Neuronal and Glioneuronal Tumors

Slide 1 · Neuronal and

Glioneuronal Tumors

Ganglioglioma and dysembryoplastic neuroepithelial tumor

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Recognize the clinical setting in which neuronal or glioneuronal tumors are suspected.

Distinguish the mixed cellular composition of ganglioglioma from the specific glioneuronal architecture of DNET.

Explain the significance of CNS WHO grade 1, surgical control of epilepsy, and selected molecular findings.

Apply morphologic criteria in focused differential diagnoses.

Slide 3 · A small but distinctive CNS tumor category

Tumors with neuronal differentiation are less common than glial tumors.

The patients emphasized are children and young adults.

Epilepsy is a prominent presenting context for this group.

Cortex

Subcortex

Superficial cortical lesion

The clinical clue is important, but it does not replace tissue-based classification.

Slide 4 · What “glioneuronal” describes

The term signals neuronal and glial differentiation in the tumor.

Ganglioglioma contains a conspicuous mixture of mature neuronal and glial components.

DNET shows a characteristic glioneuronal architectural pattern.

Neuronal

Glial

Slide 5 · Why these tumors commonly enter an epilepsy work-up

Seizures prompt evaluation of a cortical brain lesion.

Many described lesions are superficial or intracortical.

Pathology interprets the lesion using its specific architecture—not seizure history alone.

Seizure presentation

Cortical lesion

Histologic pattern

Slide 6 · CNS WHO grade 1: Meaning within this lecture

Robbins assigns CNS WHO grade 1 to ganglioglioma and DNET.

Grade 1 here accompanies generally slow or benign behavior.

Extent of resection and seizure outcomes are clinically relevant, particularly in epilepsy-associated presentations.

Do not equate grade 1 with “requires no clinical management.”

Slide 7 · The two core entities

Ganglioglioma

Dysembryoplastic neuroepithelial tumor

Mixed neuronal and glial cells

Specific glioneuronal nodules

Commonly temporal; Often cystic

Superficial temporal cortex; Other sites possible

Dysmorphic / binucleate neurons

Floating neurons in mucin-rich pools

BRAF V600E in a subset

FGFR1 alterations are a molecular adjunct*

*FGFR1: EANO / WHO CNS5 supplementary context; Not stated in the Robbins topic excerpt.

Slide 8 · Clinical and diagnostic lens

Age and epilepsy history provide the clinical context.

Anatomic relationship to cortex guides lesion sampling.

Microscopic pattern establishes the key discriminators.

Molecular testing can be an adjunct when clinically indicated.

Clinical context

Histology + architecture

Integrated interpretation

Slide 9 · Ganglioglioma: Defining lesion

Composed of mature neuronal and glial tumor cells.

Typically superficial and associated with seizures.

Robbins calls it the most common neuronal tumor in the CNS.

Abnormal ganglion cells + glia

Slide 10 · Two cellular compartments in ganglioglioma

The neuronal compartment contains abnormal ganglion cells.

The glial compartment often resembles pilocytic astrocytoma.

Both are interpreted in the context of the same lesion.

Neuronal

Glial

Slide 11 · Age and clinical setting of ganglioglioma

Neuronal tumors as a group predominantly affect children and young adults.

Gangliogliomas often come to attention through seizures.

Medically refractory epilepsy is one important surgical presentation.

Seizure presentation

Cortical lesion

Histologic pattern

Slide 12 · Temporal lobe predominance in ganglioglioma

The temporal lobe is the most common site.

The lesion is often close to the cerebral surface.

Location is a clue, not a standalone histologic diagnosis.

Cortex

Subcortex

Superficial cortical lesion

Slide 13 · Superficial growth pattern

Gangliogliomas as typically superficial.

A lesion near cortex can be evaluated in an epilepsy-directed work-up.

Assess the neuron–glia relationship in the tissue sample.

Cortex

Subcortex

Superficial cortical lesion

Slide 14 · Cystic components in ganglioglioma

A cystic component is frequently present.

This is an anatomic feature, not the defining microscopic criterion.

The diagnosis still requires evaluation of the neuronal and glial cells.

Cortex

Subcortex

Cystic component within a lesion

Slide 15 · Slow growth and symptom burden

Most gangliogliomas grow slowly.

Nevertheless, their seizure burden can be substantial.

Clinical impact is not determined by proliferative tempo alone.

A slow-growing cortical tumor may still motivate surgery because of epilepsy.

Slide 16 · Recognizing neoplastic ganglion cells

Ganglion cells appear atypically clustered in the lesion.

