RESUMO
Merkel cells carcinoma (MCC) is an uncommon skin lesion, considered a malignancy of the neuroendocrine system, which is found mainly in elderly people. Its incidence is highly correlated with sun exposure or immunodeficiency syndromes. MCC is often an aggressive tumour with high tendency for local recurrence, lymph node involvement and distant metastasis. To our best knowledge 20 cases originated from the auricle have been described, 2 of them arising from external ear canal. The authors report a case of the ear canal characterized by two others synchronous tumours and the occurrence of a malignant high grade lymphoma, in which contribute of the pathologist was essential for a critical review. MCC diagnosis is not always easy for its pathological and clinical features and it should always be considered in presence of lymphoma. A multidisciplinary approach is basic.
Assuntos
Carcinoma de Célula de Merkel/diagnóstico , Neoplasias da Orelha/diagnóstico , Orelha Externa , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Biópsia por Agulha Fina , Carcinoma de Célula de Merkel/tratamento farmacológico , Carcinoma de Célula de Merkel/patologia , Neoplasias da Orelha/tratamento farmacológico , Neoplasias da Orelha/patologia , Orelha Externa/patologia , Evolução Fatal , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Queratinas/análise , Linfoma Folicular/diagnóstico , Linfoma Folicular/terapia , Imageamento por Ressonância Magnética , Masculino , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/patologia , Glândula Parótida/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapiaRESUMO
In multiple myeloma (MM), circulating endothelial cells (CECs) represent a vascular marker of angiogenesis and may reflect tumor mass. In this report, we showed that, in 5 MM patients with 13q14 deletion, CECs carried the same chromosome aberration as the neoplastic plasma cells (11%-32% of CECs with 13q14 deletion). Most of the CECs displayed immunophenotypic features of endothelial progenitor cells as they expressed CD133, a marker gradually lost during endothelial differentiation and absent on mature endothelial cells. To the contrary, in 3 patients with monoclonal gammopathy of undetermined significance and 13q14 deletion, CECs were cytogenetically normal and had a mature immunophenotype. In MM CECs, immunoglobulin genes were clonally rearranged. These findings suggest a possible origin of CECs from a common hemangioblast precursor that can give rise to both plasma cells and endothelial cells and point to a direct contribution of MM-derived CECs to tumor vasculogenesis and possibly to the spreading and progression of the disease.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 13 , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Estudos de Casos e Controles , Células Endoteliais/patologia , Feminino , Rearranjo Gênico , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/etiologia , Plasmócitos/patologia , Células-Tronco/patologiaRESUMO
AIMS: There is increasing evidence that stem cell (SC) mobilization to the heart and their differentiation into cardiac cells is a naturally occurring process. We sought to assess the safety and feasibility of granulocyte-colony stimulating factor (G-CSF) administration in humans to enhance SC mobilization and left ventricle (LV) injury repair during myocardial infarction (MI). METHODS AND RESULTS: Twenty patients with STEMI (mean age, 61+/-10 years), of whom 14 were submitted to primary percutaneous coronary intervention, were randomized to G-CSF (5 microg/kg/day s.c. for 4 consecutive days) or placebo. At entry and then at months 3 and 6, (99m)Tc-sestamibi gated-SPECT was performed to estimate extension of perfusion defect (PD) and LV function. The study drug was well tolerated and induced a significant increase of white blood count, CD34(+) cells, and CD34(+) cells coexpressing AC133 and VEGFR-2. At follow-up, treated and placebo groups did not differ for the angiographic coronary late loss and showed a similar pattern of PD recovery, whereas in the former at 6 months LVEF and especially LVEDV tended to be relatively higher (P=0.068) and lower (P=0.054), respectively. CONCLUSION: G-CSF administration in acute MI patients was feasible and did not lead to any clinical or angiographic adverse events and resulted in CD34(+) and CD34(+)AC133(+)VEGFR2(+) cell mobilization.
Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Infarto do Miocárdio/terapia , Antígenos CD34 , Angiografia Coronária , Circulação Coronária , Reestenose Coronária/etiologia , Estenose Coronária/terapia , Estudos de Viabilidade , Feminino , Filgrastim , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Proteínas Recombinantes , Recuperação de Função Fisiológica , Método Simples-Cego , Resultado do Tratamento , Disfunção Ventricular Esquerda/terapiaRESUMO
Using quantitative fluorescence in situ hybridisation and flow cytometry (flow-FISH), we investigated the biological and clinical relevance of telomere length in 55 patients affected by myelodysplastic syndromes (MDS) compared with 55 sex- and age-matched controls. We found that telomere fluorescence in MDS granulocytes, and CD34+ cells did not decline with age as in normal controls and that MDS granulocytes and CD34+ cells had significantly shorter telomeres than healthy controls. A significant higher incidence of cases with intermediate-unfavourable cytogenetics and International Prognostic Scoring System (IPSS) int-2/high-risk group was observed among patients with lower telomere fluorescence. We also found that apoptosis in CD34+ cells was significantly higher in IPSS int-1 low-risk patients when compared with IPSS int-2 high-risk cases and healthy controls and that CD34+ cell telomere fluorescence directly correlated with CD34+ cell apoptosis. Reduced telomere fluorescence was associated with a history of occupational exposure to toxic agents and with worse survival in univariate and multivariate analyses. Our results suggest that flow-cytometry assessment of telomere dynamics may represent a valuable tool in the biological and clinical-prognostic characterisation of MDS disorders.
