RESUMO
BACKGROUND: To assess the response of patients with soft tissue sarcoma (STS) to the combination of docetaxel, bevacizumab, and gemcitabine. Vascular endothelial growth factor (VEGF)-A levels and expression of VEGF-A and VEGF receptors 1 and 2 were evaluated. PATIENTS AND METHODS: Thirty-eight chemotherapy-naive patients with STS were enrolled. A dose-finding study for gemcitabine from 1000, 1250, then 1500 mg/m(2) was done in nine patients (three cohorts), followed by an expansion cohort of 27 patients. Dose of docetaxel was 50 mg/m(2), bevacizumab was 5 mg/kg, and gemcitabine was 1500 mg/m(2), every 2 weeks. Serum VEGF-A was measured by enzyme-linked immunosorbent assay and tissue VEGF-A and its receptors by immunohistochemistry. RESULTS: The median follow-up was 36 months. The overall response rate observed was 31.4%, with 5 complete and 6 partial responses, and 18 stable diseases lasting for a median of 6 months. There was no significant hematologic toxicity. The adverse events with the highest grade were attributed to bevacizumab. There was no correlation of VEGF pathway biomarkers with outcome. CONCLUSIONS: The combination of gemcitabine, docetaxel, and bevacizumab is safe and effective in patients with STS. The most concerning adverse events were consequences of bevacizumab administration. The benefit of bevacizumab in this patient population remains unclear.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Bevacizumab , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Docetaxel , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Receptores de Fatores de Crescimento do Endotélio Vascular/biossíntese , Sarcoma/metabolismo , Sarcoma/mortalidade , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/mortalidade , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Fator A de Crescimento do Endotélio Vascular/biossíntese , Adulto Jovem , GencitabinaRESUMO
AIMS: IgA nephropathy (IgAN) is the most frequent glomerulonephritis around the globe, but its incidence in the United States is unknown. The disease has a preponderance for certain racial/ethnic groups. Our goals were to retrospectively analyze a series of IgAN biopsies from the state of New Mexico and to calculate an estimated incidence. Then we compared the racial/ethnic composition of our patient cohort to the composition of the New Mexico population and examined the three main racial/ethnic groups for differences in clinical and pathologic parameters. MATERIALS AND METHODS: Renal biopsies and clinical data from IgAN cases newly diagnosed in New Mexico between 2000 and 2005 were reviewed. We compared the racial/ethnic composition of our patient cohort to the demographic composition of the New Mexico population. Demographic, clinical, and histopathologic variables were analyzed with respect to the patients' race/ethnicity. RESULTS: The incidence of IgAN in New Mexico was 10.2 cases per million persons per year (9.3 when Henoch-Schönlein purpura cases were excluded). American Indians were twice as frequent in our patient cohort when compared to their demographic representation, with the reverse finding for Non-Hispanic Whites. Hispanics more frequently had nephrotic range proteinuria than Non-Hispanic Whites and American Indians. On renal biopsy, endocapillary proliferative glomerulonephritis was the most common glomerular abnormality, followed by the focal segmental glomerulosclerosis (FSGS)-like pattern. The FSGS-like pattern was more frequent in American Indians and Hispanics than in Non-Hispanic Whites. CONCLUSIONS: This is the first report of an incidence figure of IgAN for an entire state in the US. American Indian and Hispanic patients had a stronger representation in our cohort than Non-Hispanic Whites, when compared to the general New Mexico population.
Assuntos
Glomerulonefrite por IGA , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Grupos Raciais , Estudos Retrospectivos , Adulto JovemRESUMO
The role of Epstein-Barr virus (EBV) in the development of sinonasal undifferentiated carcinoma (SNUC) remains unresolved. Reports of EBV-positivity in SNUC may reflect inclusion of lymphoepithelioma-like carcinomas within this group. In addition, SNUC have been incompletely characterized immunohistochemically, and their undifferentiated appearance often requires such ancillary studies to aid in their distinction from other high-grade neoplasms. To address these two issues, 25 cases of SNUC diagnosed between the years 1983 and 1999 were selected from our files. EBER in situ hybridization (ISH) was performed on the paraffin-embedded tissue by using 3H-labeled EBER-1 RNA probes. Neoplasms with sufficient tissue (22 of 25) were evaluated immunohistochemically for Ki-67, p53, chromogranin, synaptophysin, placental alkaline phosphatase (PLAP), CD99, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), neuron-specific enolase (NSE), and latent membrane protein-1 (LMP-1). The median patient age was 58 years (range, 20-81 years), with a male-to-female ratio of approximately 3:1. The most common tumor location was the nasal cavity (18 cases), followed by the ethmoid and maxillary sinuses. Median survival was 18 months. All 25 tumors were negative for EBER-I by ISH. Ki-67 was negative in one case, 1+ in nine, 2+ in six, 3+ in five, and 4+ in one. P53 was negative in nine, 1+ in five, 2+ in two, 3+ in none, and 4+ in six. CD99 expression was strongly positive in 3 of 22 (14%) and completely negative in the remainder. Variably intense focal staining for EMA was present in 4 of 22 (18%). NSE faintly stained 4 of 22 (18%). Chromogranin, synaptophysin, PLAP, CEA, and LMP-1 were negative (0 of 22). Our results suggest that EBV does not play a role in the development of SNUC. Strict histologic criteria are necessary to avoid confusion with lymphoepithelioma-like carcinoma or other high-grade malignancies in this region. The finding of occasional CD99-positive cases adds SNUC to the growing list of CD99-positive neoplasms.
