RESUMO
OBJECTIVE: To report two rare cases of medulloblastoma in pregnant patients and a review of the literature. MATERIAL AND METHODS: Report of patients diagnosed with medulloblastoma during their pregnancies, who were treated with surgery and adjuvant therapy. We also reviewed other cases reported in the literature and the association made with hormonal receptors. RESULTS: Brain tumors in coincidence with pregnancy are unusual, and the incidence of medulloblastoma in pregnancy is still rarer. We found 8 cases of medulloblastomas diagnosed during pregnancy. Reports suggest that hormonal changes and increases in the levels of growth factors and angiogenic factors during pregnancy influence the rate of growth of brain tumors (not only medulloblastomas but also meningiomas or glial tumors). CONCLUSIONS: The uniqueness of these cases is their rarity. The symptoms are usually masked by the symptoms of pregnancy. At present, there is still little evidence regarding the pathogenesis and treatment of medulloblastoma in pregnancy.
Assuntos
Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/cirurgia , Meduloblastoma/diagnóstico por imagem , Meduloblastoma/cirurgia , Complicações Neoplásicas na Gravidez/diagnóstico por imagem , Complicações Neoplásicas na Gravidez/cirurgia , Neoplasias Cerebelares/sangue , Feminino , Hormônios Esteroides Gonadais/sangue , Humanos , Meduloblastoma/sangue , Gravidez , Complicações Neoplásicas na Gravidez/sangue , Adulto JovemRESUMO
Primary central nervous system (CNS) tumors are the most common deadly childhood cancer. Several patients with medulloblastoma experience local or metastatic recurrences after standard treatment, a condition associated with very poor prognosis. Current neuroimaging techniques do not accurately detect residual stem-like medulloblastoma cells promoting tumor relapses. In attempt to identify candidate tumor markers that could be circulating in blood or cerebrospinal (CSF) fluid of patients, we evaluated the proteome and miRNome content of extracellular microvesicles (MVs) released by highly-aggressive stem-like medulloblastoma cells overexpressing the pluripotent factor OCT4A. These cells display enhanced tumor initiating capability and resistance to chemotherapeutic agents. A common set of 464 proteins and 10 microRNAs were exclusively detected in MVs of OCT4A-overexpressing cells from four distinct medulloblastoma cell lines, DAOY, CHLA-01-MED, D283-MED, and USP13-MED. The interactome mapping of these exclusive proteins and miRNAs revealed ERK, PI3K/AKT/mTOR, EGF/EGFR, and stem cell self-renewal as the main oncogenic signaling pathways altered in these aggressive medulloblastoma cells. Of these MV cargos, four proteins (UBE2M, HNRNPCL2, HNRNPCL3, HNRNPCL4) and five miRNAs (miR-4449, miR-500b, miR-3648, miR-1291, miR-3607) have not been previously reported in MVs from normal tissues and in CSF. These proteins and miRNAs carried within MVs might serve as biomarkers of aggressive stem-like medulloblastoma cells to improve clinical benefit by helping refining diagnosis, patient stratification, and early detection of relapsed disease.
Assuntos
Neoplasias Cerebelares/diagnóstico , Vesículas Extracelulares/metabolismo , Meduloblastoma/diagnóstico , MicroRNAs/análise , Proteoma/análise , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/líquido cefalorraquidiano , Linhagem Celular Tumoral , Neoplasias Cerebelares/sangue , Neoplasias Cerebelares/líquido cefalorraquidiano , Humanos , Meduloblastoma/sangue , Meduloblastoma/líquido cefalorraquidiano , Prognóstico , ProteômicaRESUMO
INTRODUCCIÓN: La radioterapia, quimioterapia y la cirugía empleada en el tratamiento de los tumores cerebrales tienen efectos en el eje hipotálamo-hipofisario y pueden resultar en disfunción endocrina hasta en el 96% de los casos. PACIENTES Y MÉTODO: Estudio retrospectivo y descriptivo en pacientes diagnos ticados de meduloblastoma sometidos a tratamiento con quimio y radioterapia en los últimos 20 años en un hospital terciario. Se analizan variables edad, sexo, peso, talla, índice de masa corporal (IMC) al final del seguimiento, estadio de maduración sexual, niveles séricos de TSH y T4 libre, ACTH/cortisol e IGF-1, FSH, LH, estradiol, testosterona, perfil lipídico (colesterol total) y prueba de función dinámica de hormona de crecimiento. RESULTADOS: Muestra total de 23 pacientes. El déficit de hormona de crecimiento es la secuela más frecuente (82 %) seguido de disfunción ti roidea (44,8%) y disfunción puberal (24,1%). Solo se diagnosticó un caso de diabetes insípida y 2 casos de déficit de corticotrofina. CONCLUSIONES: El seguimiento a largo plazo de los supervivientes de meduloblastoma tratados con quimio y radioterapia revela una prevalencia muy alta de disfun ción endocrina, particularmente de deficiencia de hormona del crecimiento y de hipotiroidismo. Creemos oportuna la monitorización y el seguimiento a largo plazo de estos pacientes con el fin de garantizar un manejo terapéutico adecuado de aquellas disfunciones tratables.
