Pilocytic astrocytoma in adults: Histopathological, immunohistochemical and molecular study with clinical association.

Pilocytic astrocytoma is the most common primary CNS neoplasm in children and adolescents, rare after the first two decades of life. While some authors report a favorable prognosis in the adult age group with the tumor, others have associated it with higher mortality. The molecular alteration most observed in cases of pilocytic astrocytoma in the pediatric group is the BRAF-KIAA1549 gene fusion, and there are still few studies confirming the presence of this fusion in the adult population. This work investigated genetic alterations involving the 7q34 region in BRAF gene in 21 adult individuals with pilocytic astrocytoma, by FISH. In addition, was identified the immunohistochemical expression of BRAFV600E, correlating these findings with histopathological and clinical ones. BRAF-KIAA1549 fusion appeared in only one case, while in two other cases were found deletions related to the FAM131B-BRAF fusion, suggesting that maybe the latter is more frequently in this population. Through the evaluation of immunoreactivity, 71% of the cases were considered positive and 29% negative. Cases considered positive for BRAFV600E immunoreactivity can potentially be treated through drug therapy with BRAF inhibitors; however, it is always recommended to carry out a molecular study for diagnostic confirmation. This is the first Brazilian study that aimed to investigate possible genetic alterations in the BRAF gene in pilocytic astrocytomas, specifically in adults. Only 1 patient died, but due to operative complications and not the disease itself, suggesting a good evolution of these individuals.

Pathophysiological evaluation of pilocytic astrocytoma in adults: Histopathological and immunohistochemical analysis.

Pilocytic astrocytoma is a central nervous system tumor of slow growth, which represents 5 % of all gliomas and most often develops in the cerebellum (42-60 %), but can also arise in other neural areas, such as the optic pathway or hypothalamus (9-30 %); brainstem (9 %); spinal cord (2 %). In the pediatric population, this tumor is the second most common cause of neoplasms and, on the other hand, in adults, it is often rare, probably due to its aggressiveness in these individuals. Studies reveal that the origin of pilocytic astrocytoma is characterized by a fusion between the BRAF gene and the KIAA1549 locus, and the application of the immunohistochemistry technique for the analysis of BRAF protein expression can be a valuable tool for diagnostic purposes. Due to the relative rarity of this disease in adults, there are few publications on the most effective diagnostic and treatment strategies for this tumor. The general objective of this study was to analyze the histopathological and immunohistochemical characteristics of pilocytic astrocytoma in these patients. For this, a retrospective study of patients aged over 17 years with a diagnosis of pilocytic astrocytoma was carried out at the Department of Pathology of UNIFESP/EPM, from 1991 to 2015. In order to define BRAF positivity in the immunohistochemical analysis, at least three consecutive fields with more than 50 % immunostaining were used as criteria and, thus, it was inferred that the 7 cases analyzed were considered positive for the cytoplasmic marker BRAF V600E. Histopathological analysis associated with BRAF immunostaining is of paramount importance as a diagnostic method in these cases. However, future molecular studies will be necessary both for a better understanding of the aggressiveness and prognostic of this tumor and for research involving specific therapies for pilocytic astrocytoma in adults.

The involvement of the MAPK pathway in pilocytic astrocytomas.

Pilocytic astrocytomas are the primary tumors most found in the first two decades of life, accounting for around 15% of all brain tumors. Research at the molecular level of pilocytic astrocytoma makes possible to compose an overview of what is known about the origin and development of the tumor. It is known that there are alterations in the Mitogen Activated Protein Kinase (MAPK) signaling pathway that are important auxiliary markers in diagnosis. This study seeks to list the main points about the involvement of this pathway in tumor formation in pilocytic astrocytoma. A review was conducted in search of published studies available in NCBI, PubMed, MEDLINE, Scielo and Google Scholar. The most frequent alteration is the gene fusion between BRAF and KIAA1549 genes, found in approximately 90% of pediatric cases. The second most common event is the BRAFV600E mutation, also often found in children than in adult cases. The molecular origin of pilocytic astrocytomas is related to alterations in the MAPK pathway, which acts with several functions in the brain such as memory formation, pain perception, induction of cortical neurogenesis, and midbrain and cerebellum development. Alterations in this pathway can be therapeutic targets in the treatment of patients with pilocytic astrocytoma. The MAPK pathway is extremely important and knowledge about its involvement in astrocytic tumors is essential for a better approach to the patient.

