Search

We describe a case of a young patient with a recurrent pleomorphic xanthoastrocytoma (PXA) showing unusual cell-in-cell (CiC) phenomena. We observed mostly viable but also necrotic neutrophils engulfed within tumor cells. The recurrent tumor was immunopositive for BRAFV600E mutant protein and showed CDKN2 homozygous deletions typical of PXA. Both genetic alterations were also reported in the original primary tumor. Unlike the original tumor that was GFAP and Olig-2 immunopositive, the recurrent neoplasm was largely negative for GFAP and Olig-2 suggesting dedifferentiation. The large malignant cells that contained the neutrophils were negative for histiocytic and lymphohematopoietic markers. Whereas CDKN2 homozygous deletion is common in PXA, its presence is rare in histiocytic neoplasms. Both reactive astrocytes and glial neoplasms very rarely may engulf neutrophils in a process resembling emperipolesis or cellular cannibalism. Future work may clarify which type of CiC pathway is involved.

A 45‐year‐old woman with neurofibromatosis type 1 (NF1) developed a tumor in the left frontal lobe that showed features of giant cell glioblastoma (GC‐GB). In addition to the typical GC‐GB features, the tumor showed lipogenic differentiation, with many atypical lipoblasts and mature adipocytes. Tumor cells, including the lipogenic cells, were immunoreactive for GFAP, S‐100 protein, ATRX, and p53. They were negative for IDH1‐R132H, BRAF V600E, synaptophysin, NeuN, p16, mismatch repair proteins, and CD34. The patient is free from recurrence at approximately two years postoperatively. This is the fifth reported case of NF1‐associated GC‐GB (the second adult case). NF1 gene mutation might have played a role in the pathogenesis of lipogenic differentiation of GC‐GB. The differential diagnosis of lipidized GC‐GB from gliosarcoma or anaplastic pleomorphic xanthoastrocytoma is briefly discussed. [ABSTRACT FROM AUTHOR]

Abstract Background Pleomorphic xanthoastrocytoma is a rare astrocytic tumor often diagnosed at a young age. Typically, they appear as supratentorial cortical tumors, frequently involving the temporal lobe with few reported rare locations. The prognosis is favorable following surgical excision; however, recurrence, dissemination, and anaplastic transformation occurred in some cases. Case presentation A 50-year-old female presented with convulsions and an altered consciousness. Imaging showed a periventricular mixed solid and cystic lesion. Histopathological examination revealed features of pleomorphic xanthoastrocytoma WHO grade 2 without necrosis or mitotic activity. Conclusions This report highlights the classic imaging findings of pleomorphic xanthoastrocytoma but in an atypical periventricular location. Although rare, pleomorphic xanthoastrocytoma should be considered in the differential diagnosis of mixed solid and cystic periventricular lesions.

Background/Aim: Gliomas are highly heterogeneous malignancies originating from diverse cell types within the brain. Although their precise etiology is frequently unknown, risk factors, such as chemical exposure, radiation, and specific uncommon genetic disorders have been identified. Diagnosis typically entails imaging tests, such as magnetic resonance imaging and computed tomography, complemented by a biopsy for confirmation, which may be further validated through genetic testing. Case Report: Next-generation sequencing technology revealed germline co-deletion deletion of cyclindependent kinase inhibitor 2 A and B genes (CDKN2A and CDKN2B) in a patient diagnosed with pleomorphic xanthoastrocytoma based on the tumor's molecular characteristics. Following this result, we performed focused genetic analysis with use of multiplex ligation-dependent probe amplification technology for the mother that revealed the same co-deletion. Moreover, due to the father's neuroendocrine pancreatic cancer, application of the NGS technology detected a pathogenic variant in the BRCA1-interacting helicase 1 (BRIP1) gene. Comprehensive multi-gene testing conducted within the familial context, marked by a varied spectrum of cancer type, revealed a constellation of genetic predispositions. Conclusion: This case study underscores the critical importance of molecular testing for tumor characterization and highlights the pivotal role of genetic testing in facilitating early intervention and screening for at-risk family members. Furthermore, the identification of germline co-deletions in cancer lays the foundation for the development of targeted therapeutic strategies aimed at restoring normal cellular regulation and improving patient management. [ABSTRACT FROM AUTHOR]

Dabrafenib plus trametinib is a promising new therapy for patients affected by BRAFV600E-mutant glioma, with high overall response and manageable toxicity. We described a complete and long-lasting response in a case of recurrent anaplastic pleomorphic xanthoastrocytoma CNS WHO-grade 3 BRAFV600E mutated. Due to very poor prognosis, there are a few described cases of highgrade glioma (HGG) patients treated with the combined target therapy as thirdline treatment. The emergence of optimized sequencing strategies and targeted agents, including multimodal and systemic therapy with dabrafenib plus trametinib, will continue to broaden personalized therapy in HGG improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Pleomorphic xanthoastrocytoma is a rare astrocytic tumor often diagnosed at a young age. Typically, they appear as supratentorial cortical tumors, frequently involving the temporal lobe with few reported rare locations. The prognosis is favorable following surgical excision; however, recurrence, dissemination, and anaplastic transformation occurred in some cases. Case presentation: A 50-year-old female presented with convulsions and an altered consciousness. Imaging showed a periventricular mixed solid and cystic lesion. Histopathological examination revealed features of pleomorphic xanthoastrocytoma WHO grade 2 without necrosis or mitotic activity. Conclusions: This report highlights the classic imaging findings of pleomorphic xanthoastrocytoma but in an atypical periventricular location. Although rare, pleomorphic xanthoastrocytoma should be considered in the differential diagnosis of mixed solid and cystic periventricular lesions. [ABSTRACT FROM AUTHOR]

