Vascular Malformations

Slide 1 · Vascular Malformations

Cerebral vascular pathology

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Classify the four principal cerebral vascular malformations.

Relate AVM and cavernous malformation architecture to blood flow.

Recognize characteristic pathology and clinical consequences.

Explain the contrasting endothelial molecular mechanisms.

Use morphology and clinical context to distinguish major lesions.

Slide 3 · Cerebral vascular malformations are not conventional neoplasms

These lesions lack the morphologic hallmarks that characterize neoplasms.

Their vascular anatomy is nonetheless abnormal and clinically consequential.

Somatic endothelial mutations can contribute to their formation.

A pathogenic mutation does not, by itself, establish malignancy.

Slide 4 · Normal arterial–capillary–venous circulation

Feeding artery

Draining vein

Intervening capillary bed

Schematic illustration — not a specimen

Slide 5 · Four principal groups of brain vascular malformations

Category

Pathology focus

Arteriovenous malformation

High-flow shunting; hemorrhage and neurologic symptoms

Cavernous malformation

Low-flow vascular channels; hemorrhagic sequelae

Capillary telangiectasia

One of the four named groups

Venous angioma

One of the four named groups

Slide 6 · Clinically consequential hemorrhage risk is not uniform

AVMs and cavernous malformations

Capillary telangiectasias and venous angiomas

– Highlighted as the two categories linked to hemorrhage

– Neurologic symptoms may develop

– Included in the four-group classification

– Their features are not further detailed in this passage

Slide 7 · Arteriovenous malformations: Dominant clinical burden

Seizures

Intracerebral bleeding

Subarachnoid bleeding

Cerebral AVM

Slide 8 · A lesion can cause bleeding in more than one compartment

Malformed vessels

Vessel rupture

Intracerebral or subarachnoid hemorrhage

The compartment of hemorrhage is a clinical consequence, not a distinct molecular class.

Slide 9 · AVM architecture: A disorganized vascular network

Tangled networks of enlarged, wormlike vascular channels.

Prominent pulsatile arteriovenous shunting.

Vessels can involve the brain, subarachnoid space, or both.

Different vessel-wall phenotypes coexist in one lesion.

Slide 10 · Arteriovenous shunting bypasses a capillary bed

Feeding artery

Draining vein

Direct high-flow shunt through tortuous channels

Schematic illustration — not a specimen

Slide 11 · High flow is intrinsic to AVM architecture

Abnormal artery–vein connection

Prominent shunting

High-flow vascular network

Pulsatile shunting is the defining hemodynamic feature.

Slide 12 · AVMs can occupy two anatomic compartments

Brain parenchyma

Subarachnoid space

– Large abnormal channels within cerebral tissue

– Parenchymal hemorrhage can occur

– Malformed channels can extend over brain surfaces

– Subarachnoid hemorrhage can occur

Slide 13 · AVM gross pathology: Enlarged tortuous channels

Schematic illustration — not a histologic specimen

Dilated vascular profiles

Intervening reactive brain tissue

Slide 14 · AVM vessels are separated by gliotic brain tissue

Gliosis is a tissue response adjacent to abnormal vessels.

Microscopy may show enlarged channels interspersed with gliotic parenchyma.

The presence of gliosis explains why an AVM is not just a bag of isolated vascular spaces.

Slide 15 · Evidence of older hemorrhage may accompany AVMs

Abnormal vascular channels

Prior hemorrhage

Residual tissue injury / gliosis

Evidence of previous bleeding in the AVM-associated brain.

Slide 16 · An arterial component can retain a distorted elastic lamina

Some channels can be recognized as arteries.

Their internal elastic lamina may show duplication.

Fragmentation of the internal elastic lamina may coexist.

These abnormalities support arterial wall remodeling.

Slide 17 · The media can undergo marked structural change

Vessel-wall thickening may be prominent.

The media may be partially replaced by hyalinized connective tissue.

Marked differences in arterial wall architecture may occur within one AVM.

Slide 18 · AVM histology: A mixed population of vascular walls

Arterial-type channels

Remodeled vascular channels

– Elastic lamina duplication or fragmentation

– Varying medial preservation

– Hyalinized connective tissue

– Markedly thickened wall segments

Slide 19 · A compact morphologic recognition checklist

Tortuous, greatly enlarged channels rather than a uniform capillary proliferation.

