RESUMO
Two distinct primary cutaneous large B cell lymphomas are recognized: primary cutaneous follicle centre lymphoma (PCFCL), characterized by an excellent prognosis, and primary cutaneous large B cell lymphoma, leg-type (PCLBCL leg-type), with an unfavourable prognosis. To determine whether inhibition of the apoptosis pathways may underlie the difference in clinical outcome between PCFCL and PCLBCL leg-type, we investigated the expression of only apoptosis-related genes by microarray expression profiling. Unsupervised cluster analysis was carried out using 169 genes involved in apoptosis on a group of 21 previously untreated patients diagnosed with primary cutaneous large B cell lymphoma. Cluster analysis resulted in two separate groups which showed large overlap with the PCFCL and PCLBCL leg-type. One group was characterized by high expression levels of pro- and anti-apoptotic genes. The other group was characterized by high expression levels of apoptosis-inducing cytotoxic effector genes, possibly reflecting a cellular cytotoxic immune response. Our results suggest that the clinically favourable PCFCLs are characterized by a relatively intense cellular cytotoxic immune response and that PCLBCL leg-types are characterized by constitutive activation of the intrinsic mediated apoptosis pathway, with concomitant downstream inhibition of this apoptosis pathway. Thus, strategies neutralizing the function of apoptosis-inhibiting proteins might be effective in PCLBCL leg-type.
Assuntos
Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Linfoma Difuso de Grandes Células B/genética , Neoplasias Primárias Múltiplas/genética , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Análise por Conglomerados , Citotoxicidade Imunológica/genética , Feminino , Humanos , Imuno-Histoquímica , Perna (Membro) , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Couro Cabeludo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/mortalidade , Análise de Sobrevida , TóraxRESUMO
BACKGROUND: Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is a low-grade B-cell lymphoma that originates in the skin, with no evidence of extracutaneous disease. Studies focusing on the optimal treatment of PCMZL have not been published thus far. We describe 50 patients with PCMZL to further characterize clinical characteristics and outcome and, in particular, to evaluate our current therapeutic approach. OBSERVATIONS: The majority of the patients (36/50 [72%]) presented with multifocal skin lesions, and 14 patients (28%) presented with solitary or localized lesions. The initial treatment of patients with solitary lesions consisted of radiotherapy or excision, whereas patients with multifocal lesions received a variety of initial treatments, most commonly radiotherapy and chlorambucil therapy. Cutaneous relapses developed in 19 (48%) of 40 patients who had complete remission and were more common in patients with multifocal disease. After a median period of follow-up of 36 months, 2 patients developed extracutaneous disease, but none of the patients died of lymphoma. CONCLUSIONS: Patients with PCMZL who have solitary lesions can be treated effectively with radiotherapy or excision. For patients with PCMZL who have multifocal lesions, chlorambucil therapy and radiotherapy are suitable therapeutic options. In case of cutaneous relapses, the beneficial effects of treatment should carefully be weighed against the potential adverse effects.
Assuntos
Linfoma de Células B/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Feminino , Humanos , Metástase Linfática , Linfoma de Células B/terapia , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Neoplasias Cutâneas/terapiaRESUMO
Primary cutaneous marginal zone lymphomas (PCMZL) share histological and clinical characteristics with mucosa-associated lymphoid tissue (MALT) lymphomas suggesting a common pathogenesis. A number of recurrent structural and numerical chromosomal aberrations have been described in MALT lymphoma, but their incidence in PCMZL is largely unknown, as is their relation with clinical and pathological data. In this study, the incidence of t(11;18)(q21;q21), t(1;14)(p22;q32), two different t(14;18)(q32;q21), involving either IGH/MALT1 or IGH/BCL2, and numerical aberrations of chromosomes 3, 7, 12 and 18 were analysed in 12 patients with PCMZL, with follow-up of up to 10 years. Nuclei were isolated from paraffin wax sections for dual-colour interphase fluorescence in situ hybridization (FISH) using various probe sets either flanking or spanning the involved genes. T(14;18)(q32;q21), with breakpoints in IGH and MALT1, was found in three cases. All three had partly monocytoid histological appearances and lacked blastic transformation. An additional trisomy of chromosome 3 was detected in one of these cases. Trisomy 18 was present in two lymphomas without monocytoid morphology. No definite correlation was seen with any clinical feature, including Borrelia serology. Neither t(11;18)(q21;q21), nor t(1;14)(p22;q32) or any other translocation involving IGH, BCL10, MALT1, BCL2 and API2, amplification or deletion of chromosomal region 11q21, 18q21, 1p22, and 14q32 was detected. These results indicate that a subgroup of PCMZL with partly monocytoid morphology is genetically related to MZL at other extranodal sites.