Assuntos
Adenocarcinoma/patologia , Herpesvirus Humano 4/isolamento & purificação , Neoplasias dos Seios Paranasais/patologia , Adenocarcinoma/química , Adenocarcinoma/terapia , Adenocarcinoma/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico , DNA de Neoplasias/análise , Diagnóstico Diferencial , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/patologia , Feminino , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/patogenicidade , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Neoplasias dos Seios Paranasais/terapia , Neoplasias dos Seios Paranasais/virologia , RNA Viral/análiseRESUMO
The chromosomal locus 9p21 contains the p16(INK4a/CDKN2/MTS1) tumor suppressor gene that has been implicated in a variety of tumor types, including carcinomas of the head and neck, esophagus, and pancreas. To determine whether the loss of this gene is involved in salivary gland cancers, 35 carcinomas and paired nonneoplastic specimens were analyzed for loss of heterozygosity (LOH) of polymorphic genetic markers located in the region of interest. Five types of salivary gland tumors were studied: mucoepidermoid carcinoma, salivary duct carcinoma, adenoid cystic carcinoma, acinic cell carcinoma, and polymorphous low-grade adenocarcinoma. Seven of 9 salivary duct carcinomas showed LOH of 1 or more polymorphic markers. In 1 case of salivary duct carcinoma with LOH, we confirmed a deletion of bp 240-254 within exon 2. In addition, another salivary duct carcinoma showed a homozygous deletion of p16 in differential polymerase chain reaction analysis. Loss of heterozygosity was found in 1 of 10 adenoid cystic carcinomas and 1 of 8 mucoepidermoid carcinomas and was absent in the remaining subtypes. No mutations in exon 1 or exon 2 or homozygous deletion of p16 were found in these 2 particular neoplasms with LOH. These results suggest that inactivation of p16 is important in the development or progression of at least some salivary duct carcinomas, but we found no evidence that its alteration plays a role in the other subtypes examined.
Assuntos
Cromossomos Humanos Par 9 , Inibidor p16 de Quinase Dependente de Ciclina/genética , Neoplasias das Glândulas Salivares/genética , Adenocarcinoma/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/genética , Feminino , Humanos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da PolimeraseRESUMO
Neuroendocrine tumors of the lung continue to be difficult nosologic and diagnostic problems, centering on the time-honored terms of "carcinoid," "atypical carcinoid," and "small cell carcinoma." Problems that are encountered in the classification of such neoplasms revolve around the differing criteria that have been advanced for their definition and variable application of such criteria in common practice. This review considers the epithelial and nonepithelial lesions of the lung that may demonstrate neuroendocrine and neuroectodermal differentiation. A proposal is made for a simplified system of classifying the epithelial tumors, dividing them into 3 grades with appended descriptive modifiers.
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Neoplasias Pulmonares/patologia , Tumores Neuroendócrinos/patologia , Tumor Carcinoide/patologia , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/patologia , Diferenciação Celular , Divisão Celular , Diagnóstico Diferencial , Humanos , Neuroblastoma/patologia , Paraganglioma/patologia , Resultado do TratamentoRESUMO
Immunohistochemistry involves the binding of an antibody to a cellular or tissue antigen of interest and then visualization of the bound product by a detection system. With the ever-increasing number of antibodies against cellular epitopes, immunohistochemistry is an extremely useful diagnostic tool as well as a means to guide specific therapies that target a particular antigen on neoplastic cells. As many antibodies are effective in fixed paraffin-embedded tissues, large retrospective studies of protein expression in a variety of human cancers can easily be performed.
