Spontaneous contrast enhancement fluctuation in adult pilocytic astrocytoma

Pilocytic astrocytoma (PA) is rare in adults despite being the most common pediatric brain tumor. KIAA1549::BRAF fusion and BRAF p.V600E mutation are common in PA, yet prognostic impact of these alterations remains uncertain. We highlight clinical characteristics and tumor genomics in PA across the lifespan, exploring factors associated with disease progression. Pediatric and adult patients who underwent biopsy or resection of PA from 2000 to 2023 were retrospectively studied. Clinical data and tumor genomics were collected, and progression/recurrence-free survival (PRFS) analysis was performed. We identified 334 pediatric and 32 adult PA patients. Tumor location distribution did not differ between groups, with the cerebellum being the predominant location (59.3% pediatric and 50.0% adult). Gross total resection (GTR) was more common in children (79.1% versus 62.1%, p = 0.04). KIAA1549::BRAF fusion was more frequent in children (59.6% versus 23.1%, p = 0.02). BRAF p.V600E mutations were rarer in both groups (14.6% pediatric versus 8.3% adult, p = 1). In children, GTR was associated lower rates of tumor progression/recurrence (9.8% versus 41.2%, p < 0.001) and longer PRFS (p < 0.001). Cerebellar tumors in children were also associated with lower rates of tumor progression/recurrence (13.1% versus 31.6%, p < 0.001) and longer PRFS (p < 0.001). No operative/genomic predictors of PRFS were identified in adults. Overall rate of tumor progression/recurrence did not differ between groups (21.3% pediatric versus 15.6% adult, p = 0.65). Clinical characteristics and factors influencing tumor progression/recurrence differ in children and adults with PA. This work highlights current knowledge gaps on age-related differences in PA, providing clinical and genomic context for future studies.

INTRODUCTION: Recent work demonstrates significant associations between genomic status and clinical outcomes in pediatric pilocytic astrocytoma (PA). To date, a detailed comparison with adult PA patients has yet to be made. METHODS: We retrospectively reviewed treatment for pediatric and adult PA (2000-2023). BRAF-KIAA1549(B-K) fusion and BRAF-V600E mutations detected through immunohistochemistry, chromosomal-microarray, and next-generation sequencing were identified via pathology records. RESULTS: We identified 315 children (mean age at diagnosis 8.1 years, 50.8% female) and 29 adults (34.5 years, 41.4% female). Most common tumor locations were posterior fossa (59.7% pediatric, 51.7% adult) and suprasellar (21.3% pediatric, 24.1% adult). Pediatrics were more likely to experience obstructive hydrocephalus (p&lt;0.01) necessitating EVD placement (p=0.02). Gross-total resection was achieved in 59.4% pediatric and 48.3% adults (p=0.08). Median length of postoperative stay was shorter in adults (4 versus 8 days, p=0.002). Adjuvant chemotherapy was more common in children (26% versus 3.4%, p=0.013), while adults were more likely to receive adjuvant radiotherapy (27.6% versus 1.3%, p&lt; 0.001). BRAF-V600E mutations were identified in 8/67 children and 1/9 adults (p=0.48); B-K fusions were identified in 44/76 (57.9%) children and 2/10(20%) adults tested (p=0.055). Tumor progression/recurrence occurred in 5 (17.2%) adults and 69(21.9%) children (p=0.65). Median progression/recurrence-free survival (PRFS) time for children and adults was 4.6 and 2.2 years respectively (p=0.81, log-rank test). BRAF-V600E mutation did not confer worse PRFS compared to wildtype in either population. B-K fusion was associated with significantly shorter PRFS in pediatrics (3.0 versus 5.4 years, p=0.036), a trend which was not statistically significant in adults (p=0.2). CONCLUSIONS: This represents the largest cohort comparing genetics/clinical course of pediatric versus adult PA. Rates of obstructive hydrocephalus and adjuvant chemotherapy use were more common in children; radiotherapy was favored for adults. B-K fusions were more frequent in pediatrics and associated with worse PRFS than adults.

