Pleomorphic Xanthoastrocytoma Research Articles

Molecular Testing of Brain Tumor.

The World Health Organization (WHO) classification of central nervous system (CNS) tumors was revised in 2016 with a basis on the integrated diagnosis of molecular genetics. We herein provide the guidelines for using molecular genetic tests in routine pathological practice for an accurate diagnosis and appropriate management. While astrocytomas and IDH-mutant (secondary) glioblastomas are characterized by the mutational status of IDH, TP53, and ATRX, oligodendrogliomas have a 1p/19q codeletion and mutations in IDH, CIC, FUBP1, and the promoter region of telomerase reverse transcriptase (TERTp). IDH-wildtype (primary) glioblastomas typically lack mutations in IDH, but are characterized by copy number variations of EGFR, PTEN, CDKN2A/B, PDGFRA, and NF1 as well as mutations of TERTp. High-grade pediatric gliomas differ from those of adult gliomas, consisting of mutations in H3F3A, ATRX, and DAXX, but not in IDH genes. In contrast, well-circumscribed low-grade neuroepithelial tumors in children, such as pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and ganglioglioma, often have mutations or activating rearrangements in the BRAF, FGFR1, and MYB genes. Other CNS tumors, such as ependymomas, neuronal and glioneuronal tumors, embryonal tumors, meningothelial, and other mesenchymal tumors have important genetic alterations, many of which are diagnostic, prognostic, and predictive markers and therapeutic targets. Therefore, the neuropathological evaluation of brain tumors is increasingly dependent on molecular genetic tests for proper classification, prediction of biological behavior and patient management. Identifying these gene abnormalities requires cost-effective and high-throughput testing, such as next-generation sequencing. Overall, this paper reviews the global guidelines and diagnostic algorithms for molecular genetic testing of brain tumors.

Recurrent copy number alterations in low-grade and anaplastic pleomorphic xanthoastrocytoma with and without BRAF V600E mutation.

Pleomorphic xanthoastrocytoma (PXA) is a rare localized glioma characterized by frequent BRAF V600E mutation and CDKN2A/B deletion. We explored the association of copy-number variants (CNVs) with BRAF mutations, tumor grade, and patient survival in a cohort of 41 PXA patients using OncoScan chromosomal microarray. Primary resection specimens were available in 38 cases, including 24 PXA and 14 anaplastic PXA (A-PXA), 23 BRAF V600E mutant tumors (61%). CNVs were identified in all cases and most frequently involved chromosome 9 with homozygous CDKN2A/B deletion (n = 33, 87%), a higher proportion than previously detected by comparative genomic hybridization (50%-60%) (37). CDKN2A/B deletion was present in similar proportion of PXA (83%), A-PXA (93%), BRAF V600E (87%), and wild-type (87%) tumors. Whole chromosome gains/losses were frequent, including gains +7 (n = 15), +2 (n = 11), +5 (n = 10), +21 (n = 10), +20 (n = 9), +12 (n = 8), +15 (n = 8), and losses -22 (n = 11), -14 (n = 7), -13 (n = 5). Losses and copy-neutral loss of heterozygosity were significantly more common in A-PXA, involving chromosomes 22 (P = 0.009) and 14 (P = 0.03). Amplification of 8p and 12q was identified in a single tumor. Histologic grade was a robust predictor of overall survival (P = 0.003), while other copy-number changes, including CDKN2A/B deletion, did not show significant association with survival. Distinct histologic patterns of anaplasia included increased mitotic activity in an otherwise classic PXA or associated with small cell, fibrillary, or epithelioid morphology, with loss of SMARCB1 expression in one case. In 10 cases, matched specimens were compared, including A-PXA with areas of distinct low- and high-grade morphology (n = 2), matched primary/tumor recurrence (n = 7), or both (n = 1). Copy-number changes on recurrence/anaplastic transformation were complex and highly variable, from nearly identical profiles to numerous copy-number changes. Overall, we confirm CDKN2A/B deletion as key a feature of PXA not associated with tumor grade or BRAF mutation, but central to the underlying genetics of PXA.

