AOSNP‐ADAPTR resource level‐based recommendations on practical diagnostic strategies for medulloblastomas and other embryonal tumors

Abstract

WHO CNS5 mandates integrated histo-molecular classification of medulloblastomas (MBs) and other CNS embryonal tumors. However, advanced molecular diagnostics remain inaccessible in many low- and lower-middle-income countries (LICs/LMICs), limiting implementation of molecularly informed risk stratification and therapy. The ADAPTR group (Adapting Diagnostic Approaches for Practical Taxonomy in Resource-Restrained Regions) is an initiative of the Asian Oceanian Society of Neuropathology (AOSNP) and aims to provide practical guidelines for CNS tumor diagnostics at various levels of pathology resource restraints. In this manuscript, we propose a practical approach to diagnosis of MBs and other CNS embryonal tumors based on ADAPTR resource levels (RLs). The emphasis is mainly on using histopathological approaches with immunohistochemistry (IHC), while molecular testing recommendations are categorized as "can be considered," "highly recommended" or "obligatory" to reach the next level diagnosis. In each RL, either a WHO CNS5 diagnosis with an accompanying CNS WHO grade or an ADAPTR descriptive diagnosis with an associated ADAPTR histologic grade and comment is provided, depending on the context. "Histology-oriented integrated diagnosis format" for each tumor type at different RLs along with diagnostic flow charts has been generated to suit these RLs. For MBs, at RL I-II, diagnosis relies on histopathology and basic IHC with structured ADAPTR descriptive reporting. At RL III, surrogate IHC panels enable assignment to WNT-activated, SHH-activated and non-WNT/non-SHH groups, facilitating clinically actionable risk stratification. RL IV incorporates targeted molecular tests (e.g., MYC/MYCN amplification, CTNNB1 and TP53 mutations) for prognostic refinement. RL V supports comprehensive molecular classification through next-generation sequencing and DNA methylation profiling. Parallel RL-based algorithms are proposed for other CNS embryonal tumors, incorporating essential surrogate and confirmatory markers. These AOSNP-ADAPTR recommendations provide a practical adaptation of WHO CNS5 guidelines suited to routine diagnosis in resource-restrained regions. This model promotes equitable, risk-adapted care while supporting progressive strengthening of global neuropathology capacity.