Adult Pilocytic Astrocytoma Research Articles

Rapid postradiation malignant transformation of a pilocytic astrocytoma in an adult with neurofibromatosis type 1: illustrative case.

Juvenile pilocytic astrocytoma (JPA) is the most common primary brain tumor of childhood and is rarely seen in adults. Neurofibromatosis type 1 (NF1), a common tumor predisposition syndrome, demonstrates a strong association with low-grade gliomas, most notably pilocytic astrocytoma, which are relatively indolent. Unlike its juvenile counterpart, reports of adult pilocytic astrocytoma (APA) vary widely in terms of disease progression from benign to much more malignant courses. Moreover, current studies discussing APA report different treatment approaches and outcomes (e.g., malignant transformation of JPA and APA with or without radiation), as little is known regarding the management of recurrent tumors and how adjuvant therapies may alter disease progression. The authors report the unique case of an adult male with NF1 and APA who underwent rapid malignant conversion after intensity-modulated radiation therapy. The authors demonstrate that caution should be taken in utilizing radiotherapy instead of resection in cases of APA and NF1, with close monitoring for posttreatment recurrence. https://thejns.org/doi/10.3171/CASE24241.

Hypothalamic Hemangioma-like Pilocytic Astrocytoma in an Adult Patient: A Systematic Review with a Focus on Differential Diagnosis and Neurological Presentation.

Background: Pilocytic astrocytoma (PCA) are commonly observed as slow-growing noncancerous brain tumors in pediatric populations, but they can also occur in adults, albeit rarely. When located in diencephalic regions, particularly in the hypothalamus, they present unique diagnostic and management challenges due to their rarity and overlapping clinical and radiological features with other intracranial pathologies. This systematic review aims to provide a comprehensive understanding of hypothalamic PCA in adults, focusing on their differential diagnosis, neurological presentation, diagnostic modalities, treatment strategies. A case illustration is also described in order to better underline all the difficulties related to the diagnostic process. Material and methods: A systematic literature search was conducted in the PubMed/MEDLINE, Embase, and Scopus databases up to November 2023 to identify studies. Results: The systematic literature search identified a total of 214 articles. Following screening by title and abstract and full-text review, 12 studies were deemed eligible and are included here. Conclusions: Adult-onset PCA in diencephalic regions pose diagnostic challenges due to their rarity and overlapping features with other intracranial lesions. Advanced imaging techniques play a crucial role in diagnosis, while surgery remains the cornerstone of treatment. Multidisciplinary collaboration is essential for the optimal management and long-term follow-up of these patients.

P.073 Spontaneous fluctuation of contrast enhancement in adult pilocytic astrocytoma and other low-grade brain tumors

Background: Pilocytic astrocytoma and other circumscribed low-grade brain tumors can exhibit spontaneous enhancement changes despite stable size and clinical status. We aimed to describe this phenomenon in adults. Methods: We performed a retrospective review of our MRI database (2011-2021) to identify cases with enhancement changes in otherwise stable tumors. We searched for reports containing: “pilocytic”, “pilomyxoid”, “RGNT”, “rosette”, “glioneuronal”, “DNET”, and “dysembryoplastic”. Exclusion criteria included WHO grade 3/4 tumors, patients <19 years, equivocal diagnostic findings, and no serial MRIs. We reviewed 238 patients. Results: We identified 12 adult patients with the desired phenomenon: 6 pilocytic astrocytoma, 1 pilomyxoid astrocytoma, 2 rosette-forming glioneuronal tumor, 1 unverified low-grade glioma, and 2 cases without biopsy. Seven were untreated, while five were residual or recurrent tumors. Six showed a pattern of new/increasing and subsequent decreasing/disappearing enhancement over 1-4 years. One exhibited spontaneous regression of enhancement over 1 year. Five showed repeating cycles of increasing and decreasing enhancement over longer monitoring periods of 7-15 years, with mean duration of increasing enhancement prior to decline of 21.4 months (SD 5.9). Conclusions: Spontaneous contrast enhancement fluctuation in adult pilocytic astrocytoma and other circumscribed low-grade brain tumors can occur, and on its own should not be misconstrued as evidence of tumor progression/regression.