P10.10 Pleomorphic xanthoastrocytoma without a tumor mass lesion influences intracranial hemorrhage: case report

P10.10 Pleomorphic xanthoastrocytoma without a tumor mass lesion influences intracranial hemorrhage: case report

Mixed pleomorphic xanthoastrocytoma and ganglioglioma with existence of BRAF V600E mutation

Objective To investigate the clinicopathological and molecular genetic features of one case of mixed pleomorphic xanthoastrocytoma (PXA) and ganglioglioma (GG) with BRAF V600E mutation. Methods and Results A 14-year-old boy mainly presented paroxymal loss of consciousness and tic of limbs for 6 years. Head MRI displayed circular abnormal signal on the hippocampus of left temporal lobe, considering space-occupying lesion. The patient underwent operation, and the lesion was totally removed. Pink gyri in deep temporal lobe could be seen during the operation. The tumor tissue was red grey, tough, nonencapsulated, with calcification, cystic degeneration, rich blood supply and clear boundary. Morphology showed the tumor grew diffusely and was heterogeneous: some areas showed the structure of GG and others showed the structure of PXA. Immunohistochemical staining and special staining showed in the region of GG, the tumor was scatteredly positive for glial fibrillary acidic protein (GFAP) and neurofilament protein (NF), gangliocyte-like cells were positive for microtubule associated protein-2 (MAP-2) and neuronal nuclei (NeuN), Ki-67 labeling index was 2%; in the region of PXA, spindle tumor cells were scatteredly positive for GFAP and NF, xanthomatoid cells were positive for CD163 and CD68, Ki-67 labeling index was 3%-5%, reticular fibers were abundant. Molecular detection showed that BRAF V600E mutation existed in both parts of the tumor. The patient was not treated by postoperative radiotherapy or chemotherapy. He took antiepileptic drugs (AEDs) orally [sodium valproate 1.20 g (twice a day) and levetiracetam 0.50 g (twice a day)] for one year, and the symptoms were greatly improved. He had no evidence of tumor recurrence in the 18-month follow-up period. Conclusions Combined PXA and GG is a rare tumor of the central nervous system (CNS). The tumor showed different morphological features of PXA and GG, but with the same BRAF V600E mutation molecular characteristics. This case may support the study on morphology, histological origin and molecular genetics for PXA and GG. DOI: 10.3969/j.issn.1672-6731.2017.03.008

Thyroid transcription factor-1 distinguishes subependymal giant cell astrocytoma from its mimics and supports its cell origin from the progenitor cells in the medial ganglionic eminence

Subependymal giant cell astrocytoma is a benign brain tumor mostly associated with tuberous sclerosis complex. However, it may be misinterpreted as other high-grade brain tumors due to the presence of large tumor cells with conspicuous pleomorphism and occasional atypical features, such as tumor necrosis and endothelial proliferation. In this study, we first investigated thyroid transcription factor-1 (TTF-1) expression in a large series of subependymal giant cell astrocytomas and other histologic and locational mimics to validate the diagnostic utility of this marker. We then examined TTF-1 expression in non-neoplastic brain tissue to determine the cell origin of subependymal giant cell astrocytoma. Twenty-four subependymal giant cell astrocytoma specimens were subjected to tissue microarray construction. For comparison, a selection of tumors, including histologic mimics (21 gemistocytic astrocytomas and 24 gangliogliomas), tumors predominantly occurring at the ventricular system (50 ependymomas, 19 neurocytomas, and 7 subependymomas), and 134 astrocytomas (3 pleomorphic xanthoastrocytomas, 45 diffuse astrocytomas, 46 anaplastic astrocytomas, and 40 glioblastomas) were used. Immunohistochemical stain for TTF-1 was positive in all 24 subependymal giant cell astrocytomas, whereas negative in all astrocytomas, gangliogliomas, ependymomas, and subependymomas. Neurocytomas were positive for TTF-1 in 4/19 (21%) of cases using clone 8G7G3/1 and in 9/19 (47%) of cases using clone SPT24. In the three fetal brains that we examined, TTF-1 expression was seen in the medial ganglionic eminence, a transient fetal structure between the caudate nucleus and the thalami. There was no BRAFV600E mutation identified by direct sequencing in the 20 subependymal giant cell astrocytomas that we studied. In conclusion, TTF-1 is a useful marker in distinguishing subependymal giant cell astrocytoma from its mimics. Expression of TTF-1 in the fetal medial ganglionic eminence indicates that subependymal giant cell astrocytoma may originate from the progenitor cells in this region.

Commentary: Susceptibility Sensitive Magnetic Resonance Imaging Displays Pallidofugal and Striatonigral Fiber Tracts.

