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1.
Anticancer Res ; 41(4): 1715-1726, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813375

RESUMO

Medulloblastoma (MB) is the most frequent malignant brain tumor in children. Treatment of MB is based on histopathological and molecular stratification, and includes surgical intervention, often with craniospinal irradiation and adjuvant chemotherapy. Unfortunately, however, this treatment leads to a high morbidity rate, and it does not cure all patients either, with around 30% succumbing to their disease. With improved cancer genomics and better molecular characterization, MB has been classified into four major subgroups, wingless-activated, sonic hedgehog-activated, Group 3, and Group 4, with each group consisting of additional subtypes. Recently disclosed genetic drivers of MB may in the future help improve treatment, and in this way reduce therapy-related toxicity. In this review, we describe the heterogeneity of the MB subgroups, and potential new options for targeted therapy.


Assuntos
Neoplasias Cerebelares/terapia , Imunoterapia , Meduloblastoma/terapia , Terapia de Alvo Molecular , Procedimentos Neurocirúrgicos , Medicina de Precisão , Biomarcadores Tumorais/genética , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/mortalidade , Neoplasias Cerebelares/patologia , Quimioterapia Adjuvante , Criança , Pré-Escolar , Irradiação Craniana , Feminino , Humanos , Imunoterapia/efeitos adversos , Lactente , Masculino , Meduloblastoma/genética , Meduloblastoma/mortalidade , Meduloblastoma/patologia , Terapia de Alvo Molecular/efeitos adversos , Procedimentos Neurocirúrgicos/efeitos adversos , Radioterapia Adjuvante , Resultado do Tratamento
2.
Medicine (Baltimore) ; 100(5): e24566, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592913

RESUMO

RATIONALE: Extra-axial cavernous malformations (ECMs) arising from cranial nerves (CNs) are rare. Complete "en bloc" lesion resection and hemosiderin-stained tissue preservation remain the standard treatment, while a different strategy may be needed when the lesion is highly calcified . We report the 3rd calcified ECM-CN and review the clinical features and surgical strategy for this rare condition considering previous literature. PATIENT CONCERNS: We present a 52-year-old woman with a calcified lesion located in the right lower 1/3 of the cerebellopontine angle. DIAGNOSIS: The diagnosis was calcified ECM-CNs according to the pathological and radiological features. INTERVENTIONS: A posterior midline craniotomy was performed, and piecemeal resection of the lesion was carried out. Subtotal resection of the lesion was achieved with a small piece left in situ. OUTCOMES: No symptom or lesion-related recurrence was found during 28 months of follow-up. LESSONS: Calcified ECM-CNs are unique cavernous malformations arising from CNs. Piecemeal resection and subtotal or near-total excision are 2 major aspects that differ from the surgical strategy for general ECM-CNs.


Assuntos
Neoplasias Cerebelares/patologia , Nervos Cranianos/patologia , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Neoplasias Cerebelares/cirurgia , Nervos Cranianos/cirurgia , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Humanos , Pessoa de Meia-Idade
3.
Clin Nucl Med ; 46(6): 485-487, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33492863

RESUMO

ABSTRACT: Hemangioblastoma (HB) is the most common primary intra-axial posterior fossa tumor in adults and is a benign vascular neoplasm. We report the case of a 73-year-old man suffering from biochemical recurrence of prostate cancer where intense overexpression of prostate-specific membrane antigen (PSMA) was observed in HB in a PSMA PET/CT. Overexpression of PSMA in tumor-associated vascular structures has been proposed as an explanation of PSMA ligand uptake in several nonprostatic tumors. Given the pathological nature of HB, this mechanism may explain the intense overexpression of PSMA observed in present case.


