Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Cerebelares/induzido quimicamente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , MasculinoRESUMO
BACKGROUND: Retrospective and prospective cohort studies suggest that central nervous system involvement occurs in approximately 0.5% of patients with advanced Hodgkin's lymphoma. The isolated primary intracranial manifestation of Hodgkin's lymphoma is an extremely rare finding, with few cases reported in the literature. Little is known about the optimal treatment and prognosis of these tumors. Here, we present a case report with a review of the literature. CASE PRESENTATION: A 47-year-old Caucasian man with persistent frontal headache and unspecific vertigo for half a month was diagnosed with nodular space-occupying lesions in the cerebellum. His medical history included multiple sclerosis, which was treated for 20 years with the immunosuppressive drug azathioprine. Further staging revealed no additional lesions suspected of being malignant. The patient underwent total tumor resection. Immunohistopathological examination showed Epstein-Barr virus-associated classic Hodgkin's lymphoma. Diagnostic bone marrow punction excluded lymphoma involvement of the bone marrow. The patient had no B symptoms. Consequently, the patient was classified as having stage IEA disease according to the Modified Ann Arbor Classification of Hodgkin Lymphoma and received systemic chemotherapy followed by radiation therapy for the former cerebellar tumor region. He was in complete clinical remission at the last follow-up 9 months after the initial diagnosis. CONCLUSION: This case report and literature review suggest that multimodal treatment leads to a remarkable clinical outcome in Hodgkin's lymphoma with intracranial involvement.
Assuntos
Azatioprina/efeitos adversos , Neoplasias Cerebelares/induzido quimicamente , Neoplasias Cerebelares/terapia , Infecções por Vírus Epstein-Barr/induzido quimicamente , Infecções por Vírus Epstein-Barr/terapia , Doença de Hodgkin/induzido quimicamente , Doença de Hodgkin/terapia , Imunossupressores/efeitos adversos , Azatioprina/uso terapêutico , Neoplasias Cerebelares/patologia , Quimiorradioterapia Adjuvante , Terapia Combinada , Craniotomia , Infecções por Vírus Epstein-Barr/patologia , Doença de Hodgkin/patologia , Humanos , Doença Iatrogênica , Imunossupressores/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios XAssuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Poluentes Atmosféricos/efeitos adversos , Neoplasias Encefálicas/induzido quimicamente , Neoplasias Encefálicas/genética , Neoplasias Cerebelares/induzido quimicamente , Neoplasias Cerebelares/genética , Interação Gene-Ambiente , Genótipo , Hidrocarbonetos Clorados/efeitos adversos , Meduloblastoma/induzido quimicamente , Meduloblastoma/genética , Tumores Neuroectodérmicos Primitivos/induzido quimicamente , Tumores Neuroectodérmicos Primitivos/genética , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: There is evidence that exposure to chlorinated solvents may be associated with childhood medulloblastoma and primitive neuroectodermal tumor (M/PNET) risk. Animal models suggest genes related to detoxification and DNA repair are important in the carcinogenicity of these pollutants; however, there have been no human studies assessing the modifying effects of these genotypes on the association between chlorinated solvents and childhood M/PNET risk. PROCEDURE: We conducted a case-only study to evaluate census tract-level exposure to chlorinated solvents and the risk of childhood M/PNET in the context of detoxification and DNA repair genotypes. Cases (n = 98) were obtained from Texas Children's Hospital and MD Anderson Cancer Center. Key genotypes (n = 22) were selected from the Illumina Human 1M Quad SNP Chip. Exposure to chlorinated solvents (methylene chloride, perchloroethylene, trichloroethylene, and vinyl chloride) was estimated from the US EPA's 1999 Assessment System for Population Exposure Nationwide (ASPEN). Logistic regression was used to estimate the case-only odds ratios and 95% confidence intervals (CIs). RESULTS: There were 11 significant gene-environment interactions associated with childhood M/PNET risk. However, after correcting for multiple comparisons, only the interaction between high trichloroethylene levels and OGG1 rs293795 significantly increased the risk of childhood M/PNET risk (OR = 9.24, 95% CI: 2.24, 38.24, Q = 0.04). CONCLUSIONS: This study provides an initial assessment of the interaction between ambient levels of chlorinated solvents and potentially relevant genotypes on childhood M/PNET risk. Our results are exploratory and must be validated in animal models, as well as additional human studies.
Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Poluentes Atmosféricos/efeitos adversos , Neoplasias Encefálicas/induzido quimicamente , Neoplasias Encefálicas/genética , Neoplasias Cerebelares/induzido quimicamente , Neoplasias Cerebelares/genética , Interação Gene-Ambiente , Genótipo , Hidrocarbonetos Clorados/efeitos adversos , Meduloblastoma/induzido quimicamente , Meduloblastoma/genética , Tumores Neuroectodérmicos Primitivos/induzido quimicamente , Tumores Neuroectodérmicos Primitivos/genética , Criança , Reparo do DNA/genética , Feminino , Humanos , Masculino , Desintoxicação Metabólica Fase I/genética , Desintoxicação Metabólica Fase II/genética , Solventes/efeitos adversosRESUMO
INTRODUCTION: Massive intracranial hemorrhage is a very rare initial presentation of cerebellar pilocytic astrocytomas. There are no reports in the medical literature on a cerebellar pilocytic astrocytoma presenting with intratumor bleeding (ITB), subarachnoid hemorrhage (SAH), and subdural hematoma (SDH). CASE REPORT: A 15-month-old boy presented with lethargy and nausea to our hospital. Magnetic resonance imaging showed a mass with ITB at the left cerebellar hemisphere in addition to SDH in the posterior fossa and SAH at the interpeduncular cistern. The patient underwent emergency surgery. On incising the dura, we found SDH, the tumor was visible at the cerebellar cortex, and near total removal followed. Microscopic examination of tissue sections revealed a pilocytic astrocytoma. DISCUSSION: The authors' case is the first report with a presentation including ITB, SAH, and SDH. The presumed mechanism of the SAH and SDH was leaking of the ITB into subarachnoid and subdural spaces.
Assuntos
Astrocitoma/complicações , Neoplasias Cerebelares/complicações , Hematoma Subdural/etiologia , Hemorragia Subaracnóidea/etiologia , Astrocitoma/diagnóstico , Neoplasias Cerebelares/induzido quimicamente , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/cirurgia , Diagnóstico Diferencial , Hematoma Subdural/induzido quimicamente , Hematoma Subdural/cirurgia , Humanos , Lactente , Masculino , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/cirurgia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Medulloblastomas are among the most common malignancies in childhood, and they are associated with substantial mortality and morbidity. The molecular pathogenesis as well as the ontogeny of these neoplasms is still poorly understood. We have generated a mouse model for medulloblastoma by Cre-LoxP-mediated inactivation of Rb and p53 tumor suppressor genes in the cerebellar external granular layer (EGL) cells. GFAP-Cre-mediated recombination was found both in astrocytes and in immature precursor cells of the EGL in the developing cerebellum. GFAP-Cre;Rb(LoxP/LoxP);p53(-/- or LoxP/LoxP) mice developed highly aggressive embryonal tumors of the cerebellum with typical features of medulloblastoma. These tumors were identified as early as 7 weeks of age on the outer surface of the molecular layer, corresponding to the location of the EGL cells during development. Our results demonstrate that loss of function of RB is essential for medulloblastoma development in the mouse and strongly support the hypothesis that medulloblastomas arise from multipotent precursor cells located in the EGL.
Assuntos
Neoplasias Cerebelares/induzido quimicamente , Cerebelo/metabolismo , Genes do Retinoblastoma/genética , Genes p53/genética , Meduloblastoma/induzido quimicamente , Proteínas Virais , Animais , Astrócitos/metabolismo , Neoplasias Cerebelares/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Hibridização In Situ , Integrases/metabolismo , Camundongos , Camundongos Mutantes , Mutação , Plasmídeos , Regiões Promotoras Genéticas , Distribuição Tecidual , Transcrição Gênica , Transgenes , beta-Galactosidase/metabolismoRESUMO
Morphological and immunohistochemical studies of cerebellar tumor induction with neonatal administration of N-ethyl-N-nitrosourea (ENU) were conducted in four strains of rats and their hybrids, i.e., noninbred Wistar, Fischer (F344), Long-Evans, Wistar/Furth, and hybrids of Long-Evans and Wistar/Furth. Neonatal s.c. injection of 40 mg ENU/kg body weight produced 53 cerebellar tumors in 46 (8.4%) rats among 550 animals. There was no sex difference in the incidence (male = 9.6%; female = 7.0%). Histological examination showed that most of the tumors (83%) were oligodendrogliomas and the neoplastic cells were positively stained immunohistochemically with anti-Leu-7 monoclonal antibody. In examining the location of cerebellar tumors, 22 (42%) were located in the vermis, 11 (21%) in the hemisphere, 9 (17%) in the flocculus, 6 (11%) in the peduncle, and 5 (9%) in other sites. When their origins were examined in relation to their location to the internal granular layer of the cerebellum, 40 (75%) tumors were found just under the internal granular layer (subcortical region) and 9 (17%) in the white matter or cerebellar nuclei. Only 2 (4%) subependymal tumors were observed. Ontogenic study of the rat cerebellum revealed the presence of an aggregation of primitive glial cells in the subcortical region during the neonatal period, and the [3H]thymidine pulse-labeling index of these cells was 13.7%. Electron microscopic study showed the primitive nature of these cells and they reacted positively with anti-Leu-7 monoclonal antibody. These results indicate that cerebellar tumors are induced in an appreciable incidence with neonatal injection of ENU in rats and that cerebellar target cells in the subcortical region are present after ENU carcinogenesis.