Abstract BACKGROUND: Patients with pleomorphic xanthoastrocytoma (PXA) routinely undergo multiple procedures to ensure recurrence-free survival and are resultantly at increased risk of experiencing perioperative complications (regional, medical, and/or neurological), a combination of which has not been recorded in previous studies. OBJECTIVE: To determine perioperative outcomes in a cohort of patients (adult and pediatric) with intracranial PXA. METHODS: We retrospectively identified 39 patients who underwent surgery at our institution for intracranial PXA between 1994 and 2011. Demographic factors were recorded along with Karnofsky Performance Status (KPS), complications, and mortality. RESULTS: Mean patient age was 31 years at the most recent surgery. A majority of patients (24; 62%) had multiple surgeries with a mean of 2 operations per patient. Eleven PXAs (28%) were malignant (grade III or IV). Perioperative complications included permanent neurological worsening in 4 patients (10%), regional complications in 4 (10%), and medical complications in 3 (8%). Preoperative KPS was ≥70 in 34 of 38 patients (89%). Long-term postoperative KPS was ≥70 in 36 of 37 patients (97%), suggesting good functional outcomes. There was no perioperative mortality, but 7 patients (18%) died of tumor progression. Patients with malignant PXAs trended toward higher risk of regional complications (3 of 11 patients [27%]; P = .06), received adjuvant therapy more often (10 of 11 patients [91%]; P < .001), had higher mortality from tumor progression (7 of 11 patients [64%]; P < .001), and were significantly larger (mean, 6.05 ± 0.73 cm standard error of the mean; n = 7; P < .01). CONCLUSION: Both pediatric and adult PXAs may be resected with good functional outcomes. Perioperative neurological complications are relatively common, but do not affect long-term functional outcome or mortality. Malignant PXAs are higher risk for perioperative complications and, ultimately, death from tumor progression, despite increased use of adjuvant radiation and chemotherapy.

Malignant Transformation of Cerebellar Pleomorphic Xanthoastrocytoma: A Case Report

Pleomorphic xanthoastrocytoma (PXA) generally occurs in children and young adults and is classified as a low-grade astrocytic tumor with a potential favorable prognosis. But these data must be interpreted with much caution, because of some rapid progression or malignant transformation during the postoperative follow-up. We report herein a rare case of a cerebellar PXA manifested as a benign lesion at first time in a 39 year-old woman, but with malignant transformation two years later. In this paper, we discuss the clinical signs, radiological findings and the therapeutic data on the subject according to literature review.

Prophylactic CNS Therapy (with or without Radiation Therapy) in Medium-High Risk Acute Lymphoblastic Leukemia (ALL) Children: Long-Term Outcome Evaluation of the Randomized BFM-Oriented Trial 58832 (period 1983-1989) of the EORTC Children Leukemia Group