Assuntos
Antígenos de Superfície/metabolismo , Neoplasias Cerebelares/diagnóstico por imagem , Glutamato Carboxipeptidase II/metabolismo , Hemangioblastoma/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Neoplasias Cerebelares/metabolismo , Neoplasias Cerebelares/patologia , Regulação Neoplásica da Expressão Gênica , Hemangioblastoma/metabolismo , Hemangioblastoma/patologia , Humanos , Masculino
4.
Am J Surg Pathol ; 45(4): 558-566, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33323893

RESUMO

Medulloblastomas (MBs) are the most frequent childhood malignant brain tumor. Four histopathologic variants and 4 genetic subgroups have been defined in the World Health Organization (WHO) 2016 Classification and constitute major risk stratification items directly affecting the patient management. Although MB subgroups have been molecularly defined, immunohistochemical surrogates are needed. The aim of our retrospective study was to evaluate the concordance between immunohistochemistry, using 4 antibodies (YAP1, GAB1, OTX2, and ß-catenin), and DNA-methylation profiling in MB subgrouping. From a series of 155 MBs, the κ coefficient of concordance was almost perfect (0.90), with only 8/152 discrepant cases (no DNA-methylation analysis was available in 3 cases). Interestingly, the discrepancies mostly concerned (7/8 cases) MBs with divergent differentiations (myogenic, melanotic, and others) with all of those classified into group 3 (n=6) and group 4 (n=1) by DNA-methylation profiling. Another discrepant case concerned a WNT-activated MB (showing only 1% of immunopositive tumor cell nuclei), highlighting the difficulties of determining an appropriate ß-catenin immunostaining cutoff. The high concordance of the routine immunohistochemical panel (YAP1, GAB1, OTX2, and ß-catenin) and DNA-methylation profiling confirm its utility as a reliable predictive marker of molecular subtype in MBs. We analyzed the accuracy of 10 different IHC combinations for the determination of MB subtype and found that a combination of 2 antibodies (YAP1 and OTX2) allows for the successful characterization of 144 cases of 152 cases. Finally, our series extends the molecular data of the rare morphologic variant of MBs with melanotic/myogenic differentiations.


Assuntos
Biomarcadores Tumorais , Neoplasias Cerebelares/classificação , Metilação de DNA , Imuno-Histoquímica , Meduloblastoma/classificação , Proteínas Adaptadoras de Transdução de Sinal/análise , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias Cerebelares/química , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/patologia , Humanos , Hibridização in Situ Fluorescente , Meduloblastoma/química , Meduloblastoma/genética , Meduloblastoma/patologia , Fatores de Transcrição Otx/análise , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Transcrição/análise , beta Catenina/análise
5.
Clin Nucl Med ; 46(5): e262-e263, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33315670

RESUMO

ABSTRACT: We describe the utility of molecular imaging with 18F-FDG and 68Ga-DOTANOC PET for treatment response assessment in a case of metastatic medulloblastoma. 18F-FDG and 68Ga-DOTANOC PET/CT revealed extensive metastases to bone and bone marrow. Patient subsequently had an excellent response to systemic chemotherapy which was evidenced by resolution of tracer-avid skeletal lesions on both FDG and DOTANOC PET/CT.


Assuntos
Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/patologia , Fluordesoxiglucose F18 , Meduloblastoma/diagnóstico por imagem , Meduloblastoma/patologia , Compostos Organometálicos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias Cerebelares/terapia , Feminino , Humanos , Meduloblastoma/terapia , Metástase Neoplásica , Resultado do Tratamento
6.
Nat Commun ; 11(1): 4323, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859895

RESUMO

Medulloblastoma (MB) is defined by four molecular subgroups (Wnt, Shh, Group 3, Group 4) with Wnt MB having the most favorable prognosis. Since prior reports have illustrated the antitumorigenic role of Wnt activation in Shh MB, we aimed to assess the effects of activated canonical Wnt signaling in Group 3 and 4 MBs. By using primary patient-derived MB brain tumor-initiating cell (BTIC) lines, we characterize differences in the tumor-initiating capacity of Wnt, Group 3, and Group 4 MB. With single cell RNA-seq technology, we demonstrate the presence of rare Wnt-active cells in non-Wnt MBs, which functionally retain the impaired tumorigenic potential of Wnt MB. In treating MB xenografts with a Wnt agonist, we provide a rational therapeutic option in which the protective effects of Wnt-driven MBs may be augmented in Group 3 and 4 MB and thereby support emerging data for a context-dependent tumor suppressive role for Wnt/ß-catenin signaling.


