The 2007 WHO classification of tumours of the central nervous system

The 2007 WHO classification of tumours of the central nervous system David N. Louis Hiroko Ohgaki Otmar D. Wiestler Webster K. Cavenee Peter C. Burger Anne Jouvet Bernd W. Scheithauer Paul Kleihues

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The 2007 WHO classification of tumours of the central nervous system 2007 Acta Neuropathologica 10.1007/s00401-007-0243-4 louis2007-the-2007-who-classification-of-tum louis2007-the-2007-who-classification-of-tum.txt, the project's staged copy d29d58c3ba5df8baf42a26d96a84b75972165678 cc-by-nc medicine

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0 spans located by searching the stored text for the quote's exact words, allowing any whitespace between them AN ENTIRE TAXONOMY BEING REVISED BY A NAMING AUTHORITY - the fourth edition of the WHO classification of CNS tumours, with eight entities added, three variants added, two entities demoted to descriptive phrases, and the admission rules for each rank printed Quotation withheld because this record is not cleared for redistribution. what must be true of a lesion before it may be called a new entity, a variant, or merely a pattern of differentiation Quotation withheld because this record is not cleared for redistribution. a three-rank membership vocabulary with explicit criteria, an updated grading scheme, and ICD-O codes for every entity - presented as 'the standard for the definition of brain tumours' worldwide Quotation withheld because this record is not cleared for redistribution. method Quotation withheld because this record is not cleared for redistribution. a classification whose grade label decides therapy while spanning outcomes from death within a year to 80% five-year survival Quotation withheld because this record is not cleared for redistribution. expert-consensus expert-consensus Quotation withheld because this record is not cleared for redistribution. A THREE-RANK MEMBERSHIP VOCABULARY WITH PUBLISHED ADMISSION RULES: `The Working Group distinguished between clinico-pathological entities, variants of entities and histological patterns. To be included in the WHO classification, two or more reports from different institutions were considered mandatory. Quotation withheld` An evidence threshold, an independence requirement and three ranks of thinghood - the most complete published set of admission rules for a class in this corpus Quotation withheld because this record is not cleared for redistribution. AND THE AUTHORITY SAYS ITS OWN PAST ADMISSIONS FAILED ITS OWN RULE: `histological variants have been introduced if there was evidence that a particular morphological pattern was associated with a different biological or clinical behaviour. Admittedly, in retrospect, this criterion was not always fulfilled.` Four editions of a standard, and the fourth says the first three admitted things they should not have Quotation withheld because this record is not cleared for redistribution. AND AN ENTITY IS DEMOTED TO A DESCRIPTIVE PHRASE, WITH ITS CODE REDIRECTED: `Medulloblastoma with myogenic differentiation was previously termed MEDULLOMYOBLASTOMA ... since its clinical features and genetic profile are similar to those of other medulloblastomas, this lesion is no longer considered A DISTINCT ENTITY and it is suggested that the code for medulloblastoma (9470/3) be applied.` The name survives as a description and loses its standing as a thing - and melanotic medulloblastoma goes the same way in the next paragraph Quotation withheld because this record is not cleared for redistribution. AND A CLASS IS PARKED WITH THE CONDITION FOR ITS PROMOTION NAMED: `Quotation withheld` A pre-registered promotion criterion for a category - and the glioneuronal tumour with neuropil-like islands is parked the same way, needing `more cases with genetic analysis and clinical follow-up` Quotation withheld because this record is not cleared for redistribution. AND THE DISSENT IS PRESERVED WITH THE RIVAL NAMES: `At the WHO consensus meeting, the designation of these tumours was controversial. Some participants proposed the term `OLIGOASTROCYTOMA WHO GRADE IV` or `OLIGODENDROGLIAL GLIOBLASTOMA MULTIFORME`. The majority of pathologists thought that more clinico-pathological data should be available before this tumour is considered a new disease entity.` The losing names are printed, and the interim label - `glioblastoma with oligodendroglioma component` - is explicitly provisional Quotation withheld because this record is not cleared for redistribution. AND A TERM IS NARROWED, WITH ITS DEPRECATED SYNONYMS LISTED: `In the past, the term pituicytoma was also applied to other tumours in the sellar and suprasellar region, particularly granular cell tumours and pilocytic astrocytomas. Presently, it is reserved for low-grade glial neoplasms that originate in the neurohypophysis ... Less preferred terms for pituicytoma include `POSTERIOR PITUITARY ASTROCYTOMA` and ... `INFUNDIBULOMA`.