RESUMO
PURPOSE: This study aimed to explore the genetic alterations and to identify good responders in the experimental arm in the tumor samples from newly diagnosed glioblastoma (GBM) patients enrolled in JCOG0911; a randomized phase II trial was conducted to compare the efficacy of interferonß (IFNß) plus temozolomide (TMZ) with that of TMZ alone. EXPERIMENTAL: DESIGN: Of 122 tumors, we performed deep targeted sequencing to determine the somatic mutations, copy number variations, and tumor mutation burden; pyrosequencing for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation; Sanger sequencing for the telomerase reverse transcriptase (TERT) promoter; and microsatellite instability (MSI) testing in 95, 91, 91 and 72 tumors, respectively. We performed a multivariable Cox regression analysis using backward stepwise selection of variables including clinical factors (sex, age, performance status, residual tumor after resection, tumor location) and genetic alterations. RESULTS: Deep sequencing detected an IDH1 mutation in 13 tumors (14%). The MGMT promoter methylation by quantitative pyrosequencing was observed in 41% of the tumors. A mutation in the TERT promoter was observed in 69% of the tumors. While high tumor mutation burden (> 10 mutations per megabase) was seen in four tumors, none of the tumors displayed MSI-high. The clinical and genetic factors considered as independent favorable prognostic factors were gross total resection (hazard ratio [HR]: 0.49, 95% confidence interval, 0.30-0.81, P = 0.0049) and MGMT promoter methylation (HR: 0.43, 0.21-0.88, P = 0.023). However, tumor location at the temporal lobe (HR: 1.90, 1.22-2.95, P = 0.0046) was an independent unfavorable prognostic factor. No predictive factors specific to the TMZ + IFNß + Radiotherapy (RT) group were found. CONCLUSION: This additional sub-analytical study of JCOG0911 among patients with newly diagnosed GBM showed that tumor location at the temporal lobe, gross total resection, and MGMT promoter methylation were significant prognostic factors, although no factors specific to IFNß addition were identified.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Interferon beta/uso terapêutico , Temozolomida/uso terapêutico , Adulto , Idoso , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Feminino , Humanos , Isocitrato Desidrogenase/genética , Masculino , Pessoa de Meia-Idade , Telomerase/genética , Resultado do Tratamento , Proteínas Supressoras de Tumor/genética , Adulto JovemRESUMO
PURPOSE: This study explored the superiority of temozolomide (TMZ) + interferonß (IFNß) to standard TMZ as treatment for newly diagnosed glioblastoma (GBM) via randomized phase II screening design. EXPERIMENTAL DESIGN: Eligibility criteria included histologically proven GBM, with 50% of the tumor located in supratentorial areas, without involvement of the optic, olfactory nerves, and pituitary gland and without multiple lesions and dissemination. Patients in the TMZ + radiotherapy (RT) arm received RT (2.0 Gy/fr/day, 30 fr) with TMZ (75 mg/m2, daily) followed by TMZ maintenance (100-200 mg/m2/day, days 1-5, every 4 weeks) for 2 years. Patients in the TMZ + IFNß + RT arm intravenously received IFNß (3 MU/body, alternative days during RT and day 1, every 4 weeks during maintenance period) and TMZ + RT. The primary endpoint was overall survival (OS). The planned sample size was 120 (one-sided alpha 0.2; power 0.8). RESULTS: Between Apr 2010 and Jan 2012, 122 patients were randomized. The median OS with TMZ + RT and TMZ + IFNß + RT was 20.3 and 24.0 months (HR 1.00, 95% CI 0.65-1.55; one-sided log rank P = 0.51). The median progression-free survival times were 10.1 and 8.5 months (HR 1.25, 95% CI 0.85-1.84). The incidence of neutropenia with the TMZ + RT and the TMZ + IFNß + RT (grade 3-4, CTCAE version 3.0) was 12.7 versus 20.7% during concomitant period and was 3.6 versus 9.3% during maintenance period. The incidence of lymphopenia was 54.0 versus 63.8% and 34.5 versus 41.9%. CONCLUSIONS: TMZ + IFNß + RT is not considered as a candidate for the following phase III trial, and TMZ + RT remained to be a most promising treatment. This trial was registered with the UMIN Clinical Trials Registry: UMIN000003466.