Assuntos
Neoplasias Cerebelares/terapia , Meduloblastoma/terapia , Proteínas Wnt/farmacologia , Proteínas Wnt/uso terapêutico , Animais , Carcinogênese , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Cerebelares/patologia , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Meduloblastoma/genética , Meduloblastoma/patologia , Camundongos , Células-Tronco , Proteínas Wnt/genética , Via de Sinalização Wnt , beta Catenina/uso terapêutico
7.
J Neuropathol Exp Neurol ; 79(7): 734-745, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32417918

RESUMO

Medulloblastomas (MBs) are currently divided into 4 molecular subgroups: WNT, SHH, Group 3, and Group 4. Among them, Group 3 MB has the worst prognosis, and 40%-50% of Group 3 cases are already metastatic at the time of diagnosis. Emerging evidence indicates that exosomes drive tumor invasion, but very little is known about exosomes in MBs. In this study, we initially discovered that exosomes isolated from Group 3 MB cell lines altered in vitro behaviors of a less invasive SHH MB cell line and yielded a much more aggressive phenotype. RNA-sequencing analysis revealed 7 exosomal miRNAs with markedly different expression levels between the SHH and Group 3 MB cell lines. They were all predicted to be related to the Ras/MAPK pathway according to the Kyoto Encyclopedia of Genes and Genomes data analysis. Increased expression of miR-181a-5p, miR-125b-5p, and let-7b-5p was further confirmed in Group 3 MB cells with real-time PCR and was shown to increase in vitro invasion and migratory abilities of tumor cells through the activation of ERK in Ras/MAPK pathway. Collectively, our findings suggest that exosomal miRNAs have a critical role in MB progression in vitro and might serve as diagnostic biomarkers and therapeutic targets.


Assuntos
Movimento Celular/fisiologia , Neoplasias Cerebelares/metabolismo , Exossomos/metabolismo , Genes ras/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Meduloblastoma/metabolismo , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/patologia , Exossomos/genética , Humanos , Meduloblastoma/genética , Meduloblastoma/patologia , MicroRNAs/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia
8.
J Pathol ; 251(3): 249-261, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32391583

RESUMO

Central nervous system (CNS) tumors are the most common solid tumor in pediatrics, accounting for approximately 25% of all childhood cancers, and the second most common pediatric malignancy after leukemia. CNS tumors can be associated with significant morbidity, even those classified as low grade. Mortality from CNS tumors is disproportionately high compared to other childhood malignancies, although surgery, radiation, and chemotherapy have improved outcomes in these patients over the last few decades. Current therapeutic strategies lead to a high risk of side effects, especially in young children. Pediatric brain tumor survivors have unique sequelae compared to age-matched patients who survived other malignancies. They are at greater risk of significant impairment in cognitive, neurological, endocrine, social, and emotional domains, depending on the location and type of the CNS tumor. Next-generation genomics have shed light on the broad molecular heterogeneity of pediatric brain tumors and have identified important genes and signaling pathways that serve to drive tumor proliferation. This insight has impacted the research field by providing potential therapeutic targets for these diseases. In this review, we highlight recent progress in understanding the molecular basis of common pediatric brain tumors, specifically low-grade glioma, high-grade glioma, ependymoma, embryonal tumors, and atypical teratoid/rhabdoid tumor (ATRT). © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Cerebelares/genética , Ependimoma/genética , Glioma/genética , Meduloblastoma/genética , Tumor Rabdoide/genética , Teratoma/genética , Idade de Início , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Cerebelares/classificação , Neoplasias Cerebelares/mortalidade , Neoplasias Cerebelares/patologia , Ependimoma/classificação , Ependimoma/mortalidade , Ependimoma/patologia , Predisposição Genética para Doença , Glioma/classificação , Glioma/mortalidade , Glioma/patologia , Humanos , Meduloblastoma/classificação , Meduloblastoma/mortalidade , Meduloblastoma/patologia , Gradação de Tumores , Fenótipo , Tumor Rabdoide/classificação , Tumor Rabdoide/mortalidade , Tumor Rabdoide/patologia , Teratoma/classificação , Teratoma/mortalidade , Teratoma/patologia
9.
Cancer Res ; 80(13): 2818-2832, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32371475