BackgroundCranial radiotherapy (CRT) is associated with early and late side effects. Intrathecal (IT) and systemic chemotherapy could successfully replace CRT in most protocols for standard risk ALL. However, in medium and high risk ALL patients (pts) its omission is still debatable.AimWe investigated the long-term outcome, the occurrence of second malignant neoplasms (SMN) and the incidence of late toxicities in pts randomized for receiving or not CRT in the EORTC 58832 study.MethodsFrom 1983 to 1989, ALL children under 18 years (yrs) were included in EORTC Children Leukemia Group BFM-oriented studies, either 58831, for standard risk pts (Riehm-Langerman Risk Factor (RF) < 1.2), or 58832, for medium risk (RF 1.2-1.69) and high risk pts (RF ≥1.7). Pts with central nervous system (CNS) involvement at diagnosis were ineligible.The present report focusses on pts included in the 58832 trial (randomized for receiving or not prophylactic CRT).Prophylactic CNS therapy consisted of 4 high-dose methotrexate (HD-MTX) injections (2500 mg/m2) during consolidation and 7 IT MTX injections scheduled during the treatment period.Pts still in complete remission (CR) after the end of late intensification were randomized for receiving prophylactic CRT (standard arm) or not (experimental arm) before the start of continuation therapy. Dose of CRT was age dependent: 24 Gy (> 2 yrs), 20 Gy (1-2 yrs) and 16 Gy (< 1 yr).Endpoints were: disease-free survival (DFS) (event: relapse, death in CR), incidence of SMN, event-free survival (EFS) (event: relapse, death in CR, SMN), incidence of late toxicities, and overall survival (OS) from randomization.Results788 pts were included in the 58831/58832 study. Among them, 189 were randomized in the 58832 study to receive CRT (n=93) or No CRT (n=96). A total of 6 pts did not meet eligibility criteria, 2 had an early relapse, 3 had an early protocol violation and 2 refused allocated treatment. Finally, 176 randomized pts were included in the analyses: 84 in the CRT group and 92 in the No CRT group.The median follow-up was 20 yrs (range 4-32 yrs). Omission of CRT did not increase the 25-yr incidence of isolated CNS relapse, any CNS relapse or non-CNS relapse (4.8 vs 6.5; 11.9 vs 8.7 and 16.7 vs 21.8 in the CRT vs No CRT arms, respectively). No relapses occurred after 10 yrs. The 25-yr DFS rates were similar in both arms: 70.2% with CRT and 67.4% without CRT; No CRT vs CRT hazard ratio (HR)=1.08, 95% CI (0.63, 1.83).CRT was associated with an increase of the 25-yr SMN incidence: 13.2% with CRT and 3.9% without CRT. In the CRT arm, 9 pts (10.7%) developed SMN: 2 acute myeloid leukemias (AML), 1 non-Hodgkin lymphoma, 1 thyroid carcinoma, 4 meningiomas and 1 malignant histiocytosis. One SMN (meningioma) occurred after a CNS combined relapse. Three pts developed second SMN (meningiomas): 1 after an AML and 2 after a first meningioma. In the No CRT arm, 3 pts (3.3%) had SMN: 1 pleomorphic xanthoastrocytoma, 1 melanoma and 1 adenocarcinoma of the ileum. One SMN occurred after a bone marrow (BM) relapse.The 25-yr EFS rates were similar in both arms: 60.3% with CRT and 63.2% without CRT, HR=0.90, 95% CI (0.55, 1.46).CRT was also associated with an increase of late CNS and endocrine toxicities. Five pts (19.2% of the pts with available data) developed leukoencephalopathy in the CRT arm, versus 2 pts (8.7%) in the No CRT arm. Noteworthy, 1 of those 2 pts received CRT for a BM relapse, while the other received total body irradiation for a CNS relapse. Stroke was observed in 2 pts (7.7%) who received CRT. In contrast, there was no clear increase of the incidence of cognitive disturbance after CRT: 33.3% in the CRT arm vs 25.0% in the No CRT arm. Regarding endocrine toxicities, GH deficiency, hypothyroidism and precocious puberty were more frequent in the CRT arm: 53.1% vs 29.6%, 27.8% vs 0% and 29.4% vs 0%, respectively.Finally, the 25-yr OS rates were similar in both arms: 78.5% with CRT and 78.1% without CRT, HR=1.00, 95% CI (0.53, 1.88).ConclusionIn medium and high risk pts without CNS involvement at diagnosis and treated with HD-MTX in the EORTC trial 58832 (1983-1989), omission of CRT did not increase the risk of CNS or non-CNS relapse. On long-term evaluation, CRT was associated with a higher incidence of SMN, late CNS and endocrine toxicities. These long-term results indicate that prophylactic CRT can be safely omitted in childhood medium and high risk ALL pts receiving IT and systemic chemotherapy (including HD-MTX) as CNS prophylaxis. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Targeted next-generation sequencing of pediatric neuro-oncology patients improves diagnosis, identifies pathogenic germline mutations, and directs targeted therapy.

Molecular profiling is revolutionizing cancer diagnostics and leading to personalized therapeutic approaches. Herein we describe our clinical experience performing targeted sequencing for 31 pediatric neuro-oncology patients. We sequenced 510 cancer-associated genes from tumor and peripheral blood to identify germline and somatic mutations, structural variants, and copy number changes. Genomic profiling was performed on 31 patients with tumors including 11 high-grade gliomas, 8 medulloblastomas, 6 low-grade gliomas, 1 embryonal tumor with multilayered rosettes, 1 pineoblastoma, 1 uveal ganglioneuroma, 1 choroid plexus carcinoma, 1 chordoma, and 1 high-grade neuroepithelial tumor. In 25 cases (81%), results impacted patient management by: (i) clarifying diagnosis, (ii) identifying pathogenic germline mutations, or (iii) detecting potentially targetable alterations. The pathologic diagnosis was amended after genomic profiling for 6 patients (19%), including a high-grade glioma to pilocytic astrocytoma, medulloblastoma to pineoblastoma, ependymoma to high-grade glioma, and medulloblastoma to CNS high-grade neuroepithelial tumor with BCOR alteration. Multiple patients had pathogenic germline mutations, many of which were previously unsuspected. Potentially targetable alterations were identified in 19 patients (61%). Additionally, novel likely pathogenic alterations were identified in 3 cases: an in-frame RAF1 fusion in a BRAF wild-type pleomorphic xanthoastrocytoma, an inactivating ASXL1 mutation in a histone H3 wild-type diffuse pontine glioma, and an in-frame deletion within exon 2 of MAP2K1 in a low-grade astrocytic neoplasm. Our experience demonstrates the significant impact of molecular profiling on diagnosis and treatment of pediatric brain tumors and confirms its feasibility for use at the time of diagnosis or recurrence.