We describe a case of a young patient with a recurrent pleomorphic xanthoastrocytoma (PXA) showing unusual cell-in-cell (CiC) phenomena. We observed mostly viable but also necrotic neutrophils engulfed within tumor cells. The recurrent tumor was immunopositive for BRAFV600E mutant protein and showed CDKN2 homozygous deletions typical of PXA. Both genetic alterations were also reported in the original primary tumor. Unlike the original tumor that was GFAP and Olig-2 immunopositive, the recurrent neoplasm was largely negative for GFAP and Olig-2 suggesting dedifferentiation. The large malignant cells that contained the neutrophils were negative for histiocytic and lymphohematopoietic markers. Whereas CDKN2 homozygous deletion is common in PXA, its presence is rare in histiocytic neoplasms. Both reactive astrocytes and glial neoplasms very rarely may engulf neutrophils in a process resembling emperipolesis or cellular cannibalism. Future work may clarify which type of CiC pathway is involved.

Abstract Pleomorphic xanthoastrocytomas (PXA) are rare, accounting for

This study was designed to investigate the value of nomograms based on MRI radiomics and clinical semantic features in identifying pleomorphic xanthoastrocytoma (PXA) and ganglioglioma (GG) as well as predicting BRAFV600E expression. This study included 265 patients histologically diagnosed with PXA (n = 113) and GG (n = 152). T1WI, T2WI, and CET1 sequences were utilized to extract radiomics features. Univariate analysis, Spearman correlation analysis, and the least absolute shrinkage and selection operator were used for dimensionality reduction and feature selection. Following this, logistic regression was utilized to establish the radiomics model. Univariate and multivariate analyses of clinical semantic features were applied, and clinical models were constructed. The nomograms were established by merging radiomics and clinical features. Furthermore, ROC curve analysis was used for examining the model performance, whereas the decision curve analysis (DCA) examined the clinical utility of the nomograms. Nomograms achieved the best predictive efficacy compared to clinical and radiomics models alone. Concerning the differentiation between PXA and GG, the area under the curve (AUC) values of the nomogram were 0.879 (0.828–0.930) and 0.887 (0.805–0.969) for the training and testing cohorts, respectively. For predicting BRAFV600E expression, the AUC values of the nomogram were 0.873 (0.811–0.936) and 0.851 (0.740–0.963) for the training and testing cohorts, respectively. DCA confirmed the clinical utility of the nomograms. Nomograms based on radiomics and clinical semantic features were noninvasive tools for differential diagnosis of PXA and GG and predicting BRAFV600E expression, which may be helpful for assessing patient prognosis and developing individualized treatment strategies. [ABSTRACT FROM AUTHOR]

Pleomorphic xanthoastrocytomas (PXA) are rare, accounting for < 1% of all astrocytomas. Literature on the clinical course and treatment outcomes of PXAs is limited. The study aimed to determine prognosis and treatment strategies for PXAs. Patients who had PXAs surgery between 2000–2021 were retrospectively analyzed for demographics and radiological characteristics. Initial and salvage treatment outcomes were recorded. Overall, 40 and 9 patients had grade 2 and 3 PXAs; their 5-year progression-free survival (PFS) rates were 75.8% and 37.0%, respectively (p = 0.003). Univariate analysis revealed that strong T1 enhancement (p = 0.036), infiltrative tumor margins (p < 0.001), peritumoral edema (p = 0.003), WHO grade (p = 0.005), and gross total resection (p = 0.005) affected the PFS. Multivariate analysis revealed that the WHO grade (p = 0.010) and infiltrative tumor margins (p = 0.008) influenced the PFS. The WHO grade (p = 0.027) and infiltrative tumor margins (p = 0.027) also affected the overall survival (OS). Subgroup analysis for grade 2 PXAs revealed no significant associations between adjuvant radiation therapy and the PFS and OS. This study highlighted the heterogeneous nature of PXAs and its impact on patient prognosis. Infiltrative tumor margins emerged as a key prognostic factor. Our findings have emphasized the prognostic relevance of radiological features and the need for larger studies on comprehensive management. [ABSTRACT FROM AUTHOR]

BackgroundPleomorphic xanthoastrocytoma (PXA) is a rare brain tumor that accounts for

Dabrafenib plus trametinib is a promising new therapy for patients affected by BRAFV600E-mutant glioma, with high overall response and manageable toxicity. We described a complete and long-lasting response in a case of recurrent anaplastic pleomorphic xanthoastrocytoma CNS WHO-grade 3 BRAFV600E mutated. Due to very poor prognosis, there are a few described cases of high-grade glioma (HGG) patients treated with the combined target therapy as third-line treatment. The emergence of optimized sequencing strategies and targeted agents, including multimodal and systemic therapy with dabrafenib plus trametinib, will continue to broaden personalized therapy in HGG improving patient outcomes.

Composite pleomorphic xanthoastrocytoma-ganglioglioma (PXA-GG) is an extremely rare central nervous system neoplasm with 2 distinct but intermingled components. Whether this tumor represents a "collision tumor" of separate neoplasms or a monoclonal neoplasm with divergent evolution is poorly understood. Clinicopathologic studies and capture-based next generation sequencing were performed on extracted DNA from all available PXA-GG at 2 medical centers. Five PXA-GG were diagnosed in 1 male and 4 female patients ranging from 13 to 25 years in age. Four arose within the cerebral hemispheres; 1 presented in the cerebellar vermis. DNA was sufficient for analysis in 4 PXA components and 3 GG components. Four paired PXA and GG components harbored BRAF p.V600E hotspot mutations. The 4 sequenced PXA components demonstrated CDKN2A homozygous deletion by sequencing with loss of p16 (protein product of CDKN2A) expression by immunohistochemistry, which was intact in all assessed GG components. The PXA components also demonstrated more frequent copy number alterations relative to paired GG components. In one PXA-GG, shared chromosomal copy number alterations were identified in both components. Our findings support divergent evolution of the PXA and GG components from a common BRAF p.V600E-mutant precursor lesion, with additional acquisition of CDKN2A homozygous deletion in the PXA component as is typically seen in conventional PXA.