RESUMO

Aberrant activation of the Hedgehog (HH) signaling pathway underlines the initiation and progression of a multitude of cancers. The effectiveness of the leading drugs vismodegib (GDC-0449) and sonidegib (LDE225), both Smoothened (SMO) antagonists, is compromised by acquisition of mutations that alter pathway components, notably secondary mutations in SMO and amplification of GLI2, a transcriptional mediator at the end of the pathway. Pharmacologic blockade of GLI2 activity could ultimately overcome these diversified refractory mechanisms, which would also be effective in a broader spectrum of primary tumors than current SMO antagonists. To this end, we conducted a high-content screening directly analyzing the ciliary translocation of GLI2, a key event for GLI2 activation in HH signal transduction. Several prostaglandin compounds were shown to inhibit accumulation of GLI2 within the primary cilium (PC). In particular, prostaglandin E1 (PGE1), an FDA-approved drug, is a potent GLI2 antagonist that overcame resistance mechanisms of both SMO mutagenesis and GLI2 amplification. Consistent with a role in HH pathway regulation, EP4 receptor localized to the PC. Mechanistically, PGE1 inhibited HH signaling through the EP4 receptor, enhancing cAMP-PKA activity, which promoted phosphorylation and degradation of GLI2 via the ubiquitination pathway. PGE1 also effectively inhibited the growth of drug refractory human medulloblastoma xenografts. Together, these results identify PGE1 and other prostaglandins as potential templates for complementary therapeutic development to circumvent resistance to current generation SMO antagonists in use in the clinic. SIGNIFICANCE: These findings show that PGE1 exhibits pan-inhibition against multiple drug refractory activities for Hedgehog-targeted therapies and elicits significant antitumor effects in xenograft models of drug refractory human medulloblastoma mimicking GLI2 amplification.


Assuntos
Alprostadil/farmacologia , Neoplasias Cerebelares/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Amplificação de Genes , Proteínas Hedgehog/antagonistas & inibidores , Meduloblastoma/tratamento farmacológico , Proteínas Nucleares/genética , Proteína Gli2 com Dedos de Zinco/genética , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Neoplasias Cerebelares/metabolismo , Neoplasias Cerebelares/patologia , Regulação Neoplásica da Expressão Gênica , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Meduloblastoma/metabolismo , Meduloblastoma/patologia , Camundongos , Camundongos Endogâmicos NOD , Inibidores da Agregação de Plaquetas/farmacologia , Receptores de Prostaglandina E Subtipo EP4/genética , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Nat Med ; 26(5): 720-731, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32341580

RESUMO

Recurrent medulloblastoma and ependymoma are universally lethal, with no approved targeted therapies and few candidates presently under clinical evaluation. Nearly all recurrent medulloblastomas and posterior fossa group A (PFA) ependymomas are located adjacent to and bathed by the cerebrospinal fluid, presenting an opportunity for locoregional therapy, bypassing the blood-brain barrier. We identify three cell-surface targets, EPHA2, HER2 and interleukin 13 receptor α2, expressed on medulloblastomas and ependymomas, but not expressed in the normal developing brain. We validate intrathecal delivery of EPHA2, HER2 and interleukin 13 receptor α2 chimeric antigen receptor T cells as an effective treatment for primary, metastatic and recurrent group 3 medulloblastoma and PFA ependymoma xenografts in mouse models. Finally, we demonstrate that administration of these chimeric antigen receptor T cells into the cerebrospinal fluid, alone or in combination with azacytidine, is a highly effective therapy for multiple metastatic mouse models of group 3 medulloblastoma and PFA ependymoma, thereby providing a rationale for clinical trials of these approaches in humans.