Pilocytic astrocytomas (PA) in adult patients are rare and the efficacy of postoperative adjuvant treatments remains unclear. This study aims to investigate the survival outcome and prognostic factors in surgically treated adult PA. A total of 90 consecutive adult patients with newly diagnosed PA were enrolled. Among the patients, 47 (52%) were male, with a median age of 28 years (18-70 years). Preoperative neurological deficits were observed in 43 (48%) patients. The most common tumor locations were cerebellar and cerebral hemispheres (28% and 27%, respectively), while 23% of tumors were located in deeper brain structures. The median follow-up duration was 88months (12-304 months). Gross total removal (GTR) was achieved in 55 (61%) patients. At the final follow-up, 12 (13%) patients had died, and 23 (26%) experienced disease progression. The 1, 2, and 5-year overall survival (OS) rates were 93%, 91%, and 87%, respectively, while the progression-free survival (PFS) rates were 88%, 80%, and 77%, respectively. The recurrence rate in patients who underwent GTR was 11%, compared with 53% and 45% in those without GTR, with or without adjuvant treatments, respectively. The tumors in the deeper brain locations had significantly lower GTR rates (14%) compared with other locations (75%; p < 0.001). Multivariate analysis identified the absence of preoperative neurological deficits (p = 0.048; HR = 2.878), not deeper tumor location (p = 0.017; HR = 3.471) and GTR (p = 0.007; HR = 3.884) as significant factors for improved PFS. Adult PA exhibited more aggressive behavior compared with pediatric PA. These aggressive behaviors including preoperative neurological deficits, deeper tumor location, and lower GTR rates were significantly associated with poor prognosis.

Purpose Adult pilocytic astrocytoma (APA) is rare and clinically distinct from pediatric counterparts. Despite generally favorable prognosis, recurrence rates vary significantly based on tumor characteristics and surgical approaches. Literature regarding the influence of tumor volume, location, and patient age on surgical outcomes and survival is limited and inconclusive. This study addresses these gaps, evaluating the combined impact of these variables on APA prognosis and management. Methods We retrospectively analyzed 32 adult patients with surgically treated APA at our institution (2014–2023), examining demographics, imaging, histology, and outcomes. Results Mean age was 35.8 years (SD 11.6); 59% were male. Median Karnofsky Performance Score (KPS) at admission was 90% (range 50–100%). Infratentorial tumors (56%) correlated significantly with lower KPS, increased cranial nerve deficits, cerebellar symptoms, hydrocephalus risk, prolonged operative time, higher CSF leaks (11%), and frequent revision surgeries. Gross total resection was achieved less frequently in infratentorial (33%) compared to supratentorial tumors (43%). Overall recurrence rate was 50%, strongly predicted by higher Ki-67 proliferation indices (p < 0.05), whereas resection extent alone lacked significant correlation. BRAF mutations occurred in only 38% of recurrent cases, highlighting APA’s distinct molecular profile. Five-year mortality was 6%, exclusively in High-Grade Astrocytoma with Piloid Features (HGAP). Conclusion Our findings challenge assumptions of benign clinical courses for APAs. Infratentorial tumors present increased surgical challenges and require tailored management. With recurrence rates of 50% and Ki-67 as a key prognostic marker, APA treatment demands personalized, biomarker-guided strategies beyond conventional surgical approaches.

Pilocytic astrocytomas (PAs) are benign grade 1 gliomas according to the World Health Organization (WHO). They are common in children but rare in adults in whom they may have a worse prognosis. Pediatric PAs are usually associated with dysregulation of the mitogen-activated protein kinase (MAPK) pathway, often involving BRAF alterations such as the KIAA1549::BRAF (K-B) fusion or V600E mutation. We investigated the molecular characteristics of adult PA using gene-targeted next-generation sequencing and specific gene tests, including for K-B fusion, TERT promoter, and FGFR1 hotspot mutations. The most frequent molecular alterations detected involved the MAPK pathway, particularly affecting BRAF and NF1 genes (55%). The prevalence of the K-B fusion (>40%) was higher than previously reported, likely due to challenges in detecting it. We identified molecular alterations in some cases that raised the differential diagnosis of other tumor types, revealing limitations in the 2021 WHO classification for adult PA. After removing other diagnostic types that may mimic PA histology, no adult patients with a diagnosis of PA and K-B fusion died after more than 10 years of mean follow-up. These findings suggest that, similar to pediatric cases, PA in adults may be driven by a single molecular hit, where the K-B fusion is not related to poor outcome.

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.

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.

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 &lt;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.

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) 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

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

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.

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.

Background: Pilocytic astrocytoma (PA) is classified as a benign tumor, which is rarely reported in adults.We present two case reports of adult PAs (APAs) and a literature review. Case descriptions:In Case 1, a 25-year-old man presented with progressive right parieto-temporal head puffing.Head computed tomography (CT) revealed multiple large cystic tumors with a midline shift.Gross total removal (GTR) was performed.No recurrence was observed in 3 months.In Case 2, a 38-year-old man presented with cerebellar symptoms.His head CT and brain magnetic resonance imaging revealed a cystic tumor in the cerebellar region.Surgical GTR was performed.No recurrence was observed in 3 months.An examination of previous reports of supratentorial or cerebellar APAs in the PubMed database suggested recurrence only in subtotal rection cases.Discussion: GTR or radiation therapy, if GTR is not achieved, is the most important factor for minimizing recurrence after removing the tumor.

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.

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.