Assuntos
Linfoma de Células B/genética , Neoplasias Cutâneas/genética , Translocação Genética , Trissomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Caspases , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 18/genética , Feminino , Seguimentos , Humanos , Hibridização in Situ Fluorescente , Linfoma de Células B/patologia , Linfoma de Zona Marginal Tipo Células B/genética , Masculino , Pessoa de Meia-Idade , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa , Proteínas de Neoplasias/genética , Prognóstico , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Primary cutaneous follicle centre cell lymphomas (PCFCCLs) are the most common type of cutaneous B-cell lymphoma. There is ongoing discussion on the origin of the neoplastic B cells in these PCFCCLs, and consequently on their relation to the groups of primary cutaneous marginal zone B-cell lymphomas (PCMZLs) and nodal follicular lymphomas. OBJECTIVES: To define better the neoplastic B cells in PCFCCLs, and to find out if differences in the expression of the antiapoptopic protein Bcl-2, and Bcl-6 and CD10, molecules which are normally expressed by the neoplastic B cells in nodal follicular lymphomas, might have diagnostic or prognostic significance in cutaneous B-cell lymphoproliferative disorders. METHODS: Pretreatment biopsies of well-defined groups of PCFCCL (n = 24), PCMZL (n = 14), primary cutaneous large B-cell lymphoma of the leg (PCLBCL-leg; n = 19), secondary cutaneous follicular lymphoma (n = 3) and cutaneous pseudo-B-cell lymphoma (n = 6) were investigated by immunohistochemistry for expression of Bcl-2, Bcl-6 and CD10. RESULTS: The PCFCCLs consistently expressed Bcl-6, whereas CD10 and Bcl-2 were expressed in only one and two of 24 cases, respectively. In contrast, PCMZLs were always negative for Bcl-6 and CD10, but were Bcl-2 positive, whereas skin and lymph node localizations of secondary cutaneous follicular lymphomas consistently expressed all of Bcl-2, Bcl-6 and CD10. Reactive follicle centre cells in pseudo-B-cell lymphomas expressed Bcl-6 (six of six cases) and CD10 (five of six cases), but not Bcl-2. PCLBCL-leg was Bcl-6 positive and CD10 negative in all cases, irrespective of clinical outcome, and strongly expressed Bcl-2 protein in all but two cases. CONCLUSIONS: The results of the present study provide further support for the follicle centre cell origin of both PCFCCL and PCLBCL-leg, and indicate that staining for Bcl-2, Bcl-6 and CD10 can serve as an important adjunct in the differential diagnosis of cutaneous B-cell lymphoproliferative disorders.