Assuntos
Neoplasias Encefálicas/terapia , Vacinas Anticâncer/administração & dosagem , Líquido Cefalorraquidiano/efeitos dos fármacos , Ependimoma/terapia , Imunoterapia Adotiva/métodos , Meduloblastoma/terapia , Animais , Neoplasias Encefálicas/líquido cefalorraquidiano , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Cerebelares/líquido cefalorraquidiano , Neoplasias Cerebelares/imunologia , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/terapia , Líquido Cefalorraquidiano/imunologia , Criança , Pré-Escolar , Sistemas de Liberação de Medicamentos/métodos , Ependimoma/líquido cefalorraquidiano , Ependimoma/imunologia , Ependimoma/patologia , Feminino , Células HEK293 , Humanos , Lactente , Injeções Intraventriculares , Masculino , Meduloblastoma/líquido cefalorraquidiano , Meduloblastoma/imunologia , Meduloblastoma/patologia , Camundongos , Metástase Neoplásica , Receptores de Antígenos Quiméricos/administração & dosagem , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/transplante , Resultado do Tratamento , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
11.
World Neurosurg ; 139: 223-225, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32305611

RESUMO

BACKGROUND: Osteosarcoma is a common malignant bone tumor that occurs in children or adolescents but rarely in the skull. Epidermoid cysts, also known as cholesteatomas, represent approximately 0.2%-1.8% of all intracranial tumors. The occurrence of osteosarcoma with an epidermoid cyst is extremely rare. CASE DESCRIPTION: A 41-year-old woman had both osteosarcoma and cholesteatoma in the left cerebellopontine angle. We resected the 2 tumors using the suboccipital retrosigmoid approach, and she received radiotherapy and chemotherapy after the surgery. One year after surgery, the patient is healthy and has recovered well. CONCLUSIONS: Osteosarcomas and epidermoid cysts should be completely resected to prevent tumor recurrence and aseptic meningitis. Postoperative osteosarcoma treatment should include radiotherapy and chemotherapy to improve the survival rate of patients. It is hoped that this report will help clinicians in diagnosis and treatment of patients with similar conditions.


Assuntos
Encefalopatias/patologia , Neoplasias Cerebelares/patologia , Ângulo Cerebelopontino/patologia , Colesteatoma/patologia , Osteossarcoma/patologia , Adulto , Encefalopatias/complicações , Neoplasias Cerebelares/complicações , Colesteatoma/complicações , Cisto Epidérmico/complicações , Cisto Epidérmico/patologia , Feminino , Humanos , Osteossarcoma/complicações
12.
Nature ; 580(7803): 396-401, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32296180

RESUMO

Cancer genomics has revealed many genes and core molecular processes that contribute to human malignancies, but the genetic and molecular bases of many rare cancers remains unclear. Genetic predisposition accounts for 5 to 10% of cancer diagnoses in children1,2, and genetic events that cooperate with known somatic driver events are poorly understood. Pathogenic germline variants in established cancer predisposition genes have been recently identified in 5% of patients with the malignant brain tumour medulloblastoma3. Here, by analysing all protein-coding genes, we identify and replicate rare germline loss-of-function variants across ELP1 in 14% of paediatric patients with the medulloblastoma subgroup Sonic Hedgehog (MBSHH). ELP1 was the most common medulloblastoma predisposition gene and increased the prevalence of genetic predisposition to 40% among paediatric patients with MBSHH. Parent-offspring and pedigree analyses identified two families with a history of paediatric medulloblastoma. ELP1-associated medulloblastomas were restricted to the molecular SHHα subtype4 and characterized by universal biallelic inactivation of ELP1 owing to somatic loss of chromosome arm 9q. Most ELP1-associated medulloblastomas also exhibited somatic alterations in PTCH1, which suggests that germline ELP1 loss-of-function variants predispose individuals to tumour development in combination with constitutive activation of SHH signalling. ELP1 is the largest subunit of the evolutionarily conserved Elongator complex, which catalyses translational elongation through tRNA modifications at the wobble (U34) position5,6. Tumours from patients with ELP1-associated MBSHH were characterized by a destabilized Elongator complex, loss of Elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response, consistent with loss of protein homeostasis due to Elongator deficiency in model systems7-9. Thus, genetic predisposition to proteome instability may be a determinant in the pathogenesis of paediatric brain cancers. These results support investigation of the role of protein homeostasis in other cancer types and potential for therapeutic interference.


