Molecular Stratification of Childhood Ependymomas as a Basis for Personalized Diagnostics and Treatment

Abstract

Ependymomas are among the most enigmatic tumors of the central nervous system, posing enormous challenges for pathologists and clinicians. Despite the efforts made, the treatment options are still limited to surgical resection and radiation therapy, while none of conventional chemotherapies is beneficial. While being histologically similar, ependymomas show considerable clinical and molecular diversity. Their histopathological evaluation alone is not sufficient for reliable diagnostics, prognosis, and choice of treatment strategy. The importance of integrated diagnosis for ependymomas is underscored in the recommendations of Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy. These updated recommendations were adopted and implemented by WHO experts. This minireview highlights recent advances in comprehensive molecular-genetic characterization of ependymomas. Strong emphasis is made on the use of molecular approaches for verification and specification of histological diagnoses, as well as identification of prognostic markers for ependymomas in children.

Posterior fossa ependymomas in children and adolescents - the state of the art

“…The PF-A subgroup represents 90% of posterior fossa tumors and occurs mainly in young patients, with a median age of 3 years, a slight prevalence of males, and has a worse prognosis, with lower overall and disease-free survival (19)(20)(21)(22). In molecular studies, hypermethylation of CpG islands and global hypomethylation of DNA are observed and on immunohistochemical analysis with H3K27me3 (Figure 11), and a global reduction of this histone confirms the diagnosis.…”

“…These are differentiated by the degree of DNA methylation and CpG islands, which can be evaluated by immunohistochemical analysis with H3K27me3 (15)(16)(17). Notably, the PF-A and PF-B subgroups are still molecularly heterogeneous, pointing to a future distinction into additional subgroups according to the expression of specific gene families (18)(19)(20).…”

“…In molecular studies, hypermethylation of CpG islands and global hypomethylation of DNA are observed and on immunohistochemical analysis with H3K27me3 (Figure 11), and a global reduction of this histone confirms the diagnosis. Other chromosomal mutations identified for PF-A tumors include gain of segment 1q or loss of segment 6q, both with a negative effect on prognosis (19)(20)(21)23).…”

“…The PF-B subgroup, on the other hand, occurs more commonly in patients with a median age around 30 years, and may affect adolescents, with a slight prevalence of females and a better prognosis compared with the A subgroup (19)(20)(21)(22)24). On immunohistochemistry with H3K27me3, PF-B shows a retention of at least 80% (Figure 12).…”

Extra-Neural Metastases of Late Recurrent Myxopapillary Ependymoma to Left Lumbar Paravertebral Muscles: Case Report and Review of the Literature

“…( Figure 6 ). In particular, the gain of chromosome 11, 13, 17, 20, and 21 identified in this case are highly specific for MPE [ 12 , 13 , 14 ].…”