Anaplastic Pilocytic Astrocytoma Research Articles

QLTI-01. HIGH-GRADE ASTROCYTOMA WITH PILOID FEATURES RESPONSE TO TREATMENT WITH CARBOPLATIN AND VINCRISTINE

Abstract High-grade astrocytoma with piloid features (HGAP) is a brain tumor that requires distinct DNA methylation profiling for diagnosis. The current literature on HGAP response to treatment is limited. This case details the response to treatment of a young female patient initially with a pilocytic astrocytoma that at progression transformed into HGAP, both diagnoses confirmed with methylation testing. At 12 years old, the patient initially presented with unremitting headaches and syncopal episodes. Imaging revealed a non-enhancing non-cystic lesion in the roof of the fourth ventricle measuring 5 mm in the greatest dimension. She was followed by serial surveillance until undergoing surgical resection four years later. Histologically the tumor was grade I pilocytic astrocytoma containing a KIAA1549-BRAF fusion; the diagnosis was subsequently confirmed with methylation array testing. The patient transitioned to serial surveillance until she was lost to follow-up. At 27 years old, she presented with progressive headaches, gait instability, and agraphia. MRI revealed a posterior fossa cerebellar mass and surgical resection was performed. Histologically this was an anaplastic pilocytic astrocytoma with KIAA1549-BRAF fusion; however, DNA methylation profiling confirmed the diagnosis of HGAP. The patient was treated with postoperative radiation and demonstrated asymptomatic tumor progression in the left cerebellar hemisphere fourteen months later. She received carboplatin and vincristine with radiographic response and stability for four months until discontinuation due to tumor progression with infiltrative disease within the posterior fossa and brainstem. Her treatment was transitioned to selumetinib with mixed radiographic response but continued clinical deterioration after three months. Selumetinib was terminated and best supportive care was initiated. The patient died 216 months from initial presentation with pilocytic astrocytoma and 28 months from transformation into HGAP. To our knowledge, this is the first report of HGAP with treatment response to carboplatin and vincristine. Further research into the best treatments for HGAP is needed.

OS04.4.A LONG- AND SHORT-TERM SURVIVORS AMONG ADULT PATIENTS WITH DIFFUSE WHO GRADE 2-3 GLIOMA: CLINICAL FEATURES, MOLECULAR RECLASSIFICATION AND DNA METHYLATION PATTERNS

Abstract BACKGROUND Diffuse gliomas show considerable heterogeneity in terms of survival. The WHO classifications of 2016 and 2021 improved prognostic stratification due to the definition of biologically and clinically homogeneous tumor entities. However, further prognostic models considering clinical and molecular factors are needed to balance survival benefit with adverse treatment-related long-term effects in therapeutic decisions. MATERIALS AND METHODS Patients with diffuse gliomas of WHO grades 2 and 3 diagnosed in 2000 - 2019 have been included. Long term survivors (LTS) were defined as patients with an overall survival (OS) of >10 years after radiological diagnosis, whereas short-term survivors (STS) had an OS of <1 year. Histological diagnosis was performed by a board-certified neuropathologist. DNA methylation analysis of formalin-fixed, paraffin-embedded tumor tissue was conducted using the Illumina EPIC 850k platform. The Heidelberg Methylation Classifier was applied to obtain methylation-based diagnoses. RESULTS Of 697 patients with WHO grade 2 and 3 glioma, 182 (26.1%) were LTS, and 42 (6.0%) were STS. LTS were younger than STS (median age: 36 vs. 59.5; p<0.001) and had a higher Karnofsky Performance Score at diagnosis (median: 90% vs. 80%; p<0.001). LTS more frequently presented with epileptic seizures (p<0.001), while more STS had motoric (p<0.001), sensory (p=0.021), and visual deficits (p=0.027) as well as aphasia (p<0.001) and behavioral changes (p=0.009). Histological diagnoses (including pre-2016) showed astrocytic histology in 117 (70.9% LTS, 29.1% STS), oligodendroglial in 61 (93.4% LTS, 6.6% STS), oligo-astroglial in 43 (97.7% LTS, 2.3% STS) and not otherwise specified in 3 (all STS; p<0.001). Molecular reclassification of pre-2016 diagnoses (n = 143) yielded divergent entities in 46 (32.2%) cases. Overall, integrated molecular diagnoses included astrocytoma (isocitrate dehydrogenase [IDH]-mutant] in 65 patients (95.4% LTS and 4.6% STS), oligodendroglioma (IDH-mutant, 1p/19q-codeleted) in 64 patients (98.4% LTS and 1.6% STS), IDH-wildtype gliomas in 24 patients (100% STS), anaplastic pilocytic astrocytoma in 2 STS, diffuse midline glioma (H3K27-altered) in 1 STS, and dysembryoplastic neuroepithelial tumor in 1 LTS, while not otherwise specified diagnoses were found in 4 patients (75% LTS, 25% STS; p<0.001). Unsupervised clustering based on DNA methylation profiling revealed two major clusters consisting of IDH-wildtype STS (cluster A) and IDH-mutant patients (cluster B; 94.6% LTS, 5.4% STS). In cluster B, one subcluster (n = 8) contained 3/4 IDH-mt STS. Further analyses of these cases including validation with publicly available DNA methylation data are ongoing. CONCLUSION LTS and STS show distinct clinical and molecular features. Further profiling of cases with divergent survival could provide more refined prognostic stratification.