Assuntos
Neoplasias Cerebelares/metabolismo , Mutação em Linhagem Germinativa , Meduloblastoma/metabolismo , Fatores de Elongação da Transcrição/metabolismo , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/patologia , Criança , Feminino , Humanos , Masculino , Meduloblastoma/genética , Linhagem , RNA de Transferência/metabolismo , Fatores de Elongação da Transcrição/genética
13.
Pediatr Blood Cancer ; 67(6): e28189, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32286018

RESUMO

BACKGROUND: Despite improved survival, many pediatric brain tumor survivors receiving radiation therapy (RT) experience late effects. PROCEDURE: To study calvarial lesions in this population, we retrospectively reviewed records of patients undergoing neurosurgical evaluation for calvarial bone lesions detected in posttreatment follow-up imaging at St. Jude Children's Research Hospital. Primary tumor diagnosis, treatment, imaging, surgical intervention, and histopathology from patients with radiographic evidence of lesions followed for ≥2 years post-RT were studied. RESULTS: For 17 patients with 18 index lesions, median time to lesion manifestation was 2.34 years. Medulloblastoma patients developed lesions at a shorter interval from RT than ependymoma patients (P = .05). Twelve of 14 lesions requiring surgery were benign fibro-osseous or sclerotic. Two malignant lesions distinct from the primary tumor had genetic predisposition to malignancy. CONCLUSION: Most calvarial lesions arising post-RT are benign and fibro-osseous. Serial imaging is recommended, and high index of suspicion for malignant lesions is warranted for patients genetically predisposed to cancer.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias Cerebelares/radioterapia , Ependimoma/radioterapia , Meduloblastoma/radioterapia , Neoplasias Induzidas por Radiação/patologia , Radioterapia/efeitos adversos , Neoplasias Cranianas/patologia , Adolescente , Neoplasias Cerebelares/patologia , Criança , Pré-Escolar , Ependimoma/patologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Meduloblastoma/patologia , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/terapia , Prognóstico , Estudos Retrospectivos , Neoplasias Cranianas/etiologia , Neoplasias Cranianas/terapia
14.
World Neurosurg ; 138: 541-544.e1, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32229301

RESUMO

BACKGROUND: Superficial siderosis is an irreversible disease in the central nervous system caused by the deposition of hemosiderin in the subpial tissue due to persistent bleeding in the subarachnoid space. The main symptoms include sensorineural hearing loss, cerebellar ataxia, and pyramidal tract disorder. Superficial siderosis is mainly idiopathic, but bleeding factors such as tumors or history of surgery often play an important role in its pathogenesis. CASE DESCRIPTION: A 66-year-old man with a history of surgery for a cerebellar tumor 37 years ago complained of hearing loss. Magnetic resonance imaging showed recurrence of the tumor on T2-weighted images and hypointense areas along the cerebellar sulci on T2∗-weighted images. During the operation, microscopic bleeding was observed on the surface of the tumor. The pathologic diagnosis was pilocytic astrocytoma. A biopsy obtained during the first surgery revealed almost the same pathologic findings as those from a biopsy obtained during the second surgery, but the first specimen showed no hemosiderin deposition or active bleeding, which the second specimen did show. CONCLUSIONS: Recurrent pilocytic astrocytoma with intratumoral hemorrhage was the suspected cause for superficial siderosis. The source of chronic bleeding was identified with intraoperative and pathologic findings. We describe the first report of superficial siderosis associated with a pilocytic astrocytoma that recurred 37 years after an initial tumor was excised.


