WHO classification of tumours of the central nervous system

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MRI of a patient with anaplastic astrocytoma Anaplastic astrocytoma.jpg
MRI of a patient with anaplastic astrocytoma

The WHOclassification of tumours of the central nervous system is a World Health Organization Blue Book that defines, describes and classifies tumours of the central nervous system (CNS).

Contents

Currently, as of 2023, clinicians are using the 5th edition, which incorporates recent advances in molecular pathology. [1] The books lists ICD-O codes, CNS WHO grades and describes epidemiological, clinical, macroscopic and histopathological features, among others. [2] The following is a simplified (deprecated) version of the fifth edition.

Types

1. Gliomas, glioneuronal tumors, and neuronal tumours

1.1 Adult-type diffuse gliomas
1.1.1 Astrocytoma, IDH-mutant
1.1.2 Oligodendroglioma, IDH-mutant, and 1p/19q-codeleted
1.1.3 Glioblastoma, IDH-wildtype
1.2 Pediatric-type diffuse low-grade gliomas
1.2.1 Diffuse astrocytoma, MYB- or MYBL1-altered
1.2.2 Angiocentric glioma
1.2.3 Polymorphous low-grade neuroepithelial tumor of the young (PLNTY)
1.2.4 Diffuse low-grade glioma, MAPK pathway-altered
1.3 Pediatric-type diffuse high-grade gliomas
1.3.1 Diffuse midline glioma, H3 K27-altered
1.3.2 Diffuse hemispheric glioma, H3 G34-mutant
1.3.3 Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype
1.3.4 Infant-type hemispheric glioma
1.4 Circumscribed astrocytic gliomas
1.4.1 Pilocytic astrocytoma
1.4.2 High-grade astrocytoma with piloid features
1.4.3 Pleomorphic xanthoastrocytoma
1.4.4 Subependymal giant cell astrocytoma
1.4.5 Chordoid glioma
1.4.6 Astroblastoma, MN1-altered
1.5 Glioneuronal and neuronal tumours
1.5.1 Ganglioglioma
1.5.2 Desmoplastic infantile ganglioglioma / desmoplastic infantile astrocytoma
1.5.3 Dysembryoplastic neuroepithelial tumor
1.5.4 Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters
1.5.5 Papillary glioneuronal tumor
1.5.6 Rosette-forming glioneuronal tumor
1.5.7 Myxoid glioneuronal tumor
1.5.8 Diffuse leptomeningeal glioneuronal tumor
1.5.9 Gangliocytoma
1.5.10 Multinodular and vacuolating neuronal tumor
1.5.11 Dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease)
1.5.12 Central neurocytoma
1.5.13 Extraventricular neurocytoma
1.5.14 Cerebellar liponeurocytoma
1.6 Ependymal tumours
1.6.1 Supratentorial ependymoma
1.6.1.1 Supratentorial ependymoma, ZFTA fusion-positive
1.6.1.2 Supratentorial ependymoma, YAP1 fusion-positive
1.6.2 Posterior fossa ependymoma
1.6.2.1 Posterior fossa ependymoma, group PFA
1.6.2.2 Posterior fossa ependymoma, group PFB
1.6.3 Spinal ependymoma
1.6.3.1 Spinal ependymoma, MYCN-amplified
1.6.4 Myxopapillary ependymoma
1.6.5 Subependymoma

2. Choroid plexus tumours

2.1 Choroid plexus papilloma
2.2 Atypical choroid plexus papilloma
2.3 Choroid plexus carcinoma

3. Embryonal tumours

3.1 Medulloblastoma
3.2 Atypical teratoid/rhabdoid tumour
3.3 Cribiform neuroepithelial tumour
3.4 Embryonal tumour with multilayered rosettes
3.5 CNS neuroblastoma, FOXR2-activated
3.6 CNS tumor with BCOR internal tandem duplication

4. Pineal tumours

4.1 Pineocytoma
4.2 Pineal parenchymal tumour of intermediate differentiation
4.3 Pineoblastoma
4.4 Papillary tumor of the pineal region
4.5 Desmoplastic myxoid tumour of the pineal region, SMARCB1-mutant

5. Cranial and paraspinal nerve tumours

5.1 Schwannoma
5.2 Neurofibroma
5.3 Perineurioma
5.4 Hybrid nerve sheath tumour
5.5 Malignant melanotic nerve sheath tumour
5.6 Malignant peripheral nerve sheath tumour
5.7 Paraganglioma

