Oligodendroglioma IDH mutant and 1p 19q codeleted

Slide 1 · Oligodendroglioma

IDH-mutant and 1p/19q-codeleted

Molecular neuropathology • morphology • grading • clinical correlation

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Define

Recognize the integrated entity

Identify its anatomic and clinical setting

Diagnose

Explain the two required molecular findings

Link typical architecture to pathology

Apply

Distinguish grades 2 and 3

Resolve astrocytic mimics with molecular results

Slide 3 · Oligodendroglioma: The entity in one sentence

A diffusely infiltrating glioma with an IDH mutation and whole-arm 1p/19q codeletion.

Defined by combined histologic and molecular assessment.

Assigned CNS WHO grade 2 or 3.

Slide 4 · Adult-type diffuse gliomas: Three molecular entities

Astrocytoma, IDH-mutant

IDH mutation

Often TP53 mutation and ATRX inactivation

Oligodendroglioma

IDH mutation

Whole-arm 1p/19q codeletion

Glioblastoma, IDH-wildtype

IDH-wildtype

Common EGFR amplification, TERT alteration or +7/−10

The genetic groups have different behaviors; The table is not a severity spectrum.

Slide 5 · Integrated diagnosis requires two kinds of evidence

Histologic assessment

Molecular classification

Integrated tumor name

Morphology establishes an infiltrating glioma phenotype.

Genetics assigns the molecular entity; Morphology alone is insufficient.

Slide 6 · Two indispensable molecular findings

IDH1 or IDH2 mutation

Whole-arm 1p / 19q codeletion

Oligodendroglioma

Both alterations are required for the named entity.

Neither “fried eggs” nor delicate capillaries can substitute for molecular confirmation.

Slide 7 · Histology and genetics answer different questions

Histomorphology

Molecular profile

What cellular architecture is present?

Are there mitoses, anaplasia or necrosis?

Is the process infiltrative?

Is an IDH1/IDH2 mutation present?

Are 1p and 19q both lost as whole arms?

Does the result support oligodendroglioma?

Slide 8 · Frequency within the glioma family

Oligodendrogliomas represent approximately 5%–15% of gliomas.

This percentage uses gliomas—not all brain tumors—as the denominator.

Frequency estimates reflect the tumor category and its molecular redefinition.

Textbook frequency; Avoid applying this range to unselected CNS lesions.

Slide 9 · The typical patient: Fourth to fifth decade

Presentation is most common during the fourth and fifth decades of life.

The age distribution overlaps other diffuse adult gliomas.

Age therefore contributes clinical context but cannot establish the subtype.

Slide 10 · Characteristic neuroanatomic location

Neocortex

Superficial white matter

Most lesions occur in the cerebral hemispheres.

The neocortex and superficial white matter are favored.

Cortical involvement provides a substrate for seizures.

Schematic anatomic relationship

Slide 11 · A common clinical presentation: Seizures

Seizures are a frequent manifestation of the superficial hemispheric distribution.

Patients may have neurologic complaints for several years before diagnosis.

A seizure presentation is suggestive of cortical disease, not specific for oligodendroglioma.

Slide 12 · Why the clinical history may be prolonged

Infiltrating glioma

Slow symptom evolution

Delayed tumor recognition

Patients may report years of intermittent seizures or other neurologic complaints.

Long duration does not establish grade 2; Pathology and molecular testing remain necessary.

Slide 13 · The pathogenesis has a molecular foundation

An IDH mutation is necessary—but not sufficient—for oligodendroglioma.

A second defining event is whole-arm 1p/19q codeletion.

Molecular classification is stronger than oligodendrocyte-like cell morphology alone.