EPEN-19. Impact of molecular classification on prognosis in children and adolescents with spinal ependymoma: Results from the HIT-MED database

Abstract PURPOSE: Ependymomas of the spinal cord are rare among children, and individual risks of disease progression are difficult to predict. This study aims at evaluating the prognostic impact of DNA methylation-based classification in children with spinal ependymoma. METHODS: Eighty-two patients with spinal ependymoma <22 years registered in the HIT-MED database between 1992 and 2021 were included. Clinical, radiological, and histopathological data were collected retrospectively. DNA methylation profiles of 46 tumors were classified according to the Heidelberg Brain Tumor Classifier. RESULTS: Spinal myxopapillary ependymoma (SP-MPE, n=27) was the most common methylation group followed by spinal ependymoma (SP-EPN, n=15). Two cases belonged to MYCN-amplified subgroup, one had no match, and one was re-classified as anaplastic pilocytic astrocytoma (the latter excluded from final analysis). WHO grade I and III ependymomas (according to the WHO 2016 classification) classified predominantly as SP-MPE, whereas grade II ependymomas clustered into SP-MPE and SP-EPN. 6/15 patients with SP-EPN (40%) suffered from Neurofibromatosis type 2. Among patients with SP-MPE, 23 underwent gross-total and four a subtotal resection (GTR/STR). Relapses of SP-MPE were more common following STR (5-year progression-free survival (5y-PFS) [STR] 25.0% [95% confidence interval: 0.0-68.4], [GTR] 75.0% [53.4-96.6], p=0.003). In the SP-EPN group, 2/8 patients relapsed after STR (5y-PFS 64.3% [22,3-100]) and 0/7 after GTR (n.s.). WHO I° ependymoma had significantly inferior PFS than II° and III° ependymoma (5y-PFS [I°] 39.0% [5.8-62.2], [II°] 82.4% [67.8-97.0], [III°] 50.5% [18.9-82.1], p=0.009). However, PFS did not significantly differ between SP-MPE and SP-EPN (5y-PFS 65.9% [44.9-86.9], 76.9% [46.3-100], respectively). CONCLUSION: Spinal ependymomas of WHO grade I go along with relatively poor PFS in our cohort, while DNA methylation profiling does not segregate patients into distinct risk groups. Still, larger cohorts and further investigations of methylation class heterogeneity in pediatric spinal ependymomas are needed to complete the basis for future clinical decision-making.