` Our `alternatives` layer again, in a real classification, with a preference order Quotation withheld because this record is not cleared for redistribution. AND A PREFIX IS ADDED BECAUSE ANOTHER FIELD USES THE SAME NAME: the previous edition's `supratentorial primitive neuroectodermal tumours` becomes the more general PNET, and then `Since this designation is also used for similar ... tumours at extracerebral sites, the WHO Working Group proposes to add the prefix CNS to these entities, in order to avoid any confusion.` A name disambiguated by construction rather than by context Quotation withheld because this record is not cleared for redistribution. AND THE GRADING SCHEME DISCLAIMS ITSELF AND IS OPTIONAL: `The WHO classification ... includes a grading scheme that is A `MALIGNANCY SCALE` ranging across a wide variety of neoplasms rather than a strict histological grading system. It is widely used, but not a requirement for the application of the WHO classification.` The instrument that decides radiation and chemotherapy is declared not to be part of the classification it accompanies Quotation withheld because this record is not cleared for redistribution. AND ONE GRADE LABEL SPANS UNDER A YEAR AND OVER 80% FIVE-YEAR SURVIVAL: `The majority of glioblastoma patients ... succumb to the disease within a year. For those with other grade IV neoplasms, the outlook may be considerably better. For example, cerebellar medulloblastomas and germ cell tumours such as germinomas, both WHO grade IV lesions, are rapidly fatal if untreated, while state-of-the-art radiation and chemotherapy result in 5-year survival rates exceeding 60 and 80%.` A class whose members are not alike in the thing the class predicts Quotation withheld because this record is not cleared for redistribution. AND THE GRADES OF THE NEW ENTITIES ARE PROVISIONAL BECAUSE n IS SMALL: `since the number of cases of some newly defined entities is limited, the assignment of grades remains preliminary, pending publication of additional data and long-term follow-up.` Angiocentric glioma rests on 28 reported cases, RGNT on 17, spindle cell oncocytoma on ten from three institutions - and the grade decides the therapy Quotation withheld because this record is not cleared for redistribution. AND TWO GRADING SYSTEMS USE ONE NUMBER FOR DIFFERENT THINGS: `This system is similar to the St Anne/Mayo classification, with the only major difference being grade I; in the WHO system, grade I is assigned to the more circumscribed pilocytic astrocytoma, whereas the St Anne/Mayo classification assigns grade 1 to an exceedingly rare diffuse astrocytoma without atypia.` Same label, different extension, and both live in the same clinics Quotation withheld because this record is not cleared for redistribution. AND THE CRITERION FOR THE TOP GRADE VARIES BY AUTHOR: `For WHO grade IV, some authors accept only the criterion of endothelial proliferation, i.e. an apparent multi-layering of endothelium. The WHO classification also accepts glomeruloid microvascular proliferations. Necrosis may be of any type; perinecrotic palisading need not be present.` The classification is more permissive than some of its users, and says which way Quotation withheld because this record is not cleared for redistribution. TWO DISTINCT ENTITIES SHARE ONE CODE, SO THE REGISTRY CANNOT SEE WHAT THE CLASSIFICATION DISTINGUISHES: `the rosette-forming glioneuronal tumour (RGNT) corresponds to WHO grade I. It shares the new ICD-O code 9509/1 with the papillary glioneuronal tumour (PGNT).` Anaplastic and large cell medulloblastoma likewise share 9474/3. The paper says ICD-O `assures that histopathologically stratified population-based incidence and mortality data become available` - and the stratification stops one level above the entities the same paper just created Quotation withheld because this record is not cleared for redistribution. AND A PATTERN IS NOT A VARIANT, WHICH LEAVES REAL DIFFERENCES UNNAMED: `Surgical pathologists need to know such divergent patterns of differentiation but not every pattern warrants designation as a variant, since some patterns do not have distinct clinical or genetic features.` The rank is decided by consequence, not by appearance - so a reliably recognisable thing can have no name in the system Quotation withheld because this record is not cleared for redistribution. AND THE WORKING GROUP IS ONE MEETING: `a group of 25 pathologists and geneticists convened at the German Cancer Research Center in Heidelberg in November 2006 and the results of their deliberations and those of an additional 50 contributors are contained in the 2007 WHO classification.