derivados , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias das Glândulas Sudoríparas/tratamento farmacológico , Neoplasias das Glândulas Sudoríparas/patologiaAssuntos
Hematoma/etiologia , Hemorragia/etiologia , Melanoma/secundário , Neoplasias Musculares/secundário , Neoplasias Cutâneas/diagnóstico , Neoplasias Vasculares/secundário , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/uso terapêutico , Encéfalo/irrigação sanguínea , Dacarbazina/uso terapêutico , Diagnóstico Diferencial , Evolução Fatal , Hematoma/patologia , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , Melanoma/complicações , Melanoma/diagnóstico , Melanoma/tratamento farmacológico , Melanoma/epidemiologia , Neoplasias Musculares/diagnóstico , Neoplasias Musculares/tratamento farmacológico , Neoplasias Musculares/epidemiologia , Paresia/etiologia , Pele/irrigação sanguínea , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Vasculares/complicações , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/tratamento farmacológico , Neoplasias Vasculares/epidemiologia , Neoplasias Vasculares/patologiaRESUMO
BACKGROUND: A 72-year-old man presented with a Merkel cell carcinoma (MCC) of the left cheek with concomitant nodal spread. A 61-year-old man presented with an MCC of the right thigh with rapid nodal recurrence. INVESTIGATIONS: Skin biopsy samples proved the MCC nature of the neoplasm in both patients. Staging procedure included clinical and radiological investigations. DIAGNOSIS: Advanced stage II MCC. MANAGEMENT: Neoadjuvant cisplatin, etoposide and cyclophosphamide (EPC) regimen led to local control in the first patient and allowed curative surgery associated with adjuvant radiation therapy. Complete remission was maintained for 32 months. The second patient was treated by surgery plus radiation therapy. Nodal and cutaneous recurrences were treated with a neoadjuvant EPC regimen leading to a 5-year complete remission.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Célula de Merkel/tratamento farmacológico , Carcinoma de Célula de Merkel/patologia , Carcinoma de Célula de Merkel/radioterapia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Idoso , Cisplatino/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Etoposídeo/administração & dosagem , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Radioterapia Adjuvante/métodos , Indução de Remissão , Neoplasias Cutâneas/cirurgia , Análise de SobrevidaRESUMO
OBJECTIVE: To assess the rate of objective response to pegylated liposomal doxorubicin hydrochloride (Caelyx) in patients with advanced or refractory cutaneous T-cell lymphoma (CTCL). DESIGN: Prospective, open, multicenter study. SETTING: Thirteen dermatology departments in France. PATIENTS: Twenty-five patients with either (1) stage II to stage IV CTCL previously unsuccessfully treated with at least 2 lines of treatments or (2) histologically transformed epidermotropic CTCL requiring chemotherapy. INTERVENTION: Administration of Caelyx intravenously once every 4 weeks at a dose of 40 mg/m(2). MAIN OUTCOME MEASURES: The response to treatment was evaluated by clinical evaluation. RESULTS: At the end of treatment, we observed an objective response (primary end point) in 56% of the patients (14 of 25): 5 complete responses and 9 partial responses. The median overall survival time was 43.7 months. For the 14 patients who experienced an objective response, the median progression-free survival time after the end of treatment was 5 months. CONCLUSIONS: This prospective study demonstrates the effectiveness of Caelyx in treating CTCL, with an overall response rate of 56% in spite of the high proportion of patients with advanced-stage disease. Responses were observed in 2 subpopulations of patients in which the prognosis is known to be poorer: Sézary syndrome (overall response rate, 60%) and transformed CTCL (overall response rate, 50%). Moreover, this study shows that dose escalation to 40 mg/m(2) does not seem to improve the effectiveness but increases toxic effects (especially hematologic toxic effects) compared with the dose previously tested of 20 mg/m(2).
