WHO classification of CNS tumors

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The WHO classification of CNS tumors is the most widely accepted system for classifying CNS tumors and was based on the histological characteristics of the tumor. Although the most recent version of the 'blue book' is the 4edition from 2007, an update has been released in 2016 , which should be considered a replacement for the earlier version.

This 2016 update has, for the first time, included molecular parameters into the diagnostic schema, and in fact, has elevated them in some instances above histological features .

The 5th edition should become available towards the end of 2020 and incorporates some important changes to diffuse gliomas and glioblastoma as outlined in cIMPACT recommendations for the classification of diffuse gliomas 2020 .

This is a fairly dry article, primarily for reference. For more readable versions, see the article on brain tumors and brain tumors in infancy for general discussion of these topics.

Main changes since previous (2007) version

The most recent update (2016) has significantly changed the classification of a number of tumor 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 .

Medulloblastomas have also been divided into distinct molecular subgroups.

Another change is the combining of solitary fibrous tumors of the dura with hemangiopericytoma, which although appearing very different on imaging seem now to be manifestations of the same tumor.

Structure

Despite a move towards molecular markers for some entities, the classification continues to be organized according to the cell of origin (e.g. ependymal tumors) or anatomical origin (e.g. tumors of the sellar region).

For entities that now incorporate molecular markers into their definition (e.g. oligodendroglioma IDH-mutant, 1p19q co-deleted) it is recognized that such markers are not always available or identified. In such cases, a 'not otherwise specified (NOS)' option is available (e.g. oligodendroglioma NOS).

Classification

NOS: not otherwise specified
four digit code: is from the International Classification of Disease for Oncology (ICD-O)
/: the number after the slash (/) refers to biological behavior, not WHO Grade
*: refers to a 'new' tumor in the classification
italics: refers to a provisional inclusion

Diffuse astrocytic and oligodendroglial tumors

WHO grade II
- diffuse astrocytoma
  - IDH-mutant - 9400/3
    - gemistocytic astrocytoma - 9411/3
  - IDH-wildtype - 9400/3
  - NOS - 9400/3
- oligoastrocytoma NOS - 9382/3
- oligodendroglioma - 9450/3
  - IDH-mutant, 1p19q co-deleted
  - oligodendroglioma NOS
WHO grade III
- anaplastic astrocytoma - 9401/3
  - IDH-mutant
  - IDH-wildtype
  - NOS
- anaplastic oligoastrocytoma NOS - 9382/3
- anaplastic oligodendroglioma - 9451/3
  - IDH-mutant, 1p19q co-deleted
  - anaplastic oligodendroglioma NOS
WHO grade IV
- glioblastoma
  - IDH wildtype - 9440/3
    - giant cell glioblastoma - 9441/3
    - gliosarcoma 9442/3
    - epithelioid glioblastoma - 9440/3
  - IDH mutant - 9440/3 *
  - NOS - 9440/3
diffuse midline glioma, H3K27M-mutant *

Other astrocytic tumors

WHO grade I
- pilocytic astrocytoma 9421/11 - WHO grade I
- subependymal giant cell astrocytoma 9384/1 - WHO grade I
WHO grade II
- pilomyxoid astrocytoma 9425/3
- pleomorphic xanthoastrocytoma 9424/3 - WHO grade II
WHO grade III
- anaplastic pleomorphic xanthoastrocytoma 9424/3 - WHO grade III

Ependymal tumors

WHO grade I
- subependymoma - 9383/1
- myxopapillary ependymoma - 9394/1
WHO grade II
- ependymoma - 9391/3
  - papillary ependymoma
  - clear cell ependymoma
  - tanycytic ependymoma
  - RELA fusion-positive - 9396/3 *
WHO grade III
- anaplastic ependymoma - 9392/3

Other gliomas

WHO grade I
- angiocentric glioma - 9431/1
WHO grade II
- chordoid glioma of the third ventricle - 9444/1
WHO grade not yet assigned
- astroblastoma - 9430/3

Embryonal tumors

WHO grade IV
- medulloblastoma
  - genetically defined
    - WNT-activated - 9475/3 *
    - SHH-activated & TP53-mutant - 9476/3
    - medulloblastoma SHH-activated & TP53-wildtype - 9471/3
    - group 3 - 9477/3
    - group 4 - 9477/3
  - histologically defined
    - classic - 9470/3
    - desmoplastic/nodular - 9471/3
    - extensive nodularity - 9471/3
    - large cell/anaplastic - 9470/3
    - NOS - 9470/3
- CNS neuroblastoma 9500/3
- CNS ganglioneuroblastoma 9490/3
- embryonal tumors with multilayered rosettes - 9478/3 *
  - C19MC-altered
  - NOS
- medulloepithelioma 9501/3
- atypical teratoid / rhabdoid tumor 9508/3
- CNS embryonal tumor with rhabdoid features 8508/3
- CNS embryonal tumor, NOS 9473/3