MPTH-40. COPY NUMBER ALTERATIONS IN PLEOMORPHIC XANTHOASTROCYTOMA AND ANAPLASTIC PLEOMORPHIC XANTHOASTROCYTOMA: CHARACTERIZATION OF 40 CASES BY SNP ARRAY

Pleomorphic xanthoastrocytoma (PXA), a rare localized brain tumor morphologically and genetically distinct from infiltrating astrocytoma, shows frequent BRAF V600E mutation, frequent loss of CDKN2A/B and lacks IDH1/2 mutation. To further characterize its underlying genetic alterations, we performed OncoScan SNP array in 40 PXAs: 26 PXA (WHO grade II) and 14 anaplastic (A-PXA) (WHO grade III). BRAF V600E mutation was present in 24 (60%) cases: 17 PXA (65%) and 7 A-PXA (50%). Homozygous CDKN2A/B deletion, the most frequent alteration (n=34,85%) together with other chromosome 9 alterations [including copy neutral loss of heterozygosity (cnLOH), loss, and gain], was present in an equal proportion of PXA (81%) and A-PXA (92%) and of BRAF V600E mutant (83%) and wildtype (88%) tumors. In 5 PXAs, chromosome 9 alterations were present in isolation. Whole chromosome gains/losses were frequent, including gains +7 (n=13), +5 (9), +20 (8), +21 (8), +2 (8), +12 (7), +15 (6) and losses -22 (14), -14 (8), -13 (6). Losses were significantly more common in A-PXA, including -22 (p=0.001), -14 (p=0.015), and -13 (p<0.001). Whole chromosome/whole arm cnLOH was identified in 14 cases, most commonly involving chromosome 9 (n=8). High level 8p and 12q amplification was identified in a single tumor. Five matched PXA and recurrent A-PXA were compared. Upon anaplastic transformation, two tumors demonstrated nearly identical copy number alterations (CNAs), two cases showed additional complex CNAs, and one case showed additional loss of -18q and partial -11q. Distinct areas of low- and high-grade morphology were analyzed in two tumors; one showed identical CNAs and one numerous additional complex CNAs. Overall, CDKN2A/B homozygous deletion is identified in the vast majority of PXA regardless of grade and BRAF mutation status and persists on recurrence/anaplastic transformation. The presence of BRAF mutation and CDKN2A/B loss may help to differentiate A-PXA from glioblastoma in morphologically challenging cases.

RARE-54. FIRST CASE OF PLEOMORPHIC XANTHOASTROCYTOMA OF THE PINEAL REGION IN A PATIENT WITH NEUROFIBROMATOSIS TYPE I

Pleomorphic Xanthoastrocytoma (PXA) describes a relatively rare and often focal glioma most commonly affecting children and young adults. Lesions are preferentially supratentorial and superficially located with a close association and occasional involvement of the leptomeninges, although infratentorial masses have been described. The World Health Organization (WHO) categorizes such tumors as Grade II, and surgical excision carries a favorable prognosis. Reportedly, PXA may be associated with Neurofibromatosis Type I (NF1), although such tumors are not a hallmark of the classic phenotype. In this report we describe a novel case of a pineal region PXA in a patient with a history of NF1. A 17-year-old male with a history of NF1 presented with complaints of bifrontal headache. Imaging of the head was ordered. Magnetic resonance imaging (MRI) was significant for a heterogeneous tectal mass suspicious for glioma extending to the level of the 4th ventricle with cerebral aqueduct displacement but no obstructive hydrocephalus. The patient underwent suboccipital craniotomy for an infratentorial supracerebellar approach to the pineal region and resection of tumor. Histopathology confirmed a low-grade variable neoplasm consistent with PXA. Post-operative imaging demonstrated gross total resection. There is no evidence of residual or recurrence at 3months follow-up. To the best of our knowledge, there are 8 prior reported cases of pineal region PXA with such lesions rarely occurring in individuals with NF1. These masses present similarly to dysplastic tumor types, and should be considered as a rare etiology of NF1 associated tectal masses.

A comprehensive analysis identifies BRAF hotspot mutations associated with gliomas with peculiar epithelial morphology.