Assuntos
Proteínas de Ligação a DNA/análise , Linfoma de Células B/química , Linfoma Folicular/química , Neprilisina/análise , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas/análise , Neoplasias Cutâneas/química , Fatores de Transcrição/análise , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica/métodos , Imunofenotipagem , Perna (Membro) , Linfoma de Células B/patologia , Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/química , Linfoma Difuso de Grandes Células B/patologia , Proteínas Proto-Oncogênicas c-bcl-6 , Pseudolinfoma/metabolismo , Pseudolinfoma/patologiaRESUMO
BACKGROUND: Therapy with fumaric acid esters (FAE) has been shown to be safe and effective in patients with severe psoriasis in several clinical studies with limited follow-up periods. In view of the chronic character of psoriasis, long-term safety aspects are of major importance in determining the suitability of a drug during prolonged periods of treatment. OBJECTIVES: To investigate adverse events of therapy with systemic FAE with follow-up periods of up to 14 years, in order to determine safety aspects of their long-term use in patients with severe psoriasis. METHODS: Current and/or past therapeutic use of FAE was reviewed in 66 patients with severe psoriasis. RESULTS: Forty-one of 66 patients had received FAE for at least 1 year, and 12 of these 41 patients had received FAE for between 10 and 14 years. Adverse events were reported in 73% of the patients. These were usually mild and mainly consisting of flushing (55%), diarrhoea (42%), nausea (14%), tiredness (14%) and stomach complaints (12%). A relative lymphocytopenia was observed in 76% of patients during therapy with FAE, resulting in a permanent discontinuation of therapy with FAE in four patients. A transient eosinophilia and moderate liver enzyme elevations were observed in 14% and 25% of patients, respectively. CONCLUSIONS: The present study indicates that FAE can be considered as a safe long-term treatment in patients with severe psoriasis.
Assuntos
Fármacos Dermatológicos/efeitos adversos , Fumaratos/efeitos adversos , Psoríase/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Creatinina/sangue , Esquema de Medicação , Feminino , Fumaratos/uso terapêutico , Humanos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Linfopenia/induzido quimicamente , Masculino , Pessoa de Meia-IdadeRESUMO
Basal cell carcinomas (BCC) are among the most common cancers in white subjects. Etiologic factors include ultraviolet and ionizing radiation, chemical carcinogens, and possibly infection with human papillomaviruses. Because of clinical and histologic differences, differential pathogenetic mechanisms have been suggested for different BCC subtypes. We studied the patient and tumor characteristics of all BCC diagnosed and/or treated at the departments of Dermatology and Plastic Surgery of our hospital between 1985 and 1996, and a review of the literature was carried out. Some important differences between patients with nodular BCC and patients with superficial BCC were observed. The frequency of superficial BCC was higher in females and was seen in younger patients as compared with nodular BCC. The latter occurred mainly in the head/neck region: in males they were seen more frequently on the ears, and in females they were predominantly seen on the eyelids, the lips, and in the neck. Superficial BCC occurred mainly on the trunk, and occurred significantly more often on the trunk in males than in females, where the legs were the most common site. These findings strongly suggest that the superficial subtype is a separate group within the clinical entity of BCC. Furthermore, our findings seem to support the etiologic role of sun exposure in these tumors; however, this role may be different for each subtype. Chronic sun exposure may be an etiologic factor in nodular BCC as compared with intermittent sun exposure in superficial BCC. Other factors, such as differences in site specific host factors and referral bias, may also play a role in the differences found between the subtypes.
Assuntos
Carcinoma Basocelular/patologia , Neoplasias Cutâneas/patologia , Abdome , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Braço , Dorso , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/etiologia , Feminino , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Perna (Membro) , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Fatores Sexuais , Pele/patologia , Pele/efeitos da radiação , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Luz Solar/efeitos adversos , Tórax , Fatores de Tempo , Transplantes/efeitos adversosRESUMO
Minocycline is the most commonly used systemic antibiotic in the long-term treatment (weeks to months) of severe acne vulgaris. Currently much attention is being paid in the Dutch and international literature to the safety of minocycline, after several reports on serious adverse events. The clinical efficacy of minocycline in the treatment of acne vulgaris is better than that of tetracycline and equal to that of doxycycline. The serious adverse events of minocycline therapy described consist of hyperpigmentation of various tissues, autoimmune disorders (systemic lupus erythematosus, autoimmune hepatitis) and serious hypersensitivity reactions (hypersensitivity syndrome reaction, pneumonitis and eosinophilia, and serum sickness-like syndrome). In relation to the number of prescriptions, the number of serious adverse events of minocycline described is small. However, it is very important that prescribing doctors should be aware of the possibility of these adverse events occurring during long-term minocycline therapy and able to recognize the characteristic symptoms at an early stage.