Assuntos
Citometria de Fluxo , Síndromes Mielodisplásicas/sangue , Telômero/ultraestrutura , Idoso , Idoso de 80 Anos ou mais , Anemia Refratária/sangue , Anemia Refratária com Excesso de Blastos/sangue , Antígenos CD34/análise , Apoptose , Cromossomos Humanos Par 19 , Cromossomos Humanos Par 5 , Cromossomos Humanos Par 8 , Cromossomos Humanos Y , Feminino , Citometria de Fluxo/métodos , Deleção de Genes , Granulócitos/ultraestrutura , Humanos , Hibridização in Situ Fluorescente , Leucemia Mielomonocítica Crônica/sangue , Masculino , Pessoa de Meia-Idade , Monossomia , Síndromes Mielodisplásicas/etiologia , Síndromes Mielodisplásicas/genética , Praguicidas/toxicidade , Prognóstico , Solventes/toxicidade , Taxa de Sobrevida , TrissomiaRESUMO
The in vivo effect of recombinant human erythropoietin (rHuEpo) and granulocyte colony-stimulating factor (G-CSF) combined treatment on CD34(+) cells was evaluated by fluorescence in situ hybridization (FISH) in 13 myelodysplastic syndrome (MDS) patients with known cytogenetic abnormalities. After treatment, responsive patients presented a significantly lower proportion of FISH abnormal CD34(+) cells than before treatment (P = 0.003), and in comparison with unresponsive cases (P = 0.007). Response to treatment was associated with a reduced degree of apoptosis in CD34(+) cells (P = 0.021): however, no difference in telomere length was observed in responsive patients after growth factor administration. Although the number of patients analysed was relatively small, the present data suggest that, in MDS patients, response to rHuEpo and G-CSF may be related to the proliferation of karyotypically normal but potentially defective CD34(+) progenitor cells.
Assuntos
Aberrações Cromossômicas , Eritropoetina/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Células-Tronco Hematopoéticas/patologia , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/análise , Apoptose/efeitos dos fármacos , Células da Medula Óssea/patologia , Divisão Celular/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Proteínas Recombinantes , Telômero/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Peripheral blood CD34(+) cells and circulating endothelial progenitor cells (EPCs) increase in myocardial infarction and vascular injuries as a reflection of endothelial damage. Despite the occurrence of endothelial dysfunction in heart failure (HF), no data are available on EPC mobilization in this setting. We investigated the pattern of CD34(+) cells and EPC mobilization during HF and their correlation with the severity and origin of the disease. METHODS AND RESULTS: Peripheral blood CD34(+) cells (n=91) and EPCs (n=41), assessed both as CD34(+) cells coexpressing AC133 and vascular endothelial growth factor (VEGF) receptor-2 and as endothelial colony-forming units, were studied in HF patients (mean age 67+/-11 years) and 45 gender- and age-matched controls. Tumor necrosis factor-alpha (TNF-alpha) and its receptors (sTNFR-1 and sTNFR-2), VEGF, stromal derived factor-1 (SDF-1), granulocyte-colony stimulating factor (G-CSF), and B-type natriuretic peptide were also measured. CD34(+) cells, EPCs, TNF-alpha and receptors, VEGF, SDF-1, and B-type natriuretic peptide were increased in HF. CD34(+) cells and EPCs were inversely related to functional class and to TNF-alpha, being decreased in New York Heart Association class IV compared with class I and II and controls. No role was found for the origin of the disease. CONCLUSIONS: CD34(+) cells and EPC mobilization occurs in HF and shows a biphasic response, with elevation and depression in the early and advanced phases, respectively. This could be related to the myelosuppressive role of TNF-alpha.
Assuntos
Antígenos CD34/análise , Insuficiência Cardíaca/sangue , Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Quimiocina CXCL12 , Quimiocinas CXC/sangue , Ensaio de Unidades Formadoras de Colônias , Endotélio Vascular/patologia , Feminino , Fator Estimulador de Colônias de Granulócitos/sangue , Células-Tronco Hematopoéticas/química , Humanos , Masculino , Células-Tronco Mesenquimais/química , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Fator de Necrose Tumoral alfa/análise , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/análiseRESUMO
In a rare case of follicluar dendritic cell sarcoma, malignant cells were isolated and cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 4 (IL-4) and tumor necrosis factor alpha (TNF-alpha). After 14 d, 15% of neoplastic cells differentiated into myeloid-dendritic cell-like elements as demonstrated by immunological and functional characteristics. These cells showed the same cytogenetic abnormality of the malignant clone (fluorescence in situ hybridisation analysis performed on CD1a+ cells) and were able to induce allogenic T-cell proliferation in the mixed leucocyte reaction. These data may indicate that antigen presenting capacity could be a functional state inducible in cellular elements which are believed not to be of hemopoietic origin. Further studies are warranted to confirm these findings and to clarify the possibility to use these cells to generate specific anti-tumoral immune responses.