6. Meningioma

Subtypes:
6.1 Meningothelial meningioma
6.2 Fibrous meningioma
6.3 Transitional meningioma
6.4 Psammomatous meningioma
6.5 Angiomatus meningioma
6.6 Microcystic meningioma
6.7 Secretory meningioma
6.8 Lymphoplasmacyte-rich meningioma
6.9 Metaplastic meningioma
6.10 Chordoid meningioma
6.11 Clear cell meningioma
6.12 Atypical meningioma
6.13 Papillary meningioma
6.14 Rhabdoid meningioma
6.15 Anaplastic (malignant) meningioma

7. Mesenchymal, non-meningothelial tumours

7.1 Soft tissue tumours
7.1.1 Fibroblastic and myofibroblastic tumours
7.1.1.1 Solitary fibrous tumour
7.1.2 Vascular tumours
7.1.2.1 Hemangiomas and vascular malformations
7.1.2.2 Hemangioblastoma
7.1.3 Skeletal muscle tumours
7.1.3.1 Rhabdomyosarcoma
7.1.4 Uncertain differentiation
7.1.4.1 Intracranial mesenchymal tumour, FET-CREB fusion-positive
7.1.4.2 CIC-rearranged sarcoma
7.1.4.3 Primary intracranial sarcoma, DICER1-mutant
7.1.4.4 Ewing sarcoma
7.2 Chondro-osseous tumours
7.2.1 Chondrogenic tumours
7.2.1.1 Mesenchymal chondrosarcoma
7.2.1.2 Chondrosarcoma
7.2.2 Notochordal tumours
7.2.2.1 Chordoma (including poorly differentiated chordoma)

8. Melanocytic tumours

8.1 Diffuse meningeal melanocytic neoplasms
8.1.1 Meningeal melanocytosis and meningeal melanomatosis
8.2 Circumscribed meningeal melanocytic neoplasms
8.2.1 Meningeal melanocytoma and meningeal melanoma

9. Hematolymphoid tumours

9.1 Lymphomas
9.1.1 CNS lymphomas
9.1.1.1 Primary diffuse large B-cell lymphoma of the CNS
9.1.1.2 Immunodeficiency-associated CNS lymphoma
9.1.1.3 Lymphomatoid granulomatosis
9.1.1.4 Intravascular large B-cell lymphoma
9.1.2 Miscellaneous rare lymphomas in the CNS
9.1.2.1 MALT lymphoma of the dura
9.1.2.2 Other low-grade B-cell lymphomas of the CNS
9.1.2.3 Anaplastic large cell lymphoma (ALK+/ALK−)
9.1.2.4 T-cell lymphomas and NK/T-cell lymphomas
9.2 Histiocytic tumors
9.2.1 Erdheim–Chester disease
9.2.2 Rosai–Dorfman disease
9.2.3 Juvenile xanthogranuloma
9.2.4 Langerhans cell histiocytosis
9.2.5 Histiocytic sarcoma

10. Germ cell tumours

10.1 Mature teratoma
10.2 Immature teratoma
10.3 Teratoma with somatic-type malignancy
10.4 Germinoma
10.5 Embryonal carcinoma
10.6 Yolk sac tumor
10.7 Choriocarcinoma
10.8 Mixed germ cell tumor

11. Tumors of the sellar region

11.1 Adamantinomatous craniopharyngioma
11.2 Papillary craniopharyngioma
11.3 Pituicytoma, granular cell tumor of the sellar region, and spindle cell oncocytoma
11.4 Pituitary adenoma/PitNET
11.5 Pituitary blastoma

12. Metastases to the CNS

12.1 Metastases to the brain and spinal cord parenchyma
12.2 Metastases to the meninges

Terminology

The 5th WHO classification delineates distinct types of tumors, some of them being further divided into subtypes, rendering the former terms entity and variant obsolete. When molecular diagnostics are not complete enough to allow precise classification, diagnosis should be designated by appending not otherwise specified (NOS). In case of a full molecular workup which does not match any of the standard WHO diagnosis, tumors are to be labeled not elsewhere classified (NEC). [3]

History

1979 WHO classification (1st edition)

Zülch, Histological typing of tumours of the central nervous system. World Health Organization, Geneva

1993 WHO classification (2nd edition)

reflected the advances brought about by the introduction of immunohistochemistry into diagnostic pathology

Kleihues P, Burger PC, Scheithauer BW (eds) (1993) Histological typing of tumours of the central nervous system. World Health Organization international histological classification of tumours. Springer, Heidelberg

2000 WHO classification (3rd edition)

edited by Kleihues and Cavenee

Kleihues P, Cavenee WK (eds) (2000) World Health Organization Classification of Tumours. Pathology and genetics of tumours of the nervous system. IARC Press

2007 WHO classification (4th edition)

This is the classification that began to suggest the use genetic information for classification.

