RESUMO
Spinal cord astrocytoma (SCA) is a rare subtype of astrocytoma, posing challenges in diagnosis and treatment. Low-grade SCA can achieve long-term survival solely through surgery, while high-grade has a disappointing prognosis even with comprehensive treatment. Diagnostic criteria and standard treatment of intracranial astrocytoma have shown obvious limitations in SCA. Research on the molecular mechanism in SCA is lagging far behind that on intracranial astrocytoma. In recent years, huge breakthroughs have been made in molecular pathology of astrocytoma, and novel techniques have emerged, including DNA methylation analysis and radiomics. These advances are now making it possible to provide a precise diagnosis and develop corresponding treatment strategies in SCA. Our aim is to review the current status of diagnosis and treatment of SCA, and summarize the latest research advancement, including tumor subtype, molecular characteristics, diagnostic technology, and potential therapy strategies, thus deepening our understanding of this uncommon tumor type and providing guidance for accurate diagnosis and treatment.
Assuntos
Astrocitoma , Neoplasias da Medula Espinal , Humanos , Astrocitoma/genética , Astrocitoma/terapia , Astrocitoma/diagnóstico , Astrocitoma/patologia , Neoplasias da Medula Espinal/terapia , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/patologia , Biomarcadores Tumorais/genética , Patologia Molecular , Metilação de DNA , Gerenciamento Clínico , Prognóstico , Gradação de TumoresAssuntos
Ependimoma , Neoplasias da Medula Espinal , Humanos , Ependimoma/genética , Ependimoma/patologia , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/patologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Criança , Adulto Jovem , Pré-Escolar , IdosoRESUMO
BACKGROUND: Ependymoma is a central nervous system (CNS) tumor that arises from the ependymal cells of the brain's ventricles and spinal cord. The histopathology of ependymomas is indistinguishable regardless of the site of origin, and the prognosis varies. Recent studies have revealed that the development site and prognosis reflect the genetic background. In this study, we used genome-wide DNA methylation array analysis to investigate the epigenetic background of ependymomas from different locations treated at our hospital. METHODS: Four cases of posterior fossa ependymomas and 11 cases of spinal ependymomas were analyzed. RESULTS: DNA methylation profiling using the DKFZ methylation classifier showed that the methylation diagnoses of the 2 cases differed from the histopathological diagnoses, and 2 cases could not be classified. Tumor that spread from the brain to the spinal cord was molecularly distinguishable from other primary spinal tumors. CONCLUSIONS: Although adding DNA methylation classification to conventional diagnostic methods may be helpful, the diagnosis in some cases remains undetermined. This may affect decision-making regarding treatment strategies and follow-up. Further investigations are required to improve the diagnostic accuracy of these tumors.
Assuntos
Metilação de DNA , Ependimoma , Neoplasias da Medula Espinal , Humanos , Ependimoma/genética , Ependimoma/diagnóstico , Ependimoma/classificação , Ependimoma/patologia , Metilação de DNA/genética , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Criança , Adolescente , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/diagnóstico , Adulto Jovem , Pré-Escolar , Neoplasias Infratentoriais/genética , Neoplasias Infratentoriais/classificação , Neoplasias Infratentoriais/diagnóstico , IdosoRESUMO
BACKGROUND: Ependymomas (EPNs) of the spinal region are a heterogeneous group of tumors that account for 17.6 % in adults. Four types have been recognized: subependymoma, spinal ependymoma (Sp-EPN), myxopapillary ependymoma (MPE), and Sp-EPN-MYCN amplified, each with distinct histopathological and molecular features. METHODS: This study investigated the clinical and pathological characteristics and MYCN expression levels of 35 Sp-EPN and MPE cases diagnosed at a tertiary university hospital over a decade-long period. RESULTS: Twenty-five cases were Sp-EPN and 10 cases were MPE, and were graded as WHO grade 2, except for 1 Sp-EPN case with grade 3 features. The most common symptoms were lower back pain and difficulty in walking. Radiology showed different tumor sizes and locations along the spinal cord, with MPEs exclusively in the lumbosacral region. Surgery was the main treatment, and gross total resection was achieved in all cases except for one. Immunohistochemistry showed low Ki-67 proliferation indices in all cases, and no MYCN expression. During follow-up, 3 (8.6 %) cases recurred and/or metastasized and 5 cases (14.3 %) died. No significant difference was found in disease-free survival or overall survival between Sp-EPN and MPE cases. However, 3 cases with grade 2 histology demonstrated recurrence and/or metastasis, despite the lack of MYCN expression. CONCLUSION: Our results underscore the multifactorial nature of tumor aggressiveness in EPNs of the spinal region. This study enhances our knowledge of the clinical and pathological features of Sp-EPNs and MPEs and highlights the need for better diagnostic and prognostic markers in these rare tumors.