Pleomorphic xanthoastrocytoma (PXA) is a rare low-grade glial neoplasm of the central nervous system accounting for less than 1% of all astrocytomas. Similar to other gliomas, it can rarely arise from glial nests in the meninges, manifesting as an extra-axial mass mimicking a meningioma. Extra axial PXA is an extremely rare entity. Therefore, there are no standardized guidelines. In this article, we report the fourth case, so far, of a solitary primary extra-axial PXA mimicking a meningioma in a 23-year-old woman who presented with temporal seizures and features of raised intracranial pressure. Through this case, we tried to discuss all treatment options. [ABSTRACT FROM AUTHOR]

Background: BRAF V600E mutation is a common genomic alteration in gangliogliomas (GGs) and pleomorphic xanthoastrocytomas (PXAs) with prognostic and therapeutic implications. Purpose: To investigate the ability of magnetic resonance imaging (MRI) features to predict BRAF V600E status in GGs and PXAs and their prognostic values. Material and Methods: A cohort of 44 patients with histologically confirmed GGs and PXAs was reviewed retrospectively. BRAF V600E status was determined by immunohistochemistry (IHC) staining and fluorescence quantitative polymerase chain reaction (PCR). Demographics and MRI characteristics of the two groups were evaluated and compared. Univariate and multivariate Cox regression analyses were performed to identify MRI features that were prognostic for progression-free survival (PFS). Results: T1/FLAIR ratio, enhancing margin, and mean relative apparent diffusion coefficient (rADCmea) value showed significant differences between the BRAF V600E -mutant and BRAF V600E -wild groups (all P < 0.05). Binary logistic regression analysis revealed only rADCmea value was the independent predictive factor for BRAF V600E status (P = 0.027). Univariate Cox regression analysis showed age at diagnosis (P = 0.032), WHO grade (P = 0.020), enhancing margin (P = 0.029), and rADCmea value (P = 0.005) were significant prognostic factors for PFS. In multivariate Cox regression analysis, increasing age (P = 0.040, hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 1.002–1.079) and lower rADCmea values (P = 0.021, HR = 0.036, 95% CI = 0.002–0.602) were associated with poor PFS in GGs and PXAs. Conclusion: Imaging features are potentially predictive of BRAF V600E status in GGs and PXAs. Furthermore, rADCmea value is a valuable prognostic factor for patients with GGs or PXAs. [ABSTRACT FROM AUTHOR]

This article presents a case report of a 68-year-old female patient who was admitted to the emergency department with symptoms of headache, mental confusion, and mild hemiparesis. The patient underwent surgery to remove a right temporal mass lesion, which was found to be a primary diffuse large B-cell lymphoma of the central nervous system (CNS-DLBCL). The article provides detailed information about the imaging findings, histology, and immunohistochemistry of the tumor. It also discusses the differential diagnoses considered for the patient's condition, including glioblastoma, gliosarcoma, metastasis, and pleomorphic xanthoastrocytoma. The article concludes by highlighting the rarity of CNS-DLBCL and its poor prognosis compared to systemic DLBCL. [Extracted from the article]

This study adopts an innovative approach to utilize the DNA methylation class (MC) by prioritizing the understanding of discrepancies over traditional direct comparisons with the pathological diagnosis (PD). The aim is to clarify the morphological criteria for pleomorphic xanthoastrocytoma (PXA). Using the Children's Brain Tumor Network online database, PXA-diagnosed cases were sourced. MCs and CDKN2A/B statuses were ascertained using the Heidelberg methylation brain tumor classifier v12.5 (v12.8 for selected cases). Three distinct groups emerged: Group 1 confirmed PXA through both PD and MC (7 cases); Group 2 identified PXA via PD alone (7 cases); and Group 3 diagnosed PXA using MC (5 cases). Key insights from the study include the frequent local infiltration of PXA into gray matter structures, mirroring infiltrative astrocytoma. The MC for PXA stands out for its sensitivity. Cases with a PXA morphological diagnosis diverging from the DNA methylation class warrant attention to newer differential diagnoses such as high-grade astrocytoma with piloid features, pilocytic astrocytoma NF1-associated, and NET-PATZ1. Tumors with a MC indicative of PXA but lacking its typical features may, if high-grade, behave as grade 4 gliomas. In contrast, their low-grade counterparts could belong to the PXA morphological continuum. Further research is pivotal for cementing these findings. [ABSTRACT FROM AUTHOR]

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome caused by inactivating pathogenic variants in the tumor suppressor gene menin 1 on chromosome 11q13 (Falchetti et al., 2009). The syndrome is characterized by neoplasia in two or more endocrine glands and has a high degree of penetrance. Pathogenic germline multiple neoplasia type 1 variants primarily result in neoplasia affecting the parathyroid glands, the pancreatic islet cells, and the anterior pituitary in combination. Primary hyperparathyroidism is the most common pathological manifestation of the syndrome, followed by pancreatic neuroendocrine tumors. Important genetic confirmation has been provided showing that ependymoma should be considered as a neoplasm that can occur in patients with MEN1 (Kato et al., 1996; Cuevas-Ocampo et al., 2017). The biphasic histopathological tumor entity shown in the present case we name Pleomorphic Xanthoastocytoma grade 3 differential pathology (PDP) in association with Multiple Endocrine Neoplasia type 1. This MEN1 associated tumor subtype is an extension of the findings on MEN1 associated ependymoma, where we show that the clinical phenotype itself may potentially be triggered by a frameshift germline pathogenic variant for the MEN1 gene, in combination with cyclin-dependent kinase inhibitor 1B gene germline variant and cyclin dependent kinase inhibitor 2A somatic deletion downstream of menin.