Trans-Sylvian and Transanterior Ascending Ramus Approach for Insular Gliomas at Zone I: 2-Dimensional Operative Video.

Insular gliomas present significant challenges because of their deep-seated location and proximity to critical structures, including Sylvian veins, middle cerebral arteries, lenticulostriate arteries,1 long insular arteries,2 and functional cortices.3-6 The Berger-Sanai classification categorizes them into 4 zones (I-IV), providing a framework for understanding insular gliomas.7 The key factors for successful insular glioma removal are achieving the greatest insular exposure and surgical freedom.3 Given that the trans-Sylvian approach8,9 creates a narrow, linear surgical window,3 regardless of the zones, various surgical options have been employed, such as the trans-Sylvian approach with bridging vein cuts and the transcortical approach through functionally silent cortex.3,7,9-13 Dissecting sulci in glioma surgeries has proven beneficial.14-16 In this video publication, we dissected the anterior ascending ramus (AAR) and the Sylvian fissure, creating a triangular window instead of a linear one. A 74-year-old right-handed woman with a zone I insular glioma underwent a trans-Sylvian and trans-AAR approach, achieving total resection of the tumor without new neurological deficits. This approach provided maximum exposure of the insular region, offering a wide view from the anterior limiting sulcus to the anterior half of the superior limiting sulcus of the insula. The histological diagnosis revealed a rare adult pilocytic astrocytoma at the insula, documented in only one case report.17 The AAR,4 defined as a lateral sulcus (Sylvian fissure) branch,18 is present in 98.89% of hemispheres19; therefore, this surgical approach demonstrates broad applicability to zone I insular tumors. The patient provided consent for the procedure and the publication of her image under institutional review board approval (G23-08).

Intraventricular Pilocytic Astrocytoma in Adults: A 25-year Single-Center Case Series and Systematic Review of the Literature

Pilocytic astrocytomas (PA) are the most common gliomas in children/adolescents but are less common and poorly studied in adults. Here, we describe the clinical presentation, surgical management, and outcomes of surgically treated adult patients with intraventricular (IV) PA and review the literature. Consecutive adult patients treated for IV brain tumors at a tertiary academic center over 25years (1997-2023) were identified. Clinical data were reviewed retrospectively for adult IV PA patients. A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Eight patients with IV PA were included. Median age was 25years (range, 18-69years), and 4 (50%) were female. The most common tumor location was the lateral ventricle (5, 63%), followed by the fourth ventricle (3, 37%). Subtotal and near total resection were the most common surgical outcomes (6 patients, 75%), followed by gross total resection in 2 (25%). Progression or recurrence occurred in 3 patients (37%), requiring repeat resection in 2 patients. The 5-year overall survival and progression-free survival were 67% and 40%, respectively. In addition, 42 cases were identified in the literature. PAs in adults are rare and an IV location is even more uncommon. The findings demonstrate the challenges in caring for these patients, with overall- and progression-free survival outcomes being poorer than the general adult PA population. Findings support the employment of surgical techniques and approaches that favor gross total resection when possible. Further studies are needed to better characterize this unique presentation.

Molecular refinement of pilocytic astrocytoma in adult patients.

Pilocytic astrocytomas (PA) in adults are rare and may be challenging to identify based only on histomorphology. Compared to their paediatric counterparts, they are reportedly molecularly more diverse and associated with a worse prognosis. We aimed to describe the characteristics of adult PAs more precisely by comprehensively profiling a series of 79 histologically diagnosed adult cases (≥18 years). We performed global DNA methylation profiling and DNA and RNA panel sequencing, and integrated the results with clinical data. We further compared the molecular characteristics of adult and paediatric PAs that had a significant match to one of the established PA methylation classes in the Heidelberg brain tumour classifier. The mean age in our cohort was 33 years, and 43% of the tumours were located supratentorially. Based on methylation profiling, only 39% of the cases received a significant match to a PA methylation class. Sixteen per cent matched a different tumour type and 45% had a Heidelberg classifier score <0.9 with an affiliation to diverse established methylation classes in t-SNE analyses. Although the KIAA1549::BRAF fusion was found in 98% of paediatric PAs, this was true for only 27% of histologically defined and 55% of adult PAs defined by methylation profiling. A particularly high fraction of adult tumours with histological features of PA do not match current PA methylation classes, indicating ambiguous histology and an urgent need for molecular profiling. Moreover, even in adult PAs with a match to a PA methylation class, the distribution of genetic drivers differs significantly from their paediatric counterparts (p<0.01).

