Frequência dos tipos histológicos de tumores no sistema nervoso central em um hospital universitário: levantamento de casos ao longo de quatro anos / Frequency of central nervous tumors histological types in an university hospital: data from a four-year period

Introdução: A realização de um padrão epidemiológico das neoplasias do sistema nervoso central (SNC) é prejudicada pela sua heterogeneidade de apresentações, causando uma falta de dados a respeito da incidência de seus diversos tipos. É necessário, dessa forma, realizar estudos com a adoção de critérios de classificação. Objetivo: Desenvolver um banco de dados das neoplasias do SNC, incluindo além dos cânceres primários do SNC, os tumores benignos primários do SNC e as metástases. Método: Foram acessados 1010 casos de biópsias no sistema eletrônico de arquivos do Serviço de Anatomia Patológica, sendo incluídos 381 diagnósticos no estudo, em concordância com os critérios de inclusão e exclusão (neoplasias benignas e malignas do SNC). Resultado: A análise dos diagnósticos histológicos demonstrou um total de 212 pacientes do gênero feminino (55,64%) e 169 do gênero masculino (44,36%). Do total de neoplasias, 307 foram primárias do SNC (80,58%) e 74metástases (19,42%). A distribuição etária variou de 1 a 85 anos, com uma média de idade de 48,953 e a mediana de 52 anos. Os gliomas foram o grupo histológico mais frequente, correspondendo a 30,45% (116 casos), sendo “gliomas difusos” o subtipo histológico mais frequente (73%). Conclusão: O presente estudo documenta a frequência dos tipos histológicos das neoplasias do SNC no Serviço de Anatomia Patológica em um Hospital Universitário entre os anos de 2015 e 2018.Palavras chave: Neoplasias, Neuropatologia, Patologia cirúrgica, Neoplasias do sistema central nervoso, Neoplasias encefálicas AbstractIntroduction: The achievement of an epidemiological pattern of central nervous system tumors (CNS) is hampered by their heterogeneity of presentations, causing a lack of dataregarding the incidence of their various types. Therefore, it is necessary to carry out studies with the adoption of classification criteria. Objective: Develop a database of CNStumors including primary cancers, primary benign tumors and metastases. Methods: A total of 1010 cases of biopsies were accessed in the Department of Pathological Anatomy’selectronic archive system, 381 of which were included in the study, in accordance with the inclusion and exclusion criteria (benign and malignant CNS neoplasms). Results: The histological diagnoses analysis revealed a total of 212 female patients (55.64%) and 169 male patients (44.36%). Overall, 307 were primary CNS neoplasms (80.58%) and 74 CNS metastases (19.42%). The age distribution span ranged from 1 to 85 years of age, with a mean age of 48.953 and a median of 52 years of age. Gliomas were the most frequenthistological group, corresponding to 30.45% (116 cases), with “diffuse gliomas” being the most frequent histological subtype (73%). Conclusion: The present study documentsthe frequency of histological types of CNS neoplasms in the Pathological Anatomy Service of a University Hospital between 2015 and 2018.Keywords: Neoplasms, Neuropathology, Surgical pathology, Central nervous system neoplasms, Brain tumors

Cervical intradural intramedullary collision tumor of schwannoma and hemangioblastoma origin

Background: Primary spinal tumors are rare benign lesions that represent around 2–4% of all central nervous system neoplasms.[1,2] Intradural intramedullary tumors are predominately glial in origin and are most commonly astrocytomas or ependymomas. Intradural extramedullary tumors, on the other hand, are usually neurofibromas, schwannomas, or meningiomas.[2] Here, we report the case of an intradural intramedullary collision tumor of schwannoma-hemangioblastoma origin. Case Description: A 61-year-old female presented with a 2-year history of the right arm numbness, weakness, and tingling. She reported some lower extremity numbness but an otherwise normal neurological examination. She had a prior carpal tunnel release that did not alleviate her symptoms. Noncontrast MRI of the cervical spine demonstrated a holocord syrinx from C2 to C7 and spondylolisthesis from C4 to C5. MRI with contrast then displayed an enhancing nodule behind the vertebral body of C4. A standard posterior approach and subperiosteal dissection were performed. Lateral mass screws were placed at C3-C5, and the laminectomy was performed en bloc. Intraoperative ultrasound was used to locate the lesion, and intraoperative dorsal column mapping was used to identify the midline before performing a midline myelotomy. The arachnoid over the lesion was opened and an extracapsular dissection was performed. Hemostasis was obtained, and a watertight dural closure was performed. Conclusion: The patient tolerated the procedure well and achieved relief from cervical myelopathy symptoms. Pathology indicated positive biomarkers for S-100, SOX10, and NSE indicating a schwannoma hemangioblastoma collision tumor. This is unusual in its nature given two benign lesions with differing underlying cell types of origin.