Brain tumors harbor various BRAF alterations, the vast majority of which are the BRAF kinase-activating V600E mutation. BRAF mutations are most frequently detected in certain subtypes of low-grade glioma, such as pilocytic astrocytoma (PA), pleomorphic xanthoastrocytoma (PXA), ganglioglioma (GG) and dysembryoplastic neuroepithelial tumor (DNT). However, it is unclear whether gliomas harboring BRAF mutations can be invariably regarded as these glioma subtypes or their derivatives. To address this question, we analyzed 274 gliomas in our institutional case series. We performed high-resolution melting analyses and subsequent direct Sanger sequencing on DNA isolated from snap-frozen tumor tissues. As expected, BRAF mutations were detected in the aforementioned low-grade gliomas: in 4/27 PAs, 2/3 PXAs, 4/8 GGs, and 1/6 DNTs. In addition to these gliomas, 1/2 astroblastomas (ABs) and 2/122 glioblastomas (GBs) harbored BRAF mutations. Pathological investigation of the two GBs revealed that one was a GB displaying epithelial features that presumably arose from a precedent GG, whereas the other GB, which harbored a rare G596A mutation, showed marked epithelial features, including astroblastic rosettes. Our results indicate that in addition to being present in established BRAF-associated gliomas, BRAF mutations might be associated with epithelial features in high-grade gliomas, including sheet-like arrangement of polygonal tumor cells with a plump cytoplasm and astroblastic rosettes, and thus could potentially serve as a genetic marker for these features.

336P - Case report of the effective use of BRAF inhibitor vemurafenib in a patient with relapse of pleomorphic xanthoastrocytoma

Pleomorphic xanthoastrocytoma is a rare tumor of the brain. It is approximately 1% of the astocytomas of the brain. In some cases, the tumor is well-demarcated and slow-growing with a favorable prognosis. At the same time reported cases of its malignant transformation with a poor prognosis. Most often this tumor occurs in a young age and manifest with epileptic syndrome. The main treatment is surgical. According to the literature, 30-40% of patients with pleomorphic xanthoastrocytoma detected mutation of V600E BRAF was. The patient 25 years old in January 2011 revealed a tumor of the left occipital lobe of the brain. 22 Jan 2011 completed the removal of a brain tumor. Morphologically diagnosed as a pleomorphic xanthoastrocytoma with signs of anaplasia grade 3, Ki-67 – 15%. In the postoperative, in February-April 2012, conducted a course of radiation therapy to the left occipital lobe of the brain with total focal dose 60 Gy. In September 2014 after 2 years and 8 months after the operation revealed a relapse of a brain tumor. 25 Sep 2014 made the removal of the recurrence of a brain tumor. Morphologically diagnosed as a pleomorphic xanthoastrocytoma with signs of anaplasia grade 4, Ki-67 > 20%. Carried out a genetic examination of the tumor. Revealed no methylation of the MGMT gene in the tumor. The identified mutation V600E BRAF in the tumor. In December 2014 marked the progression of the disease. Revealed continued tumor growth in the brain. The size of the recurrent tumor 4 x 3 cm. From December 2014 we started the targeted therapy with Vemurafenib. Achieved partial regression of the tumor in the brain. The size of residual tumors currently, less than 1 cm. Therapy with Vemurafenib lasts 1 year and 6 months. Thus, the presence of the V600E BRAF mutation is another target for effective treatment of recurrences of pleomorphic xanthoastrocytoma. Further studies are needed for the study of BRAF inhibitors in patients with pleomorphic xanthoastrocytoma.

Pediatric Pleomorphic Xanthoastrocytoma Treated With Surgical Resection Alone: Clinicopathologic Features.

Pleomorphic xanthoastrocytoma (PXA) is a rare brain tumor that usually occurs in children and young adults. It has characteristic histologic features and is regarded as a WHO grade II lesion. Overall survival is reported to be >60%, but published series usually consist of a range of ages and treatment modalities. Gross total resection is associated with superior survival but recurrence rates after gross total resection are not well described, particularly in a pediatric population. We describe 16 cases over 20 years at our institution of pediatric PXA treated with surgical resection alone with a 5-year relapse-free survival of 40% (95% confidence interval, 20%-82%) and overall survival of 76% (95% confidence interval, 55%-100%). Gross total resection was associated with superior relapse-free survival (P<0.05). Some cases have a very long period between symptom onset or radiologic detection and resection, but neither length of symptoms nor radiologic signs of slow growth were associated with survival. PXA is a rare and unusual entity with unpredictable behavior. Complete surgical resection is optimal but does not guarantee relapse-free survival. We propose separation of PXA from other low-grade gliomas in childhood given differing biology and behavior.

An integrative molecular and genomic analysis of pediatric hemispheric low-grade gliomas: an update.