Tumors of cranial and paraspinal nerves

WHO grade I
- schwannoma (neurilemoma, neurinoma) - 9560/0
  - cellular schwannoma
  - plexiform schwannoma
  - melanotic schwannoma- 9560/1
- neurofibroma - 9540/0
  - atypical neurofibroma - 9540/0
  - plexiform neurofibroma - 9550/0
- perineurioma 9571/0
WHO grade II, III or IV
- malignant peripheral nerve sheath tumor (MPNST) - 9540/3
  - epithelioid
  - with perineural differentiation

Tumors of meningothelial cells

WHO grade I
- meningioma - 9530/0
- meningothelial meningioma - 9531/0
- fibrous meningioma - 9532/0
- microcystic meningioma - 9530/0
- psammomatous meningioma - 9533/0
- angiomatous meningioma - 9534/0
- secretory meningioma - 9530/0
- metaplastic meningioma - 9530/0
- lymphoplasmacyte-rich meningioma - 9530/0
WHO grade II
- atypical meningioma - 9539/1
- clear cell meningioma - 9538/1
- chordoid meningioma - 9538/1
WHO grade III
- anaplastic meningioma (malignant) - 9530/3
- papillary meningioma - 9538/3
- rhabdoid meningioma - 9538/3

Mesenchymal, non-meningothelial tumors

WHO grade I, II or III
- solitary fibrous tumor of the dura/hemangiopericytoma - 8815/0 /1 /3
WHO grade I
- angiolipoma - 8861/0
- chondroma - 9220/0
- desmoid-type fibromatosis - 8821/1
- hemangioblastoma - 9161/1
- hemangioma - 9120/0
- hibernoma - 8880/0
- leiomyoma - 8890/0
- lipoma - 8850/0
- myofibroblastoma - 8825/0
- osteochondroma - 9210/0
- osteoma 9180/0
- rhabdomyoma - 8900/0
WHO grade III
- epithelioid hemangioendothelioma - 9133/3
- angiosarcoma - 9120/3
- chondrosarcoma - 9220/3
- Ewing sarcoma / PNET - 9364/3
- fibrosarcoma - 8810/3
- Kaposi sarcoma - 9140/3
- leiomyosarcoma - 8890/3
- liposarcoma (intracranial) - 8850/3
- osteosarcoma - 9180/3
- rhabdomyosarcoma - 8900/3
- undifferentiated pleomorphic sarcoma / malignant fibrous histiocytoma - 8830/3

Melanocytic lesions

primary melanocytic tumors of the CNS
- meningeal melanocytosis - 8728/0
- meningeal melanocytoma - 8728/1
- meningeal melanomatosis - 8728/3
- meningeal melanoma - 8720/3

Lymphomas

diffuse large B-cell lymphoma of the CNS - 9680/3
immunodeficiency-associated CNS lymphomas
intravascular large B-cell lymphoma - 9712/3
Low-grade B-cell lymphomas of the CNS
T-cell and NK/T-cell lymphomas of the CNS
anaplastic large cell lymphoma
- ALK-positive - 9714/3
- ALK-negative - 9702/3
MALT lymphoma of the dura - 9699/3

Histiocytic tumors

Germ cell tumors

choriocarcinoma - 9100/3
embryonal carcinoma - 9070/3
germinoma - 9064/3
mixed germ cell tumors - 9085/3
teratoma
- mature - 9080/0
- immature - 9080/3
- with malignant transformation - 9084/3
yolk sac tumor - 9071/3

Tumors of the sellar region

WHO grade I
- craniopharyngioma - 9350/1
  - adamantinomatous - 9351/1
  - papillary - 9352/1
- granular cell tumor - 9582/0
- pituicytoma - 9432/1
- spindle cell oncocytoma - 8291/0

Entities removed

The following entities are no longer found in the 2016 WHO classification, last seen in the 2007 version.

gliomatosis cerebri - 9381/3
protoplasmic astrocytoma - 9410/3
fibrillary astrocytoma - 9420/3
primitive neuroectodermal tumor (PNET) - 9473/3 (now part of ETMR)
ependymoblastoma - 9392/3 (now part of ETMR)
cellular variant of ependymoma

Although oligoastrocytomas remain entities, they are now going to be rare, requiring molecularly distinct populations of both components: astrocytes (IDH-mutant, ATRX-mutant, 1p19q-intact) and oligodendroglial cells (IDH-mutant, ATRX-wildtype, 1p19q-co-deleted) .