Pleomorphic xanthoastrocytoma (PXA) poses a diagnostic challenge. The present study relies on methylation-based predictions and focuses on copy number variations (CNV) in PXA. We identified 551 tumors from patients having received the histologic diagnosis or differential diagnosis pleomorphic xanthoastrocytoma (PXA) uploaded to the web page www.molecularneuropathology.org. Of these 551 tumors, 165 received the prediction “methylation class (anaplastic) pleomorphic xanthoastrocytoma” with a calibrated score >=0.9 by the brain tumor classifier version v12.8 and, therefore, were defined the PXA reference set designated mcPXAref. In addition to these 165 mcPXAref, 767 other tumors received the prediction mcPXA with a calibrated score >=0.9 but without a histological PXA diagnosis. The total number of individual tumors predicted by histology and/or by methylome based classification as PXA, mcPXA or both was 1318, and these were designated the study cohort. The selection of a control cohort was guided by methylation-based predictions recurrently observed for the other 386/551 tumors diagnosed as histologic PXA. 131/386 received predictions for another entity besides PXA with a score >=0.9. Control tumors corresponding to the 11 most common other predictions were selected, adding up to 1100 reference cases. CNV profiles were calculated from all methylation datasets of the study and control cohorts. Special attention was given to the 7/10 signature, gene amplifications and homozygous deletion of CDKN2A/B. Comparison of CNV in the subsets of the study cohort and the control cohort were used to establish relations independent of histological diagnoses. Tumors in mcPXA were highly homogenous in regard to CNV alterations, irrespective of the histological diagnoses. The 7/10 signature commonly present in glioblastoma, IDH-wildtype, was present in 15-20% of mcPXA, whereas amplification of oncogenes (likewise common in glioblastoma) was very rare in mcPXA (

Images were taken at 100 × magnification and the scale bars represent 200 µm Differential diagnoses included high-grade gliomas, astrocytoma, oligodendroglioma, diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, diffuse hemispheric glioma, H3 G34-mutant, and some rare neuroectodermal tumors with a diffuse growth pattern. Keywords: Oligodendroglioma; Pleomorphic xanthoastrocytoma; Ganglioglioma; Angiocentric glioma; Polymorphous low-grade neuroepithelial tumor of the young EN Oligodendroglioma Pleomorphic xanthoastrocytoma Ganglioglioma Angiocentric glioma Polymorphous low-grade neuroepithelial tumor of the young 869 876 8 08/28/23 20230901 NES 230901 The authors C. Storz and R. Sankowski contributed equally to the manuscript. Pleomorphic Xanthoastrocytoma Pleomorphic xanthoastrocytomas (PXA) are rare astrocytic tumors, classified as WHO CNS grade II-III tumors, depending on the histological features [[1]]. Dysembryoplastic Neuroepithelial Tumor Dysembryoplastic neuroepithelial tumors (DNET) are slowly growing, well-circumscribed, cortically based tumors, classified as CNS WHO grade I neoplasms [[1], [7]]. [Extracted from the article]

Purpose: Pleomorphic xanthoastrocytoma (PXA) is an uncommon astrocytoma that tends to occur in children and young adults and has a relatively favorable prognosis. The 2021 WHO classification of tumors of the central nervous system (CNS WHO), 5th edition, rates PXAs as grade 2 and grade 3. The histological grading was based on mitotic activity (≥2.5 mitoses/mm2). This study specifically evaluates the clinical, morphological, and, especially, the molecular characteristics of grade 2 and 3 PXAs. Methods: Between 2003 and 2021, we characterized 53 tumors with histologically defined grade 2 PXA (n = 36, 68%) and grade 3 PXA (n = 17, 32%). Results: Compared with grade 2 PXA, grade 3 PXA has a deeper location and no superiority in the temporal lobe and is more likely to be accompanied by peritumoral edema. In histomorphology, epithelioid cells and necrosis were more likely to occur in grade 3 PXA. Molecular analysis found that the TERT promoter mutation was more prevalent in grade 3 PXA than in grade 2 PXA (35% vs. 3%; p = 0.0005) and all mutation sites were C228T. The cases without BRAF V600E mutation or with necrosis in grade 3 PXA had a poor prognosis (p = 0.01). Conclusion: These data define PXA as a heterogeneous astrocytoma. Grade 2 and grade 3 PXAs have different clinical and histological characteristics as well as distinct molecular profiles. TERT promoter mutations may be a significant genetic event associated with anaplastic progression. Necrosis and BRAF V600E mutation play an important role in the prognosis of grade 3 PXA.

