World Health Organization Classification of Tumors of the Central Nervous System 2021
World Health Organization Classification of Tumors of the Central Nervous System 2021
The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors. Building on the 2016 updated fourth edition and the work of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, the 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification. At the same time, it remains wedded to other established approaches to tumor diagnosis such as histology and immunohistochemistry. In doing so, the fifth edition establishes some different approaches to both CNS tumor nomenclature and grading and it emphasizes the importance of integrated diagnoses and layered reports. New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling. The present review summarizes the major general changes in the 2021 fifth edition classification and the specific changes in each taxonomic category. It is hoped that this summary provides an overview to facilitate more in-depth exploration of the entire fifth edition of the WHO Classification of Tumors of the Central Nervous System 1).
The newest revision of the WHO classification of tumors of the central nervous system, also known as WHO 5th edition, introduces substantial changes, especially within the glial tumor category, and separates adult-type and pediatric-type glial tumors into different categories for the first time. In addition, another category of glial tumors, “Circumscribed Astrocytic Gliomas” was also created. This group includes pilocytic astrocytoma, pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma, chordoid glioma, astroblastoma, and the highly nebulous novel entity high-grade astrocytoma with piloid features 2).
Limitations
Although the shift toward the molecular classification is inevitable, the current WHO classification system has limitations. WHO CNS5 should be regarded as an intermediate stage toward further refined, better structured classification systems in the future 3)
Gliomas, glioneuronal tumors, and neuronal tumors
Gliomas, glioneuronal tumors, and neuronal tumors:
Oligodendroglioma IDH-mutant and 1p/19q-codeleted
Pediatric-type diffuse low-grade gliomas
Diffuse astrocytoma MYB or MYBL1 altered
Polymorphous low-grade neuroepithelial tumor of the young
Diffuse low-grade glioma, MAPK pathway-altered
Pediatric-type diffuse high-grade gliomas
Diffuse midline glioma, H3 K27-altered
Diffuse hemispheric glioma, H3 G34-mutant
Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype
Infant-type hemispheric glioma
Circumscribed astrocytic gliomas
High-grade astrocytoma with piloid features
Subependymal giant cell astrocytoma
Glioneuronal and neuronal tumors
Desmoplastic infantile ganglioglioma / desmoplastic infantile astrocytoma
Dysembryoplastic neuroepithelial tumor
Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters
Rosette-forming glioneuronal tumor
Diffuse leptomeningeal glioneuronal tumor
Multinodular and vacuolating neuronal tumor
Dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease)
Ependymal tumors
Supratentorial ependymoma ZFTA fusion-positive
Supratentorial ependymoma YAP1 fusion-positive
Posterior fossa ependymoma group PFA
Posterior fossa ependymoma group PFB
Choroid plexus tumors
Embryonal tumors
Medulloblastomas, molecularly defined
Medulloblastoma, WNT-activated
Medulloblastoma, SHH-activated and TP53-wildtype
Medulloblastoma, SHH-activated and TP53-mutant
Medulloblastoma non-WNT/non-SSH
Medulloblastomas, histologically defined
Other CNS embryonal tumors
Atypical teratoid/rhabdoid tumor
Cribriform neuroepithelial tumor
Embryonal tumor with multilayered rosettes
CNS neuroblastoma, FOXR2-activated
Pineal tumors
Pineal parenchymal tumor of intermediate differentiation
Papillary tumor of the pineal region
Desmoplastic myxoid tumor of the pineal region, SMARCB1-mutant
Cranial and paraspinal nerve tumors
Meningiomas
Mesenchymal, non-meningothelial tumors
Soft tissue tumors
Fibroblastic and myofibroblastic tumors
Vascular tumors
Skeletal muscle tumors
Uncertain differentiation
Intracranial mesenchymal tumor, FET-CREB fusion-positive
CIC-rearranged sarcoma
Primary intracranial sarcoma, DICER1-mutant
Chondro-osseous tumors
Chondrogenic tumors
Mesenchymal chondrosarcoma
Chondrosarcoma
Notochordal tumors
Chordoma (including poorly differentiated chordoma)
Melanocytic tumors
Diffuse meningeal melanocytic neoplasms
Circumscribed meningeal melanocytic neoplasms
Hematolymphoid tumors
Lymphomas
CNS lymphomas
Primary diffuse large B-cell lymphoma of the Central Nervous System
Miscellaneous rare lymphomas in the CNS
Other low-grade B-cell lymphomas of the CNS
Anaplastic large cell lymphoma (ALK+/ALK−)]]
Histiocytic tumors
Germ cell tumors
Sellar region tumors
Adamantinomatous craniopharyngioma
Pituicytoma, granular cell tumor of the sellar region, and spindle cell oncocytoma
Metastases to the CNS
Metastases to the brain and spinal cord parenchyma
Metastases to the meninges
Wen PY, Packer RJ. The 2021 WHO Classification of Tumors of the Central Nervous System: clinical implications. Neuro Oncol. 2021 Aug 2;23(8):1215-1217. doi: 10.1093/neuonc/noab120. PMID: 34185090; PMCID: PMC8328017.