2016 WHO classification (4th revised edition)

This was a substantial revision of the 4th edition. [4] The reason it is not the 5th edition is that additions to the CNS volume were needed even though WHO was not up to 5th editions yet.

2021 WHO classification (5th edition)

The 5th edition [2] incorporated many of the proposed changes outlined by the cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy - Not Official WHO). [1] [5]

WHO Classification of Tumours (Online Edition)

Since February 19, 2020, the WHO tumors classification has been accessible online as a subscription service, which includes the revised 4th edition. [6]

Related Research Articles

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<span class="mw-page-title-main">Nervous tissue</span> Main component of the nervous system

Nervous tissue, also called neural tissue, is the main tissue component of the nervous system. The nervous system regulates and controls body functions and activity. It consists of two parts: the central nervous system (CNS) comprising the brain and spinal cord, and the peripheral nervous system (PNS) comprising the branching peripheral nerves. It is composed of neurons, also known as nerve cells, which receive and transmit impulses, and neuroglia, also known as glial cells or glia, which assist the propagation of the nerve impulse as well as provide nutrients to the neurons.

<span class="mw-page-title-main">Glioma</span> Tumour of the glial cells of the brain or spine

A glioma is a type of tumor that starts in the glial cells of the brain or the spine. Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours.

<span class="mw-page-title-main">Oligodendroglioma</span> Medical condition

Oligodendrogliomas are a type of glioma that are believed to originate from the oligodendrocytes of the brain or from a glial precursor cell. They occur primarily in adults but are also found in children.

<span class="mw-page-title-main">Glioblastoma</span> Aggressive type of brain cancer

Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has very poor prognosis for survival. Initial signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality changes, nausea, and symptoms similar to those of a stroke. Symptoms often worsen rapidly and may progress to unconsciousness.

<span class="mw-page-title-main">Astrocytoma</span> Medical condition

Astrocytoma is a type of brain tumor. Astrocytomas originate from a specific kind of star-shaped glial cell in the cerebrum called an astrocyte. This type of tumor does not usually spread outside the brain and spinal cord and it does not usually affect other organs. After glioblastomas, astrocytomas are the second most common glioma and can occur in most parts of the brain and occasionally in the spinal cord.

This is a list of terms related to oncology. The original source for this list was the US National Cancer Institute's public domain Dictionary of Cancer Terms.

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<span class="mw-page-title-main">Hemangiopericytoma</span> Medical condition

A hemangiopericytoma is a type of soft-tissue sarcoma that originates in the pericytes in the walls of capillaries. When inside the nervous system, although not strictly a meningioma tumor, it is a meningeal tumor with a special aggressive behavior. It was first characterized in 1942.

<span class="mw-page-title-main">Neurofibromatosis type II</span> Type of neurofibromatosis disease

Neurofibromatosis type II is a genetic condition that may be inherited or may arise spontaneously, and causes benign tumors of the brain, spinal cord, and peripheral nerves. The types of tumors frequently associated with NF2 include vestibular schwannomas, meningiomas, and ependymomas. The main manifestation of the condition is the development of bilateral benign brain tumors in the nerve sheath of the cranial nerve VIII, which is the "auditory-vestibular nerve" that transmits sensory information from the inner ear to the brain. Besides, other benign brain and spinal tumors occur. Symptoms depend on the presence, localisation and growth of the tumor(s). Many people with this condition also experience vision problems. Neurofibromatosis type II is caused by mutations of the "Merlin" gene, which seems to influence the form and movement of cells. The principal treatments consist of neurosurgical removal of the tumors and surgical treatment of the eye lesions. Historically the underlying disorder has not had any therapy due to the cell function caused by the genetic mutation.

<span class="mw-page-title-main">Ganglioglioma</span> Medical condition

A ganglioglioma is a rare, slow-growing primary central nervous system (CNS) tumor which most frequently occurs in the temporal lobes of children and young adults. They are mixed cell tumors containing both neural ganglionic cells and neural glial cell components.

Glial tumor is a general term for numerous tumors of the central nervous system, including astrocytomas, ependymal tumors, Oligodendroglioma, and primitive neuroectodermal tumors. The World Health Organization (WHO) classifies tumors into different categories according to severity and recurrence.The first tumor classified as grade I is called pilocytic astrocytoma and it is most commonly observed in children rather than adults. The next tumor is never common in the Dns called diffuse astrocytoma and it is considered a grade II, they are benign, or noncancerous, but can become malignant, meaning cancerous, as the tumor progresses. Grades III and grade IV are considered malignant astrocytomas. Anaplastic astrocytomas are considered by the WHO to be a grade III astrocytoma and Glioblastoma is a grade IV both are referred to high-grade glial tumors.