Purpose: High grade pleomorphic xanthoastrocytomas (HGPXAs) are very rare and their management and prognostic outcomes remain unclear. To better understand the disease, we aimed to evaluate the risk factors for progressionfree survival (PFS) and overall survival (OS), and propose a treatment protocol based on cases from our institute and cases from the literature. Methods: The authors reviewed the clinical data of 26 patients with HGPXAs who underwent surgical treatment in Department of Neurosurgery of Beijing Tiantan Hospital between August 2014 and September 2021. We also searched the PubMed database using the keywords "anaplastic" combined with "pleomorphic xanthoastrocytoma(s)" between January 1997 and October 2022. Risk factors for PFS and OS were evaluated in the pooled cases. Results: The authors' cohort included 11 males and 15 females with a mean age of 36.7 ± 20.3 years (range: 5.5-71 years). Gross-total resection (GTR) and non-GTR were achieved in 17 (65.4%) and 9 (34.6%) patients, respectively. Radiotherapy and chemotherapy were administered to 22 and 20 patients, respectively. After a mean follow-up of 20.5 ± 21.2 months (range: 0.5-78.1 months), 7 patients suffered tumor recurrence and 6 patients died with a mean OS time of 19.4 ± 10.8 months (range: 8-36 months). In the literature between January 1997 and October 2022, 56 cases of HGPXAs were identified in 29 males and 27 females with a mean age of 29.6 ± 19.6 years (range; 4-74 years). Among them, 24 (44.4%) patients achieved GTR. Radiotherapy and chemotherapy was administered to 31 (62%) patients and 23 (46%) patients, respectively. After a median follow-up of 31.4 ± 35.3 months (range: 0.75-144 months), the mortality and recurrence rates were 32.5% (13/40) and 70% (28/40), respectively. Multivariate Cox regression model demonstrated that non-GTR (HR 0.380, 95% CI 0.174-0.831, p=0.015), age=30 (HR 2.620, 95% CI 1.183-5.804, p=0.018), no RT (HR 0.334,95% CI 0.150-0.744, p=0.007) and no CT (HR 0.422, 95% CI 0.184-0.967, p=0.042) were negative prognostic factors for PFS. Non-GTR (HR 0.126, 95% CI 0.037-0.422, p=0.001), secondary HGPXAs (HR 7.567, 95% CI 2.221-25.781, p=0.001), age=30 (HR 3.568, 95% CI 1.190-10.694, p=0.023) and no RT (HR 0.223,95% CI 0.073-0.681, p=0.008) were risk factors for OS. Conclusion:: High grade pleomorphic xanthoastrocytomas are very rare brain tumors. Children and younger adults have better clinical outcome than elderly patients. Secondary HGPXAs had worse OS than primary HGPXAs. Complete surgical excision plus RT and CT is recommended for this entity. The frequency of BRAF mutations in HGPXAs is 47.5% (19/40) in this study, however, we do not find the connections between BRAF mutations and clinical outcomes. Future studies with larger cohorts are necessary to verify our findings. [ABSTRACT FROM AUTHOR]

Background Molecular brain tumor classification using DNA methylation profiling has revealed that the methylation-class of pleomorphic xanthoastrocytoma (mcPXA) comprised a substantial portion of divergent initial diagnoses, which had been established based on histology alone. This study aimed to characterize the survival outcome in patients with mcPXAs—in light of the diverse selected treatment regimes. Methods A retrospective cohort of adult mcPXAs were analyzed in regard to their progression-free survival following surgical resection and postoperative radiotherapy. Radiotherapy treatment plans were correlated with follow-up images to characterize the pattern of relapse. Treatment toxicities and molecular tumor characteristics were further analyzed. Results Divergent initial histological diagnoses were encountered in 40.7%. There was no significant difference in local progression-free (PFS) and overall survival (OS) following gross total or subtotal resection. Postoperative radiotherapy was completed in 81% (22/27) following surgical intervention. Local PFS was 54.4% (95% CI: 35.3–84.0%) and OS was 81.3% (95% CI: 63.8–100%) after 3 years following postoperative radiotherapy. Initial relapses post-radiotherapy were primarily located in the previous tumor location and/or the planning target volume (PTV) (12/13). All patients in our cohort demonstrated the prognostically favorable pTERT -wildtype mcPXA. Conclusion Our study demonstrated that adult patients with mcPXAs display a worse progression-free survival compared to the reported WHO grade 2 PXAs. Future matched-pair analyses are required with a non-irradiated cohort to elucidate the benefit of postoperative radiotherapy in adult patients with mcPXAs. [ABSTRACT FROM AUTHOR]

Objective: A case of low-grade glioma in which 5-aminolevulinic acid (5-ALA) fluorescence was visualized by a digital exoscope is presented. Case presentation: A 14-year-old girl with recurrent paroxysmal episodes of a strange smell and nausea underwent magnetic resonance imaging (MRI) for further investigation. The MRI showed a tumor with an enhanced nodule in the right temporal lobe. The patient received 5-ALA preoperatively, and intraoperative observation using a 4 K-3-dimension digital exoscope (Olympus ORBEYE) showed that the tumor was fluorescent, which was useful in determining the extent of tumor removal. Postoperative MRI showed that the tumor was completely removed. The histopathological diagnosis was pleomorphic xanthoastrocytoma. She was discharged without any complications. Conclusions: 5-ALA-fluorescence-guided resection of low-grade glioma using the ORBEYE was useful for determining the extent of removal. [ABSTRACT FROM AUTHOR]

Purpose: Pleomorphic xanthoastrocytoma (PXA) is an uncommon astrocytoma that tends to occur in children and young adults and has a relatively favorable prognosis. The 2021 WHO classification of tumors of the central nervous system (CNS WHO), 5th edition, rates PXAs as grade 2 and grade 3. The histological grading was based on mitotic activity (≥2.5 mitoses/mm2). This study specifically evaluates the clinical, morphological, and, especially, the molecular characteristics of grade 2 and 3 PXAs. Methods: Between 2003 and 2021, we characterized 53 tumors with histologically defined grade 2 PXA (n = 36, 68%) and grade 3 PXA (n = 17, 32%). Results: Compared with grade 2 PXA, grade 3 PXA has a deeper location and no superiority in the temporal lobe and is more likely to be accompanied by peritumoral edema. In histomorphology, epithelioid cells and necrosis were more likely to occur in grade 3 PXA. Molecular analysis found that the TERT promoter mutation was more prevalent in grade 3 PXA than in grade 2 PXA (35% vs. 3%; p = 0.0005) and all mutation sites were C228T. The cases without BRAF V600E mutation or with necrosis in grade 3 PXA had a poor prognosis (p = 0.01). Conclusion: These data define PXA as a heterogeneous astrocytoma. Grade 2 and grade 3 PXAs have different clinical and histological characteristics as well as distinct molecular profiles. TERT promoter mutations may be a significant genetic event associated with anaplastic progression. Necrosis and BRAF V600E mutation play an important role in the prognosis of grade 3 PXA. [ABSTRACT FROM AUTHOR]