Meningiomas: A review of general, histopathological, clinical and molecular characteristics.

OBJECTIVES: In this review, the main histological and molecular characteristics of meningiomas will be addressed, as well as the aspects most related to clinical conditions, treatment, and survival of patients, enabling a better understanding of these tumors behavior. METHODS: This study was conducted with the search for published studies available on NCBI, PubMed, MEDLINE, Scielo and Google Scholar. Relevant documents have been identified and 50 articles were selected. RESULTS: The main points about meningiomas were characterized, as well as the histological presence of spontaneous necrosis in grade I and brain invasion as diagnostic criteria, their molecular origin related to deletion of chromosome 22 and mutations in theNF2 and TERT genes, in addition to their clinical characteristics. The preferential treatment remains the total resection of the tumor. CONCLUSION: The information about meningiomas is well known and necessary, but it is expected that more work will emerge related to the behavior of these tumors, and that the scientific community will obtain more clarity about the best ways to conduct the patients treatment.

Deletion 21pterq22.11: Report of a Patient with Dysmorphic Features, Hypertonia, and Café-au-Lait Macules and Review of the Literature.

Partial monosomy 21 results in a great variability of clinical features that may be associated with the size and location of the deletion. In this study, we report a 22-month-old girl who showed a 45,XX,add(12)(p13)dn,-21 karyotype. The final cytogenomic result was 45,XX,der(12)t(12;21)(p13;q22.11) dn,-21.arr[hg19] 21q11.2q22.11(14824453_33868129)×1 revealing a deletion from 21pter to 21q22.11. Clinical manifestation of the patient included hypertonia, a long philtrum, epicanthic folds, low-set ears, and café-au-lait macules - a phenotype considered as mild despite the relatively large size of the deletion compared to patients from the literature.

Miller-Dieker Syndrome due to a 5.5-Mb 17p Deletion in a 17;Y Pseudodicentric Chromosome.

Miller-Dieker syndrome (MDS) is a contiguous gene deletion syndrome in which almost all patients present de novo 17p13.3 deletions. We report on a male infant with MDS and an unusual unbalanced translocation involving chromosomes Y and 17 that resulted in a large 5.5-Mb 17pterp13.2 deletion and a karyotype with 45 chromosomes. Apart from the deletion of the MDS critical region, the deletion of additional distal genes seemed to have no major influence on the patient's phenotype, since he did not show any unusual clinical findings that are not commonly described in MDS patients.

Unusual Duplication in the Pericentromeric Region of Chromosome 9 in a Patient with Phenotypic Alterations.

Several alterations involving the pericentromeric region of chromosome 9 are considered as normal population variants. These heterochromatic variants or heteromorphisms can include 9qh+, 9cen+, 9ph+, 9ph-, inv(9)(p11q13), and other patterns which can only be defined by FISH studies. However, some heteromorphisms have been found more frequently in patients with several clinical disorders. Here, we report on a patient with intellectual disability, language and neurodevelopmental delay, as well as facial dysmorphism and an unusual chromosome 9. While the banding karyotype was indicative of a simple pericentric inversion of one chromosome 9 [46,XX,inv(9)(p12q13)], array comparative genomic hybridization showed a 6-Mb duplication, including 22 genes: arr[hg19] 9p13.1p11.2(38,869,901- 44,870,714)×3 dn. Molecular cytogenetics using a panel of probes specific for the pericentromeric region of chromosome 9 showed an unusual, rearranged chromosome 9, der(9)(pter→p11.2::q21.11→q12::p11.2→p13.2::q12→p11.2::q21.11→qter), that has not been described before. The patient's phenotypic alterations are probably due to the de novo 6-Mb 9p duplication, although a review of similar cases showed some reports considering this duplication in the euchromatic region as a benign variant. Interestingly, this is the first report of a possible adverse inversion loop formation due to a known heteromorphic pericentric inversion present in the phenotypically normal father of the patient.