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

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

EPID-09. VARIATION IN GLIOMA INCIDENCE AMONG US HISPANICS BY GEOGRAPHIC REGION OF ORIGIN

Abstract BACKGROUND Glioma incidence is 25% lower in U.S. Hispanics than in White non-Hispanics. The US Hispanic population is diverse and registry-based analyses may mask incidence differences associated with geographic/ancestral origins. METHODS County-level glioma incidence data in U.S. Hispanics were retrieved from the Central Brain Tumor Registry of the United States (CBTRUS), which includes data from the Centers for Disease Control’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results program and covers ~100% of the U.S. population. American Community Survey (ACS) data were used to determine county-level proportion of the Hispanic population of Mexican/Central American origin, Caribbean origin (Puerto Rican, Cuban, Dominican), or other origin. Incidence rate ratios (IRRs) were generated to assess the association of glioma incidence in Hispanics with predominant origin group. RESULTS Compared to Hispanics living in predominantly Caribbean-origin counties, Hispanics in predominantly Mexican/Central American-origin counties were at lower age-adjusted risk of glioma (IRR=0.83; P&amp;lt; 0.0001), glioblastoma (IRR=0.86; P&amp;lt; 0.0001), diffuse and anaplastic astrocytoma (IRR=0.78; P&amp;lt; 0.0001), oligodendroglioma (IRR=0.82; P&amp;lt; 0.0001), ependymoma (IRR=0.88; P=0.0121), and pilocytic astrocytoma (IRR=0.76; P&amp;lt; 0.0001). Associations were consistent in children and adults, and when using more granular regions of origin. However, Central American origin was associated with modestly increased incidence of several lower-grade glioma histologies. Associations were only partially attenuated after adjusting for state-level estimated of European admixture in Hispanics using 23andMe data. CONCLUSIONS Glioma incidence in U.S. Hispanics differs significantly in association with the geographic origins of the Hispanic community, with those of Mexican/Central American origin at significantly reduced risk relative to those of Caribbean origin. U.S. Hispanics are culturally, socioeconomically, and genetically diverse. Although classified as a single ethnic group in most registry data, more granular analytic approaches could advance cancer epidemiology and disparities research.

Anaplastic pilocytic astrocytoma of the cerebellum presenting with conus medullaris drop metastasis

Due to its rarity, a complete understanding of the clinical behavior, pathogenesis, and diagnostic definition of anaplastic pilocytic astrocytoma (APA) is currently lacking. The optimal clinical management and use of adjuvant therapies has yet to be defined. We present a 64 year-old-female with progressive headaches, dysarthria, and ataxia, who was found to have right cerebellar mass. A gross total resection was achieved through two staged operations. Pathology demonstrated focal areas of necrosis, tumor infiltration, and increased mitotic activity most consistent with APA. Adjuvant chemotherapy and stereotactic radiosurgery were administered. Approximately two years later, the patient presented with symptoms of cauda equina syndrome, and lumbar spine imaging demonstrated a large intradural mass at the conus medullaris with diffuse leptomeningeal enhancement. A biopsy was performed and was consistent with metastatic APA. APA may rarely progress to metastatic disease, most frequently involving the leptomeninges of the posterior fossa and cervical spine. This report represents the first case of metastases distal to the cervicomedullary junction.

CS-01 Rapid Recurrence and Anaplastic Transformation of a Pilocytic Astrocytoma in an Elderly Patient

BACKGROUND: Rapid recurrence of a pilocytic astrocytoma with anaplastic transformation is extremely rare. The case of an elderly patient with a cerebellar pilocytic astrocytoma with anaplastic transformation during short-term follow-up is reported. CASE DESCRIPTION: An 83-year-old woman presented initially with dizziness and a gait deviation to the right. Magnetic resonance imaging (MRI) demonstrated a homogeneously enhanced mass in the right cerebellar hemisphere, and the tumor was subtotally removed by right suboccipital craniotomy. Histological examination showed that the tumor cells contained eosinophilic cytoplasm and spindle-shaped processes with Rosenthal fibers and eosinophilic granular bodies, diagnosed as a typical pilocytic astrocytoma (PA). The MIB-1 index was less than 1%. The patient did not receive postoperative adjuvant radiation and chemotherapy. Two months after surgery, MRI showed growth of the residual tumor adjacent to the fourth ventricle, causing obstructive hydrocephalus. She underwent surgery again, and the tumor was totally removed. Histological findings showed mitotic cells and increased cellularity compared with the primary tumor, which was compatible with anaplastic transformation of PA with a MIB-1 index of 50%. Postoperatively, she was observed with best supportive care without postoperative adjuvant therapy. Nine months after the second operation, she died due to tonsillar herniation and obstructive hydrocephalus caused by a recurrent tumor. An autopsy was performed. CONCLUSION: It is extremely rare, as in the present case, that a cerebellar PA in an elderly patient recurs rapidly with anaplastic transformation, despite deferred postoperative adjuvant therapy including radiation and chemotherapy A novel molecular-targeted therapy is needed for anaplastic PA showing aggressive biological behavior.

Biology and grading of pleomorphic xanthoastrocytoma-what have we learned about it?

Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytoma predominantly affecting children and young adults. We performed comprehensive genomic characterization on a cohort of 67 patients with histologically defined PXA (n = 53, 79%) or anaplastic PXA (A‐PXA, n = 14, 21%), including copy number analysis (ThermoFisher Oncoscan, n = 67), methylation profiling (Illumina EPIC array, n = 43) and targeted next generation sequencing (n = 32). The most frequent alterations were CDKN2A/B deletion (n = 63; 94%) and BRAF p.V600E (n = 51, 76.1%). In 7 BRAF p.V600 wild‐type cases, alternative driver alterations were identified involving BRAF, RAF1 and NF1. Downstream phosphorylation of ERK kinase was uniformly present. Additional pathogenic alterations were rare, with TERT, ATRX and TP53 mutations identified in a small number of tumors, predominantly A‐PXA. Methylation‐based classification of 46 cases utilizing a comprehensive reference tumor allowed assignment to the PXA methylation class in 40 cases. A minority grouped with the methylation classes of ganglioglioma or pilocytic astrocytoma (n = 2), anaplastic pilocytic astrocytoma (n = 2) or control tissues (n = 2). In 9 cases, tissue was available from matched primary and recurrent tumors, including 8 with anaplastic transformation. At recurrence, two tumors acquired TERT promoter mutations and the majority demonstrated additional non‐recurrent copy number alterations. Methylation class was preserved at recurrence. For 62 patients (92.5%), clinical follow‐up data were available (median follow‐up, 5.4 years). Overall survival was significantly different between PXA and A‐PXA (5‐year OS 80.8% vs. 47.6%; P = 0.0009) but not progression‐free survival (5‐year PFS 59.9% vs. 39.8%; P = 0.05). WHO grade remained a strong predictor of overall survival when limited to 38 cases defined as PXA by methylation‐based classification. Our data confirm the importance of WHO grading in histologically and epigenetically defined PXA. Methylation‐based classification may be helpful in cases with ambiguous morphology, but is largely confirmatory in PXA with well‐defined morphology.

Ribosomal Protein S27/Metallopanstimulin-1 (RPS27) in Glioma-A New Disease Biomarker?

Despite its significant overexpression in several malignant neoplasms, the expression of RPS27 in the central nervous system (CNS) is widely unknown. We identified the cell types expressing RPS27 in the CNS under normal and disease conditions. We acquired specimens of healthy brain (NB), adult pilocytic astrocytoma (PA) World Health Organization (WHO) grade I, anaplastic PA WHO grade III, gliomas WHO grade II/III with or without isocitrate dehydrogenase (IDH) mutation, and glioblastoma multiforme (GBM). RPS27 protein expression was examined by immunohistochemistry and double-fluorescence staining and its mRNA expression quantified by RT-PCR. Patients’ clinical and tumor characteristics were collected retrospectively. RPS27 protein was specifically expressed in tumor cells and neurons, but not in healthy astrocytes. In tumor tissue, most macrophages were positive, while this was rarely the case in inflamed tissue. Compared to NB, RPS27 mRNA was in mean 6.2- and 8.8-fold enhanced in gliomas WHO grade II/III with (p < 0.01) and without IDH mutation (p = 0.01), respectively. GBM displayed a 4.6-fold increased mean expression (p = 0.02). Although RPS27 expression levels did not affect the patients’ survival, their association with tumor cells and tumor-associated macrophages provides a rationale for a future investigation of a potential function during gliomagenesis and tumor immune response.

PATH-52. ANAPLASTIC PILOMYXOID ASTROCYTOMA HARBORING BRAF FUSION, PTEN AND TERT MUTATIONS

Abstract Pilomyxoid astrocytomas (PMA) are focal neoplasms that are often cured with total resection. We present a case of a progressive PMA with histologic and molecular features suggestive of malignant transformation. A 13-year old boy presented with headaches, diplopia, and seizures. He had previously been followed for 7 years by serial imaging for a cystic/solid enhancing mass in the right temporal lobe without biopsy that had remained stable up to 6 months prior to his current illness. MRI of brain demonstrated significant progression of the solid component with extension into the subependymal portions of the lateral ventricles, leptomeningeal spread in brain and spine, and hydrocephalus. Patient underwent a partial resection of tumor and VP shunt placement. Pathology demonstrated a prominent myxoid matrix with angiocentric arrangement of monomorphous bipolar cells. PHH3 and Ki-67 stains confirmed multiple mitoses and elevated proliferation rate. Next Generation sequencing of tumor confirmed the presence of a KIAA1549-BRAF duplication/fusion, CDKN2A deletion, along with PTEN and TERT promoter mutations without BRAF V600E or ATRX mutations. The histology and molecular features was suggestive of a pilomyxoid astrocytoma (PMA) with anaplastic transformation. Patient is currently receiving carboplatin + vincristine plus a MEK inhibitor (TrametinibTM, Novartis Corporation, Cambridge, MA) for tumor control. We believe that the tumor was initiated by the oncogenic BRAF fusion and the dramatic progression and spread of disease after a long period of stability was probably related to recent acquisition of additional deleterious mutations that have been previously reported in anaplastic pilocytic astrocytoma.

