Primary intracranial Ewing sarcoma/ peripheral primitive neuroectodermal tumor, an entity of unacquaintance: a series of 8 cases.

PURPOSE: The purpose is to highlight the primary intracranial (meningeal-based) occurrence of Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET). METHODS: This report is a collation of clinicopathological features of eight cases of molecularly and clinicoradiologically confirmed primary (non-metastatic) intracranial (non-osseous) meningeal ES/PNET. RESULTS: The age range was 1 to 33 years with a median age of 9 years. Male to female ratio was 0.6:1. All patients were diagnosed on the debulking surgical material (gross total resection, 2 cases; subtotal resection, 6 cases) and showed primitive embryonal histomorphology with diffuse membranous CD99 immunoexpression and EWSR1 gene rearrangement by fluorescence in situ hybridization. Seven of them showed a typical FISH pattern of split signals with break-apart probe, while one showed an unusual signal pattern of loss of green signals. EFT-2001 adjuvant protocol was followed along with focal radiotherapy (RT) in all cases (except case 8, full course of chemotherapy could not be completed). Two cases had local recurrence-one of them died of disease recurrence before the administration of further treatment. CONCLUSION: This series adds non-osseous intracranial site to the list of uncommon sites of occurrence for ES/PNET and more importantly emphasizes the need to be considered in a differential list of primary intracranial primitive embryonal tumors before embarking as primary central nervous system (CNS) embryonal tumor, NOS.

Pilocytic astrocytomas: BRAFV600E and BRAF fusion expression patterns in pediatric and adult age groups.

PURPOSE: Pilocytic astrocytomas (PCAs) are characterized by two dominant molecular alterations of the BRAF gene, i.e., BRAFV600E mutation and KIAA1549-BRAF fusions which show a differential pattern of frequency across different age-groups. METHODS: Formalin-fixed paraffin-embedded tissues of 358 (pediatric 276 and adult 82) consecutive PCAs were evaluated for BRAFV600E mutation by Sanger sequencing and KIAA1549:BRAF fusion transcripts (KIAA1549:BRAF 16-9, KIAA1549:BRAF 15-9, and KIAA1549:BRAF 16-11) by reverse transcriptase polymerase chain reaction, which were correlated with different clinicopathological features. RESULTS: BRAFV600E mutation was detected in 8.9% pediatric and 9.75% adult PCAs, whereas 41.1% and 25.7% of pediatric and adult cases showed KIAA1549-BRAF fusions respectively. BRAFV600E did not show any statistically significant correlation with any of the clinical parameters (age, location, and gender). KIAA1549:BRAF fusions showed a significant statistical association with the pediatric age group and cerebellar location. KIAA1549-BRAF 16-9 was the commonest variant and was predominantly associated with cerebellar location than non-cerebellar whereas fusion variant 15-9 negatively correlated with cerebellar locations. CONCLUSIONS: The present study showed overall frequency of 53.5% and 37.3% BRAF alterations in pediatric and adult PCA cases respectively. BRAF fusion in PCA cases showed a different distribution pattern across age groups and locations; while no such differential pattern was observed for BRAFV600E.