This study adopts an innovative approach to utilize the DNA methylation class (MC) by prioritizing the understanding of discrepancies over traditional direct comparisons with the pathological diagnosis (PD). The aim is to clarify the morphological criteria for pleomorphic xanthoastrocytoma (PXA). Using the Children’s Brain Tumor Network online database, PXA-diagnosed cases were sourced. MCs and CDKN2A/B statuses were ascertained using the Heidelberg methylation brain tumor classifier v12.5 (v12.8 for selected cases). Three distinct groups emerged: Group 1 confirmed PXA through both PD and MC (7 cases); Group 2 identified PXA via PD alone (7 cases); and Group 3 diagnosed PXA using MC (5 cases). Key insights from the study include the frequent local infiltration of PXA into gray matter structures, mirroring infiltrative astrocytoma. The MC for PXA stands out for its sensitivity. Cases with a PXA morphological diagnosis diverging from the DNA class warrant attention to newer differential diagnoses such as high-grade astrocytoma with piloid features, pilocytic astrocytoma NF1-associated, and NET-PATZ1. Tumors with a MC indicative of PXA but lacking its typical features may, if high-grade, behave as grade 4 gliomas. In contrast, their low-grade counterparts could belong to the PXA morphological continuum. Further research is pivotal for cementing these findings.

Pleomorphic xanthoastrocytoma (PXA) is a rare tumor ranging from World Health Organization (WHO) grades 2–3 and can potentially recur and metastasize throughout the central nervous system (CNS). Cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion is a frequent genomic alteration of PXA. Methylthioadenosine phosphorylase (MTAP) immunohistochemistry is a promising surrogate marker for CDKN2A homozygous deletion in different cancers but has not been examined in PXA. Therefore, we performed CDKN2A fluorescence in situ hybridization and MTAP immunohistochemistry on specimens from 23 patients with CNS WHO grades 2 (n = 10) and 3 (n = 13) PXAs, including specimens from primary and recurrent tumors, and determined whether MTAP immunohistochemistry correlated with CDKN2A homozygous deletion and clinicopathological features. CDKN2A homozygous deletion was detected in 30% (3/10) and 76.9% (10/13) of CNS WHO grades 2 and 3 PXAs, respectively. In addition, MTAP loss was inconsistent with CDKN2A homozygous deletion (sensitivity = 86.7%, specificity = 100%). Furthermore, CDKN2A homozygous deletion was correlated with WHO grade (p = 0.026) and the Ki-67 labeling index (p = 0.037). Therefore, MTAP immunostaining can be a suitable surrogate marker for CDKN2A homozygous deletions in PXAs, and CDKN2A homozygous deletions may be an important prognostic factor for PXAs. [ABSTRACT FROM AUTHOR]

Neuro-oncology encompasses a broad field focusing on an array of neoplasms, many of which can mimic several diseases. Neurologists will often be involved in the initial diagnostic evaluation and management of these patients. Their insight is central to optimizing the diagnostic yield and providing high-level clinical care. Several neuro-oncologic cases are reviewed with a goal of increasing the understanding of these diseases in a clinically relevant manner and providing updates on the contemporary thinking in the subspecialty. [ABSTRACT FROM AUTHOR]

Aims: Pleomorphic xanthoastrocytoma (PXA) is a rare circumscribed glioma, characterized by frequent BRAF p. V600E mutation, and classified as grade 2 or 3. Owing to overlapping clinical–pathological features, the histological distinction from glioblastoma (GBM) with giant cells (GCs) is challenging. Based on the high frequency of TP53 and RB1 alterations in the latter, this study aimed to assess the value of BRAF, p53, and pRB immunostainings in the differential diagnosis. Methods and results: In 37 GBMs with ≥30% GCs and in eight PXAs, we assessed the alterations of 409 cancer-related genes and immunostainings for BRAF, p53, and pRB. GBMs with GCs were TP53- mutated in 30 cases, RB1-altered in 11, and BRAFmutated in none. PXAs were BRAF-mutated in six cases, TP53-mutated in three, and RB1-altered in none. pRb immunostaining was lost in 25 GBMs (11 RB1-altered and 14 RB1-unaltered), retained in all PXAs and six GBMs, and inconclusive in six GBMs. pRb loss had 100% specificity and 80.6% sensitivity for GBM with GCs. P53 immunostaining was observed in 22 TP53-mutated GBMs and in one TP53-mutated PXA. It showed 87.5% specificity and 60% sensitivity to identify GBM with GCs. BRAF immunostaining corresponded to BRAF mutation status and it had 100% specificity and 75% sensitivity for detecting PXA. Conclusion: This study shows for the first time that loss of pRB immunostaining is sensitive and specific for distinguishing GBM with GCs from PXA in routine practice. Thus, it could complement an immunohistochemical panel that includes BRAF and p53 immunostainings for the differential diagnosis. [ABSTRACT FROM AUTHOR]

The newest revision of the WHO classification of tumors of the central nervous system, also known as WHO 5th edition, introduces substantial changes, especially within the glial tumor category and separates adult-type and pediatric-type glial tumors into different categories for the first time. In addition, another category of glial tumors, “Circumscribed Astrocytic Gliomas” were also created. This group includes pilocytic astrocytoma, pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma, chordoid glioma, astroblastoma, and the highly nebulous novel entity high-grade astrocytoma with piloid features. We present a brief and critical review of the pathological and molecular characteristics of these often well-demarcated tumors that can occur in adults as well as in the pediatric population.