The histomolecular criteria established for adult anaplastic pilocytic astrocytoma are not applicable to the pediatric population

Pilocytic astrocytoma (PA) is the most common pediatric glioma, arising from a single driver MAPK pathway alteration. Classified as a grade I tumor according to the 2016 WHO classification, prognosis is excellent with a 10-year survival rate > 95% after surgery. However, rare cases present with anaplastic features, including an unexpected high mitotic/proliferative index, thus posing a diagnostic and therapeutic challenge. Based on small histomolecular series and case reports, such tumors arising at the time of diagnosis or recurrence have been designated by many names including pilocytic astrocytoma with anaplastic features (PAAF). Recent DNA methylation-profiling studies performed mainly on adult cases have revealed that PAAF exhibit a specific methylation signature, thus constituting a distinct methylation class from typical PA [methylation class anaplastic astrocytoma with piloid features—(MC-AAP)]. However, the diagnostic and prognostic significance of MC-AAP remains to be determined in children. We performed an integrative work on the largest pediatric cohort of PAAF, defined according to strict criteria: morphology compatible with the diagnosis of PA, with or without necrosis, ≥ 4 mitoses for 2.3 mm2, and MAPK pathway alteration. We subjected 31 tumors to clinical, imaging, morphological and molecular analyses, including DNA methylation profiling. We identified only one tumor belonging to the MC-AAP (3%), the others exhibiting a methylation profile typical for PA (77%), IDH-wild-type glioblastoma (7%), and diffuse leptomeningeal glioneuronal tumor (3%), while three cases (10%) did not match to a known DNA methylation class. No significant outcome differences were observed between PAAF with necrosis versus no necrosis (p = 0.07), or with 4–6 mitoses versus 7 or more mitoses (p = 0.857). Our findings argue that the diagnostic histomolecular criteria established for anaplasia in adult PA are not of diagnostic or prognostic value in a pediatric setting. Further extensive and comprehensive integrative studies are necessary to accurately define this exceptional entity in children.

Author response: Pilocytic astrocytoma with anaplasia arising from the optic chiasm in a very elderly patient.

I thank Dr. Wasilewski for the valuable comments on our NeuroImage.1 Our patient received irradiation (57.6 Gy/32 fractions) and oral temozolomide (100 mg for 5 d/mo for 14 months); however, the tumor gradually extended to the hypothalamus and he was transferred to another hospital for terminal care. We agree with Dr. Wasilewski's comment that alternative regimens for adult patients with anaplastic pilocytic astrocytoma (APA), especially showing recurrent or aggressive nature, are to be explored and established, and antiangiogenic treatment is one of the powerful tools. In our view, alternative treatments, such as bevacizumab, might be justified only when patients with APA show microvascular proliferations, as observed in our patient.1 We are not fully confident whether tests for BRAF V600E mutant proteins are mandatory, because the gene mutations are found in 6%–8% of extracerebellar pilocytic astrocytomas,2 as well as in other disorders (e.g., pleomorphic xanthoastrocytoma or ganglioglioma).3

Editors' note: Pilocytic astrocytoma with anaplasia arising from the optic chiasm in a very elderly patient

In reference to the NeuroImage “Pilocytic astrocytoma with anaplasia arising from the optic chiasm in a very elderly patient,” Dr. Wasilewski comments that there are few studies and no standard of care guidelines in the treatment of pilocytic astrocytoma in adults. However, bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown to be beneficial in case series. Author Hayashi reports on the course of their patient in the NeuroImage, who received radiation and oral temozolomide. He agrees that bevacizumab may be useful in patients with anaplastic pilocytic astrocytoma and microvascular proliferation. In reference to the NeuroImage “Pilocytic astrocytoma with anaplasia arising from the optic chiasm in a very elderly patient,” Dr. Wasilewski comments that there are few studies and no standard of care guidelines in the treatment of pilocytic astrocytoma in adults.