Assuntos
Ependimoma , Proteína Proto-Oncogênica N-Myc , Neoplasias da Medula Espinal , Humanos , Ependimoma/patologia , Ependimoma/genética , Ependimoma/metabolismo , Ependimoma/diagnóstico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Proteína Proto-Oncogênica N-Myc/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/metabolismo , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/diagnóstico , Adulto Jovem , Idoso , Adolescente , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Imuno-Histoquímica/métodosRESUMO
Astroblastoma is an uncommon circumscribed glial tumor mostly involving the cerebral hemisphere. The characteristic molecular alteration is meningioma (disrupted in balanced translocation) 1 (MN1) rearrangement. No definite World Health Organization grade has been assigned as both low- and high-grade tumors are known to occur. Tumors in the spine are extremely rare; to date only three cases have been reported in the literature. A vigilant microscopy and ancillary testing aid in diagnosis when the tumors present in unusual locations, as in our case. The prompt differentiation of this tumor from its mimickers is a mandate as modalities of management are different and not clearly established.
Assuntos
Neoplasias Neuroepiteliomatosas , Humanos , Neoplasias Neuroepiteliomatosas/patologia , Neoplasias Neuroepiteliomatosas/genética , Neoplasias Neuroepiteliomatosas/diagnóstico por imagem , Pré-Escolar , Proteínas Supressoras de Tumor/genética , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/diagnóstico por imagem , Masculino , Feminino , TransativadoresRESUMO
MYCN (master regulator of cell cycle entry and proliferative metabolism) gene amplification defines a molecular subgroup of spinal cord ependymomas that show high-grade morphology and aggressive behavior. Demonstration of MYCN amplification by DNA methylation or fluorescence-in situ hybridization (FISH) is required for diagnosis. We aimed to (i) assess prevalence and clinicopathological features of MYCN-amplified spinal ependymomas and (ii) evaluate utility of immunohistochemistry (IHC) for MYCN protein as a surrogate for molecular testing. A combined retrospective-prospective study spanning 8 years was designed during which all spinal cord ependymomas with adequate tissue were subjected to MYCN FISH and MYCN IHC. Among 77 spinal cord ependymomas included, MYCN amplification was identified in 4 samples from 3 patients (3/74, 4%) including two (1st and 2nd recurrences) from the same patient. All patients were adults (median age at diagnosis of 32 years) including two females and one male. The index tumors were located in thoracic (n = 2) and lumbar (n = 1) spinal cord. One of the female patients had neurofibromatosis type 2 (NF2). All four tumors showed anaplastic histology. Diffuse expression of MYCN protein was seen in all four MYCN-amplified samples but in none of the non-amplified cases, thus showing 100% concordance with FISH results. On follow-up, the NF2 patient developed widespread spinal dissemination while another developed recurrence proximal to the site of previous excision. To conclude, MYCN-amplified spinal ependymomas are rare tumors, accounting for ~ 4% of spinal cord ependymomas. Within the limitation of small sample size, MYCN IHC showed excellent concordance with MYCN gene amplification.