Slide 14 · IDH mutation: Diagnostic implications

Gene

Pathogenic IDH1 mutation

Or pathogenic IDH2 mutation

Function

Abnormal isocitrate dehydrogenase activity

Associated altered metabolic signaling

Diagnosis

Establishes IDH-mutant status

Does not distinguish oligodendroglioma from IDH-mutant astrocytoma

Slide 15 · What “whole-arm codeletion” means

Chromosome 1

1p deleted

1q retained

Chromosome 19

19p retained

19q deleted

Whole-arm 1p + whole-arm 19q loss

Slide 16 · Codeletion is a specific chromosomal pattern

Required finding

Not equivalent

Loss of the entire short arm of chromosome 1 (1p)

Loss of the entire long arm of chromosome 19 (19q)

Concordant losses in the same tumor

Isolated loss of 1p or 19q

Focal or partial deletions alone

Loss without evidence of the defining IDH mutation

Molecular method choice must be able to support whole-arm interpretation.

Slide 17 · Molecular lineage: Two-step interpretation

Confirm IDH mutation

Evaluate 1p/19q status

Assign entity

IDH-mutant plus whole-arm 1p/19q codeletion → oligodendroglioma.

IDH-mutant without codeletion → assess astrocytoma-associated features.

Slide 18 · TERT promoter mutations are common

TERT-promoter mutations in the vast majority of oligodendrogliomas.

TERT alteration is a frequent accompanying event—not one of the two defining criteria.

TERT promoter status alone cannot separate all oligodendrogliomas from glioblastomas.

Slide 19 · Additional changes and tumor progression

IDH mutation + codeletion

Additional alterations over time

Higher-grade behavior

Loss of chromosome 9p may delete the CDKN2A tumor-suppressor locus.

This is less common than in IDH-mutant astrocytoma.

Slide 20 · EGFR amplification: A useful contrast

Oligodendroglioma

Glioblastoma, IDH-wildtype

IDH-mutant, 1p/19q-codeleted

TERT promoter mutation frequently present

EGFR amplification not characteristic

IDH-wildtype by definition

EGFR amplification can be present

+7/−10 and TERT promoter alteration also occur

Slide 21 · Diagnostic versus associated genomic findings

Essential

IDH mutation

Whole-arm 1p/19q codeletion

Frequent, associated

TERT promoter mutation

Supports the genomic context

Progression-associated

Chromosome 9p/CDKN2A loss

Not the fundamental entity definition

Slide 22 · Gross morphology: An infiltrating gray lesion

Gray gelatinous mass

Variable cystic change

Possible hemorrhage or calcification

Gross features are characteristic but not molecularly specific.

A seemingly circumscribed mass does not prove a noninfiltrative process.

Slide 23 · Macroscopic cystic and hemorrhagic areas

Cysts and focal hemorrhage in some tumors.

These findings may contribute to heterogeneous gross appearances.

Neither is required for the diagnosis or provides a grading threshold.

Slide 24 · Calcification is a characteristic feature

Calcification may occur in as many as 90% of these tumors.

The amount ranges from microscopic deposits to extensive calcified regions.

Calcification supports recognition but is not diagnostic without molecular confirmation.

Slide 25 · Classic oligodendroglial nuclear appearance

Original schematic — not a histologic specimen

Sheets of relatively regular cells.

Round or spherical nuclei.

Clear perinuclear halos may be present.

Slide 26 · “Fried-egg” cytology is a pattern, not a mutation test

The halo is a recognizable morphologic clue.

Do not diagnose the molecular entity by halo appearance alone.

Integrate tissue morphology with IDH and chromosome-arm status.

Slide 27 · Delicate “chicken-wire” vasculature

Original schematic — not a histologic specimen

Branching fine-walled capillaries.

Network traverses cellular tumor sheets.

An architectural clue, not a genetic assay.

Slide 28 · Perineuronal satellitosis in cortical tissue

Original schematic — not a histologic specimen

Infiltrating tumor cells may collect around native cortical neurons.

The pattern reflects cortical invasion.

Recognize it as growth pattern rather than subtype-specific proof.

