Embryonal and non‐meningothelial mesenchymal tumors of the central nervous system – Advances in diagnosis and prognostication

Abstract

The 5th edition of the WHO Classification of Tumours of the Central Nervous System introduces new entities, and provides updated guidance regarding the diagnostic criteria for tumors of the central nervous system (CNS). CNS embryonal tumors and CNS non‐meningothelial mesenchymal tumors can be challenging for practicing pathologists, as the histologic features are not always specific to a particular entity, and integration of microscopic and molecular findings is necessary. This review on CNS embryonal and non‐meningothelial mesenchymal tumors is meant to provide an update with a focus on WHO changes and additions and on recent discoveries with diagnostic, prognostic, and therapeutic implications.

Clinicopathological and molecular characterization of a case classified by DNA‑methylation profiling as “CNS embryonal tumor with BRD4–LEUTX fusion”

“…While widely studied in neuroglial tumors leading to specific entities, the decrease of H3K27me3 expression is less described in CNS embryonal tumors with scarce data available regarding histone modifications alterations in these tumors. Interestingly, loss of H3K27me3 has been described by Alexandrescu et al in primary intracranial sarcoma, DICER1-mutant [1,14].…”

“…While widely studied in neuroglial tumors leading to specific entities, the decrease of H3K27me3 expression is less described in CNS embryonal tumors with scarce data available regarding histone modifications alterations in these tumors. Interestingly, loss of H3K27me3 has been described by Alexandrescu et al in primary intracranial sarcoma, DICER1 -mutant [ 1 , 14 ]. Studies reporting effects of targeting therapeutic EZH2 and BET inhibitors in ATRT [ 9 , 21 ] lead us to propose the hypothesis that the loss of H3K27me3 is linked to the inactivation of BRD4 in this case.…”

Multiomic profiling of medulloblastoma reveals subtype-specific targetable alterations at the proteome and N-glycan level

“…Immunohistochemistry is used to detect nuclear ß-Catenin staining in tumor cells. However, nuclear staining can be weak and only a subset of cell nuclei is usually stained 53,54 . Here, Tenascin C (TNC) was found elevated in pWNT MBs from proteome and mRNA data, whereas no significantly altered DNA methylation at CpG sites of TNC was seen.. TNC is a highly glycosylated extracellular matrix (ECM) protein, promoting or inhibiting proliferation and migration in cancer, depending on the present splice variant 55 , which will be a field of further study.…”

The WHO classification of tumors of the central nervous system‐finally here, and welcome!

“…Kresbach C. et al, [5] cover important advances in the classification of ependymal neoplasms, a tumor group that best illustrates the updated model of the WHO classification, merging anatomic, histologic, immunohistochemical, sequencing, and epigenetic data into a powerful classification approach that has significantly improved prognostication. Finally, Meredith DM et al, [6] address the dual topics of embryonal neoplasms and non‐meningothelial mesenchymal neoplasms. The latter group has been particularly timely, given that specific tumor types which may have counterparts in the broader field of soft tissue tumors have been teased out from historical CNS groups.…”