Assuntos
Ependimoma , Neoplasias da Medula Espinal , Adulto , Humanos , Masculino , Feminino , Proteína Proto-Oncogênica N-Myc/genética , Estudos Retrospectivos , Imuno-Histoquímica , Estudos Prospectivos , Ependimoma/diagnóstico , Ependimoma/genética , Ependimoma/patologia , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/patologia , BiomarcadoresRESUMO
BACKGROUND: Ependymomas are the third most common central nervous system tumor in the pediatric population; however, spinal ependymomas in children are rare. Ependymomas affecting the spinal cord most frequently occur in adults of 20-40 years of age. The current World Health Organization classification system for ependymomas is now composed of ten different entities based on histopathology, location, and molecular studies, with evidence that the new classification system more accurately predicts clinical outcomes. CASE PRESENTATION: We present the case of a 16-year-old Caucasian female patient with a history of type 2 neurofibromatosis with multiple schwannomas, meningioma, and spinal ependymoma. Chromosome analysis of the harvested spinal ependymoma tumor sample revealed a 46,XX,-6,+7,-22,+mar[16]/46,XX[4] karyotype. Subsequent OncoScan microarray analysis of the formalin-fixed paraffin-embedded tumor sample confirmed + 7, -22 and clarified that the marker chromosome represents chromothripsis of the entire chromosome 6 with more than 100 breakpoints. Fluorescent in situ hybridization and microarray analysis showed no evidence of MYCN amplification. The final integrated pathology diagnosis was spinal ependymoma (central nervous system World Health Organization grade 2 with no MYCN amplification. CONCLUSION: This case adds to the existing literature of pediatric patients with spinal ependymomas and expands the cytogenetic findings that may be seen in patients with this tumor type. This case also highlights the value of cytogenetics and microarray analysis in solid tumors to provide a more accurate molecular diagnosis.
Assuntos
Cromotripsia , Ependimoma , Neoplasias Meníngeas , Neoplasias da Medula Espinal , Adulto , Humanos , Criança , Feminino , Adolescente , Cromossomos Humanos Par 6 , Hibridização in Situ Fluorescente , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/patologia , Ependimoma/diagnóstico , Ependimoma/genética , Ependimoma/patologiaRESUMO
AIM: The aim of this study was to determine the usefulness of magnetic resonance imaging (MRI) characteristics in discriminating H3 K27M-mutant gliomas from wildtype gliomas in the spinal cord. MATERIALS AND METHODS: Fifty-eight patients with spinal cord gliomas were enrolled in this study. The H3 K27 gene status was identified by Sanger sequencing or immunohistochemistry test of resection tumor specimens. The MR imaging characteristics were evaluated and compared between H3 K27M-mutant and wildtype gliomas using the χ2 test and the Mann-Whitney U test. RESULTS: Of 58 recruited patients, 23 (39.7%) were diagnosed with H3 K27M-mutant glioma. The H3 K27M-mutant gliomas were found to more likely occur in men compared with wildtype gliomas (87.0% vs. 42.9%, p = 0.001). On T2-weighted MR images, the signal-to-noise ratio (SNR) of H3 K27M-mutant gliomas was significantly lower than that of wildtype gliomas (103.9 ± 72.0 vs. 168.9 ± 86.8, p < 0.001). Of 35 wildtype tumors, 60% showed well-defined margin but this feature was not found in all mutant tumors (p < 0.001). The SNR of tumors on contrast-enhanced T1-weighted images of the H3 K27M-mutant gliomas was significantly lower than that of wildtype gliomas (187.7 ± 160.4 vs. 295.1 ± 207.8, p = 0.006). Receiver operating-characteristic analysis revealed that area under curve (AUC) of combination of 1/SNR on T2-weighted images, 1/SNR on contrast-enhanced T1-weighted images, ill-defined margin, and sex reached 0.937 (95% CI, 0.873-1.000) in discriminating H3 K27M-mutant gliomas. CONCLUSIONS: The MR imaging characteristics are valuable in discriminating H3 K27M-mutant from wildtype gliomas in the spinal cord and the combination of these imaging features with sex had a high strength in this discrimination.