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Interferon beta/uso terapêutico , Temozolomida/uso terapêutico , Administração Intravenosa , Adulto , Idoso , Antineoplásicos/efeitos adversos , Neoplasias Encefálicas/mortalidade , Quimiorradioterapia , Feminino , Glioblastoma/mortalidade , Humanos , Interferon beta/efeitos adversos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Temozolomida/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: In benign pineal parenchymal tumors (PPTs), namely, pineocytoma(PC)and PPT of intermediate differentiation (PPTID), cytologic pleomorphism has occasionally been found;however, it is controversial as to whether the presence of pleomorphic cells leads to upgrading of tumors. We experienced a rare case of pleomorphic PPT in an elderly woman and compared it with a retrospective series of 12 PPTs (PC:3, PPTID:6, pineoblastoma[PB]:3)to evaluate the correlation between pleomorphism and the malignancy grade. CASE AND MATERIALS: A 76-year-old woman presented with gradual cognitive deterioration and gait disturbance. Gadolinium-enhanced magnetic resonance imaging(Gd-MRI)revealed a small, enhanced tumor in the pineal gland with marked hydrocephalus. Endoscopic tumor biopsy and third ventriculostomy were performed simultaneously. The tumor was soft, pinkish, and slightly hemorrhagic. After the biopsy, the patient underwent gamma knife radiosurgery. PATHOLOGICAL FINDINGS: The PPT presented with areas of tumor cells forming pineocytomatous rosettes and areas of giant and multinucleated cells with hyperchromatic nuclei. Neither mitosis nor necrosis was observed. The tumor cells were positive for synaptophysin(SYN)and neurofilament(NF), but negative for glial fibrillary acidic protein(GFAP)and oligodendrocyte lineage transcription factor 2 (Olig2). The MIB-1 labeling index(LI)was 8.1%. There was no difference in the MIB-1 LI between pleomorphic and non-pleomorphic areas. All the 12 PPTs were immunopositive for the neuronal markers SYN and NF. The MIB-1 LI was 0% in PC, 3.5% in PPTID, and 10.5% in PB. The proliferative potential was correlated with the WHO grade. From these findings, the final diagnosis of this pleomorphic case was PPTID grade II, not PC, because the MIB-1 LI was relatively high, even though some tumor cells were forming pineocytomatous rosettes. CONCLUSION: Although cytologic pleomorphism in PPTs is generally considered not to be correlated with the malignancy grade, the final pathological diagnosis should be determined while considering the proliferative potential.
Assuntos
Neoplasias Encefálicas/patologia , Glândula Pineal/patologia , Pinealoma , Idoso , Biópsia , Neoplasias Encefálicas/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética , Gradação de Tumores , Neuroendoscopia , Glândula Pineal/cirurgia , Pinealoma/cirurgiaRESUMO
In contrast to pilocytic astrocytomas(PAs), pilomyxoid astrocytomas(PMAs)demonstrate monophasic piloid cells with angiocentric distribution and a more aggressive clinical course. Recently, several reports have described combined histological features of both subtypes;accordingly, these were termed intermediate pilomyxoid tumors(IPTs). The KIAA1549-BRAF fusion gene has been found in approximately 70% of PAs, but is reportedly rare in PMAs. We describe a clinicopathological study of two patients with pilomyxoid-spectrum astrocytoma(PMSA). Case 1 was of a 29-year-old man who presented with a generalized seizure. Gadolinium-magnetic resonance imaging(Gd-MRI)demonstrated a less enhanced tumor in the left temporal lobe. Case 2 was of a 9-year-old boy who presented with headache. Gd-MRI revealed an irregularly enhanced tumor in the left cerebellum. In Case 1, the tumor showed monomorphous bipolar cells in a myxoid background and angiocentric arrangement;therefore, the diagnosis was PMA. In Case 2, part of the tumor had a myxoid, angiocentric pattern characteristic of PMA;the other part had a biphasic pattern characteristic of PA. PMA and PA were mixed in a 7:3 ratio;therefore, IPT was diagnosed. No BRAF V600E mutations were found by immunohistochemistry and sequencing in either case. Three major KIAA1549-BRAF fusion subtypes were analyzed by quantitative reverse transcription polymerase chain reaction(RT-PCR)and sequencing. No fusions were found in Case 1. However, K16-B9 fusion was identified in Case 2, and this fusion was more prevalent in the PA component than in the PMA component. In summary, no BRAF V600E mutations were found in PMSAs, but KIAA1549-BRAF fusion was identified in IPT, particularly in the PA component.
Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Astrocitoma/diagnóstico , Astrocitoma/fisiopatologia , Sequência de Bases , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/fisiopatologia , Criança , Eletroencefalografia , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Dados de Sequência MolecularRESUMO
Temozolomide (TMZ) is an oral alkylating agent which is widely used in the treatment of glioblastoma (GBM) and is composed of astrocytic and/or oligodendroglial tumors, and the evaluation of O(6) -methylguanine DNA methyltransferase (MGMT) expression is important to predict the response to TMZ therapy. In this study, we conducted immunohistochemical analysis of 117 cases of Japanese GBM including 19 cases of GBM with oligodendroglioma component (GBMO), using a scoring system for quantitative evaluation of staining intensity and proportion of MGMT, and performed survival analysis of these patients. Immunohistochemically, 55 cases (47%) were positive for MGMT with various intensities and proportions (total score (TS) ≥ 2), while 62 cases (53%) were negative (TS = 0). The distribution of MGMT expression pattern was not affected by any clinicopathological parameters such as the histological subtype (GBM vs. GBMO), age and gender. The survival analysis of these patients revealed that the minimal expression of MGMT (TS ≥ 2) was a significant unfavorable prognostic factor (P < 0.001) as well as resectability (P = 0.004). Moreover, multivariate analysis showed that minimal MGMT expression in GBM was the most potent independent predictor for progression free survival (P < 0.001) and also overall patient survival (P < 0.001). This is the first report employing the scoring system for both staining intensity and proportion to evaluate immunohistochemical MGMT expression in GBM. In addition, our results emphases the clinicopathological values of the immunohistochemical approach for MGMT expression in glioma patients as a routine laboratory examination.
Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias Encefálicas/enzimologia , Regulação Neoplásica da Expressão Gênica , Glioblastoma/enzimologia , O(6)-Metilguanina-DNA Metiltransferase/análise , O(6)-Metilguanina-DNA Metiltransferase/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Feminino , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida/tendênciasRESUMO
Pilocytic astrocytoma is the most common glioma in children, in whom the majority arise in the cerebellum. In contrast, pilocytic astrocytomas are less common in adults. The most frequent locations involved are the basal ganglia, cerebellum, optic chiasm, and hypothalamus. Overall survival rates are good. The case presented involved a pilocytic astrocytoma of the right parietal lobe in a 36-year-old man. Cranial magnetic resonance imaging (MRI) revealed a small mural nodule in the wall of the cyst, with no edema around the tumor. This nodule showed a hyperintense signal on gadolinium-enhanced MRI. Computed tomography (CT) scanning revealed a hypodense right parietal lobe mass with calcification. At surgery, the cyst contents were aspirated, and the mural nodule was excised. Postoperative radiotherapy was not given. Neuropathological examination revealed a pilocytic astrocytoma (Grade I). The MIB-index was 3.3%. There has been no recurrence after 1 year of postoperative follow-up.
Assuntos
Astrocitoma/terapia , Neoplasias Encefálicas/terapia , Lobo Parietal , Adulto , Astrocitoma/diagnóstico , Astrocitoma/patologia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
Meningeal melanocytomas are uncommon intracranial tumors and extremely rare in the cerebellopontine angle (CPA). The tumors are generally considered to be benign because they lack malignant features in histological examination, but several literatures describe malignant behavior of the tumors such as high frequency of local recurrence, malignant transformation with leptomeningeal seeding. We describe a case of meningeal melanocytoma in the CPA and discuss the features of the tumor. The case was a 43-year-old woman with a right CPA exta-axial mass suffering from vertigo and nausea. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a mass in the right CPA. The mass was hyperintense on T1-weighted images and hypointense on T2-weighted images. Surgical removal was done and pathological diagnosis was made as meningeal melanocytoma. Twenty months after the first surgery, MRI revealed local recurrence of the tumor and subtotal resection was performed.