Mixed vessel-wall appearance, including distorted arteries.

Gliotic brain tissue separating vascular profiles.

Possible evidence of prior bleeding.

Slide 20 · Molecular pathogenesis is endothelial in origin

Activating somatic KRAS mutation

Endothelial RAS signaling dysregulation

AVM pathogenesis implicated

The findings suggest a pathogenic role for RAS signaling; Not a complete deterministic mechanism.

Slide 21 · Somatic KRAS alterations are not germline diagnoses

Somatic in AVM endothelium

What is not established here

– Described within endothelial cells lining malformed channels

– Supports a lesion-local molecular process

– The passage does not describe universal KRAS mutation in every AVM

– It does not define a germline AVM syndrome

Slide 22 · Molecular evidence does not turn an AVM into a tumor

Genomic alteration

Activating KRAS may occur in endothelial cells.

Histologic identity

An AVM still lacks typical neoplastic morphology.

Slide 23 · The RAS hypothesis has a defined evidentiary boundary

Frequent activating somatic KRAS mutations in AVM endothelium.

This association suggests that dysregulated RAS signaling participates in pathogenesis.

It does not establish a universal mutation or an individual patient’s genotype.

Do not equate an implicated pathway with a validated therapeutic target.

Slide 24 · Clinical presentation is often in young patients

AVMs often present between 10 and 30 years of age.

The three clinical presentations highlighted are seizures, intraparenchymal hemorrhage and subarachnoid hemorrhage.

Age is a contextual clue, not a diagnostic criterion.

Slide 25 · Seizures can be the presenting manifestation

Malformed cerebral vascular network

Cerebral tissue involvement

Seizure disorder

Seizure disorder among typical AVM presentations; The precise seizure mechanism is not specified.

Slide 26 · AVMs are a cause of intracerebral hemorrhage

AVM with vulnerable abnormal vessels

Rupture

Primary intraparenchymal hemorrhage

Cerebrovascular context: AVM is one contributor to nontraumatic brain hemorrhage.

Slide 27 · Subarachnoid hemorrhage can also arise from AVM

AVM-associated SAH

Another key cause

– AVM may involve subarachnoid vessels

– Hemorrhage may enter the subarachnoid space

– Ruptured saccular aneurysm

– Discussed separately in the neighboring cerebrovascular section

Slide 28 · Typical AVM topography: Middle cerebral artery territory

The middle cerebral artery territory is the most common site noted.

Posterior branches of the MCA are particularly emphasized.

The territorial predilection is not exclusive or a formal diagnostic rule.

Slide 29 · Neonatal presentation differs from older-patient AVM

Older child / young adult

Newborn with large AVM

– Seizure disorder

– Intracerebral hemorrhage

– Subarachnoid hemorrhage

– Marked arteriovenous shunting

– Congestive cardiac failure may dominate

Slide 30 · Vein of Galen malformation: Abnormal flow path

Feeding artery

Draining vein

Direct high-flow shunt through tortuous channels

Schematic illustration — not a specimen

Conceptual depiction of arterial blood entering venous channels without a normal capillary interface.

Slide 31 · Why a large neonatal shunt can cause heart failure

High-pressure arterial inflow

Direct venous shunting

Cardiac volume burden

Congestive heart failure

Large neonatal AVMs can produce this systemic consequence, especially with vein of Galen involvement.

Slide 32 · The vein of Galen example is anatomically specific

Malformed arteries connect directly to veins instead of traversing capillaries.

High-pressure arterial inflow reaches the venous circulation.

A sufficiently large shunt can compromise cardiac function in a newborn.

Slide 33 · Clinical case: A newborn with cardiac failure

A newborn has severe congestive heart failure. Assessment shows a very large cerebral high-flow vascular lesion with direct arterial connections into deep cerebral venous drainage.

What hemodynamic mechanism links the brain lesion to the heart?

Slide 34 · Case interpretation: Cardiac burden from cerebral shunting

Large cerebral AV shunt

High-pressure blood entering veins

Sustained systemic circulatory burden

Congestive heart failure

Source-consistent reasoning from the neonatal vein of Galen example.