Assuntos
Doxorrubicina/análogos & derivados , Micose Fungoide/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Micose Fungoide/diagnóstico , Estadiamento de Neoplasias , Polietilenoglicóis/administração & dosagem , Estudos Prospectivos , Neoplasias Cutâneas/diagnóstico , Síndrome , Resultado do TratamentoRESUMO
Primary cutaneous CD30+ large T-cell lymphoma (CD30+ CTCL) is a subset of non-epidermotropic primary cutaneous T-cell lymphoma. Although frequent spontaneous regression may be observed, skin relapses occur frequently. Cytogenetic abnormalities that could play a role in CD30+ CTCL tumour pathogenesis and relapses remain unknown. The identification of recurrent cytogenetic abnormalities is hampered by difficulty in culturing tumours and the lack of CD30+ CTCL serial studies comparing genetic changes both at diagnosis and at relapse. The purpose of this study was to investigate the cytogenetic abnormalities present in a series of 13 CD30+ CTCL samples obtained from nine patients fulfilling both EORTC and WHO diagnostic criteria, by the use of comparative genomic hybridization (CGH). CGH analysis revealed a non-random distribution of genetic imbalances between relapsing and non-relapsing disease. In relapsing disease, chromosomal abnormalities were detected both in the primary tumour and in relapses. The mean number of changes in non-relapsing disease was 0.33 (range 0-1), compared with 6.29 (range 1-16) in relapsing disease. The recurrent chromosomes involved in relapsing disease were chromosomes 6 (86%), 9 (86%), and 18 (43%). While chromosome 9 was mostly affected by gain, chromosomes 6 and 18 mainly contained regions of loss, exclusively on 6q and 18p. The common regions of deletion were 6q21 and 18p11.3. In one patient, we successfully cultured tumour cells from a skin biopsy from a second relapse. The G-banded karyotype was concordant with both CGH and fluorescence in situ hybridization (FISH) results. Although further studies are required to strengthen these data, this CGH analysis demonstrates chromosomal imbalances that may be involved in the pathogenesis of relapsing CD30+ CTCL.
Assuntos
Aberrações Cromossômicas , Antígeno Ki-1/genética , Linfoma Difuso de Grandes Células B/genética , Linfoma Cutâneo de Células T/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 6/genética , Cromossomos Humanos Par 9/genética , DNA de Neoplasias/análise , Deleção de Genes , Rearranjo Gênico , Humanos , Hibridização Genética/genética , Hibridização in Situ Fluorescente/métodos , Cariotipagem/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Células Tumorais CultivadasRESUMO
Primary melanoma (MM) could be a good model to test an intuitive concept: a cancer that is growing fast in its early phase is likely to have a high aggressiveness. Since MMs are visible tumors, many patients can provide information to indirectly assess the kinetics of their lesion. A prospective study was designed to assess if the kinetics of the visible growth of a primary MM, as described by the patient, could be a noninvasive prognostic marker. The ratio of MM thickness to delay between MM appearance and MM removal was used as a surrogate value for the kinetics of the MM growth. To assess the delay between MM appearance and removal, 362 patients with self-detected invasive MM fulfilled a detailed questionnaire, which provided 2 types of estimations of this delay and thus 2 melanoma kinetics indexes (MKI and MKI*). After a median follow-up of 4 years, univariate and multivariate analyses assessed whether relapse-free survival was linked to MKI or MKI*. MKI was significantly predictive of relapse-free survival (HR = 1.84 [1.51-2.25]) and relapse at 1 year (RR = 2.93 [1.84-4.69]), independently from Breslow thickness. MKI was retained in multivariate prognostic models, just after thickness and before other usual markers. MKI* was also a significant independent risk marker, although less predictive. In this model, the initial growth kinetics of a cancer reflects its aggressiveness and a high index predicts a short-term relapse. The "subjective" data obtained from patients about their MM history, although usually neglected, can thus provide a better prognostic marker than many "objective" tests.
Assuntos
Melanoma/patologia , Neoplasias Cutâneas/patologia , Biomarcadores/análise , Progressão da Doença , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Estudos Prospectivos , Inquéritos e Questionários , Fatores de TempoRESUMO
Bcl-2 protein expression has been associated with poor prognosis in patients with noncutaneous diffuse large B-cell lymphomas. In primary cutaneous large B-cell lymphomas, the location on the leg, the round-cell morphology defined as the predominance of centroblasts and immunoblasts over large centrocytes, and multiple skin lesions were identified as adverse prognostic factors. The prognostic value of bcl-2 protein expression has not been studied in large series of patients. We evaluated 80 primary cutaneous large B-cell lymphomas collected by the French Study Group on Cutaneous Lymphomas. The prognostic value of age, sex, number of lesions, cutaneous extent, location, serum lactate dehydrogenase (LDH) level, B symptoms, morphology, and bcl-2 protein expression was studied. The overall 5-year specific survival rate was 65%. In univariate analysis, advanced age, multiple skin lesions (n = 48), location on the leg (n = 25), round-cell morphology (n = 32), and bcl-2 expression (n = 39) were significantly related to death from lymphoma. In multivariate analysis, bcl-2 expression (P =.0003), multiple skin lesions (P =.004), and age remained independent prognostic factors. The 5-year specific survival rates in bcl-2-positive and bcl-2-negative patients were 41% and 89%, respectively (P <.0001). A new prognostic classification of primary cutaneous B-cell lymphoma should be based primarily on bcl-2 protein expression rather than the location of skin lesions.