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.

Surgical Treatment of Pilocytic Astrocytoma in Adults: A Study of 50 Cases: and Literature Review

To study the effects of treatment in adults with pilocytic astrocytoma (PA), we conducted a survey including an examination of tiny case series and research in the literature. Our study comprised 50 patients who had PA surgery at MMC Mardan, Pakistan, between February 2018 and February 2023. Our main goal was overall survival (OS), whereas our secondary goals were morbidity, quality of life, and recurrence-free survival. The mean patient age was 27.7 years, with a range of 19–62 years, throughout our follow-up period of 38.3 months, which was between 0-85 months. The survival rate according to our findings was 77.2% (96% CI: 96.02-98.3%). Moreover, the adult recurrence-free survival rate after PA surgery was 95.01% (96.07% CI: 92.07-95.09%). Quality of life assessments after surgery was significantly better than before values [p 0.001]. Notably, the most frequent consequence in 7.08% of patients was postoperative seizures. These findings imply that adult patients with PA may benefit from surgical therapy in terms of quality of life and survival.

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.

A monocenter retrospective study of the surgical outcomes of adult pilocytic astrocytoma: a small case series and review of the literature

Introduction: The peak age for the development of pilocytic astrocytoma (PA), a type of benign cerebellar tumor, is between 10 and 20 years. Adult PA is extremely rare, and consequently, very little is understood about its characteristics. Methods: We retrospectively reviewed the records of patients older than 18 years with pathologically proven PA who had surgery to remove the tumor between January 2010 and January 2020 and were followed until January 2022. Results: Although 32 cases were initially flagged as PA, we included 4 patients (2 male and 2 female) with adult PA. The average age of a male patient at diagnosis was 26.75 years old, and there was no mortality or recurrence. The mean age of female patients at diagnosis was 25 years old. One female was still living after the follow-up period ended. The cause of death in one female patient was unrelated to tumor. Women had a median follow-up of 36 months, and their mean overall survival was 42 months. Conclusion: PA in adults acts differently than in children. The extent of surgical resection and the location of the tumor influenced the prognosis. When possible, total resection should be the primary treatment, as it promotes good survival rates and low recurrence risk.

Rare adult pilocytic astrocytoma of the septum pellucidum with novel RIN2::BRAF fusion.

Pilocytic astrocytoma is mostly a pediatric tumor with the majority of patients under age 20. Although tumors can occur throughout neuraxis, most tumors are in the cerebellum and optic chiasm. Pilocytic astrocytoma in unusual locations is often associated with different genetic alterations than the classic KIAA1549::BRAF fusion. We report a rare adult pilocytic astrocytoma of the septum pellucidum that presented with progressive headache. A detailed genomic evaluation found a fusion between BRAF and a novel partner RIN2, a gene overexpressed in both low-grade glioma and glioblastoma. The RIN2::BRAF transcript encodes a chimeric protein containing a dimerization domain SH2 and an intact kinase domain, consistent with a prototypic oncogenic kinase rearrangement. In addition, we discuss the potential oncogenic mechanisms of BRAF signaling and its implication in targeted therapy with kinase inhibitors.

Adult Pilocytic Astrocytoma: A Report of Two Cases and Literature Review

Adult Pilocytic Astrocytoma: A Report of Two Cases and Literature Review

Adult Intramedullary Pilocytic Astrocytomas: Clinical Features, Management, and Outcomes.