Cellular dysmorphism supports the neuronal component.

Aberrant orientation of neuronal processes is another feature noted by Robbins.

Schematic mixed cell population

Slide 17 · Irregular neuronal clustering

Normal cortical neurons are arranged in an ordered tissue context.

Ganglioglioma neurons may form irregular clusters.

Read the clustering alongside cytologic dysmorphism and the associated glial component.

Irregular neuronal grouping

Slide 18 · Dysmorphic neuronal forms

Some neoplastic neurons have conspicuously abnormal shapes.

Dysmorphism is a feature of the neuronal population.

Its significance rests on the overall lesion pattern.

Variation in neuronal form

Slide 19 · Binucleate ganglion cells

Binucleate neuronal forms are specifically described in ganglioglioma.

These coexist with other dysmorphic neuronal forms.

No single cytologic feature should substitute for an integrated interpretation.

Illustrative binucleate neuron

Slide 20 · Random orientation of neuronal processes

Neuronal processes can show disordered directionality.

The finding contrasts with the expected organization of surrounding parenchyma.

Interpret process orientation together with cell distribution and glial morphology.

Disordered process directions

Slide 21 · The glial component often looks pilocytic

Ganglioglioma: Glial component

Pilocytic astrocytoma: Nearby context

Frequently pilocytic-like in morphology

Fibrillary, bipolar “hairlike” astrocytic cells

Intermixed with abnormal neurons

Distinct circumscribed astrocytic tumor

Dual differentiation is decisive

Typical biphasic pattern, Rosenthal fibers / granular bodies

Slide 22 · Why “pilocytic-like” does not equal pilocytic astrocytoma

Similar-looking glial tissue can appear in both settings.

Ganglioglioma diagnosis requires attention to the neuronal population.

A specimen that samples only one compartment can limit confidence.

Cellular components

Tissue architecture

Differential assessment

Slide 23 · The mixed morphology in one field

Large abnormal neurons appear amid a smaller glial population.

Irregular distribution matters as much as individual cell appearance.

This diagram is a simplified model, not an H&E micrograph.

Schematic mixed cell population

Slide 24 · A practical ganglioglioma morphology checklist

Look for abnormal mature-appearing ganglion cells.

Examine clustering and orientation of neuronal processes.

Assess dysmorphic and binucleate forms.

Characterize the accompanying glial component.

Site / age / seizure

Cellular features

Integrated diagnosis

Slide 25 · BRAF V600E occurs in a subset

An activating BRAF V600E mutation in approximately 20%–50% of gangliogliomas.

A negative result does not exclude the entity.

This is a molecular feature in a fraction of tumors, not a universal defining lesion.

Ganglioglioma

BRAF V600E subset

Potential actionability

Robbins: 20%–50% V600E

Slide 26 · An activating BRAF alteration: Conceptual significance

BRAF is a signal-transduction kinase.

The V600E alteration is an activating mutation.

Molecular results complement histomorphology rather than replacing it.

BRAF V600E

Kinase activation

MAPK pathway

Conceptual, not a complete pathway

Slide 27 · When molecular information is clinically relevant

Identify whether the tumor has a therapeutically relevant molecular alteration.

Keep diagnostic classification distinct from an actionable therapeutic finding.

Use the integrated diagnosis and clinical context when interpreting a result.

Slide 28 · Targeted therapy is a selected use of BRAF status

BRAF V600E occasionally provides a basis for targeted therapy.

This does not imply that every ganglioglioma needs targeted treatment.

The source excerpt does not establish a universal treatment algorithm or drug regimen.

Genetic finding

Clinical interpretation

Selected use

Slide 29 · Resection and epilepsy control

For medically refractory epilepsy, surgery is frequently effective in controlling seizures.

This reflects a clinically important consequence of treating the lesion.

Individual outcomes should not be inferred from the general source statement.

Epilepsy-associated lesion

Surgical resection

Seizure assessment

Slide 30 · Ganglioglioma: Clinicopathologic signature

Clinical clue

Tissue discriminator

Young person with epilepsy

Mixed neuronal + glial tumor

Temporal / superficial location

Irregular neuronal clusters

Often a cystic component

Dysmorphic or binucleate neurons

Usually slow growth

Glia often pilocytic-like

Slide 31 · Case 1: Seizure-associated superficial temporal lesion

Illustrative case: A young adult has medically refractory seizures and a superficial temporal lesion.

Resection shows mature-appearing neurons in irregular clusters mixed with glial cells.

Several abnormal neurons are binucleate.

What diagnosis best explains the combined pattern?