Assuntos
Neoplasias Cerebelares/patologia , Ângulo Cerebelopontino , Melanoma/patologia , Neoplasias Meníngeas/patologia , Adulto , Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/cirurgia , Ângulo Cerebelopontino/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Melanoma/diagnóstico , Melanoma/cirurgia , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/cirurgia , Meninges/patologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The development of diffuse cerebral vasospasm after the removal of a brain tumor is extremely rare. We report a case of cerebral vasospasm after the removal of a posterior fossa hemangioblastoma. CASE DESCRIPTION: A 62-year-old woman presented with a 1-month history of vertigo and nausea. Neurologic examination revealed that she was alert, with no paresis, and a mild left-sided cerebellar ataxia. Contrast-enhanced magnetic resonance imaging showed a cystic lesion with a strongly enhancing nodule, measuring 20 × 26 mm in diameter, in the cerebellar dorsal vermis. Angiography revealed that the lesion had feeding arteries from the left posterior inferior cerebellar artery. A diagnosis of hemangioblastoma was suspected and surgery was performed. On the first postoperative day, paresis of the right-sided extremities occurred. Diffusion-weighted imaging showed a high-intensity area in the medial side of the left frontal lobe. Magnetic resonance angiography indicated diffuse cerebrovascular stenosis. Considering these findings to be caused by vasospasm, we started the treatment used for vasospasm secondary to aneurysmal subarachnoid hemorrhage. Magnetic resonance angiography on the 13th postoperative day revealed an improvement in the cerebrovascular stenosis. In this case, it appears that the cause of vasospasm was intraoperative spillage of the contents of the cyst. CONCLUSIONS: Although the occurrence of diffuse cerebral vasospasm after the removal of brain tumors in the posterior fossa is rare, this complication should be noted as a potential postoperative complication after tumor removal; this should lead to earlier diagnosis and treatment and a potentially better prognosis.
Assuntos
Hemangioblastoma/cirurgia , Neoplasias Infratentoriais/cirurgia , Complicações Pós-Operatórias/terapia , Vasoespasmo Intracraniano/etiologia , Vasoespasmo Intracraniano/terapia , Constrição Patológica , Imagem de Difusão por Ressonância Magnética , Feminino , Hemangioblastoma/complicações , Hemangioblastoma/diagnóstico por imagem , Humanos , Neoplasias Infratentoriais/complicações , Neoplasias Infratentoriais/diagnóstico por imagem , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Paresia/diagnóstico por imagem , Paresia/etiologia , Complicações Pós-Operatórias/diagnóstico por imagem , Resultado do Tratamento , Vasoespasmo Intracraniano/diagnóstico por imagemAssuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Diagnóstico Diferencial , Glioblastoma/diagnóstico , Oligodendroglioma/diagnóstico , Biomarcadores Tumorais/análise , Glioblastoma/mortalidade , Glioblastoma/terapia , Humanos , Oligodendroglioma/mortalidade , Oligodendroglioma/terapia , PrognósticoRESUMO
Central nervous system (CNS) neuroblastoma/ganglioneuroblastoma is one of the embryonal tumors with neuronal differentiation found in young adults, but it is most common in children, especially in those below the age of 5 years, whereas extraventricular neurocytoma, a rare neuroepithelial tumor with neuronal differentiation, mostly affects young adults. Here we present a rare case of cerebral ganglioneuronal tumor that occurred in a 32-year-old woman. The patient suffered from tonic convulsion, and computed tomography demonstrated a well-demarcated, round tumor 3.3 cm in size with marked calcification in the right parietal lobe. Histological analysis revealed diffuse infiltration of small, round cells with scattered large ganglion-like cells. Immunohistochemically, the tumor cells did not react with any neuronal molecules, except for chromogranin A in ganglion-like large tumor cells, but electron microscopy demonstrated the presence of synapse-like nerve terminal structures without mature postsynaptic density, suggesting the presence of neoplastic tumor components with neuronal differentiation; thus, this tumor was diagnosed as CNS ganglioneuroblastoma with possible low-grade malignancy because the Mib-1 labeling index was less than 3%-4%. Here we discuss the histological entity of cerebral ganglioneuronal tumors, including extraventricular neurocytoma.