Assuntos
Neoplasias Cerebelares/induzido quimicamente , Etilnitrosoureia/toxicidade , Glioma/induzido quimicamente , Neuroglia/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Anticorpos Monoclonais , Diferenciação Celular/efeitos dos fármacos , Neoplasias Cerebelares/patologia , Proteína Glial Fibrilar Ácida/metabolismo , Glioma/patologia , RatosRESUMO
A morphological and histochemical study of the ovaries in 79 rats with cerebellar blastomogenesis due to DMBA in comparison with the ovaries of intact rats, rats with trauma of the cerebellum, rats with a paraffin pill implanted into the cerebellum, as well as with the ovaries of rats with a chemical cancerogenesis of the intestine, permitted to claim, that the most characteristic changes of the ovaries in cerebellar blastomogenesis consist in reduced amount of premordial follicules, athresia of the growing follicles and a formation of multiple follicular cysts. These processes are underlain by destruction of premordial follicles and a degeneration of the ovule in the growing follicles.
Assuntos
Neoplasias Cerebelares/patologia , Ovário/patologia , 9,10-Dimetil-1,2-benzantraceno , Animais , Neoplasias Cerebelares/induzido quimicamente , Neoplasias Cerebelares/metabolismo , Feminino , Histocitoquímica , Neoplasias Experimentais , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , RatosRESUMO
Newborn mice of four inbred strains were injected with a single dose of N-ethyl-N-nitrosourea. The wide range of tumours induced included a small number in the central and peripheral nervous systems. The 4 brain tumours all arose in the cerebellum. Three in one strain were medulloblastomas showing continuity with the internal granular layer. All three tumours showed diffuse infiltration through the molecular layer and continuity with densely-packed islets of cells that marginated immediately beneath the pia and closely resembled remnants of a persistent fetal external granular layer. The medulloblastomas are discussed with special relevance to the histogenesis of the equivalent tumour in man.
Assuntos
Etilnitrosoureia , Meduloblastoma/induzido quimicamente , Neoplasias de Tecido Nervoso/induzido quimicamente , Compostos de Nitrosoureia , Animais , Animais Recém-Nascidos , Neoplasias Cerebelares/induzido quimicamente , Neoplasias Cerebelares/patologia , Meduloblastoma/patologia , Neoplasias Experimentais , Neoplasias do Sistema Nervoso Periférico/induzido quimicamente , Ratos , Ratos EndogâmicosRESUMO
The Feulgen-DNA cytophotometry was applied for studies of 31 rat cerebellum tumors induced by 9, 10-dimetyl-1,2-bensantracene. Most of these gliomas (22) were astrocytomas of different grades of malignancy. The histological diagnosis of other tumors was: glioblastoma -- 4, oligoastrocytoma -- 2, oligodendroglioma -- 1, gliosarcoma 1. The majority cells of 26 tumors had diploid or paradiploid DNA quantity, 4 tumors (1 astrocytoma, 3 dedifferentiated astroyctomas) had triploid modal classes. The tetraploid modal class and a large number of polyploid cells were found only once for glioblastoma multiforme. A supposition was made that drastic changes of ploidy could arise for the second time during the process of tumor evolution. The authors failed to show any exact differences in the ploidy of gliomas in rats with athyreosis or hyperthyreosis, and in the ploidy of somatic cells in control animals.
Assuntos
Neoplasias Cerebelares/metabolismo , DNA de Neoplasias/metabolismo , Glioma/metabolismo , 9,10-Dimetil-1,2-benzantraceno , Animais , Astrocitoma/induzido quimicamente , Astrocitoma/metabolismo , Neoplasias Cerebelares/induzido quimicamente , Neoplasias Cerebelares/complicações , Glioblastoma/induzido quimicamente , Glioblastoma/metabolismo , Glioma/induzido quimicamente , Histocitoquímica , Hipertireoidismo/complicações , Hipotireoidismo/complicações , Oligodendroglioma/induzido quimicamente , Oligodendroglioma/metabolismo , Fotometria , Ploidias , RatosRESUMO
In rat cerebellum development of tumor, induced by 9,10-dimethyl-1,2-benzanthracene, was accompanied by a gradual increase in concentration of corticosterone in peripheral blood and by a decrease in 5-hydroxytryptophane decarboxylase activity. Experimental athyreosis inhibited development of the tumor in cerebellum (the tumor developed in 80.8% of normothyreotic animals treated with the benzanthracene derivatives; in the athyreotic animals this figure did not exceed 55.7%), decreased the corticosterone concentration in blood and caused a subsequent decrease in the 5-hydroxytryptophane decarboxylase activity in cerebellum as compared with the corresponding values determined in rats with intact thyroid gland. These alterations are considered as possible determinants of increased resistance of thyroidectomized rats to the blastomogenous effect of 9,10-dimethyl-1,2-benzanthracene on cerebellum.