Slide 35 · Cavernous malformations: Low-flow vascular lesions

Composed of distended, loosely organized vascular channels.

Channels are low-flow rather than high-flow shunts.

They do not participate in arteriovenous shunting.

Their pathology and molecular biology differ from AVMs.

Slide 36 · Cavernous channels are arranged back-to-back

Schematic illustration — not a histologic specimen

Contiguous distended spaces

Little intervening tissue is typical

Slide 37 · Cavernous malformations have collagenized walls

The walls of the malformed channels contain collagen.

Wall thickness can vary substantially from channel to channel.

The channels appear loosely organized but closely apposed.

Slide 38 · Intervening brain is usually absent, not invariably absent

Typical pattern

Back-to-back abnormal vascular spaces with no brain tissue between them.

Important exception

Robbins explicitly allows occasional intervening parenchyma; Do not overstate an absolute rule.

Slide 39 · The preferred locations of cavernous malformations

Relative order in Robbins

Region

Most frequent

Cerebellum

Next

Pons

Then

Subcortical regions

Slide 40 · Cavernous lesions can leave hemorrhagic footprints

Old hemorrhage is commonly seen around abnormal channels.

Surrounding infarction may also be present.

Calcification may accompany the lesion.

These changes indicate associated tissue injury over time.

Slide 41 · Anatomic architecture: AVM versus cavernous lesion

Arteriovenous malformation

Cavernous malformation

– Tortuous vessels with substantial shunting

– Gliotic parenchyma often lies between channels

– Back-to-back distended vascular spaces

– Parenchyma is usually absent between channels

Slide 42 · The cerebral cavernous malformation protein complex

CCM protein complex

Limits vascular growth

Maintains a brake on malformation development

The complex as heterotrimeric.

Slide 43 · Loss-of-function mutations disable the CCM brake

Loss of function in CCM-complex genes

Reduced CCM-complex restraint

Permissive abnormal vessel growth

Schematic interpretation of the function and loss-of-function relationship stated.

Slide 44 · PIK3CA gain of function is a second molecular signal

Activating PIK3CA mutation

Pro-malformation signaling

Clinically significant lesion growth

Gain-of-function PIK3CA alterations in rapidly growing clinically significant lesions.

Slide 45 · Clinically significant cavernomas may accumulate mutations

CCM-complex genes

PIK3CA

– Loss-of-function changes

– Remove a growth-limiting function

– Gain-of-function changes

– Promote malformation growth

Slide 46 · Molecular profiles explain distinct pathogenesis models

Lesion type

Reported endothelial alterations

Interpretation

AVM

Activating somatic KRAS

Dysregulated RAS signaling implicated

Cavernous

CCM-complex loss of function; often PIK3CA gain of function in rapidly growing lesions

Reduced growth restraint with pro-growth signaling

Slide 47 · Familial cavernous malformations are a major subgroup

Familial cavernous malformations are relatively common.

Their inheritance is autosomal dominant.

Causative variants affect genes encoding CCM-complex subunits.

Affected individuals generally have multiple lesions.

Slide 48 · Autosomal dominant inheritance explains familial clustering

Pathogenic familial CCM gene variant

Autosomal dominant transmission

Multiple cavernous lesions often occur

Inheritance and lesion multiplicity are stated for familial forms; No penetrance estimate is given.

Slide 49 · Multiplicity is a useful clinical clue

Multiple cavernous lesions

A solitary lesion

– Characteristic of the familial form

– Should prompt consideration of inherited disease

– Does not by itself establish or exclude a genetic contribution

– The source does not specify a formal diagnostic algorithm

Slide 50 · Integrated molecular comparison

AVM: KRAS–RAS

Activating somatic KRAS in vascular endothelium; RAS signaling implicated.

Cavernoma: CCM–PIK3CA

Loss of CCM-complex function with PIK3CA activation in significant growing lesions.

Slide 51 · Blood-flow behavior is a major discriminator

AVM • high flow

Prominent pulsatile arteriovenous shunting drives a high-flow tangle.

