====== Posterior Fossa Ependymoma Classification ====== The current 2021 update mainly comprises molecular subtypes. More precisely, the types of [[subependymoma]]s (SE), [[myxopapillary ependymoma]]s (MPE), and [[RELA]]-fusion-positive (now: [[ZFTA]]-fusion-positive) ependymomas have been maintained in the 2021 classification, although some changes have been applied. The previously used terms [[ependymoma]] and [[anaplastic ependymoma]] are not used to define an entity anymore. Instead, [[Posterior fossa ependymoma group PFA]] and [[Posterior fossa type B ependymoma]], [[YAP1]]-fusion-positive ependymoma in the cerebrum, and spinal ependymoma, as well as spinal ependymoma, [[MYCN]]-amplified, in the [[spinal cord]], have been newly defined. This not only provides an objective molecular basis for the diagnosis and classification of [[ependymoma]]s but is also intended to better predict the clinical outcome of the patients. Notably, first studies on tumor relapse samples indicate that this molecular classification might be more stable in the course of the disease than histology alone. ---- [[Posterior fossa ependymoma]] comprise three distinct molecular variants: [[Posterior fossa ependymoma group PFA]] [[Posterior fossa type B ependymoma]] [[Subependymoma of the fourth ventricle]] The majority of [[intracranial ependymoma]]s (60%) are located in the [[posterior fossa]] ([[infratentorial]]), usually arising from the [[lateral recess]] of the [[fourth ventricle]] (molecular subgroup: [[Posterior Fossa type A ependymoma]]) and midline inferior [[fourth ventricle floor]] near the [[obex]] (molecular subgroup: [[Posterior Fossa type B ependymoma]]) ((Koeller KK, Sandberg GD. From the archives of the AFIP. Cerebral intraventricular neoplasms: radiologic-pathologic correlation. Radiographics. 22 (6): 1473-505. doi:10.1148/rg.226025118)) ((Yuh EL, Barkovich AJ, Gupta N. Imaging of ependymomas: MRI and CT. Childs Nerv Syst. 2009;25 (10): 1203-13. doi:10.1007/s00381-009-0878-7)) ((Smith A, Smirniotopoulos J, Horkanyne-Szakaly I. From the Radiologic Pathology Archives: Intraventricular Neoplasms: Radiologic-Pathologic Correlation. Radiographics. 2013;33 (1): 21-43. Radiographics (full text) - doi:10.1148/rg.331125192)). Group A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, metastases at recurrence, and death compared with Group B patients ---- Clinically, they are very disparate and PFB tumors are currently being considered for a [[trial]] of radiation avoidance. However, to move forward, unraveling the heterogeneity within PFB would be highly desirable. To discern the molecular heterogeneity within PFB, we performed an integrated analysis consisting of DNA methylation profiling, copy-number profiling, gene expression profiling, and clinical correlation across a cohort of 212 primary posterior fossa PFB tumors. Unsupervised spectral clustering and t-SNE analysis of genome-wide methylation data revealed five distinct subtypes of PFB tumors, termed PFB1-5, with distinct demographics, copy-number alterations, and gene expression profiles. All PFB subtypes were distinct from PFA and posterior fossa subependymomas. Of the five subtypes, PFB4 and PFB5 are more discrete, consisting of younger and older patients, respectively, with a strong female-gender enrichment in PFB5 (age: p = 0.011, gender: p = 0.04). Broad copy-number aberrations were common; however, many events such as chromosome 2 loss, 5 gain, and 17 loss were enriched in specific subtypes and 1q gain was enriched in PFB1. Late relapses were common across all five subtypes, but deaths were uncommon and present in only two subtypes (PFB1 and PFB3). Unlike the case in PFA ependymoma, 1q gain was not a robust marker of poor progression-free survival; however, chromosome 13q loss may represent a novel marker for risk stratification across the spectrum of PFB subtypes. Similar to PFA ependymoma, there exists a significant intertumoral heterogeneity within PFB, with distinct molecular subtypes identified. Even when accounting for this heterogeneity, extent of resection remains the strongest predictor of poor outcome. However, this biological heterogeneity must be accounted for in future preclinical modeling and personalized therapies ((Cavalli FMG, Hübner JM, Sharma T, Luu B, Sill M, Zapotocky M, Mack SC, Witt H, Lin T, Shih DJH, Ho B, Santi M, Emery L, Hukin J, Dunham C, McLendon RE, Lipp ES, Gururangan S, Grossbach A, French P, Kros JM, van Veelen MC, Rao AAN, Giannini C, Leary S, Jung S, Faria CC, Mora J, Schüller U, Alonso MM, Chan JA, Klekner A, Chambless LB, Hwang EI, Massimino M, Eberhart CG, Karajannis MA, Lu B, Liau LM, Zollo M, Ferrucci V, Carlotti C, Tirapelli DPC, Tabori U, Bouffet E, Ryzhova M, Ellison DW, Merchant TE, Gilbert MR, Armstrong TS, Korshunov A, Pfister SM, Taylor MD, Aldape K, Pajtler KW, Kool M, Ramaswamy V. Heterogeneity within the PF-EPN-B ependymoma subgroup. Acta Neuropathol. 2018 Aug;136(2):227-237. doi: 10.1007/s00401-018-1888-x. Epub 2018 Jul 17. PMID: 30019219; PMCID: PMC6373486.)). ---- The relationship between microanatomical localization and postoperative survival in [[posterior fossa ependymoma]]s has been used to classify posterior fossa ependymomas into three types: Midfloor, roof, and lateral. "Plastic ependymomas" are thought to be the lateral type. The survival rate of the lateral-type ependymomas is significantly lower than the other two types, regardless of histological malignancy, due to the difficulty in achieving total surgical resection in the lateral-type ependymomas. ===== Fourth ventricle ependymoma ===== see [[Fourth ventricle ependymoma]]. ===== Cerebellopontine angle ependymoma ===== see [[Cerebellopontine angle ependymoma]]. ===== Posterior fossa type A Ependymoma ===== see [[Posterior fossa type A Ependymoma]]. ===== Posterior fossa type B Ependymoma ===== [[Posterior fossa type B Ependymoma]]. ===== Pediatric posterior fossa ependymoma ===== [[Pediatric posterior fossa ependymoma]]. The more common [[infratentorial tumor]]s may produce [[nausea]], vomiting (particularly when the [[area postrema]] is involved), and manifestations of cerebellar compression, mainly [[ataxia]] and [[nystagmus]].