Assuntos
Glioma , Histonas , Imageamento por Ressonância Magnética , Mutação , Neoplasias da Medula Espinal , Humanos , Masculino , Glioma/genética , Glioma/diagnóstico por imagem , Glioma/patologia , Feminino , Imageamento por Ressonância Magnética/métodos , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/patologia , Adulto , Pessoa de Meia-Idade , Histonas/genética , Adulto Jovem , Idoso , Adolescente , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologiaRESUMO
Astroblastoma, MN1-altered, is a rare neoplasm of the central nervous system (CNS). This malignancy shares similar histopathological features with other CNS tumors, including ependymomas, making it challenging to diagnose. DNA methylation profiling is a new and robust technique that may be used to overcome this diagnostic hurdle. We report the case of a now 25-year-old female diagnosed with what was initially called an ependymoma located in the cervical spine at the age of 2 years old. After initial resection, the tumor recurred multiple times and within 2 years of diagnosis had disseminated disease throughout the brain and spinal cord. She has now undergone over two decades of treatment, including multiple surgical resections, radiation therapy, and administration of numerous chemotherapeutic agents. In 2021, the patient presented to our institution with lumbosacral radicular symptoms due to enlarging lesions within the lumbosacral spine. Reexamination of formalin-fixed, paraffin-embedded material from the patient's tumor using genomic DNA methylation profiling resulted in a diagnostic change from grade III anaplastic ependymoma to astroblastoma, MN1-altered. This work describes another confirmed case of astroblastoma, MN1-altered, to the growing body of literature.
Assuntos
Neoplasias Neuroepiteliomatosas , Neoplasias da Medula Espinal , Humanos , Feminino , Neoplasias Neuroepiteliomatosas/genética , Neoplasias Neuroepiteliomatosas/patologia , Neoplasias Neuroepiteliomatosas/diagnóstico por imagem , Adulto , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/diagnóstico por imagem , Fatores de Transcrição/genética , Proteínas de Fusão Oncogênica/genética , Transativadores , Proteínas Supressoras de TumorRESUMO
Hemangioblastomas (HBs) are highly vascularized, slow-growing, rare benign tumors (WHO grade I). They account for about 2% of intracranial neoplasms; however, they are the most common primary cerebellar tumors in adults. Another frequent seat is the spinal cord (2-10% of primary spinal cord tumors). HBs are constituted by stromal and capillary vascular cells; macroscopically, HBs appear as nodular tumors, with or without cystic components. Although most of the HBs are sporadic (57-75%), they represent a particular component of von Hippel-Lindau disease (VHL), an autosomal dominant syndrome with high penetrance, due to a germline pathogenic mutation in the VHL gene, which is a tumor suppressor with chromosomal location on the short arm of chromosome three. VHL disease determines a variety of malignant and benign tumors, most frequently HBs, renal cell carcinomas, pheochromocytomas/paragangliomas, pancreatic neuroendocrine tumors, and endolymphatic sac tumors. Up to 20% of cases are due to de novo pathogenic variants without a family history. Many epidemiologic details of these tumors, especially the sporadic forms, are not well known. The median age of patients with sporadic HBS is about 40 years. More than two-third of VHL patients develop one or more central nervous system HBs during their lifetime; in case of VHL, patients at first diagnosis are usually younger than the patients with sporadic tumors. The most common presenting signs and symptoms are related to increased intracranial pressure, cerebellar signs, or spinal cord alterations in case of spinal involvement. Magnetic resonance imaging is the gold standard for the diagnosis, assessment, and follow-up of HBs, both sporadic and syndrome-related; angiography is rarely performed because the diagnosis is easily obtained with magnetic resonance. However, the diagnosis of an asymptomatic lesion does not automatically result in therapeutic actions, as the risks of treatment and the onset of possible neurological deficit need to be balanced, considering that HBs may remain asymptomatic and have a static or slow-growing behavior. In such cases, regular follow-up can represent a valid therapeutic option until the patients remain asymptomatic. There are no actual pharmacological therapies that are demonstrated to be effective for HBs. Surgery represents the primary therapeutic approach for these tumors. Observation or radiotherapy also plays a role in the long-term management of patients harboring HBs, especially in VHL; in few selected cases, endovascular treatment has been suggested before surgical removal. This chapter presents a systematic overview of epidemiology, clinical appearance, histopathological and neuroradiological characteristics of central nervous system HBs. Moreover, the genetic and molecular biology of sporadic and VHL HBS deserves special attention. Furthermore, we will describe all the available therapeutic options, along with the follow-up management. Finally, we will briefly report other vascular originating tumors as hemangioendotheliomas, hemangiomas, or angiosarcomas.