Assuntos
Astrocitoma/complicações , Neoplasias Cerebelares/complicações , Hemossiderose/etiologia , Recidiva Local de Neoplasia/complicações , Idoso , Astrocitoma/diagnóstico por imagem , Astrocitoma/patologia , Astrocitoma/cirurgia , Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/cirurgia , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Neurossensorial/fisiopatologia , Hemossiderina/metabolismo , Hemossiderose/diagnóstico por imagem , Hemossiderose/patologia , Hemossiderose/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Espaço Subaracnóideo/patologia
15.
World Neurosurg ; 138: 115-119, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32147560

RESUMO

BACKGROUND: Nonlethal neural tube defects are developmental malformations with complex pathogenesis usually manifested at birth or in childhood. CASE DESCRIPTION: We report the case of a 61-year-old woman without significant previous clinical history presenting for neck pain and stiffness. An extensive workup detected multiple lytic lesions within the occipital bone and cervical vertebrae, suspicious for multiple myeloma or metastatic disease. Surgical resection of the occipital bone lesions revealed ectopic cerebellar tissue, some containing folia with mature cortical lamination, and no evidence of malignancy. CONCLUSIONS: To our knowledge, this study describes the oldest individual presenting with ectopic cerebellar tissue and the only instance in which oncologic workup for malignancy was carried out prior to resection. It also proposes surgical resection as a diagnostic and curative approach for this complex basicranium and neural developmental defect, and discusses retinoic acid toxicity as a possible cause of its occurrence.


Assuntos
Cerebelo/patologia , Coristoma/patologia , Osso Occipital/patologia , Neoplasias Cranianas/patologia , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/cirurgia , Cerebelo/cirurgia , Coristoma/diagnóstico , Coristoma/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Cervicalgia/etiologia , Procedimentos Neurocirúrgicos/métodos , Osso Occipital/cirurgia , Neoplasias Cranianas/diagnóstico , Neoplasias Cranianas/cirurgia
16.
Medicine (Baltimore) ; 99(13): e19651, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32221091

RESUMO

RATIONALE: Intracranial solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) are rare spindle cell tumors of mesenchymal origin that include benign and malignant neoplasms. PATIENT CONCERNS: We present a 66-year-old male with a 5-year history of headache and dizziness, with left progressive sensorineural hearing loss over 1 month. DIAGNOSES: WHO grade II SFT/HPC originating from the internal auditory canal in the left cerebellopontine angle. INTERVENTIONS: surgical resection. OUTCOMES: No local recurrence or metastases were observed in the follow-up 3 months after the surgery. LESSONS: Intracranial SFTs/HPCs are rare mesenchymal neoplasms that are challenging to manage. If the imaging characteristics of tumor are not typical, clinicians should depend on tissue biopsy and immunohistochemistry to make a definitive diagnosis.


Assuntos
Neoplasias Cerebelares/patologia , Ângulo Cerebelopontino/patologia , Hemangiopericitoma/patologia , Tumores Fibrosos Solitários/patologia , Idoso , Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/cirurgia , Diagnóstico Diferencial , Tontura/etiologia , Cefaleia/etiologia , Perda Auditiva/etiologia , Hemangiopericitoma/diagnóstico , Hemangiopericitoma/cirurgia , Humanos , Masculino , Gradação de Tumores , Neuroma Acústico/diagnóstico , Tumores Fibrosos Solitários/diagnóstico , Tumores Fibrosos Solitários/cirurgia
17.
Cancer Metastasis Rev ; 39(1): 235-243, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32095940

RESUMO

Pediatric brain tumors are the leading cause of childhood cancer mortality with medulloblastoma (MB) representing the most frequent malignant tumor. Although standardization of therapy resulted in a 2-fold reduction in mortality in patients with MB by 2002, it became clear that further improvements in clinical outcome would require a deeper understanding of the biology of MB. Employing the four main molecular MB subgroups (Wnt, Shh, Group 3 and Group 4), a restratification into clinicogenomic risk categories quantified an unacceptable survival for the high-risk group, urging researchers to focus their efforts towards acquiring a greater biological understanding of these children. Advancing in parallel with the molecular characterization and understanding of pediatric MB is the clinicogenomic correlations giving rise to recommendations for neurosurgical care. While unique observations that distinct radiological patterns can be identified to inform the MB molecular subgroup preoperatively, current neurosurgical practice remains maximal safe surgical resection followed by risk-adapted provision of adjuvant therapy in the context of a clinical trial.