Assuntos
Neoplasias Encefálicas/patologia , Ganglioneuroblastoma/patologia , Lobo Parietal/patologia , Adulto , Neoplasias Encefálicas/metabolismo , Feminino , Ganglioneuroblastoma/metabolismo , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Lobo Parietal/metabolismo , Tomografia Computadorizada por Raios XRESUMO
We experienced anesthetic management using target-controlled infusion (TCI) of remifentanil for craniotomy in which monitoring of motor evoked potential (MEP) was performed. Anesthesia was induced and maintained by TCI of propofol and remifentanil. Vecuronium bromide was not administered except for facilitating tracheal intubation. Target effect-site concentrations (ESCs) of remifentanil during intubation, exposure, dura incision, microsurgery and closure were 6, 10, 8, 5 and 8 ng x ml(-1), respectively. Myogenic MEP was sufficiently elicited throughout the microsurgery without patient's body movement. Extubation was completed 10 min after the end of surgery with administration of remifentanil continued at a target ESC of 2 ng ml(-1) after surgery. Emergence from anesthesia was good without complaint of pain or respiratory disorder or new neurological deficit. It has been reported that remifentanil is suitable because of its wide dosage window with respect to recording MEP. ESC of remifentanil was fixed during continuous infusion, but its absolute value varies depending on lean body mass and/or age. The use of TCI enabled easy elimination of the above effects, adjustment of ESC to the expected value and maintenance of ESC of remifentanil at a constant level. TCI of remifentanil might be suitable for anesthesia with monitoring of MEP.
Assuntos
Anestesia Intravenosa , Craniotomia , Potencial Evocado Motor , Monitorização Intraoperatória , Piperidinas , Anestesia Intravenosa/métodos , Neoplasias Encefálicas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Propofol , RemifentanilRESUMO
The anatomical relationship between the arcuate eminence (AE) and the superior semicircular canal (SSC) was examined by computed tomography (CT) in 52 petrous bones of 26 patients. After acquiring volume data by multidetector CT, 1-mm thick oblique bone window images perpendicular to the SSC were obtained from the axial images. The distances between the AE and the SSC, and the SSC and the superior surface of the petrous bone were measured. The AE corresponded exactly with the SSC in only 2/52 petrous bones, and corresponded well in 7/52. The AE was lateral to the SSC in 25/52 cases, medial to the SSC in 6/52 cases, intersected in 3/52 cases, and was indiscernible in 9/52 cases. The distance between the SSC and the petrous surface was 0 mm in 45/52 petrous bones, 1 mm in 5/52, 2 mm in 1/52, and 3 mm in 1/52. The SSC typically does not correspond exactly with the AE, and is generally located just under the surface of the petrous bone. Planning of the middle cranial fossa approach requires location of the SSC by CT.
Assuntos
Fossa Craniana Média/anatomia & histologia , Fossa Craniana Média/diagnóstico por imagem , Osso Petroso/anatomia & histologia , Osso Petroso/diagnóstico por imagem , Canais Semicirculares/anatomia & histologia , Canais Semicirculares/diagnóstico por imagem , Adolescente , Adulto , Idoso , Antropometria/métodos , Criança , Nervo Coclear/anatomia & histologia , Nervo Coclear/cirurgia , Fossa Craniana Média/cirurgia , Orelha Interna/anatomia & histologia , Orelha Interna/diagnóstico por imagem , Orelha Interna/cirurgia , Nervo Facial/anatomia & histologia , Nervo Facial/cirurgia , Doenças do Nervo Facial/cirurgia , Feminino , Humanos , Masculino , Microcirurgia/métodos , Microcirurgia/normas , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Procedimentos Neurocirúrgicos/normas , Osso Petroso/cirurgia , Valores de Referência , Canais Semicirculares/cirurgia , Osso Temporal/anatomia & histologia , Osso Temporal/diagnóstico por imagem , Osso Temporal/cirurgia , Tomografia Computadorizada por Raios X/métodos , Nervo Vestibular/anatomia & histologia , Nervo Vestibular/cirurgia , Doenças do Nervo Vestibulococlear/cirurgiaRESUMO
We report a rare case of tanycytic ependymoma arising from the cerebral hemisphere. A 59-year-old man was admitted to our hospital because of the incidental detection by MRI of a tumor lesion in the right temporooccipital paratrigonal region. The mass showed low-to iso-intensity on T1-weighted images and high intensity on T2/proton-weighted images. Partial resection was performed using a transsulcal approach to avoid compromising the visual field. Most of the tumor cells showed elongated spindle shapes arranged in dense fascicles. A few true ependymal rosettes and perivascular pseudorosettes were visible. The tumor cells were positive for GFAP, S-100, and vimentin, but negative for synaptophysin, EMA, and keratin. The MIB-1 labeling index was approximately 1%. Ultrastructurally, the tumor cells had ependymal cell features, such as microvilli and cilia. From these findings, a pathological diagnosis of tanycytic ependymoma was made.