Clinico Pathological Study of Central Nervous System Neoplasms

The central nervous system consists of brain and spinal cord invested with meninges. It is made up of two types of cells, Nerve cells or neurons which show numerous long processes and Glial cells which are the supporting cells of the nervous system, which occupy the space between neurons. Four principal types of neuroglial cells are recognized: Oligodendrocytes, Astrocytes, Microglial cells and Ependymal cells. Central Nervous System (CNS) tumors account for 85% of brain tumors and 15% of spinal cord tumors, however metastatic tumors are usually extradural. Brain tumors are the second most common solid tumors in children next to Leukemia. Medulloblastoma is the commonest tumor among the pediatrics age group. Risk factors affecting brain tumors still persist unclear. Neoplasms of central nervous system accounts for approximately 1% of tumors of the human body, and they can be primary or secondary (metastatic), benign or malignant, and intra-axial or extra-axial. Neoplasms of the CNS can occur in both adults and pediatrics populations. Although adult and children may experience similar tumors, their incidences vary greatly with age. To study the spectrum of central nervous system space occupying lesions and the grade of neoplasms according to the guidelines provided by the World Health Organization (WHO). To correlate the diagnosis of these lesions with radiological findings in certain tumors, special stains and Immunohistochemistry were applied wherever needed.

EMILIN2 Correlated With Its Methylation and Immune Infiltration Could Be an Independent Prognostic Biomarker in LGG

Low-grade gliomas (LGGs) are slow-growing brain cancer in central nervous system neoplasms. EMILIN2 is an extracellular matrix (ECM) protein which could influence the progress of some tumour which is unclear in LGG. In our study, the methylation, expression, prognosis and immune value of EMILIN2 were analysed in LGG through bioinformatics analysis. we first analysed the LGG data from TCGA and discovered that the EMILIN2 expression, negatively correlated to the EMILIN2 methylation could predict a poor prognosis and associated with different clinical parameters. Moreover, univariate and multivariate Cox regression were performed in CGGA showed that the EMILIN2 could be an independent prognostic biomarker in LGG. Finally, EMILIN2 expression showed a correlation with gene makers in some immune cells which identified the significance of EMILIN2 in immune infiltration. In conclusion, EMILIN2 could act as an independent prognostic biomarker which might be associated with the malignancy and development of gliomas and play a crucial role in glioma in immune infiltration.

Hippo Signaling Pathway in Gliomas

The Hippo signaling pathway is a highly conserved pathway involved in tissue development and regeneration that controls organ size through the regulation of cell proliferation and apoptosis. The core Hippo pathway is composed of a block of kinases, MST1/2 (Mammalian STE20-like protein kinase 1/2) and LATS1/2 (Large tumor suppressor 1/2), which inhibits nuclear translocation of YAP/TAZ (Yes-Associated Protein 1/Transcriptional co-activator with PDZ-binding motif) and its downstream association with the TEAD (TEA domain) family of transcription factors. This pathway was recently shown to be involved in tumorigenesis and metastasis in several cancers such as lung, breast, or colorectal cancers but is still poorly investigated in brain tumors. Gliomas are the most common and the most lethal primary brain tumors representing about 80% of malignant central nervous system neoplasms. Despite intensive clinical protocol, the prognosis for patients remains very poor due to systematic relapse and treatment failure. Growing evidence demonstrating the role of Hippo signaling in cancer biology and the lack of efficient treatments for malignant gliomas support the idea that this pathway could represent a potential target paving the way for alternative therapeutics. Based on recent advances in the Hippo pathway deciphering, the main goal of this review is to highlight the role of this pathway in gliomas by a state-of-the-art synthesis.