Assuntos
Neoplasias do Sistema Nervoso Central , Hemangioblastoma , Neoplasias Renais , Neoplasias da Medula Espinal , Doença de von Hippel-Lindau , Adulto , Humanos , Encéfalo/patologia , Neoplasias do Sistema Nervoso Central/complicações , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/cirurgia , Hemangioblastoma/genética , Hemangioblastoma/patologia , Hemangioblastoma/cirurgia , Medula Espinal/patologia , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/genética , Síndrome , Doença de von Hippel-Lindau/genéticaRESUMO
Malignant spinal tumors constitute around 22% of all primary spinal tumors. The most common location of metastases to the spinal region is the extradural compartment. The molecular and genetic characterization of these tumors was the basis for the updated WHO classification of CNS tumors in 2016, where many CNS tumors are now diagnosed according to their genetic profile rather than relying solely on the histopathological appearance. Magnetic resonance imaging (MRI) is the current gold standard for the initial evaluation and subsequent follow-up on intradural spinal cord tumors, and the imaging sequences must include T2-weighted images (WI), short time inversion recovery (STIR), and pre- and post-contrast T1-WI in the axial, sagittal, and coronal planes. The clinical presentation is highly variable and depends on the tumor size, growth rate, type, infiltrative, necrotic and hemorrhagic potential as well as the exact location within the spinal compartment. Surgical intervention remains the mainstay of management of symptomatic and radiographically enlarging spinal tumors, where the goal is to achieve maximal safe resection. Tumor recurrences are managed with repeat surgical resection (preferred whenever possible and safe), radiotherapy, chemotherapy, or any combination of these therapies.
Assuntos
Neoplasias da Medula Espinal , Neoplasias da Coluna Vertebral , Humanos , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/genética , Neoplasias da Coluna Vertebral/terapia , Recidiva Local de Neoplasia , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/genética , Coluna Vertebral , Imageamento por Ressonância Magnética/métodosRESUMO
Benign spinal intradural tumors are relatively rare and include intramedullary tumors with a favorable histology such as low-grade astrocytomas and ependymomas, as well as intradural extramedullary tumors such as meningiomas and schwannomas. The effect on the neural tissue is usually a combination of mass effect and neuronal involvement in cases of infiltrative tumors. The new understanding of molecular profiling of different tumors allowed us to better define central nervous system tumors and tailor treatment accordingly. The mainstay of management of many intradural spinal tumors is maximal safe surgical resection. This goal is more achievable with intradural extramedullary tumors; yet, with a meticulous surgical approach, many of the intramedullary tumors are amenable for safe gross-total or near-total resection. The nature of these tumors is benign; hence, a different way to measure outcome success is pursued and usually depends on functional rather than oncological or survival outcomes.