Assuntos
Neoplasias Encefálicas/patologia , Ependimoma/patologia , Biomarcadores Tumorais , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/ultraestrutura , Proliferação de Células , Malformações Vasculares do Sistema Nervoso Central/patologia , Angiografia Cerebral , Ependimoma/cirurgia , Ependimoma/ultraestrutura , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tálio , Tomografia Computadorizada de Emissão de Fóton Único , Campos VisuaisRESUMO
We report a case of young immunocompetent woman who was presented with a left parieto-temporal mass as the first and single manifestation of syphilis. A 23 year-old woman with no significant past medical history was reffered to our hospital due to 3 month history of headache. She had a single unprotected sexual intercourse with a promiscuous man 6 month before the time of admission. Physical and neurological examinations revealed no obvious abnormalities. A brain tumor was firstly suggested according to the findings of brain magnetic resonance imaging (MRI). However, the serologic and cerebrospinal fluid test of syphilis proved to be positive, syphilitic gumma was most likely suspected. She responded dramatically to benzylpenicillin potassium. Cerebral syphilitic gumma is a rare manifestations of the neurosyphilis. Treponemal invasion of the cerebrospinal fluid occurs in approximately 25 to 60% of patients after the infection, but most cases spend asymptomatic. Cerebral gumma should be considered in differential diagnosis of any intracranial mass lesions, even in the early syphilitic stages.
Assuntos
Neoplasias Encefálicas/diagnóstico , Diagnóstico Diferencial , Neurossífilis/diagnóstico , Adulto , Antibacterianos/administração & dosagem , Encéfalo/patologia , Neoplasias Encefálicas/tratamento farmacológico , Feminino , Humanos , Imageamento por Ressonância Magnética , Neurossífilis/tratamento farmacológico , Penicilina G/administração & dosagem , Sorodiagnóstico da Sífilis , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Pineal parenchymal tumors of intermediate differentiation (PPTID) are extremely rare tumor entities, and only limited data are available regarding their pathologic features and biologic behaviors. Because grading criteria of pineal parenchymal tumors (PPTs) have yet to be established, the treatment strategy and prognosis of PPTIDs remain controversial. We describe the clinicopathologic study of six patients with PPTID and compare responses for the treatment and prognosis with cases of pineocytoma (PC) and pineoblastoma (PB). From this analysis, we attempt to clarify the treatment strategy for PPTIDs. METHODS: This study included 15 patients with PPTs, consisting of 6 PCs, 6 PPTIDs, and 3 PBs. We focused on the 6 patients with PPTIDs. All PPTID cases were treated surgically, and radiotherapy and chemotherapy were administered as adjuvant therapies in some cases. We have earlier reported the histopathologic study (Neuropathology 32:647-653, 2012). Briefly, we examined mitotic figures and necrosis by hematoxylin-eosin staining and immunohistochemical markers such as neuronal markers (synaptophysin, neurofilament (NF), and neuronal nuclear antigen), and an MIB-1 labeling index was determined. RESULTS: In the PPTID cases, the extent of resection was variable and the recurrence rates among patients varied according to stage and treatment. All PC patients underwent total resection with no recurrence. All PB patients underwent resection and adjuvant therapy with radiotherapy and chemotherapy. There were no recurrences in patients with PC or PB. The results of histopathologic findings have been already reported as mentioned above. Briefly, the results indicated no mitotic figure or necrosis in any of the six cases of PPTID, but those features were observed in PB cases. All cases even including PC and PB were immunopositive for neuronal markers. The MIB-1 labeling index of PPTID was 3.5%, whereas it was 0% in PC and 10.5% in PB. CONCLUSIONS: Good radiosensitivity of PPTIDs was observed in our series. Because there are cases with discrepancies between images and pathologic findings, it is very difficult to determine the proper treatment strategy for PPTIDs. Proliferative potential was correlated with World Health Organization grade, although the immunoreactivity of neuronal markers did not correlate with the histologic grade.
Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Glândula Pineal/patologia , Pinealoma/patologia , Pinealoma/cirurgia , Adolescente , Adulto , Idoso , Biomarcadores , Biópsia , Neoplasias Encefálicas/terapia , Diferenciação Celular , Quimiorradioterapia/métodos , Feminino , Seguimentos , Humanos , Avaliação de Estado de Karnofsky , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Glândula Pineal/cirurgia , Pinealoma/terapia , Prognóstico , Ventriculostomia/métodos , Adulto JovemRESUMO
PURPOSE: Glioblastoma (GBM) is one of the worst cancers in terms of prognosis. Standard therapy consists of resection with concomitant chemoradiotherapy. Resistance to nimustine hydrochloride (ACNU), an alkylating agent, has been linked to methylguanine DNA methyltransferase (MGMT). Daily administration of procarbazine (PCZ) has been reported to decrease MGMT activity. This study investigated the efficacy of ACNU + PCZ compared to ACNU alone for GBM and anaplastic astrocytoma (AA). METHODS: Patients (20-69 years) who had newly diagnosed AA and GBM were randomly assigned to receive radiotherapy with ACNU alone or with ACNU + PCZ. The primary endpoint was overall survival (OS). This was designed as a phase II/III trial with a total sample size of 310 patients and was registered as UMIN-CTR C000000108. RESULTS: After 111 patients from 19 centers in Japan were enrolled, this study was terminated early because temozolomide was newly approved in Japan. The median OS and median progression-free survival (PFS) with ACNU alone (n = 55) or ACNU + PCZ (n = 56) in the intention-to-treat population were 27.4 and 22.4 months (p = 0.75), and 8.6 and 6.9 months, respectively. The median OS and median PFS of the GBM subgroup treated with ACNU alone (n = 40) or ACNU + PCZ (n = 41) were 19.0 and 19.5 months, and 6.2 and 6.3 months, respectively. Grade 3/4 hematologic adverse events occurred in more than 40 % of patients in both arms, and 27 % of patients discontinued treatment because of adverse events. CONCLUSIONS: The addition of PCZ to ACNU was not beneficial, in comparison with ACNU alone, for patients with newly diagnosed AA and GBM.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Astrocitoma/terapia , Neoplasias Encefálicas/terapia , Quimiorradioterapia , Glioblastoma/tratamento farmacológico , Nimustina/uso terapêutico , Procarbazina/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Astrocitoma/mortalidade , Neoplasias Encefálicas/mortalidade , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Glioblastoma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Nimustina/administração & dosagem , Procarbazina/administração & dosagemRESUMO
Most radiation-induced osteosarcomas of the skull are reported to arise in the facial bone or paranasal sinus after radiotherapy for retinoblastoma and/or pituitary adenoma. Here we report two cases of radiation-induced osteosarcoma in the paranasal sinus after treatment for frontal glioma. Case 1 was a 56-year-old woman who underwent surgical resection of a left frontal tumor in October 1990. The histological diagnosis was a low-grade glioma, and radiotherapy of 54 Gy was administered. Sixteen years later, in September 2006, the patient noted an enlarging subcutaneous mass in the right frontal region. CT showed an osteolytic mass in the right frontal sinus. An open biopsy established the histopathological diagnosis of osteosarcoma, and the patient subsequently died of rapid tumor regrowth. Case 2 was a 58-year-old man who underwent partial removal of a bifrontal tumor in May 1996. The histological diagnosis was anaplastic oligoastrocytoma, and radiotherapy of 56 Gy was administered. Twelve years later, in March 2008, the patient was readmitted to our hospital for reasons of marked deterioration in general physical condition. Tumor recurrence was suspected in the left frontal lobe, and CT demonstrated an osteolytic mass in the left frontal and ethmoid sinus. A secondary operation was performed, and the pathological specimens were diagnosed as osteosarcoma. Radiotherapy was readministered, but the subject died of rapid tumor regrowth. From these clinicopathological findings, both cases were diagnosed as radiation-induced osteosarcoma. Radiation-induced osteosarcomas appeared 16 and 12 years after radiotherapy in cases 1 and 2, respectively. As the prognosis of radiation-induced osteosarcoma is poorer than that of primary osteo-sarcoma, careful attention is required for consideration of the long-term survival of patients with glioma.