Reader response: Pilocytic astrocytoma with anaplasia arising from the optic chiasm in a very elderly patient.

As alluded to by the authors of this NeuroImage,1 few studies have investigated pilocytic astrocytoma (PA) in adults, given the rarity of these tumors. One study suggested anaplastic PAs have a more aggressive clinical course when compared to juvenile PA with a higher incidence of tumor recurrence (from 30% to 42%) and progression.2 Specifically, PA with anaplastic features are more aggressive and associated with decreased survival when compared with typical PA.3 No standard of care exists for treatment of PA, especially in the elderly. Anti-angiogenic treatment, such as bevacizumab (a humanized monoclonal antibody directed against vascular endothelial growth factor), should be considered in patients with recurrent or unresectable PA. The highly vascular nature of these tumors suggests they may be uniquely responsive to bevacizumab and may have a similar response as seen in glioblastoma, including decreased permeability of vasculature and decreased perilesional edema.4 Case series demonstrated clinical and radiographic improvement as well as disease control with the use of bevacizumab.5

Anaplastic astrocytoma with piloid features, a novel molecular class of IDH wildtype glioma with recurrent MAPK pathway, CDKN2A/B and ATRX alterations.

Tumors with histological features of pilocytic astrocytoma (PA), but with increased mitotic activity and additional high-grade features (particularly microvascular proliferation and palisading necrosis) have often been designated anaplastic pilocytic astrocytomas. The status of these tumors as a separate entity has not yet been conclusively demonstrated and molecular features have only been partially characterized. We performed DNA methylation profiling of 102 histologically defined anaplastic pilocytic astrocytomas. T-distributed stochastic neighbor-embedding(t-SNE) and hierarchical clustering analysis of these 102 cases against 158 reference cases from 12 glioma reference classes revealed that a subset of 83 of these tumors share a common DNA methylation profile that is distinct from the reference classes. These 83 tumors were thus denominated DNA methylation class anaplastic astrocytoma with piloid features (MC AAP). The 19 remaining tumors were distributed amongst the reference classes, with additional testing confirming the molecular diagnosis in most cases. Median age of patients with MC AAP was 41.5years. The most frequent localization was the posterior fossa (74%). Deletions of CDKN2A/B (66/83, 80%), MAPK pathway gene alterations (49/65, 75%, most frequently affecting NF1, followed by BRAF and FGFR1) and mutations of ATRX or loss of ATRX expression (33/74, 45%) were the most common molecular alterations. All tumors were IDH1/2 wildtype. The MGMT promoter was methylated in 38/83 tumors (45%). Outcome analysis confirmed an unfavorable clinical course in comparison to PA, but better than IDH wildtype glioblastoma. In conclusion, we show that a subset of histologically defined anaplastic pilocytic astrocytomas forms a separate DNA methylation cluster, harbors recurrent alterations in MAPK pathway genes in combination with alterations of CDKN2A/B and ATRX, affects patients who are on average older than those diagnosed with PA and has an intermediate clinical outcome.

Child Spinal Cord Compression without Trauma about 113 Cases in Senegal

Introduction: No-trauma spinal cord compressions are serious conditions not often described in children population. This study will discuss the epidemiological, clinical, biology and radiology assessment, the etiologies, the therapeutic and evolutionary aspects of this condition in children in Senegal. Patients and Methods: 113 children aged between 15 months and 18 years were managed in a 10 years period (from January 2005 to July 2015) for a non-traumatic spinal cord compression (average 8.3 years). Results: There was 66 males (58%) and 47 females (42%) with sex ratio of 1.40. The main reasons for consultation were spinal deformity (90 %). The syndrome was complete in 52 patients (46%) and incomplete in 61 patients (54%). Plain radiography performed in 63 patients. The CT scan was performed in 21 patients and myelography performed in 4 patients. MRI was performed in 22 patients. There was intradural extramedullary process (33.33%), the extradural lesions (14.28%) and intramedullary process (28.57%). Dorsal lesions were predominant (46%) followed by the lumbar spine (27%). The majority of the etiology was Pott’s disease (80%) followed by tumors (17%). Spondylitis to banal germs (2%) and parasitic spinal cord compression (1%) were rare. The histology of 6 patients was revealed 5% neurofibroma Type II, 5% extramedullary intradermal arachnoid cyst, 5% intramedullary arachnoid cyst with cytochemistry of the CSF—like content, 5% Anaplastic pilocytic astrocytoma, 5% ganglioneuroma I terminal cone and 5% meningothelial meningioma. Pott’s disease has been cured by TB chemotherapy associated with a corset in 88.89% of cases. 2 patients of this group had benefited fixation after laminectomy. 68% of the patients had a favorable recovery, and 20% had completely recovered after an average of 7 months of treatment and three (3) patients had died. The compression by bilharzias is be cured by myelotomy and praziquantel with a favorable outcome. We have 94.74% decompressive laminectomy or laminotomy with tumor resection and four (4) Patients of this group benefited fixation; the patients who had intramedullary tumor benefited myelotomy and tumor resection; 3 patients in this group had benefited fixation after laminectomy 58% of patients had good recovery and 1 pateint had died. Conclusion: In Africa, particularly in the tropics, Pott’s disease remains the first etiology followed by vertebra-medullary tumors for no traumatic spinal cord compression of child.