Abstract Pleomorphic xanthoastrocytoma (PXA) in its classic manifestation exhibits distinct morphological features and is assigned to CNS WHO grade 2 or grade 3. Distinction from glioblastoma variants and lower grade glial and glioneuronal tumors is a common diagnostic challenge. We compared a morphologically defined set of PXA (histPXA) with an independent set, defined by DNA methylation analysis (mcPXA). HistPXA encompassed 144 tumors all subjected to DNA methylation array analysis. Sixty-two histPXA matched to the methylation class mcPXA. These were combined with the cases that showed the mcPXA signature but had received a histopathological diagnosis other than PXA. This cohort constituted a set of 220 mcPXA. Molecular and clinical parameters were analyzed in these groups. Morphological parameters were analyzed in a subset of tumors with FFPE tissue available. HistPXA revealed considerable heterogeneity in regard to methylation classes, with methylation classes glioblastoma and ganglioglioma being the most frequent mismatches. Similarly, the mcPXA cohort contained tumors of diverse histological diagnoses, with glioblastoma constituting the most frequent mismatch. Subsequent analyses demonstrated the presence of canonical pTERT mutations to be associated with unfavorable prognosis among mcPXA. Based on these data, we consider the tumor type PXA to be histologically more varied than previously assumed. Histological approach to diagnosis will predominantly identify cases with the established archetypical morphology. DNA methylation analysis includes additional tumors in the tumor class PXA that share similar DNA methylation profile but lack the typical morphology of a PXA. DNA methylation analysis also assist in separating other tumor types with morphologic overlap to PXA. Our data suggest the presence of canonical pTERT mutations as a robust indicator for poor prognosis in methylation class PXA.

Epithelioid glioblastoma (eGBM) is a newly defined and rare GBM variant in the current WHO 2016 classification. BRAF V600E mutation is overrepresented in these tumors and there is known some morphological overlap with anaplastic epithelioid PXA (ePXA). In order to further elucidate this diagnostic category, we molecularly characterized 64 pediatric and adult examples initially diagnosed as "eGBM." Tumors were analyzed using array based methylation and direct sequencing of the BRAF and TERT genes. Our results demonstrated considerable molecular and clinical heterogeneity among eGBM cohort. Methylation patterns, copy number alterations, and mutational analysis data, in combination with clinical findings disclosed three different, well established tumor subtypes: (i) PXA-like tumors with favorable prognosis, predominantly in children and young adults (38), (ii) IDHwt GBM-like tumors with poor prognosis, mainly occurring in older adults, albeit with more frequent BRAF mutations (17), and (iii) RTK1 pediatric GBM-like neoplasms of intermediate prognosis in children and young adults, associated with chromothripsis and frequent PDGFRA amplifications (9). We conclude that the histopathologically defined eGBM do not represent a single diagnostic entity, but rather at least three molecularly and biologically distinct categories. Therefore, additional molecular testing through genome-wide molecular profiling is recommended to further stratify these rare cases.

Pleomorphic xanthoastrocytoma (PXA) is a low-grade glioma comprising 1% of all astrocytomas with an extremely rare anaplastic counterpart usually found in young adults. These tumors are most often cerebral in origin and their presentation in the elderly signifies poor prognosis. As these tumors are an important differential of glioblastoma, diagnosing them accurately is essential for management. We present a 68-year-male with positive cerebellar signs and clinico-radiological impression of cerebellar metastatic deposits, subsequently diagnosed as cerebellar PXA with anaplastic features. The case in discussion is unique in its age, site, and grade of presentation, with key histological features rebuking the clinical and radiological diagnosis of metastasis. The rarity and ambiguous management protocol of these tumors make their documentation an important addition to the existing literature with emphasis on possibility of late presentation and at sites other than the cerebrum. [ABSTRACT FROM AUTHOR]

Background: Pleomorphic xanthoastrocytoma (PXA) is a rare low-grade brain tumor. To date, limited studies have analyzed factors affecting survival outcomes and defined the therapeutic strategy. The aim of this retrospective analysis was to investigate the clinicopathologic characteristics of PXA and identify factors associated with outcomes. Methods: We retrospectively analyzed a cohort of 16 adult and children patients with PXA who underwent primary resection from 1997 to 2019, referred to our Radiation Oncology Unit and to Meyer's Paediatric Hospital. We also reviewed the relevant literature. Results: All patients underwent primary surgical resection; 10 patients received adjuvant radiation treatment course, ranging from DTF 54 to 64 Gy; 8 of them received, in addition, concurrent adjuvant chemotherapy; 6 patients underwent only radiological follow-up. After a median follow up was 60 months: median OS was 34.9 months (95% CI 30–218), 1-year OS 87%, 5-years OS 50%, 10-years OS 50%; median PFS 24.4 months (95% CI 13–156), 1-year PFS 80%, 5-years PFS 33%, 10-years PFS 33%. A chi-square test showed a significant association between OS and recurrent disease (p = 0.002) and with chemotherapy adjuvant treatment (p = 0.049). A borderline statistical significant association was instead recognized with BRAF mutation (p = 0.058). Conclusions: Despite our analysis did not reveal a strong prognostic or predictive factor able to address pleomorphic xanthoastrocytoma management; however, in selected patients could be considered the addition of adjuvant radiation chemotherapy treatment after adequate neurosurgical primary resection. Furthermore, recurrent disease evidenced a detrimental impact on survival. [ABSTRACT FROM AUTHOR]