Slide 32 · Case 1: Resolving the evidence

Ganglioglioma is supported by the combined neuronal and glial populations.

Irregularly clustered, dysmorphic / binucleate neurons are defining clues.

Clinical site and seizure association strengthen the fit but do not prove the diagnosis.

Abnormal ganglion cells + glia

Slide 33 · DNET: The essential concept

Dysembryoplastic neuroepithelial tumor is a rare, benign CNS WHO grade 1 lesion.

It is strongly linked clinically with epilepsy.

Its characteristic finding is a glioneuronal architecture in a mucin-rich cortical tumor.

Columns + floating neuron

Slide 34 · An epilepsy-associated low-grade cortical tumor

DNET is frequently identified in patients with seizures.

Good prognosis after surgical resection.

The combination of seizure presentation and characteristic tissue architecture is diagnostically useful.

Seizure presentation

Cortical lesion

Histologic pattern

Slide 35 · DNET most often arises in superficial temporal cortex

The usual site is the superficial temporal lobe.

Other locations can occur.

A superficial cortical site supports, but does not establish, the diagnosis.

Cortex

Subcortex

Superficial cortical lesion

Slide 36 · Multiple discrete intracortical nodules

DNET typically consists of multiple discrete nodules.

The nodules are located within cortex.

This low-power organization is important before examining individual cells.

Cortex

Subcortex

Multiple discrete cortical nodules

Slide 37 · The nodules have a mucin-rich matrix

The tumor is characterized by abundant mucin-rich areas.

Basophilic mucin-rich pools.

The matrix forms the setting for the characteristic “floating neurons.”

Mucin-rich extracellular matrix

Slide 38 · Small oligodendrocyte-like cells

A small, round-cell population has oligodendrocyte-like appearance.

These cells participate in the special glioneuronal architectural arrangement.

Cell appearance alone should not lead to an oligodendroglioma diagnosis.

Small oligodendrocyte-like cells

Slide 39 · Columns of small cells are a key architectural clue

Oligodendrocyte-like cells form columns.

The columns organize around central axonal bundles or capillaries.

The low-power columnar pattern is integral to recognizing DNET.

Columnar arrangement

Slide 40 · Axonal bundles may form the column centers

A central axonal bundle may provide the axis of a column.

Small oligodendrocyte-like cells flank the bundle.

The relationship is architectural and must be interpreted on histologic tissue.

Axonal-centered columns

Slide 41 · Capillaries are an alternative column center

Robbins also describes columns around capillaries.

The columnar arrangement is not restricted to axonal bundles.

Compare multiple tumor fields to understand the pattern.

Capillary-centered columns

Slide 42 · Floating neurons in mucin-rich pools

Neurons appear suspended within the basophilic mucinous matrix.

This is the “floating neuron” appearance.

It is a major diagnostic clue when paired with the other DNET architectural features.

Floating neuron in mucin

Slide 43 · Why the floating-neuron pattern is distinctive

The neuron is within a pale, mucin-rich space rather than a dense cellular cluster.

The surrounding small cells and columnar elements provide architectural context.

Do not interpret one isolated neuron without assessing the entire lesion.

Floating-neuron schematic

Slide 44 · DNET at low and higher conceptual magnification

Low-power question

Higher-power question

Are there discrete intracortical nodules?

Are oligodendrocyte-like cells present?

Is the material mucin-rich?

Do small cells form columns?

Where are the nodules distributed?

Are floating neurons present?

Slide 45 · Combining the DNET diagnostic features

Intracortical, discrete mucin-rich nodules.

Oligodendrocyte-like cells in columns around axonal bundles / capillaries.

Floating neurons within basophilic mucinous pools.

Integrated specific glioneuronal pattern

Slide 46 · DNET behavior after resection

Low recurrence rates.

Seizure control is generally favorable after surgical removal.

The grade 1 assignment is consistent with the favorable overall course described.

Epilepsy-associated lesion

Surgical resection

Seizure assessment

Slide 47 · Case 2: Cortical lesion with mucin and floating neurons

Illustrative case: Epilepsy in a young patient with a superficial temporal cortical lesion.

The specimen has multiple mucin-rich nodules.

Small cells form columns around central structures; Neurons appear suspended in mucin.

Which entity fits the architecture best?

Slide 48 · Case 2: Interpreting the pattern

DNET is favored by the combination of cortical nodules, columnar oligodendrocyte-like cells and floating neurons.

The site and epilepsy are compatible.

The diagnosis is supported by the integrated architecture rather than by mucin alone.