RESUMO
Primary angiosarcoma of the kidney is a rare tumor for which fewer than 10 case reports appear in the English literature. A case of primary renal angiosarcoma is reported, in which the tumor showed poorly differentiated spindled sarcoma admixed with typical angiomatous differentiation. Antibodies against CD31, CD34, Ulex europeus lectin type I, factor VIII-related antigen, cytokeratin (AE1/AE3), vimentin, S100 protein, epithelial membrane antigen, carcinoembryonic antigen, desmin, and smooth muscle actin were examined. CD31 showed strong diffuse membranous staining of cells in the well-differentiated areas and strong membranous staining in the spindled, poorly differentiated areas. CD34 showed strong cytoplasmic and membranous staining in both the poorly differentiated and well-differentiated areas. Staining for factor VIII-related antigen and Ulex europeus was less intense and was limited to the well-differentiated areas. Staining for cytokeratin (AE1-AE3), S100, carcinoembryonic antigen, epithelial membrane antigen, desmin, and smooth muscle actin were negative. Electron microscopy showed spindle cells containing abundant pinocytotic vesicles, vimentin-type intermediate filaments, and rare Weibel-Palade bodies. A complex karyotype was found. Our findings suggest that CD31 and CD34 are useful in defining endothelial differentiation in poorly differentiated angiosarcomas in which reactions for Ulex europeus lectin type I and factor VIII-related antigen may be equivocal.
Assuntos
Hemangiossarcoma/química , Neoplasias Renais/química , Idoso , Diferenciação Celular/fisiologia , Hemangiossarcoma/genética , Hemangiossarcoma/ultraestrutura , Humanos , Imuno-Histoquímica , Cariotipagem , Neoplasias Renais/genética , Neoplasias Renais/ultraestrutura , Masculino , Microscopia EletrônicaRESUMO
A primary angiosarcoma of the femur arose in continuity with a bone infarct in a 74-year-old man. The tumor, resected by amputation, had pleomorphic polygonal and spindle cells in solid and cystic patterns with focal vasoformative features. The immunohistochemical stains CD31, CD34, factor VIII-related antigen, and Ulex europeus corroborated the endothelial differentiation of the tumor. The patient died after developing pulmonary metastases. This is the oldest reported patient with a well-documented angiosarcoma associated with a bone infarct.
Assuntos
Neoplasias Ósseas/etiologia , Fêmur/irrigação sanguínea , Hemangiossarcoma/etiologia , Infarto/complicações , Idoso , Amputação Cirúrgica , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Evolução Fatal , Hemangiossarcoma/diagnóstico por imagem , Hemangiossarcoma/metabolismo , Hemangiossarcoma/patologia , Hemangiossarcoma/cirurgia , Humanos , Imuno-Histoquímica , Infarto/diagnóstico por imagem , Infarto/patologia , Masculino , RadiografiaRESUMO
Congenital malaria occurs infrequently in endemic areas and is even more uncommon in the United States. Although more than 300 cases of congenital malaria have been reported, only four reports describing this disease in preterm infants exist in the English-language literature. We report the first case of congenital malaria in an extremely low-birth-weight infant born in the United States. The maternal history and clinical findings and treatment of this infant are discussed and a summary of the prior reported cases is provided as aids to the early identification and management of infants with congenital malaria. The diagnosis of congenital malaria should be considered in infants with suspected congenital infection who are born to mothers with a history of even remote travel to endemic areas.
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Doenças do Prematuro , Recém-Nascido de muito Baixo Peso , Malária Falciparum/congênito , Adulto , Feminino , Testes Hematológicos , Humanos , Recém-Nascido , Doenças do Prematuro/diagnóstico , Doenças do Prematuro/terapia , Transmissão Vertical de Doenças Infecciosas , Malária Falciparum/terapia , Malária Falciparum/transmissão , Masculino , Exame Físico , Gravidez , Complicações Parasitárias na Gravidez/tratamento farmacológico , Quinina/uso terapêutico , Estados UnidosRESUMO
We report the seventh case of angiosarcoma of the heart in a child. The patient was a 23-month-old female who presented for lower extremity limping and underwent open surgical biopsy of the femur. Immediately postoperatively, she developed pericardial tamponade, and a bulky intracardiac mass was discovered as the underlying cause. The mass was composed of highly pleomorphic tumor cells reactive for the endothelial markers CD31, CD34, and factor VIII-related antigen (FVIII-RA). Staging evaluation revealed widespread metastases involving the brain, ovaries, and bone marrow. She died of complications of metastatic disease 8 months following initial presentation. Unusual features of this case include the young age of the patient, left-sided nature of the cardiac tumor, presentation secondary to metastatic disease, and the pattern of metastases. The literature on cardiac angiosarcoma, which is limited to six case reports in the pediatric population, is also reviewed.