Slide 29 · Infiltration beyond the apparent lesion

Neocortex

Superficial white matter

Tumor cells can permeate adjacent cortex and white matter.

Apparent borders do not equal the microscopic extent of disease.

Anatomic growth pattern shapes surgical and sampling challenges.

Schematic anatomic relationship

Slide 30 · Morphology: The three characteristic visual clues

Cytology

Round nuclei

Clear perinuclear halos

Vasculature

Fine branching capillaries

“Chicken-wire” arrangement

Infiltration

Cortical involvement

Perineuronal satellitosis

Any one clue may be absent; Molecular confirmation remains mandatory.

Slide 31 · Grade 2: Relatively low proliferative activity

CNS WHO grade 2 oligodendroglioma shows relatively low mitotic activity.

Proliferation indices are low description.

Morphologic low grade does not imply the absence of infiltrative growth.

Slide 32 · Grade 3: Cellularity increases

Grade 3 lesions have higher cellular density than grade 2 counterparts.

Greater cellularity should be interpreted with other anaplastic features.

No single universal numerical cellularity cutoff is supplied.

Slide 33 · Grade 3: Nuclear anaplasia

Grade 3 tumors may exhibit nuclear anaplasia.

Changes may coexist with familiar round-cell oligodendroglial areas.

Sampling multiple regions matters when the tumor is heterogeneous.

Slide 34 · Grade 3: Increased mitotic activity

An increase in mitoses is a key marker of grade 3 behavior.

Distinguish true mitotic figures from apoptotic or pyknotic nuclei.

Do not invent a mitotic-count cutoff; None is given in the primary excerpt.

Slide 35 · Necrosis can occur in grade 3 tumors

Necrosis in some grade 3 oligodendrogliomas.

In oligodendroglioma, grade 3 is the highest WHO grade.

Do not automatically apply the glioblastoma grade 4 category to a codeleted tumor.

Slide 36 · Grade 2 and grade 3: Morphologic comparison

Feature

Grade 2

Grade 3

Cellularity

Lower

Increased

Nuclear appearance

Relatively uniform

More anaplasia

Mitotic activity

Low

Increased

Necrosis

Not typical

May be present

Integrated identity

IDH-mutant + 1p/19q-codeleted

Same molecular identity

Qualitative Robbins descriptions; Not numerical grading cutoffs.

Slide 37 · Progression from grade 2 to grade 3

Grade 2 tumor

Accumulation of further changes

Grade 3 tumor

High-grade lesions can appear de novo, but progression as more common.

Clinical progression typically occurs over several years.

Slide 38 · Sampling can miss a more aggressive component

A limited sample interrogates only part of a spatially heterogeneous tumor.

Grade assignment should reflect the most aggressive representative histology sampled.

Molecular identity remains important even if the sampled morphology is deceptively bland.

Slide 39 · Tumor type and tumor grade are separate axes

Type: Oligodendroglioma

Grade: 2 or 3

Requires IDH mutation

Requires whole-arm 1p/19q codeletion

Distinct molecular lineage

Uses histologic aggressiveness

Mitoses, cellularity, anaplasia and necrosis

Does not change molecular entity name

Slide 40 · Practical integrated pathology workflow

Recognize diffuse glioma

Establish IDH status

Test 1p/19q whole-arm loss

Integrate the microscopy, IDH result and copy-number findings into the report.

Additional workup helps resolve discordant profiles.

Slide 41 · IDH1 p.R132H immunohistochemistry

Purpose

Detects a common IDH1 mutant protein

Can highlight neoplastic cells in brain

Positive result

Supports IDH-mutant status

Does not prove 1p/19q codeletion

Negative result

Does not exclude other IDH variants

Sequencing may be necessary

Slide 42 · When IDH1 R132H immunostaining is negative

Other pathogenic IDH1 and IDH2 mutations remain possible.

EANO recommends sequencing in relevant adult diffuse glioma settings.