Adult intramedullary pilocytic astrocytomas (PAs) are exceedingly rare. The aim of this study was to summarize our experiences in treating adult intramedullary PAs. We retrospectively reviewed the records of seven adult patients who underwent microsurgery for intramedullary PAs between 2010 and 2017. Magnetic resonance imaging was the standard radiological investigation. The diagnosis of PAs was based on pathology. All the follow-up data were obtained during office visits. There were three males and four females with the mean age of 40.9 years. The tumors generally exhibited hypointensity on T1-weighted images (WI) and hyperintensity on T2WI. Contrast-enhanced T1WI showed heterogeneous enhancement. Gross total resection (GTR) of the tumor was achieved in four cases and subtotal resection (STR) was achieved in three cases. Two cases of STR received postoperative radiotherapy. One STR case had mildly residual tumor regrowth. At the last follow-up, neurological status was improved in six patients. The accurate diagnosis of adult intramedullary PAs depends on pathology. GTR is the best treatment and the outcome is favorable. STR increases the risk of tumor recurrence, and regular follow-up is necessary. Due to uncertain therapeutic efficacy, radiotherapy should be considered carefully for cases of STR.

Insight about the characteristics and surgical resectability of adult pilocytic astrocytoma: tertiary center experience.

Aim: Adult pilocytic astrocytoma is a rare tumor. We aim to contribute to understanding its clinical course and prognosis. Patients & methods: We searched our database for patients older than 18 years with pathology-proven pilocytic astrocytoma. Patients’ clinical data were analyzed. Results: Fifteen patients were identified. The median age at diagnosis was 25 years (range: 18–56). Tumors were supratentorial in 47%. Gross-total and near-total resections were achieved in 40%, and sub-total resection in 47%. One (7%) recurrence and no mortality were encountered during a median follow-up of 11 months (range: 1–76). Conclusion: Pilocytic astrocytoma behaves differently in adults compared with pediatrics. It tends to arise in surgically challenging areas where the extent of resection may be limited. Total resection should be the main therapy whenever feasible. The survival rates are good, and recurrence is low.

A fully automatic multiparametric radiomics model for differentiation of adult pilocytic astrocytomas from high-grade gliomas.

To develop a fully automatic radiomics model to differentiate adult pilocytic astrocytomas (PA) from high-grade gliomas (HGGs). This retrospective study included 302 adult patients with PA (n = 62) or HGG (n = 240). The patients were randomly divided into training (n = 211) and test (n = 91) sets. Clinical data were obtained, and radiomic features (n = 372) were extracted from multiparametric MRI with automatic tumour segmentation. After feature selection with F-score, a Light Gradient Boosting Machine classifier with subsampling was trained to develop three models: (1) clinical model, (2) radiomics model, and (3) combined clinical and radiomics model. Human performance was also assessed. The performance of the classifier was validated in the test set. SHapley Additive exPlanations (SHAP) was applied to explore the interpretability of the model. A total of 15 radiomic features were selected. In the test set, the combined clinical and radiomics model (area under the curve [AUC], 0.93) showed a significantly higher performance than the clinical model (AUC, 0.79, p = 0.037) and had a similar performance to the radiomics model (AUC, 0.92, p = 0.828). The combined clinical and radiomics model also showed a significantly higher performance than humans (AUC, 0.76-0.81, p < 0.05). The model explanation by SHAP suggested that lower intratumoural heterogeneity from T2-weighted images was highly associated with PA diagnosis. The fully automatic combined clinical and radiomics model may be helpful for differentiating adult PAs from HGGs. • Differentiating adult PAs from HGGs is challenging because PAs may manifest a large spectrum of imaging presentations, often including aggressive imaging features. • The fully automatic combined clinical and radiomics model showed a significantly higher performance than the clinical model or humans. • The model explanation by SHAP suggested that second-order features from T2-weighted imaging were important in diagnosis and might reflect the underlying pathophysiology that PAs have lesser tissue heterogeneity than HGGs.

Clinical factors and conventional MRI may independently predict progression-free survival and overall survival in adult pilocytic astrocytomas.