Cavernoma • low flow

Low-flow vascular channels without direct arteriovenous shunting.

Slide 52 · Microscopic comparison: Do not use one feature alone

Feature

AVM

Cavernous malformation

Arrangement

Enlarged tortuous mixed channels

Distended spaces back-to-back

Intervening brain

Gliotic tissue described

Usually absent; not invariable

Wall structure

Distorted elastic lamina / media

Variable collagenized wall

Prior injury

Evidence of prior hemorrhage

Old bleed, infarct, calcification

Slide 53 · Clinical comparison is complementary to histology

Domain

AVM

Cavernous malformation

Hemodynamics

High-flow shunting

Low-flow; no AV shunt

Clinical context

Seizures and two hemorrhage compartments

Hemorrhage and neurologic symptoms

Inheritance

Somatic KRAS often described

Familial autosomal dominant CCM variants

Anatomic clue

MCA territory often involved

Cerebellum, pons, subcortical

Slide 54 · The other two named groups require a limited claim

Capillary telangiectasias and venous angiomas complete the four-class list.

This Robbins section emphasizes AVMs and cavernous malformations as symptomatic hemorrhage-risk lesions.

The passage does not provide detailed morphology, genetics or clinical criteria for the other two categories.

Do not invent those omitted specifics from the excerpt.

Slide 55 · Four-category synthesis

Group

Hemodynamic / pathologic cue

Source coverage

AVM

High-flow arteriovenous shunting

Detailed

Cavernous

Low-flow juxtaposed vascular spaces

Detailed

Capillary telangiectasia

Named category

Not elaborated

Venous angioma

Named category

Not elaborated

Slide 56 · A morphology-first classification pathway

Abnormal cerebral vascular channels

Assess shunting and wall pattern

High-flow AVM vs low-flow cavernous

Histology and flow behavior provide complementary—not independently definitive—evidence.

Slide 57 · Nontraumatic hemorrhage has several vascular causes

Distribution / context

Major source-derived considerations

Deep ganglionic hemorrhage

Hypertensive small-vessel disease

Lobar hemorrhage

Cerebral amyloid angiopathy

Subarachnoid hemorrhage

Saccular aneurysm or AVM

Any relevant site

Vascular malformation among broader causes

Slide 58 · Case: A young patient with seizure and vascular tangle

A 19-year-old presents with a first seizure. A cerebral lesion contains tortuous enlarged vessels, gliotic intervening tissue and abnormal arterial elastic laminae.

Which of the four vascular malformations is favored?

Slide 59 · Case interpretation: Arteriovenous malformation

The age and seizure presentation fit Robbins’ typical AVM context.

Tortuous channels plus distorted arterial elastic laminae favor AVM morphology.

Intervening gliotic parenchyma supports the described architectural pattern.

Molecularly, endothelial KRAS activation is a possible mechanism, not a patient-level assumption.

Slide 60 · Case: Multiple low-flow lesions in a family

Several family members have cerebral low-flow vascular lesions. Histology shows distended back-to-back channels with collagenized walls and old bleeding.

What lesion and inheritance pattern are most likely?

Slide 61 · Case interpretation: Familial cavernous malformations

Low-flow back-to-back spaces favor cavernous malformation.

Variable collagenized vascular walls support the distinction from AVM.

Autosomal dominant CCM-complex mutations explain familial clustering.

Multiple lesions are characteristic in affected family members.

Slide 62 · Five principles to retain

Four main cerebral vascular malformation groups are recognized.

AVMs are high-flow lesions with arterial–venous shunting and characteristic vessel-wall remodeling.

Cavernous malformations are low-flow, back-to-back collagenized vascular channels.

Endothelial KRAS alterations implicate RAS in AVMs; CCM and PIK3CA alterations are linked to cavernomas.

Morphology, molecular pathogenesis and clinical context must be interpreted together.

Slide 63 · Diagnostic self-check: classify the abnormal vessels

Are there direct high-flow connections between arteries and veins?

Is the lesion a tangle of remodeled channels with gliotic intervening brain?

Or are there low-flow, back-to-back spaces with collagenized walls?

Does the family history or lesion multiplicity suggest inherited CCM-complex disease?