Here we present a challenging case originally diagnosed as giant cell glioblastoma WHO grade 4 in a 48-year-old lady with a background of Li-Fraumeni syndrome. After an initial excision and neoadjuvant chemoradiotherapy the patient had a 5 year disease-free period before having a recurrence. The recurrent tumour alongside the original tumour were reviewed. By reviewing the clinical history and disease progression and combining this with improved genetic testing methodologies a reviewed diagnosis of anaplastic pleomorphic xanthoastrocytoma (PXA) WHO Grade 3 was made. This case highlights how many factors can affect a diagnosis and how the clinical course may require for diagnoses to be reviewed and refined. [ABSTRACT FROM AUTHOR]

The prevalence of BRAFV600E mutations in pleomorphic xanthoastrocytoma (PXA) World Health Organization (WHO) Grade 2 and PXA WHO Grade 3 reported varies from 60% to 80%, yet the prognostic implications remain unclear. We reviewed the demographic and clinicoradiologic data of 20 PXAs WHO Grade 2 and 13 PXAs WHO Grade 3, operated between 2007 and 2020, to ascertain extent of excision, recurrence, progression-free survival (PFS), and overall survival (OS). PXAs WHO Grade 3 were defined by the presence of >5 mitoses/high-power field. PXAs WHO Grade 3 received adjuvant radiation therapy and chemotherapy whereas PXAs received radiation therapy if subtotally excised. All samples were analyzed for the presence of BRAFV600E mutation using DNA obtained from paraffin blocks using droplet-digital polymerase chain reaction. The median patient age at diagnosis was 22 years with a male preponderance. BRAFV600E mutations were noted in 30% of tumors; 8 PXAs WHO Grade 2 and 2 PXAs WHO Grade 3. Recurrence occurred in 6 of 13 PXA WHO Grade 3 (55%) and 1 of 20 PXAs WHO Grade 2 (5%). At median follow-up of 45 months, the OS was 54 months and 33 months in the PXA WHO Grade 2 and PXA WHO Grade 3 groups, respectively (P = 0.02). OS and PFS did not differ between BRAF-mutated and BRAF-negative tumors. BRAFV600E mutations are less frequent in our population than reported in the literature. The BRAF mutation does not significantly impact OS and PFS. PXAs WHO Grade 3 are a distinct clinical entity, associated with worse PFS and OS than PXAs WHO Grade 2. [ABSTRACT FROM AUTHOR]

Gliosarcoma is characterized by the presence of alternating lesions of glial and mesenchymal components. Although many mesenchymal components have been reported, there are few reports on glial components. We here report two cases of gliosarcoma. Case 1 was a 42‐year‐old woman with right hemiparesis and motor aphasia. Magnetic resonance imaging (MRI) identified a tumor in the left frontal lobe. Pathological analysis of the tumor removal specimen revealed gliosarcoma, with a glial component resembling pleomorphic xanthoastrocytoma. Postoperatively, radiotherapy and chemotherapy were conducted, and the patient was symptom‐free over 12 months after surgery. Case 2 was a 67‐year‐old woman with a consciousness disorder and left hemiparesis. MRI revealed a tumor in the right frontal lobe. Pathological analysis of the first tumor removal specimen identified gliosarcoma, with a glial component characterized by large tumor cells. Additionally, the Ki‐67 labeling index of the glial component was greater than that of the mesenchymal component, and molecular genetic analysis disclosed a mutation in the telomerase reverse transcriptase (TERT) gene (TERT). Chemotherapy and radiotherapy were performed. Four months later, MRI revealed recurrence, and the second surgery was performed. Pathological analysis revealed giant cell glioblastoma without TERT mutation. The patient died due to tumor progression 12 months after the first surgery. It is essential to continue histopathological evaluation of glial components, and further genetic evaluation on gliosarcoma is required. [ABSTRACT FROM AUTHOR]

Introduction and Importance: Pleomorphic xanthoastrocytoma (PXA) was first described by Kepes et al. in 1979. Fewer than 200 cases have been reported in the literature. It generally involves the temporoparietal lobe. PXA has a favorable prognosis. The most reported clinical manifestation is epileptic seizures. Revealing psychiatric symptoms have an incidence varying from 50 to 78%. The most common symptoms encountered are anxiety disorders, depression, schizophrenia-like psychosis, cognitive dysfunction or even anorexia nervosa., Case Presentation: Here, the authors report a new case of non-anaplastic pleomorphic xanthoastrocytoma revealed by a drug-resistant schizophrenia-like psychosis in a 26-year-old male patient known with epileptic seizures in whom these two pathologies were intertwined and had been evolving for 5 years. The postoperative course was uneventful, and positive symptoms of schizophrenia were relatively stabilized at discharge., Clinical Discussion: Given the superficial hemispheric location of PXA, the most common clinical presentation is seizures. Psychiatric symptoms revealing brain tumors have an incidence varying from 50 to 78%. Most of these symptoms concern frontal and limbal tumors. In their case, the tumor was located in the right temporal lobe. Surgery was performed and postoperative course was uneventful even though there are conflicting reports regarding the importance of the surgical excision quality., Conclusion: PXA remains a rare and benign primary CNS tumor. Psychiatric disorders represent a rare revealing mode of this pathology, which must lead to neuroimaging in any patient carrying this type of symptoms., Competing Interests: The authors declared no potential conflicts of interests with respect to research, authorship and/or publication of the article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)