Pilocytic astrocytoma (PA) is rare in adults, and only limited knowledge on the clinical course and prognosis has been available. The combination of clinical information and comprehensive imaging parameters could be used for accurate prognostic stratification in adult PA patients. This study was conducted to predict the prognostic factors from clinical information and conventional magnetic resonance imaging (MRI) features in adult PAs. A total of 56 adult PA patients were enrolled in the institutional cohort. Clinical characteristics including age, sex, anaplastic PA, presence of neurofibromatosis type 1, Karnofsky performance status, extent of resection, and postoperative treatment were collected. MRI characteristics including major axis length, tumor location, presence of the typical 'cystic mass with enhancing mural nodule appearance', proportion of enhancing tumor, the proportion of edema, conspicuity of the nonenhancing margin, and presence of a cyst were evaluated. Univariable and multivariable Cox proportional hazard modeling were performed. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 83.9% and 91.l%, respectively. On univariable analysis, older age, larger proportion of edema, and poor definition of nonenhancing margin were predictors of shorter PFS and OS, respectively (all Ps < .05). On multivariable analysis, older age (hazard ratio [HR] = 1.04, P = .014; HR = 1.14, P = .030) and poor definition of nonenhancing margin (HR = 3.66, P = .027; HR = 24.30, P = .024) were independent variables for shorter PFS and OS, respectively. Age and the margin of the nonenhancing part of the tumor may be useful biomarkers for predicting the outcome in adultPAs.

A diagnostic tree for differentiation of adult pilocytic astrocytomas from high-grade gliomas

BackgroundTo develop a diagnostic tree analysis (DTA) model based on demographical information and conventional MRI for differential diagnosis of adult pilocytic astrocytomas (PAs) and high-grade gliomas (HGGs; World Health Organization grade III-IV). MethodsA total of 357 adult patients with pathologically confirmed PA (n = 65) and HGGs (n = 292) who underwent conventional MRI were included. The patients were randomly divided into training (n = 250) and validation (n = 107) datasets to assess the diagnostic performance of the DTA model. The DTA model was created using a classification and regression tree algorithm on the basis of demographical and MRI findings. ResultsIn the DTA model, tumor location (on cerebellum, brainstem, hypothalamus, optic nerve, or ventricle), cystic mass with mural nodule appearance, presence of infiltrative growth, and major axis (cutoff value, 2.9 cm) were significant predictors for differential diagnosis of adult PAs and HGGs. The AUC, accuracy, sensitivity, and specificity were 0.94 (95% confidence interval 0.86–1.00), 96.2%, 89.5%, and 97.7%, respectively, in the test set. The accuracy of the DTA model was significantly higher than the no-information rate in the test (96.2 % vs 85.0%, P < 0.001) set. ConclusionThe DTA model based on MRI findings may be useful for differential diagnosis of adult PA and HGGs.

Adult Pilocytic Astrocytoma in the Molecular Era: Surveying the Prevalence of MAPK Pathway Dysfunction and Overlap with Aggressive Features (2906)

Adult Pilocytic Astrocytoma in the Molecular Era: Surveying the Prevalence of MAPK Pathway Dysfunction and Overlap with Aggressive Features (2906)

The age of adult pilocytic astrocytoma cells

Adult pilocytic astrocytomas (PAs) have been regarded as indistinguishable from pediatric PAs in terms of genome-wide expression and methylation patterns. It has been unclear whether adult PAs arise early in life and remain asymptomatic until adulthood, or whether they develop during adulthood. We sought to determine the age and origin of adult human PAs using two types of “marks” in the genomic DNA. First, we analyzed the DNA methylation patterns of adult and pediatric PAs to distinguish between PAs of different anatomic locations (n = 257 PA and control brain tissues). Second, we measured the concentration of nuclear bomb test-derived 14C in genomic DNA (n = 14 cases), which indicates the time point of the formation of human cell populations. Our data suggest that adult and pediatric PAs developing in the infratentorial brain are closely related and potentially develop from precursor cells early in life, whereas supratentorial PAs might show age and location-specific differences.

Adult pilocytic astrocytoma in the molecular era: a comprehensive review.

Adult pilocytic astrocytoma (PA) is less prevalent than pediatric PA and is associated with a worse prognosis. In a literature review, we found that 88.3% of the molecular alterations in adult PA are associated with MAPK pathway dysregulation. The most common alterations are fusions of BRAF. Understanding of the mechanisms underlying this pathway has evolved substantially, heralding advancements in specific targeted therapy. Here, we review clinical and molecular features of adult PA, characteristics predicting aggressive behavior and approaches to standard and investigational therapies. We highlight epigenetic profiling and integrated diagnosis as an essential component of classifying PA.