Assuntos
Neoplasias Cerebelares/genética , Neoplasias Cerebelares/cirurgia , Meduloblastoma/genética , Meduloblastoma/cirurgia , Neoplasias Cerebelares/patologia , Criança , Ensaios Clínicos Fase II como Assunto , Humanos , Meduloblastoma/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia
19.
J Neuropathol Exp Neurol ; 79(4): 437-447, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32053195

RESUMO

The diagnosis of medulloblastoma incorporates the histologic and molecular subclassification of clinical medulloblastoma samples into wingless (WNT)-activated, sonic hedgehog (SHH)-activated, group 3 and group 4 subgroups. Accurate medulloblastoma subclassification has important prognostic and treatment implications. Immunohistochemistry (IHC)-based and nanoString-based subgrouping methodologies have been independently described as options for medulloblastoma subgrouping, however have not previously been directly compared. We describe our experience with nanoString-based subgrouping in a clinical setting and compare this with our IHC-based results. Study materials included FFPE tissue from 160 medulloblastomas. Clinical data and tumor histology were reviewed. Immunohistochemical-based subgrouping using ß-catenin, filamin A and p53 antibodies and nanoString-based gene expression profiling were performed. The sensitivity and specificity of IHC-based subgrouping of WNT and SHH-activated medulloblastomas was 91.5% and 99.54%, respectively. Filamin A immunopositivity highly correlated with SHH/WNT-activated subgroups (sensitivity 100%, specificity 92.7%, p < 0.001). Nuclear ß-catenin immunopositivity had a sensitivity of 76.2% and specificity of 99.23% for detection of WNT-activated tumors. Approximately 23.8% of WNT cases would have been missed using an IHC-based subgrouping method alone. nanoString could confidently predict medulloblastoma subgroup in 93% of cases and could distinguish group 3/4 subgroups in 96.3% of cases. nanoString-based subgrouping allows for a more prognostically useful classification of clinical medulloblastoma samples.


Assuntos
Neoplasias Cerebelares/diagnóstico , Perfilação da Expressão Gênica/métodos , Proteínas Hedgehog/genética , Imuno-Histoquímica , Meduloblastoma/diagnóstico , Proteínas Wnt/genética , Adolescente , Adulto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/patologia , Criança , Pré-Escolar , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Meduloblastoma/genética , Meduloblastoma/patologia , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
20.
Zhonghua Yi Xue Za Zhi ; 100(3): 178-181, 2020 Jan 21.
Artigo em Chinês | MEDLINE | ID: mdl-32008282

RESUMO

Objective: To evaluate the classification of the types of pediatric posterior fossa brain tumors based on routine MRI (T(1)WI, T(2)WI and ADC) using wavelet transformation analysis of whole tumor. Methods: MRI images of medulloblastoma (n=59), ependymoma (n=13) and pilocytic astrocytoma (n=27) confirmed by pathology before treatments in Children's Hospital of Nanjing Medical University from January 2014 to February 2019 were enrolled in this retrospective study as well as the clinical data of age, gender and symptoms. Registration was performed among the three sequences and wavelet features of ROI were acquired. Afterwards, the top ten features were ranked and trained among groups by using random forest classifier. Finally, the results were compared and analyzed according to the classification. Results: The top ten contribution three sequences and wavelet features of ROI were acquired from the ADC sequence. The random forest classifier achieved 100% accuracy on training data and was validated best accuracy (86.8%) when combined of first and third wavelet features. The sensitivity was 100%, 94.8%, 76.9%, and the specificity was 97.6%, 88.0%, 98.8% respectively. Conclusions: Features based on wavelet transformation of ADC sequence of entire tumor can provide more quantitative information, which could provide help in the differential diagnosis of pediatric posterior fossa brain tumors. The optimum combination to distinguish three pediatric posterior fossa brain tumors is sixth and twelfth wavelet features of ADC sequence.


Assuntos
Astrocitoma/classificação , Neoplasias Cerebelares/patologia , Neoplasias Infratentoriais/patologia , Imagem por Ressonância Magnética/métodos , Meduloblastoma/classificação , Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Criança , Humanos , Meduloblastoma/patologia , Estudos Retrospectivos
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