Interpret a negative antibody result as “R132H not detected,” not automatically IDH-wildtype.

Slide 43 · How to interrogate chromosome-arm status

Copy-number methods

Evaluate loss across chromosome arms

Ensure coverage supports whole-arm status

Interpretation

Both 1p and 19q arms must be deleted

Partial deletion is not equivalent

Integrated result

Combine with IDH mutation evidence

Resolve discordant morphology and molecular testing

Supplementary testing framework: EANO molecular diagnostic guideline (2023).

Slide 44 · ATRX and TP53: Discriminating context

Oligodendroglioma profile

Astrocytoma profile

IDH-mutant + 1p/19q-codeleted

ATRX nuclear expression usually retained

TERT promoter alteration frequently present

IDH-mutant without codeletion

ATRX inactivation common

TP53 mutation frequently present

Supportive markers do not replace defining chromosome-arm testing.

Slide 45 · Key molecular contrast across adult diffuse gliomas

Feature

Oligodendroglioma

Astrocytoma, IDH-mutant

Glioblastoma, IDH-wt

IDH

Mutant

Mutant

Wildtype

1p/19q

Whole-arm codeletion

Not codeleted

Not defining

ATRX / TP53

Not characteristic axis

Often altered

Variable

TERT promoter

Common

Less defining

Often altered

CNS WHO grade

2 or 3

2, 3 or 4

4

Slide 46 · Case: A cortical lesion with classic morphology

ILLUSTRATIVE TEACHING CASE

A middle-aged adult has a prolonged seizure history and a superficial hemispheric brain lesion.

Tissue: Round neoplastic nuclei, perinuclear clearing and delicate branching capillaries.

What is required before signing out oligodendroglioma?

Slide 47 · Case interpretation: Confirm the genotype

Histology suggests oligodendroglioma

Demonstrate IDH mutation

Demonstrate 1p/19q codeletion

Only the integrated findings support the specific molecular entity.

The vignette is illustrative; No actual patient data are shown.

Slide 48 · Case: Greater cellularity and mitotic activity

ILLUSTRATIVE TEACHING CASE

An infiltrating hemispheric tumor has the molecular signature of oligodendroglioma.

The tissue shows conspicuous cellularity, anaplasia and increased mitotic activity.

Which grade is supported by these high-grade features?

Slide 49 · Case interpretation: CNS WHO grade 3

The molecular entity remains oligodendroglioma.

Greater cellularity, nuclear anaplasia and mitotic activity support grade 3.

The grade is not converted to “glioblastoma” by high-grade morphology.

Slide 50 · Case: A morphological mimic

ILLUSTRATIVE TEACHING CASE

A diffuse glioma has cells with round nuclei and apparent perinuclear halos.

IDH mutation is identified, but whole-arm 1p/19q codeletion is absent; ATRX nuclear loss is present.

Does the classic-looking cytology establish oligodendroglioma?

Slide 51 · Case interpretation: Phenotype does not override genotype

No: Oligodendroglioma requires whole-arm 1p/19q codeletion.

This molecular pattern directs evaluation toward IDH-mutant astrocytoma.

Cell shape alone is inadequate for assigning tumor lineage.

Slide 52 · Clinical prognosis: Relative—not absolute

Oligodendroglioma

Other diffuse gliomas

Better prognosis than astrocytic counterparts

Long clinical course possible

Grade still modifies outcome

Prognosis varies strongly by molecular type

IDH-wildtype glioblastoma often behaves aggressively

Grade alone is not a cross-entity comparator

Slide 53 · Survival figures reported

Entity

Average survival in textbook

Oligodendroglioma, CNS WHO grade 2

15–20 years

Oligodendroglioma, CNS WHO grade 3

10–15 years

Textbook historical estimates under stated multimodal management; Not individualized prognosis or contemporary cohort data.