LGG-51. BRAF ALTERATIONS IN PEDIATRIC LOW-GRADE GLIOMAS: RESULTS FROM A BRAZILIAN COHORT

BACKGROUND Pediatric low grade gliomas (PLGG) are the most common central nervous system neoplasms in children. These are driven almost exclusively by alterations in the RAS/MAPK pathway. Specifically, alterations in the BRAF gene have emerged as an important target for therapy. This study aimed to identify the frequency of BRAF alterations in a Brazilian cohort of PLGGs. RESULTS Forty-one patients diagnosed between 2001 and 2017 had enough FFPE tissue available for analysis. Real-time PCR test (n=35) was used to assess for BRAFV600E mutations, while BRAF fusions were detected by break-apart fluorescence in situ hybridization (n=30). The histologic distribution was as follows: 73% pilocytic astrocytoma, 12% ganglioglioma, 3% diffuse astrocytoma, 5% pleomorphic xanthoastrocytomas (PXA) and 7% NOS (n = 41). BRAF fusions were present in 21 patients (51%): 17 pilocytic astrocytomas, 2 xanthoastrocytoma, 1 pilomyxoid astrocytoma and 1 diffuse astrocytoma. BRAFV600E was detected in 4 cases (10%): 2 pilocytic astrocytomas, 1 ganglioglioma and 1 PXA. As expected, BRAF translocations were more frequent in pilocytic astrocytomas (p<0.001). From 22 patients treated in our institution, 59% were male with a mean age of 9.7 years, 50% occurred in the posterior fossa and 77% treated by surgery only. One patient relapsed and died from disease (BRAF V600E positive) (follow-up median=44.7 months). These are the first results using a CLIA method showing the frequency of BRAF abnormalities in a Brazilian population. Although preliminary, BRAF alterations are present in 61% of the cases emphasizing the importance of incorporating this analysis in the current work-up guidelines.

Molecular Profiling of Pediatric and Adult Glioblastoma

Objectives Although glioblastoma (GBM) is rare in the pediatric population, it is the most common cause of death among children with central nervous system neoplasms. Recent molecular profiling of these neoplasms has demonstrated distinct differences in comparison to their adult counterparts. Moreover, many pediatric GBMs occur within the context of cancer predisposition syndromes, such as constitutional mismatch repair deficiency syndrome (CMMRD). Children with CMMRD who develop GBM exhibit a high tumor mutational burden and may benefit from treatment with immune checkpoint inhibitors. Methods We performed next-generation sequencing and immunohistochemistry for mismatch repair proteins in our cohort of pediatric and adult GBMs to further characterize the molecular profiles of these groups. Results We examined a total of 11 pediatric and 11 adult GBMs. Pediatric patients had a higher number of alterations compared to their adult counterparts. They also had a higher frequency of alterations in the mismatch repair genes, which can be detected by immunohistochemistry (IHC). We also identified one pediatric patient with CMMRD syndrome. Conclusions Our study highlighted the distinct molecular differences between pediatric and adult GBM. We also demonstrated that pediatric patients have a higher frequency of alterations in the mismatch repair genes, which may render them susceptible to treatment with immune checkpoint inhibitors. These alterations can be detected using routine IHC and should be performed on all pediatric GBM.

A rare cystic lymphoplasmacyte-rich meningioma: A case report and review of the literature

Background: Meningiomas are common central nervous system neoplasms, accounts for 30% of all primary intracranial neoplasms; the occurrence of meningiomas with cystic lesions is an exceptionally rare. Lymphoplasmacyte-rich meningioma (LPRM) is a rare pathological entity belong to the World Health Organization Grade I meningiomas. LPRM is characterized by abundant lymphoplasmacytic infiltrates which over-shadow the underlying meningothelial component. Case Description: A 42-year-old male was admitted to our hospital with a chronic headache for about 3 weeks prior to admission. His symptoms worsen, and subsequently, he experienced left extremities weakness about 1 week before admission. His brain magnetic resonance imaging revealed an irregular and heterogeneously enhancing solid lesion with intratumoral cystic changes at the temporal lobe. A gross total resection was performed; pathological examination revealed a cystic LPRM. Conclusion: This rare variant of meningioma is a benign tumor entity featured with massive inflammatory cell infiltration and often less proportion of meningothelial elements. Surgical resection remains the treatment of choice. This is the first report regarding cystic LPRM from Indonesia; we also summarized relevant literature upto-date, May 2020, reported LPRM cases.

Central Nervous System Neoplasms in Hong Kong: An Inscription of Local Studies

: A registry of brain and central nervous system (CNS) tumor patients in Hong Kong comprising of data from both public and private neurosurgical practices (with approximately 98% patients of Chinese origin), suggested geographical or racial variations in disease incidence. The data confers the finding of a comparatively lower incidence rate of meningioma and malignant gliomas as in other parts of Southeast Asia. : With data suggesting epidemiological difference, the treatment response, particularly in highgrade glioma, was studied. Patients suffering from glioblastoma (GBM) in Hong Kong received the standard of care, which involves safe, maximal resection followed by the Stupp regime. 5-aminolevulinic acid (5-ALA)-based fluorescence-guided surgery was found to be feasible and safe to adopt in the treatment of local WHO Grade III & IV gliomas patients. Survival benefit was seen in a group of patients using extended adjuvant temozolomide (TMZ) treatment for newly diagnosed GBM as compared to those treated with the standard 6 cycles. Salvage therapies with either single agent bevacizumab or bevacizumab plus irinotecan appeared to be effective treatment options in Hong Kong patients with recurrent malignant glioma, with a good associated 6- month progression-free survival (PFS) rate which was comparable to previously published overseas data in this disease type in the same overall population.