Hemispheric low-grade gliomas account for the second most common location in pediatric low-grade gliomas (PLGGs) after the cerebellum. The pathological spectrum includes gangliogliomas, dysembryoplastic neuroepithelial tumors (DNETs), diffuse astrocytomas, pilocytic astrocytomas, and pleomorphic xanthoastrocytomas (PXAs), among others. Clinically, hemispheric PLGGs represent a well-recognized cause of intractable epilepsy in children and adolescents. With an excellent long-term outcome, surgery remains the cornerstone and patients with gross total resection typically do not need any further therapies. The recent literature about hemispheric PLGGs was reviewed to provide an up-to-date overview of the molecular and cell biology of these tumors. Hemispheric PLGGs can harbor multiple alterations involving BRAFV600E, FGFR, NTRK, MYB/MYBL1, IDH, and BRAF-KIAA1549 fusions. However, the clinical significance of most of these alterations is still to be defined. The role of RAS/MAPK mutations and other alterations in hemispheric PLGGs is of interest from diagnostic, prognostic, and therapeutic perspectives. Molecular testing for these tumors should be encouraged, since the findings can have an important impact not only in prognosis but also in therapeutic strategies.

Pleomorphic xanthoastrocytoma with anaplastic features: A rare case report and review of literature with reference to current management

Pleomorphic xanthoastrocytoma (PXA) is an uncommon tumor constitutes less than 1% of all astrocytic glial neoplasms was first reported in 1979. PXA commonly occurs in young patients and manifests itself first as seizures followed by focal neurological deficits. The role of radiotherapy or chemotherapy has not yet been established because of the relative infrequency of this disease. PXA is classified as grade II tumor in the WHO classification of tumors of the CNS. In literature 9 to 20 % PXA may undergo malignant change at recurrence or may display at the time of initial presentation. Malignant transformation is mainly associated with high mitotic activity and necrosis. The criteria for PXA with anaplastic features was five or more mitotic activity per 10 high power fields, necrosis, microvascular proliferation, marked cellular anaplasia, and high Ki-67 labeling indices. PXA with anaplastic features management is highly controversial as very sparse literature is available. We are reporting a case of PXA with anaplastic features with atypical radiology and tried to review the up to date literature regarding this rare tumor.

Cerebellar Pleomorphic Xanthoastrocytoma in an 18-Year-Old Patient with Neurofibromatosis Type 1

Cerebellar Pleomorphic Xanthoastrocytoma in an 18-Year-Old Patient with Neurofibromatosis Type 1

Pleomorphic Xanthoastrocytoma with Anaplastic Features: Retrospective Case Series

Pleomorphic xanthoastrocytoma (PXA) is a unique meningocerebral glioma with a relatively favorable prognosis. PXA also possesses a variant with anaplastic features (aPXA), which is associated with poor outcomes. To date, few studies have examined the clinicopathologic importance of these anaplastic features. From 1999-2012, 8 patients with aPXA were treated at the University of California, San Francisco, California, United States. Cases were reconfirmed by neuropathology, and clinical information regarding patient demographics, tumor characteristics, and treatment outcomes was assembled. Tumors were classified as aPXA according to the World Health Organization diagnostic criteria established in2007. There were 5 female and 3 male patients inour cohort, ranging in age from 4-74 years at initial diagnosis. Seizure was the most common presenting symptom (50%), and the majority of tumors arose in the frontal or temporal lobes (88%). Six patients received subtotal resection (STR), and all suffered from progression despite adjuvant radiotherapy and chemotherapy. Median time to progression was 20 months, with a 1-year progression-free survival rate of 57%. Three aPXA patients expired with a median survival of 87 months. Four patients developed disseminated disease. Three of 8 (38%) showed BRAFv600 mutation. aPXA is associated with poorer clinical outcomes compared with PXA. Gross total resection should be the goal of initial treatment. It remains unclear whether adjuvant radiation and chemotherapy are able to prevent progression or dissemination. Long-term monitoring of all patients is a critical step in management due to the potential for tumors to transform into higher-grade lesions.