Adult anaplastic pilocytic astrocytoma – a diagnostic challenge? A case series and literature review

IntroductionAnaplastic pilocytic astrocytoma (APA) is an exceptionally rare type of high-grade glioma in adults. Establishing histopathological diagnosis is challenging and its clinical and radiological appearance insidious. By this case series and first literature review we investigated the various clinical, neuroradiological, and histopathological features of APA in adults. MethodsAn in hospital screening of the database from the Institute of Pathology was conducted to identify cases of APA. Further, we performed a literature review in PubMed using the keywords “anaplastic/malignant/atypical AND pilocytic astrocytoma” and “anaplastic astrocytoma/glioblastoma AND Rosenthal fibers” and summarized the current knowledge about APA in adults. ResultsOver the last decade we were able to identify 3 adult patients with APA in our hospital. According to the pertinent literature, the prognosis of APA in adults (documented survival of up to 10 years) appears to be better than in other high-grade gliomas. Few cases were associated with neurofibromatosis type 1, which seems to predispose for development of APA. Although molecular genetics is still of limited value for differentiation of APA from other high-grade glioma, advanced neuroimaging techniques such as magnetic resonance perfusion imaging and spectroscopy allow improved differential work-up. In particular, APA in adults has the ability to mimic various neurological diseases such as tumefactive demyelinating lesions, low-, or high-grade gliomas. ConclusionsAlthough currently not explicitly recognized as a distinct clinico-pathologic entity it seems that adult APA behaves differently from conventional high-grade glioma and should be included in differential diagnostics to enable adequate patient care. However, further studies are needed to better understand this extremely rare disease.

HG-68COMBINED ALTERATIONS IN MAPK PATHWAY GENES, CDKN2A/B AND ATRX CHARACTERIZE ANAPLASTIC PILOCYTIC ASTROCYTOMA

Introduction: Tumors with histological features of pilocytic astrocytoma but with increased mitotic activity and additional high grade features (i.e. microvascular proliferation, necrosis) have been designated anaplastic pilocytic astrocytomas (APA). Patients with such tumors are thought to have an [for full text, please go to the a.m. URL]

Does BRAF V600E Mutation Enable Vemurafenib to be a Universal Candidate for Treating a Plethora of Cancers?

Neurologically, BRAF V600E mutation was detected in cerebellar anaplastic pilocytic astrocytoma, ganglioglioma, desmoplastic infantile astrocytoma, indeterminate cell tumor and interdigitating dendritic cell sarcoma. Hematologically, BRAF V600E mutation was also detected in multiple myeloma and several leukemias (hairy cell, chronic lymphocytic, prolymphocytic and acute lymphoblastic leukaemia).

Clinicopathological and molecular features of malignant optic pathway glioma in an adult

Malignant gliomas of the optic pathway are rare, and their genetic alterations are poorly understood. We describe a 64-year-old woman with anaplastic astrocytoma originating from the optic pathway, together with the molecular features. She presented with progressive visual field loss, and a biopsy sample was obtained from the lesion in the optic chiasm. She underwent radiosurgery concomitant with temozolomide chemotherapy, and subsequently remained stable for 10months after initial presentation. Molecular analysis indicated that the mass may have shared common molecular genetic features with conventional primary astrocytic gliomas but not pilocytic gliomas, which supported the morphologic diagnosis of anaplastic astrocytoma. Molecular analysis of malignant optic pathway gliomas in adults is useful for distinguishing between high-grade gliomas and anaplastic pilocytic astrocytomas, and for determining further therapy.