Slide 54 · Progression occurs over years, not never

Initial disease

Clinical and molecular evolution

More aggressive recurrence

Progression from lower to higher grade, typically over ≥5 years.

Long survival does not mean cure or absence of recurrence.

Slide 55 · Clinical management

Surgery

Obtain diagnosis and reduce tumor burden

Extent depends on anatomic feasibility

Radiation therapy

Used in treatment strategies

Part of multimodal management

Chemotherapy

Used with surgery and radiotherapy

Therapy details depend on clinical context

This is pathology-oriented context, not a treatment protocol or prescription.

Slide 56 · Grading and prognosis require careful language

Avoid treating textbook average survival as a personal prediction.

Age, lesion location, extent of resection and treatment context may influence patient course.

The molecular diagnosis informs interpretation of histologic grade.

Slide 57 · Common diagnostic errors to avoid

Morphology only

Assuming clear halos prove oligodendroglioma

Ignoring genomic findings

Molecular shortcut

Equating partial-arm loss with codeletion

Treating R132H-negative as IDH-wildtype

Grading shortcut

Automatically using grade 4 for necrosis

Overinterpreting a limited sample

Slide 58 · Oligodendroglioma versus pilocytic astrocytoma

Oligodendroglioma

Pilocytic astrocytoma

Diffuse infiltrating glioma

IDH mutation + 1p/19q codeletion

Typically adult hemispheric tumor

Relatively circumscribed architecture

MAP kinase pathway alterations

Commonly in younger patients and cerebellum

Slide 59 · Oligodendroglioma versus ependymoma

Oligodendroglioma

Ependymoma

Diffuse cortical/subcortical infiltration

Round nuclei and fine capillaries

IDH-mutant and 1p/19q-codeleted

Often ventricular/spinal relation

Perivascular pseudorosettes and true rosettes

Classification also uses location and molecular subtype

Slide 60 · Integrated diagnosis: How to phrase the report

Oligodendroglioma

IDH-mutant and 1p/19q-codeleted

CNS WHO grade 2 or 3

The name documents the molecular definition.

The grade communicates the histologic aggressiveness within this entity.

Slide 61 · Before finalizing the diagnosis

Check

Required interpretation

Histology

Infiltrating glioma; characteristic pattern and grade-relevant features

IDH testing

Pathogenic IDH1 or IDH2 mutation demonstrated

1p/19q testing

Whole-arm codeletion confirmed

Grade

CNS WHO grade 2 or 3 justified

Integrated wording

Entity, molecular status and grade internally consistent

Diagnostic checklist derived with EANO molecular-testing context.

Slide 62 · Summary: Diagnosis, grade, outcome

Identity

Diffuse glioma

IDH mutation + whole-arm 1p/19q codeletion

Morphology

Round nuclei and clear halos

Delicate branching capillaries; Infiltration

Course

Grades 2 and 3

Relatively favorable among gliomas; May progress

Slide 63 · Self-assessment: An apparently low-grade tumor

ILLUSTRATIVE TEACHING CASE

A diffuse cortical glioma contains regular round cells with low mitotic activity.

IDH1 p.R132H is positive. Cytogenetic testing shows no whole-arm 1p/19q codeletion.

Can this be diagnosed as oligodendroglioma, grade 2?

Slide 64 · Answer: Absence of codeletion prevents the diagnosis

The defining molecular pair is incomplete.

Evaluate the alternative adult-type diffuse glioma lineage.

Assign entity and grade only after integrating molecular and histologic information.

Slide 65 · Source references and classification context

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. (2026). Chapter 28, pp. 1177–1180.

WHO Classification of Tumours Editorial Board. Central Nervous System Tumours. 5th ed. (2021).

Sahm et al. Molecular diagnostic tools for WHO 2021 glioma classification: EANO guideline. Neuro-Oncology. 2023.

ASCO–SNO clinical practice guideline for diffuse astrocytic and oligodendroglial tumors in adults (2022).