` No voting rule, no agreement threshold and no dissent count is reported - against bishop2017 and staab2017, which publish all three Quotation withheld because this record is not cleared for redistribution. AND THE NEW-VARIANT RULE IS LOOSER IN THE ABSTRACT THAN IN THE TEXT: the abstract says `Histological variants were added if there was evidence of a different age distribution, location, genetic profile or clinical behaviour` - four alternatives joined by OR - while the Entities section requires a new ENTITY to have distinctive morphology AND location AND age distribution AND biologic behaviour. The conjunction changes between the two statements of the same rule family Quotation withheld because this record is not cleared for redistribution. THE SHARED-CODE ACT IS PERFORMED THREE TIMES IN THIS PAPER AND THE CORPUS RECORDED IT ONCE. Already tagged: RGNT `shares the new ICD-O code 9509/1 with the papillary glioneuronal tumour`. Also in the text, untagged until now: `the 2007 WHO classification recommends the term `EXTRAVENTRICULAR NEUROCYTOMA` and proposes an ICD-O code identical to that of central neurocytoma (9506/1)`. The existing tag says `TWO DISTINCT ENTITIES SHARE ONE CODE, SO THE REGISTRY CANNOT SEE WHAT THE CLASSIFICATION DISTINGUISHES` - that sentence is equally true of 9506/1, and one instance made a policy look like a slip. Quotation withheld because this record is not cleared for redistribution. requiring two or more reports from DIFFERENT INSTITUTIONS before a lesion may be admitted as an entity eliminates: a single centre's case series becoming a worldwide diagnostic category · outcome: held Quotation withheld because this record is not cleared for redistribution. the three-rank scheme itself - refusing varianthood to patterns without distinct clinical or genetic features eliminates: a recognisable appearance being mistaken for a distinct disease · outcome: partial Quotation withheld because this record is not cleared for redistribution. marking the grades of newly defined entities as preliminary until case numbers and follow-up accumulate eliminates: nothing at the bedside - the grade still decides radiation and chemotherapy while it is provisional · outcome: failed Quotation withheld because this record is not cleared for redistribution. Variants Variants Quotation withheld because this record is not cleared for redistribution. a previously defined, overarching entity a previously defined, overarching entity Quotation withheld because this record is not cleared for redistribution. a new entity a new entity Quotation withheld because this record is not cleared for redistribution. an unusual histopathological pattern an unusual histopathological pattern Quotation withheld because this record is not cleared for redistribution. CNS PNET CNS PNET Quotation withheld because this record is not cleared for redistribution. Supratentorial PNET Supratentorial PNET Quotation withheld because this record is not cleared for redistribution. the WHO system the WHO system Quotation withheld because this record is not cleared for redistribution. the St Anne/Mayo classification the St Anne/Mayo classification Quotation withheld because this record is not cleared for redistribution. tumour grade tumour grade Quotation withheld because this record is not cleared for redistribution. the choice of therapies the choice of therapies Quotation withheld because this record is not cleared for redistribution. `entity` (clinico-pathological) - admitted only on TWO OR MORE REPORTS FROM DIFFERENT INSTITUTIONS plus distinctive morphology, location, age distribution and biologic behaviour, and NOT on an unusual histopathological pattern alone Quotation withheld because this record is not cleared for redistribution. `variant` - reliably identifiable histologically and with some relevance for clinical outcome, but STILL PART OF a previously defined overarching entity Quotation withheld because this record is not cleared for redistribution. `pattern of differentiation` - an identifiable histological appearance WITHOUT distinct clinical or pathological significance; the rank for things that look different and do not behave differently Quotation withheld because this record is not cleared for redistribution. `WHO grade` - a `malignancy scale` across all neoplasms rather than a histological grading system, explicitly NOT a requirement for applying the classification, and preliminary for the new entities because their case numbers are small Quotation withheld because this record is not cleared for redistribution. extends → the third edition of the WHO Blue Book (Kleihues & Cavenee 2000), which first incorporated genetic profiles as aids to the definition of brain tumours Quotation withheld because this record is not cleared for redistribution. critiques → the series' own earlier variant admissions - 'Admittedly, in retrospect, this criterion was not always fulfilled' Quotation withheld because this record is not cleared for redistribution. contradicts → the St Anne/Mayo grading of astrocytomas at grade I, which assigns the number to a different tumour Quotation withheld because this record is not cleared for redistribution. Variants —part-of→ a previously defined, overarching entity Variants a previously