Macrocephaly and right arm disuse in a 7-month-old boy

B.Desmoplastic infantile ganglioglioma The patient underwent gross total resection, and final pathology was consistent with desmoplastic infantile ganglioglioma (DIG). Intraoperatively, the tumor body was firmly attached to the dura and had an associated cystic nodule (Fig. 2A). Pathological examination of the specimen demonstrated tumor mainly in the leptomeninges, which was well-demarcated from the adjacent brain (Fig. 2B). The leptomeningeal component consisted primarily of desmoplastic areas and scattered foci with different cell types. Mitotic figures were very rare and only very minimal necrosis was visualized. The adjacent brain demonstrated mainly perivascular infiltrate, with few individual tumor cells infiltrating the cortex. Accordingly, the Ki-67 immunolabeling was low (1–5%). As the patient underwent gross total surgical resection (Fig. 2C, D) with no residual enhancement on MRI (Fig. 2E), no further adjuvant therapy was necessary. DIG is a very rare childhood tumor almost always presenting before 2 years of age [[1]Tamburrini G. Colosimo Jr., C. Giangaspero F. et al.Desmoplastic infantile ganglioglioma.Child’s Nerv Syst: ChNS. 2003; 19: 292-297Crossref PubMed Scopus (72) Google Scholar]. Its etiology is unknown, although is likely prenatal in origin. Common presenting signs and symptoms include macrocephaly, hemiparesis, and/or signs of elevated intracranial pressure [[2]Blount J.P. Bauer D.F. Desmoplastic infantile gangliogliomas.in: Tonn J.-C. Westphal M. Rutka J.T. Oncology of CNS Tumors. Springer, Berlin Heidelberg2010: 477-481Crossref Scopus (2) Google Scholar]. CT scan and MRI demonstrate an aggressive-appearing tumor, which can appear similar to primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, pleomorphic xanthoastrocytoma, or ganglioglioma [[3]Alexiou G.A. Stefanaki K. Sfakianos G. et al.Desmoplastic infantile ganglioglioma: a report of 2 cases and a review of the literature.Pediatr Neurosurg. 2008; 44: 422-425Crossref PubMed Scopus (22) Google Scholar]; therefore the diagnosis cannot definitively be made with imaging alone. The mainstay of treatment is surgical resection, which is considered curative [[1]Tamburrini G. Colosimo Jr., C. Giangaspero F. et al.Desmoplastic infantile ganglioglioma.Child’s Nerv Syst: ChNS. 2003; 19: 292-297Crossref PubMed Scopus (72) Google Scholar]. Chemotherapy is reserved for cases of brain invasion, or when partial resection is followed by radiographic evidence of non-operable disease progression. Radiotherapy may be used as a last resort in children over 5 years of age when other approaches have failed. The prognosis of both complete and partially resected DIG is excellent. Partial resection is often followed by disease stability or spontaneous regression, with a median disease-free survival of 8 to 30 years reported [[3]Alexiou G.A. Stefanaki K. Sfakianos G. et al.Desmoplastic infantile ganglioglioma: a report of 2 cases and a review of the literature.Pediatr Neurosurg. 2008; 44: 422-425Crossref PubMed Scopus (22) Google Scholar]. There are rare reports of local recurrence and/or metastasis, usually associated with deep-seated, particularly suprasellar tumor locations. Surveillance MRIs are generally recommended until stable disease has persisted for some time. Lifetime surveillance does not appear to be necessary as there are no reports of long-term recurrence [[2]Blount J.P. Bauer D.F. Desmoplastic infantile gangliogliomas.in: Tonn J.-C. Westphal M. Rutka J.T. Oncology of CNS Tumors. Springer, Berlin Heidelberg2010: 477-481Crossref Scopus (2) Google Scholar]. Macrocephaly and right arm disuse in a 7-month-old boyJournal of Clinical NeuroscienceVol. 34PreviewA 7-month-old boy presented with macrocephaly (head circumference of 52 cm, 2.5 standard deviations above the 98th percentile). An examination of his cranial contour demonstrated prominent dilated scalp vessels, an elevated and full anterior fontanelle, and mild splaying of the coronal and sagittal sutures. He maintained his right hand in a fisted position, and would not reach towards objects or faces with his right hand; his right upper extremity was also significantly hypertonic. A neurological examination of his cranial nerves and other limbs was otherwise normal. Full-Text PDF

Pleomorphic xanthoastrocytoma arising from the suprasellar region: A report of two cases

Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic neoplasm that usually arises in children and young adults. Typically, lesions of PXA are superficially located in the cerebral hemispheres. Herein, we report two extremely rare patients with PXA arising from suprasellar regions. One of the patients is a 29-year-old man admitted to our hospital with a history of progressive headache for 1month. The patient’s brain MRI revealed a large tumor arising from the suprasellar cistern of the third ventricle. The second patient, a 52-year-old woman, presented with progressive dizziness and visual disturbance that had developed over the course of 1year. The MRI revealed a well-enhanced suprasellar solid mass measuring 1.4×1.2×1.4cm. Both patients underwent surgical removal of their tumors, and both patients showed similar microscopic structures and immunohistochemical phenotypes: the tumor cells were pleomorphic with mixtures of spindle-shaped, and multinuclear giant cells. In addition, eosinophilic granular bodies and xanthomatous cells were seen on section. Immunohistochemistry was positive for GFAP, S-100, and CD34, and was negative for IDH 1, CK, and Syn. The Ki-67 proliferation index was less than 1%. Silver impregnation revealed reticulin fibers surrounding the individual tumor cells, and small cell groups. Based on these findings, the two patients were diagnosed with PXA in the suprasellar region. To date, only five such patients have been reported in the literature. PXA should be included in the differential diagnosis for tumors arising in the sellar region.