Assuntos
Neoplasias Ósseas/patologia , Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Neoplasias Induzidas por Radiação/patologia , Osteossarcoma/patologia , Neoplasias dos Seios Paranasais/patologia , Biópsia , Neoplasias Ósseas/etiologia , Neoplasias Encefálicas/cirurgia , Meios de Contraste , Relação Dose-Resposta à Radiação , Feminino , Lobo Frontal/patologia , Lobo Frontal/cirurgia , Gadolínio DTPA , Glioma/cirurgia , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteossarcoma/etiologia , Neoplasias dos Seios Paranasais/etiologia , Fixação de Tecidos , Tomografia Computadorizada por Raios XRESUMO
Evaluation of O6-methylguanine-DNA methyltransferase (MGMT) expression is important for antiglioma therapy as many clinical trials have demonstrated that promoter hypermethylation and low level expression of MGMT are associated with an enhanced response to alkylating agents. However, here we report that the current strategies used to evaluate MGMT status in gliomas are unreliable. We observed discordance in the MGMT expression status when immunohistochemical evaluation and polymerase chain reaction-based methylation assessments were used: 73% of gliomas with methylated MGMT promoter had substantial numbers of MGMT-immunopositive tumor cells. Furthermore, when MGMT expression was tested in tumor homogenates using reverse transcription-polymerase chain reaction, 43% of tumors were found positive, in comparison to only 24%, when histologic samples were assayed immunohistochemically. To explain these inconsistencies we undertook a detailed immunohistochemical evaluation of tumor samples and found that some gliomas demonstrated remarkably high expression of MGMT in the entire tumor whereas others contained only a small immunopositive area. Additionally, we found that gliomas contained various types of non-neoplastic cells expressing MGMT, including lymphocytes, vascular endothelial cells, and macrophages/microglias, which contribute to overall MGMT expression detected in tumor homogenates, and thus result in overestimation of tumor MGMT expression. Therefore, to correctly establish MGMT expression in the tumor, which could be informative of glioma sensitivity to alkylating agents, exclusion of non-neoplastic brain components from analysis is required.
Assuntos
Neoplasias Encefálicas/enzimologia , Encéfalo/enzimologia , Metilação de DNA , Metilases de Modificação do DNA/análise , Enzimas Reparadoras do DNA/análise , Glioma/enzimologia , Imuno-Histoquímica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Manejo de Espécimes , Proteínas Supressoras de Tumor/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/uso terapêutico , Encéfalo/patologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glioma/tratamento farmacológico , Glioma/genética , Glioma/patologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Regiões Promotoras Genéticas , Reprodutibilidade dos Testes , Proteínas Supressoras de Tumor/genéticaRESUMO
Tanycytic ependymomas are a subtype of ependymomas that were formally recognized as a new pathological entity in the latest World Health Organization (WHO) classification of 2000. They occur mostly in the spinal cord. Only a few reports have analyzed the proliferative potentials of these tumors; however, it has been reported that the MIB-1 labeling index of tanycytic ependymoma is lower than that of other subtypes of WHO grade II ependymomas. We report a rare case of cervicomedullary junction tanycytic ependymoma associated with marked cyst formation. A 62-year-old man had a history of progressive gait disturbance, diplopia, and swallowing disturbance over a one-month period prior to admission. Magnetic resonance imaging (MRI) showed a cystic mass with a mural nodule at the cervicomedullary junction with Gd-DTPA enhancement. Cyst-subarachnoid shunt was performed using a far lateral approach. After 6 years, however, the man was readmitted to the hospital because of reaccumulation of the cyst. Partial removal of a mural nodule and a cyst-subarachnoid shunt were performed simultaneously by a midline suboccipital approach. The pathological diagnosis was tanycytic ependymoma. Postoperatively, the patient recovered well and was discharged from the hospital without further treatment. Most of the tumor cells had small, round nuclei; pleomorphism was minimal. The cytoplasm was dilated. The tumor cells were positive for EMA and s-100, and negative for CD-34. GFAP was not determined due to difficulty caused by background glial processes. The MIB-1 labeling index was less than 1%. Ultrastructurally, the tumor cells had ependymal cell features, such as desmosomes and microvilli. Based on these findings, the pathological diagnosis was tanycytic ependymoma.