Assuntos
Neoplasias Meníngeas , Meningioma , Neurilemoma , Neoplasias da Medula Espinal , Neoplasias da Coluna Vertebral , Humanos , Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/patologia , Meningioma/genética , Meningioma/cirurgia , Neurilemoma/genética , Neurilemoma/cirurgiaRESUMO
Several medical conditions that interest both the brain and the spinal cord have been described throughout the history of medicine. Formerly grouped under the term Phacomatosis because lesions of the eye were frequently encountered or genodermatosis when typical skin lesions were present, these terms have been progressively discarded. Although originally reported centuries ago, they still represent a challenge for their complexity of cure. Nowadays, with the introduction of advanced genetics and the consequent opportunity of whole-genome sequencing, new single cancer susceptibility genes have been identified or better characterized; although there is evidence that the predisposition to a few specific tumor syndromes should be accounted to a group of mutations in different genes while certain syndromes appeared to be manifestations of different mutations in the same gene adding supplementary problems in their characterization and establishing the diagnosis. Noteworthy, many syndromes have been genetically determined and well-characterized, accordingly in the near future, we expect that new targeted therapies will be available for the definitive cure of these syndromes and other gliomas (Pour-Rashidi et al. in World Neurosurgery, 2021). The most common CNS syndromes that will be discussed in this chapter include neurofibromatosis (NF) types 1 and 2, von Hippel-Lindau (VHL) disease, and tuberous sclerosis complex (TSC), as well as syndromes having mostly extra-neural manifestations such as Cowden, Li-Fraumeni, Turcot, and Gorlin syndromes.
Assuntos
Neoplasias Encefálicas , Neurofibromatose 1 , Neoplasias da Medula Espinal , Esclerose Tuberosa , Doença de von Hippel-Lindau , Humanos , Neoplasias Encefálicas/patologia , Encéfalo/patologia , Neoplasias da Medula Espinal/genéticaRESUMO
Spinal ependymoma with MYCN amplification is a newly recognized type of spinal ependymoma that is known to be associated with poor prognosis. Available studies on this relatively rare tumor type have observed that these tumors tend to disseminate along the spinal cord and behave aggressively with worse overall and progression-free survival compared to the other types of ependymoma. In this study, we describe the clinical and histopathological features of spinal ependymomas in a single institution cohort with emphasis on those with MYCN amplification.
Assuntos
Ependimoma , Neoplasias da Medula Espinal , Humanos , Estudos Retrospectivos , Proteína Proto-Oncogênica N-Myc/genética , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/patologia , Ependimoma/genética , Ependimoma/patologiaRESUMO
H3 K27-altered diffuse midline glioma is a highly lethal pediatric-type tumor without efficacious treatments. Recent findings have highlighted the heterogeneity among diffuse midline gliomas with different locations and ages. Compared to tumors located in the brain stem and thalamus, the molecular and clinicopathological features of H3 K27-altered spinal cord glioma are still largely elusive, thus hindering the accurate management of patients. Here we aimed to characterize the clinicopathological and molecular features of H3 K27M-mutant spinal cord glioma in 77 consecutive cases. We found that the H3 K27M-mutant spinal cord glioma, with a median age of 35 years old, had a significantly better prognosis than H3 K27M-mutant brain tumors. We noticed a molecular heterogeneity of H3 K27M-mutant spinal cord astrocytoma via targeted sequencing with 34 cases. TP53 mutation which occurred in 58.8% of cases is mutually exclusive with PPM1D (26%) and NF1 (44%) mutations. The TP53-mutant cases had a significantly higher number of copy number variants (CNV) and a marginally higher proportion of pediatric patients (age at diagnosis <18 years old, p = 0.056). Cox regression and Kaplan-Meier curve analysis showed that the higher number of CNV events (≥3), chromosome (Chr) 9p deletion, Chr 10p deletion, ATRX mutation, CDK6 amplification, and retinoblastoma protein (RB) pathway alteration are associated with worse survival. Cox regression analysis with clinicopathological features showed that glioblastoma histological type and a high Ki-67 index (>10%) are associated with a worse prognosis. Interestingly, the histological type, an independent prognostic factor in multivariate Cox regression, can also stratify molecular features of H3 K27M-mutant spinal cord glioma, including the RB pathway, KRAS/PI3K pathway, and chromosome arms CNV. In conclusion, although all H3 K27M-mutant spinal cord diffuse glioma were diagnosed as WHO Grade 4, the histological type, molecular features representing chromatin instability, and molecular alterations associated with accelerated cell proliferative activity should not be ignored in clinical management.
Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias da Medula Espinal , Humanos , Criança , Adulto , Adolescente , Histonas/genética , Prognóstico , Fosfatidilinositol 3-Quinases/genética , Glioma/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias da Medula Espinal/genética , Mutação , GenômicaRESUMO
Inflammation and innate immune system play a central role in cancers, including those affecting the central nervous system (CNS). Currently, classification of neoplasms, especially regarding gliomas, is established on molecular mutations in isocitrate dehydrogenase (IDH) genes and the presence of co-deletion 1p/19q. Treatment, in most of brain and spinal cord tumors, is centered on surgery, radiotherapy and pharmacological approaches with chemotherapeutic agents. However, the results of the treatments, after several decades, are not completely satisfactory. Cytokines and angiogenic factors are closely linked to the brain cancer behavior. Moreover, recent studies suggest a link between inflammation and tumorigenesis, underlying the complex nature of this topic, especially the anti- and pro-tumoral activities of inflammation and the two-way interactions between immune and tumor cells. The current understanding of the mechanisms by which CNS cancer cells modulate the immune system, especially how bi-directional communications between immune cells and tumor cells create an immunosuppressed microenvironment, gives important information about the promotion of tumor survival and growth. Here, we have briefly reviewed the current literature on this topic, focusing on the possible role of inflammation and innate immunity involved in the origin and in the development of CNS tumors.
Assuntos
Neoplasias Encefálicas , Neoplasias da Medula Espinal , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Encéfalo/metabolismo , Mutação , Imunidade Inata , Inflamação , Neoplasias da Medula Espinal/genética , Isocitrato Desidrogenase/genética , Microambiente TumoralRESUMO
CNS tumors are a diverse group of neoplasms that emerge from a variety of different CNS cell types. These tumors may be benign, malignant, or borderline in nature. The majority of high grade glial tumors are fatal, with the exception of pilocytic astrocytoma. Primary malignant CNS tumors occur at a global annual rate of 2.1 to 5.8 per 100,000 persons. Males are more likely to develop malignant brain tumors than females, whereas benign meningiomas are more common in adult females. Additionally, gender inequalities in non-malignant tumors peak between the ages of 25 and 29 years. Only a small number of genetic variants have been associated with survival and prognosis. Notably, central nervous system (CNS) tumors exhibit significant age, gender, and race variation. Race is another factor that affects the incidence of brain and spinal cord tumors. Different races exhibit variation in terms of the prevalence of brain and CNS malignancies. This chapter discusses ongoing research on brain and spinal cord tumor epidemiology, as well as the associated risks and accompanied disorders.
Assuntos
Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Neoplasias da Medula Espinal , Adulto , Masculino , Feminino , Humanos , Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias da Medula Espinal/epidemiologia , Neoplasias da Medula Espinal/genética , Encéfalo/patologia , IncidênciaRESUMO
BACKGROUND: Determination of H3 K27M mutation in diffuse midline glioma (DMG) is key for prognostic assessment and stratifying patient subgroups for clinical trials. MRI can noninvasively depict morphological and metabolic characteristics of H3 K27M mutant DMG. PURPOSE: This study aimed to develop a deep learning (DL) approach to noninvasively predict H3 K27M mutation in DMG using T2-weighted images. STUDY TYPE: Retrospective and prospective. POPULATION: For diffuse midline brain gliomas, 341 patients from Center-1 (27 ± 19 years, 184 males), 42 patients from Center-2 (33 ± 19 years, 27 males) and 35 patients (37 ± 18 years, 24 males). For diffuse spinal cord gliomas, 133 patients from Center-1 (30 ± 15 years, 80 males). FIELD STRENGTH/SEQUENCE: 5T and 3T, T2-weighted turbo spin echo imaging. ASSESSMENT: Conventional radiological features were independently reviewed by two neuroradiologists. H3 K27M status was determined by histopathological examination. The Dice coefficient was used to evaluate segmentation performance. Classification performance was evaluated using accuracy, sensitivity, specificity, and area under the curve. STATISTICAL TESTS: Pearson's Chi-squared test, Fisher's exact test, two-sample Student's t-test and Mann-Whitney U test. A two-sided P value <0.05 was considered statistically significant. RESULTS: In the testing cohort, Dice coefficients of tumor segmentation using DL were 0.87 for diffuse midline brain and 0.81 for spinal cord gliomas. In the internal prospective testing dataset, the predictive accuracies, sensitivities, and specificities of H3 K27M mutation status were 92.1%, 98.2%, 82.9% in diffuse midline brain gliomas and 85.4%, 88.9%, 82.6% in spinal cord gliomas. Furthermore, this study showed that the performance generalizes to external institutions, with predictive accuracies of 85.7%-90.5%, sensitivities of 90.9%-96.0%, and specificities of 82.4%-83.3%. DATA CONCLUSION: In this study, an automatic DL framework was developed and validated for accurately predicting H3 K27M mutation using T2-weighted images, which could contribute to the noninvasive determination of H3 K27M status for clinical decision-making. EVIDENCE LEVEL: 2 Technical Efficacy: Stage 2.