<span class="mw-page-title-main">Giant-cell glioblastoma</span> Tumor of the central nervous system

The giant-cell glioblastoma is a histological variant of glioblastoma, presenting a prevalence of bizarre, multinucleated giant cells.

<span class="mw-page-title-main">Grading of the tumors of the central nervous system</span>

The concept of grading of the tumors of the central nervous system, agreeing for such the regulation of the "progressiveness" of these neoplasias, dates back to 1926 and was introduced by P. Bailey and H. Cushing, in the elaboration of what turned out the first systematic classification of gliomas.
In the following, the grading systems present in the current literature are introduced. Then, through a table, the more relevant are compared.

Neuro-oncology is the study of brain and spinal cord neoplasms, many of which are very dangerous and life-threatening. Among the malignant brain cancers, gliomas of the brainstem and pons, glioblastoma multiforme, and high-grade astrocytoma/oligodendroglioma are among the worst. In these cases, untreated survival usually amounts to only a few months, and survival with current radiation and chemotherapy treatments may extend that time from around a year to a year and a half, possibly two or more, depending on the patient's condition, immune function, treatments used, and the specific type of malignant brain neoplasm. Surgery may in some cases be curative, but, as a general rule, malignant brain cancers tend to regenerate and emerge from remission easily, especially highly malignant cases. In such cases, the goal is to excise as much of the mass and as much of the tumor margin as possible without endangering vital functions or other important cognitive abilities. The Journal of Neuro-Oncology is the longest continuously published journal in the field and serves as a leading reference to those practicing in the area of neuro-oncology.

Pediatric ependymomas are similar in nature to the adult form of ependymoma in that they are thought to arise from radial glial cells lining the ventricular system. However, they differ from adult ependymomas in which genes and chromosomes are most often affected, the region of the brain they are most frequently found in, and the prognosis of the patients. Children with certain hereditary diseases, such as neurofibromatosis type II (NF2), have been found to be more frequently afflicted with this class of tumors, but a firm genetic link remains to be established. Symptoms associated with the development of pediatric ependymomas are varied, much like symptoms for a number of other pediatric brain tumors including vomiting, headache, irritability, lethargy, and changes in gait. Although younger children and children with invasive tumor types generally experience less favorable outcomes, total removal of the tumors is the most conspicuous prognostic factor for both survival and relapse.

<span class="mw-page-title-main">Diffuse midline glioma</span> Highly aggressive brain tumor, mostly found in children

Diffuse midline glioma, H3 K27-altered (DMG) is a fatal tumour that arises in midline structures of the brain, most commonly the brainstem, thalamus and spinal cord. When located in the pons it is also known as diffuse intrinsic pontine glioma (DIPG).

<span class="mw-page-title-main">Angiocentric glioma</span>

Angiocentric glioma (AG) refers to a rare neuroepithelial tumor when the superficial brain malignant cells enclose the brain vessels, commonly found in children and young adults. Initially identified in 2005 by Wang and his team from the University of Texas, AG was classified as Grade I by 2007 WHO Classification of Tumors of the Central Nervous System due to its benign clinical behavior, low proliferation index, and curative properties. AG primarily affects children and young adults at an average initial diagnosis age of 16 years old. Over 85% AG patients experience intractable seizures since childhood, especially partial epilepsy.

References

  1. 1 2 Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW (Aug 2021). "The 2021 WHO Classification of Tumors of the Central Nervous System: a summary". Neuro-Oncology. 23 (8): 1231–1251. doi:10.1093/neuonc/noab106. PMC   8328013 . PMID   34185076.
  2. 1 2 Central Nervous System Tumours. International Agency for Research on Cancer. 2022. ISBN   9789283245087.
  3. Central Nervous System Tumours (5th ed.). International Agency for Research on Cancer. 2022. p. 12. ISBN   9789283245087.
  4. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, eds. (2016). WHO Classification of Tumours of the Central Nervous System (Revised 4th ed.). Lyon: International Agency for Research on Cancer. ISBN   9789283244929.
  5. Louis, David N.; Aldape, Ken; Brat, Daniel J.; Capper, David; Ellison, David W.; Hawkins, Cynthia; Paulus, Werner; Perry, Arie; Reifenberger, Guido; Figarella-Branger, Dominique; Wesseling, Pieter; Batchelor, Tracy T.; Cairncross, J. Gregory; Pfister, Stefan M.; Rutkowski, Stefan (2017). "Announcing cIMPACT-NOW: the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy". Acta Neuropathologica. 133 (1): 1–3. doi: 10.1007/s00401-016-1646-x . ISSN   0001-6322. PMID   27909809.
  6. "WHO Classification of Tumours Online". International Agency for Research on Cancer.