"The 5th edition (2021) builds on the prior version by placing greater emphasis on molecular markers in terms of classification and grading. It incorporates most of the recommendations made in the cIMPACT-NOW publications 6. This approach, however, results in a fairly heterogeneous classification depending on the specific entity. At one end of the spectrum, some tumours remain primarily assessed histologically, while at the other end, some are assessed entirely on the basis of molecular parameters."
"It should also be noted that generally there is shift towards placing less importance on grade as it is often less relevant than location or available therapies. For example, medulloblastoma, WNT activated, despite being a grade 4 tumour, if treated has a good prognosis far better than other medulloblastoma types."
"For the first time, molecular features have been explicitly added to the grading schema and may supersede histological features. For example, an IDH-wildtype astrocytoma with low-grade histologic features can be considered grade 4 (glioblastoma) in the presence of EGFR amplification, TERT promoter mutation or the combined gain of chromosome 7 and loss of chromosome 10 [+7/-10] 8."
"For the first time, molecular features have been explicitly added to the grading schema and may supersede histological features. For example, an IDH-wildtype astrocytoma with low-grade histologic features can be considered grade 4 (glioblastoma) in the presence of EGFR amplification, TERT promoter mutation or the combined gain of chromosome 7 and loss of chromosome 10 [+7/-10] 8."
"supratentorial ependymoma, ZFTA fusion-positive"
"posterior fossa ependymoma, group PFA"
"posterior fossa ependymoma, group PFB"
"medulloblastoma, WNT-activated"
"medulloblastoma, SHH-activated and TP53-wildtype"
"medulloblastoma, SHH-activated and TP53-mutant"
"medulloblastoma, non-WNT/non-SHH"
"medulloblastoma, non-WNT/non-SHH"
"CNS tumour with BCOR internal tandem duplication"
"intracranial mesenchymal tumour, FET-CREB fusion-positive (provisional inclusion)"
"anaplastic large cell lymphoma (ALK+/ALK−)"
"anaplastic large cell lymphoma (ALK+/ALK−)"
"T-cell and NK/T-cell lymphomas"
"The 2016 revised 4th edition significantly changed the classification of a number of tumour families, introducing a greater reliance on molecular markers. The most notable changes involve diffuse gliomas, in which IDH status (mutated vs. wildtype) and 1p19q co-deletion (for oligodendrogliomas) have risen to prominence. Importantly if histological phenotype and genotype are not-concordant (e.g. looks like diffuse astrocytoma but is 1p19q co-deleted, ATRX-wildtype) then genotype wins, and it is used to determine diagnosis 3."
"Classification"
"Ewing sarcoma"
"Langerhans cell histiocytosis"
"The 2016 revised 4th edition significantly changed the classification of a number of tumour families, introducing a greater reliance on molecular markers. The most notable changes involve diffuse gliomas, in which IDH status (mutated vs. wildtype) and 1p19q co-deletion (for oligodendrogliomas) have risen to prominence. Importantly if histological phenotype and genotype are not-concordant (e.g. looks like diffuse astrocytoma but is 1p19q co-deleted, ATRX-wildtype) then genotype wins, and it is used to determine diagnosis 3."
Expected headings
"Main changes in the 5th edition (2021)"
"Terminology"
"Grading"
"Grading within tumour types"
"Arabic numerals"
"Anaplastic modifier"
"Molecular grading"
"Essential and desirable diagnostic criteria"
"Not elsewhere classified (NEC)"
"Structure"
"Classification"
"Gliomas, glioneuronal tumours, and neuronal tumours"
"Adult-type diffuse gliomas"
"Paediatric-type diffuse low-grade gliomas"
"Paediatric-type diffuse high-grade gliomas"
"Circumscribed astrocytic gliomas"
"Glioneuronal and neuronal tumours"
"Ependymal tumours"
"Choroid plexus tumours"
"Embryonal tumours"
"Medulloblastoma"
"Other CNS embryonal tumours"
"Pineal tumours"
"Cranial and paraspinal nerve tumours"
"Meningiomas"
"Mesenchymal, non-meningothelial tumours"
"Soft tissue tumours"
"Chondro-osseous tumours"
"Melanocytic tumours"
"Hematolymphoid tumours"
"Lymphomas"
"Histiocytic tumours"
"Germ cell tumours"
"Tumours of the sellar region"
"Metastases to the CNS"
"Main changes in the revised 4th edition (2016)"
"This will be reflected in a "layered report structure" wherein histological features, grading and molecular information will be combined to form an integrated diagnosis."
"Due to the inertia of prior classifications and the desire to avoid additional confusion, however, this has only been adopted in a way that does not overly clash with prior grading. For example, despite grading within tumour types, no grade 1 astrocytoma, IDH-mutant exists (only grades 2, 3 and 4 are available). Similarly, glioblastoma, IDH-wildtype can only ever be a grade 4 tumour 8."
"Previously the Roman numerals I, II, III and IV were used for grading. These will be replaced by the Arabic numerals 1, 2, 3 and 4 to bring CNS tumour grades in line with other systems. However, since the features used to grade CNS tumours remain different from those used systemically, it is recommended that the grade be preceded by "CNS WHO", e.g. "meningioma CNS WHO grade 1" 8."
"Previously the Roman numerals I, II, III and IV were used for grading. These will be replaced by the Arabic numerals 1, 2, 3 and 4 to bring CNS tumour grades in line with other systems. However, since the features used to grade CNS tumours remain different from those used systemically, it is recommended that the grade be preceded by "CNS WHO", e.g. "meningioma CNS WHO grade 1" 8."
"Other WHO classification systems generally grade each tumour independently; i.e. the most low-grade version of a particular tumour is given grade 1 regardless of how aggressive it is relative to other diagnoses."
"Despite a move towards molecular markers for some entities, the classification continues to be organised according to the cell of origin (e.g. ependymal tumours) or anatomical origin (e.g. tumours of the sellar region)."