Assuntos
Neoplasias Encefálicas , Aprendizado Profundo , Glioma , Neoplasias da Medula Espinal , Masculino , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Histonas/genética , Estudos Retrospectivos , Estudos Prospectivos , Mutação , Glioma/diagnóstico por imagem , Glioma/genética , Imageamento por Ressonância Magnética , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/genéticaRESUMO
Gliomas are the most common central nervous tumors in children and adolescents. However, spinal cord low-grade gliomas (sLGGs) are rare, with scarce information on tumor genomics and epigenomics. To define the molecular landscape of sLGGs, we integrated clinical data, histology, and multi-level genetic and epigenetic analyses on a consecutive cohort of 26 pediatric patients. Driver molecular alteration was found in 92% of patients (24/26). A novel variant of KIAA1549:BRAF fusion (ex10:ex9) was identified using RNA-seq in four cases. Importantly, only one-third of oncogenic drivers could be revealed using standard diagnostic methods, and two-thirds of pediatric patients with sLGGs required extensive molecular examination. The majority (23/24) of detected alterations were potentially druggable targets. Four patients in our cohort received targeted therapy with MEK or NTRK inhibitors. Three of those exhibited clinical improvement (two with trametinib, one with larotrectinib), and two patients achieved partial response. Methylation profiling was implemented to further refine the diagnosis and revealed intertumoral heterogeneity in sLGGs. Although 55% of tumors clustered with pilocytic astrocytoma, other rare entities were identified in this patient population. In particular, diffuse leptomeningeal glioneuronal tumors (n = 3) and high-grade astrocytoma with piloid features (n = 1) and pleomorphic xanthoastrocytoma (n = 1) were present. A proportion of tumors (14%) had no match with the current version of the classifier. Complex molecular genetic sLGGs characterization was invaluable to refine diagnosis, which has proven to be essential in such a rare tumor entity. Moreover, identifying a high proportion of drugable targets in sLGGs opened an opportunity for new treatment modalities.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Glioma , Neoplasias da Medula Espinal , Adolescente , Astrocitoma/genética , Neoplasias Encefálicas/genética , Criança , Genômica , Glioma/genética , Glioma/patologia , Humanos , Quinases de Proteína Quinase Ativadas por Mitógeno , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Medula Espinal/genéticaRESUMO
Diffuse spinal cord gliomas (SCGs) are rare tumors associated with a high morbidity and mortality that affect both pediatric and adult populations. In this retrospective study, we sought to characterize the clinical, pathological, and molecular features of diffuse SCG in 22 patients with histological and molecular analyses. The median age of our cohort was 23.64 years (range 1-82) and the overall median survival was 397 days. K27M mutation was significantly more prevalent in males compared to females. Gross total resection and chemotherapy were associated with improved survival, compared to biopsy and no chemotherapy. While there was no association between tumor grade, K27M status (p = 0.366) or radiation (p = 0.772), and survival, males showed a trend toward shorter survival. K27M mutant tumors showed increased chromosomal instability and a distinct DNA methylation signature.