Columns + floating neuron

Slide 49 · Ganglioglioma versus DNET: Primary discriminators

Ganglioglioma

DNET

Mixed ganglion + glial cells

Intracortical, mucin-rich nodules

Dysmorphic / binucleate neurons

“Floating” neurons

Irregular neuronal clustering

Oligodendrocyte-like cells in columns

Glia often resemble pilocytic astrocytoma

Columns centered on axons or capillaries

Slide 50 · Shared features must not collapse two diagnoses

What both can share

What separates them

Temporal / superficial association

Distinct cellular / architectural patterns

Epilepsy in young patients

Ganglion-cell dysmorphism vs floating neurons

CNS WHO grade 1

Mixed tumor vs specific mucin-rich nodules

Potential benefit from resection

Histology remains indispensable

Slide 51 · Molecular context: BRAF and FGFR1

Ganglioglioma

DNET

BRAF V600E in ~20%–50% (Robbins)

FGFR1 alterations (WHO CNS5 / EANO)

Activation may occasionally inform targeted therapy

Molecular adjunct to DNET classification

Mutation absence does not erase morphology

Do not substitute a single marker for histology

Slide 52 · Molecular profiling: What a result can and cannot do

A molecular result can support classification in the appropriate morphology.

Ganglioglioma may carry BRAF / MAPK pathway changes (EANO).

DNET is associated with FGFR1 alterations (EANO).

No molecular result should be treated as isolated proof without integrated evaluation.

Slide 53 · Differential: Glial tumor with pilocytic morphology

Pilocytic astrocytoma

Ganglioglioma

Circumscribed astrocytic tumor

Neuronal–glial tumor

Often biphasic microcystic / compact architecture

Neoplastic dysmorphic ganglion cells present

Rosenthal fibers and eosinophilic granular bodies

Glial tissue can itself look pilocytic

Slide 54 · Differential: Small round cells are not sufficient

DNET

Oligodendroglioma, IDH-mutant / 1p19q-codeleted

Oligodendrocyte-like cells in columns

Typically uniform clear-halo cells; Infiltrative glioma

Mucin-rich nodules with floating neurons

Characteristic delicate branching capillary network

CNS WHO grade 1

Requires IDH alteration and whole-arm 1p/19q codeletion

Slide 55 · Differential: Avoid confusing ependymal rosettes with DNET columns

DNET architecture

Ependymoma architecture

Mucin-rich cortical nodules

Often associated with ventricular / spinal system

Small-cell columns around axons / capillaries

Perivascular pseudorosettes with fibrillary nuclear-free zones

Floating neurons may occur

True rosettes may surround a lumen

Slide 56 · Diagnostic sampling: Seek the defining compartment

For suspected ganglioglioma, identify abnormal neuronal cells as well as the glial component.

For suspected DNET, assess low-power nodules and the specific glioneuronal element.

The decision should integrate clinical, anatomic, microscopic and selective molecular findings.

Cellular components

Tissue architecture

Differential assessment

Slide 57 · Pattern-based diagnostic synthesis

Start with cortical location and seizure-associated clinical context.

Ask whether the dominant signature is dysmorphic ganglion cells plus glia, or mucin-rich nodules with floating neurons.

Consider relevant glial/ependymal mimics if the expected architecture is missing.

Clinical context

Histology + architecture

Integrated interpretation

Slide 58 · Morphology challenge: Two schematic fields

Field A: Irregularly clustered, enlarged abnormal ganglion cells mixed with glia.

Field B: Cortical mucin-rich nodules with columnar small cells and floating neurons.

Field A

Field B

Assign the most likely entity to field A and field B.

Slide 59 · Morphology challenge: Answers

Field A → Ganglioglioma: Abnormal mature ganglion cells with a glial component.

Field B → DNET: Distinctive mucin-rich nodules, columnar elements and floating neurons.

Clinical context reinforces—but does not replace—these patterns.

Field A

Field B

Slide 60 · Five distinctions to retain

Ganglioglioma and DNET are CNS WHO grade 1 tumors.

Both often occur in young patients presenting with epilepsy.

Ganglioglioma: Mixed glia plus irregular, often dysmorphic or binucleate ganglion cells.

DNET: Mucin-rich cortical nodules, columns of small cells and floating neurons.

BRAF V600E can have treatment relevance in some gangliogliomas; Molecular findings require context.

Site / age / seizure

Cellular features

Integrated diagnosis

Slide 61 · Selected primary and supplementary references

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. 2026. Chapter 28, pp. 1181–1182.

Louis DN et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro-Oncology. 2021.

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