INTRODUCTION: Radiation therapy, chemotherapy, and surgery used to treat brain tumors have effects on the hy pothalamic-pituitary-adrenal axis and can result in endocrine dysfunction in up to 96% of cases. PATIENTS Y METHOD: Retrospective and descriptive study in patients diagnosed with medulloblasto ma who underwent treatment with chemo and radiotherapy in the last 20 years in a tertiary hospital. The variables analyzed were age, sex, weight, height, body mass index (BMI) at the end of follow-up, sexual maturity stage, serum levels of TSH and free T4, ACTH/cortisol and IGF-1, FSH, LH, estradiol, testosterone, lipid profile (total cholesterol), and growth hormone dynamic function test. RESULTS: Total sample of 23 patients. Growth hormone deficiency is the most frequent sequelae (82%) fo llowed by thyroid dysfunction (44.8%), and disorders of puberty (24.1%). Only one case of diabetes insipidus and two cases of corticotropin deficiency were diagnosed. CONCLUSIONS: Long-term follow- up of medulloblastoma survivors treated with chemo and radiotherapy reveals a very high prevalence of endocrine dysfunction, especially growth hormone deficiency and hypothyroidism. We believe that monitoring and long-term follow-up of these patients is necessary in order to ensure adequate therapeutic management of those treatable dysfunctions.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Neoplasias Cerebelares/terapia , Quimiorradioterapia/efeitos adversos , Meduloblastoma/terapia , Puberdade Precoce/etiologia , Doenças da Glândula Tireoide/etiologia , Neoplasias Cerebelares/sangue , Estudos Retrospectivos , Hormônio Adrenocorticotrópico/deficiência , Hormônio do Crescimento Humano/deficiência , Diabetes Insípido/etiologia , Doenças do Sistema Endócrino/etiologia , Sobrepeso/etiologia , Sobreviventes de Câncer , Hipogonadismo/etiologia , Meduloblastoma/sangueRESUMO
INTRODUCTION: Radiation therapy, chemotherapy, and surgery used to treat brain tumors have effects on the hy pothalamic-pituitary-adrenal axis and can result in endocrine dysfunction in up to 96% of cases. PATIENTS AND METHOD: Retrospective and descriptive study in patients diagnosed with medulloblasto ma who underwent treatment with chemo and radiotherapy in the last 20 years in a tertiary hospital. The variables analyzed were age, sex, weight, height, body mass index (BMI) at the end of follow-up, sexual maturity stage, serum levels of TSH and free T4, ACTH/cortisol and IGF-1, FSH, LH, estradiol, testosterone, lipid profile (total cholesterol), and growth hormone dynamic function test. RESULTS: Total sample of 23 patients. Growth hormone deficiency is the most frequent sequelae (82%) fo llowed by thyroid dysfunction (44.8%), and disorders of puberty (24.1%). Only one case of diabetes insipidus and two cases of corticotropin deficiency were diagnosed. CONCLUSIONS: Long-term follow- up of medulloblastoma survivors treated with chemo and radiotherapy reveals a very high prevalence of endocrine dysfunction, especially growth hormone deficiency and hypothyroidism. We believe that monitoring and long-term follow-up of these patients is necessary in order to ensure adequate therapeutic management of those treatable dysfunctions.