defined, overarching entity the relation itself is separately evidenced · strength of the relation: 0.95 · note: 'VARIANTS WERE DEFINED…' The rank is defined by containment, not by resemblance - and the paper then demotes medullomyoblastoma out of entityhood and parks small cell glioblastoma below varianthood, so all three ranks are exercised in one document · the relation stated: a variant is recognisable and clinically relevant but does not leave its parent entity - which is exactly what separates it from a new entity Quotation withheld because this record is not cleared for redistribution. a new entity —distinct-from→ an unusual histopathological pattern a new entity an unusual histopathological pattern the relation itself is separately evidenced · strength of the relation: 0.95 · note: 'a new entity…' A published statement of what does NOT count, which the corpus has only in the ENCODE blacklist and in bishop2017's exclusionary-criteria section. Note the conjunction: the abstract's rule for VARIANTS uses OR across the same four properties, and this rule for ENTITIES uses AND · the relation stated: an unusual appearance is explicitly insufficient - a new entity needs distinctive morphology AND location AND age distribution AND biologic behaviour Quotation withheld because this record is not cleared for redistribution. CNS PNET —same-as→ Supratentorial PNET CNS PNET Supratentorial PNET the relation itself is separately evidenced · strength of the relation: 0.95 · note: 'THE TERM CNS…' The reason is a cross-field collision: 'tumours AT EXTRACEREBRAL…' A rename that changes nothing about the object and everything about the reader - and the old name keeps the code · the relation stated: the prefixed name is declared synonymous with the existing ICD-O term, so the rename carries no change of extension - only a change of who can be confused Quotation withheld because this record is not cleared for redistribution. the WHO system —distinct-from→ the St Anne/Mayo classification the WHO system the St Anne/Mayo classification the relation itself is separately evidenced · strength of the relation: 0.95 · note: 'This system is…' Two systems, one number, different referents, both live - and a grade decides whether a patient gets radiation · the relation stated: the two astrocytoma grading systems agree everywhere except grade I, where they assign the same number to different tumours Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span says the WHO system is SIMILAR to the St Anne/Mayo classification with one major difference; distinct-from is loose. Quotation withheld because this record is not cleared for redistribution. tumour grade —causes→ the choice of therapies tumour grade the choice of therapies the relation itself is separately evidenced · strength of the relation: 0.95 · note: 'Histological grading is…' Read against two other sentences in the same paper: the scale is 'NOT A REQUIREMENT…', and for the new entities 'THE ASSIGNMENT…'. An optional, provisional label with a treatment attached · the relation stated: the grade is a key factor in choosing therapy, and in particular in deciding adjuvant radiation and chemotherapy protocols Quotation withheld because this record is not cleared for redistribution. A CLASSIFICATION THAT PUBLISHES ITS ADMISSION RULES: `two or more reports from different institutions were considered mandatory ... and not simply by an unusual histopathological pattern` A CLASSIFICATION THAT PUBLISHES ITS ADMISSION RULES: `two or more reports from different institutions were considered mandatory ... and not simply by an unusual histopathological pattern` Quotation withheld because this record is not cleared for redistribution. AND SAYS ITS OWN PAST ADMISSIONS FAILED THEM: `Admittedly, in retrospect, this criterion was not always fulfilled` AND SAYS ITS OWN PAST ADMISSIONS FAILED THEM: `Admittedly, in retrospect, this criterion was not always fulfilled` Quotation withheld because this record is not cleared for redistribution. AND AN ENTITY DEMOTED TO A DESCRIPTIVE PHRASE: medullomyoblastoma is `no longer considered a distinct entity` and its cases take the medulloblastoma code AND AN ENTITY DEMOTED TO A DESCRIPTIVE PHRASE: medullomyoblastoma is `no longer considered a distinct entity` and its cases take the medulloblastoma code Quotation withheld because this record is not cleared for redistribution. AND A CLASS PARKED WITH ITS PROMOTION CRITERION PRE-REGISTERED: `If future clinical trials show a difference in prognosis and/or response to therapy, the small cell glioblastoma may be reconsidered as a variant` AND A CLASS PARKED WITH ITS PROMOTION CRITERION PRE-REGISTERED: `If future clinical trials show a difference in prognosis and/or response to therapy, the small cell glioblastoma may be reconsidered as a variant` Quotation withheld because this record is not cleared for redistribution. AND ONE GRADE LABEL SPANS DEATH WITHIN A YEAR AND 80% FIVE-YEAR SURVIVAL: glioblastoma against medulloblastoma and germinoma, `both WHO grade IV lesions` AND ONE GRADE LABEL SPANS DEATH WITHIN A YEAR AND 80% FIVE-YEAR SURVIVAL: glioblastoma against medulloblastoma and germinoma, `both WHO grade IV lesions` Quotation withheld because this record is not cleared for redistribution. AND TWO GRADING SYSTEMS USE ONE NUMBER FOR DIFFERENT TUMOURS: `the only major difference being grade I ... whereas the St Anne/Mayo classification assigns grade 1 to an exceedingly rare diffuse astrocytoma without atypia` AND TWO GRADING SYSTEMS USE ONE NUMBER FOR DIFFERENT TUMOURS: `the only major difference being grade I ... whereas the St Anne/Mayo classification assigns grade 1 to an exceedingly rare diffuse astrocytoma without atypia` Quotation withheld because this record is not cleared for redistribution. RGNT, WHO grade I, shares the new ICD-O code 9509/1 with PGNT RGNT, WHO grade I, shares the new ICD-O code 9509/1 with PGNT Quotation withheld because this record is not cleared for redistribution. the term extraventricular neurocytoma is recommended, with an ICD-O code identical to central neurocytoma's (9506/1) the term extraventricular neurocytoma is recommended, with an ICD-O code identical to central neurocytoma's (9506/1) Quotation withheld because this record is not cleared for redistribution. atypical choroid plexus papilloma shares the choroid plexus code but with the /1 extension (9390/1) atypical choroid plexus papilloma shares the choroid plexus code but with the /1 extension (9390/1) Quotation withheld because this record is not cleared for redistribution. `a `MALIGNANCY SCALE` ranging across a wide variety of neoplasms rather than a strict histological grading system ... not a requirement for the application of the WHO classification` WHO grade Quotation withheld because this record is not cleared for redistribution. `two or more reports from different institutions were considered mandatory ... a new entity had to be characterized by distinctive morphology, location, age distribution and biologic behaviour, and not simply by an unusual histopathological pattern. Variants ... still being part of a previously defined, overarching entity. ... patterns ... did not have a distinct clinical or pathological significance` clinico-pathological entities Quotation withheld because this record is not cleared for redistribution. `two or more reports from different institutions were considered mandatory ... a new entity had to be characterized by distinctive morphology, location, age distribution and biologic behaviour, and not simply by an unusual histopathological pattern. Variants ... still being part of a previously defined, overarching entity. ... patterns ... did not have a distinct clinical or pathological significance` variants of entities Quotation withheld because this record is not cleared for redistribution. `two or more reports from different institutions were considered mandatory ... a new entity had to be characterized by distinctive morphology, location, age distribution and biologic behaviour, and not simply by an unusual histopathological pattern. Variants ... still being part of a previously defined, overarching entity. ... patterns ... did not have a distinct clinical or pathological significance` histological patterns Quotation withheld because this record is not cleared for redistribution. plus distinctive morphology, location, age distribution and biologic behaviour evidence threshold for a new entity Quotation withheld because this record is not cleared for redistribution. no voting rule, agreement threshold or dissent count is reported the Working Group Quotation withheld because this record is not cleared for redistribution. and grade II typically survive more than 5 years, grade III 2-3 years outcome span within WHO grade IV Quotation withheld because this record is not cleared for redistribution. `patients with WHO grade II tumours typically survive more than 5 years and those with grade III tumours survive 2-3 years` - an ordered scale - and then grade IV contains both `succumb ... within a year` and `5-year survival rates exceeding 60 and 80%`. The scale is monotone until its last step, where it stops being a scale at all a label that predicts opposite outcomes inside itself Quotation withheld because this record is not cleared for redistribution. the property that decides rank at every level - it separates an entity from a pattern, a variant from a pattern, and it is what a grade is meant to predict. And it is the one property that cannot be read off the slide, which is why two of the new categories are parked pending clinical follow-up biologic behaviour Quotation withheld because this record is not cleared for redistribution.

The full text of this article is not redistributable, so it is not included here. The evidence sentences are withheld with it; the tag layer and its grounding status remain. The article itself is at https://doi.org/10.1007/s00401-007-0243-4.