Practical Imaging for the Surgical Pathologist

Gregory N. Fuller, MD, PhDProfessor and Chief Neuropathologist

M D Anderson Cancer CenterHouston, Texas

gfuller@mdanderson.org

3rd Annual

SoutheasternPathology Conference

November 2018

The Importance of Imaging Studies to the Pathologist Cannot be Stressed Enough!

Rubin’s Pathology7th Edition

2015

The Importance of Imaging Studies to the Pathologist Cannot be Stressed Enough!

The Importance of Imaging Studies to the Pathologist Cannot be Stressed Enough!

Rubin’s Pathology7th Edition

2015

The Importance of Imaging Studies to the Pathologist Cannot be Stressed Enough!

Rubin’s Pathology7th Edition

2015

The Importance of Imaging Studies to the Pathologist Cannot be Stressed Enough!

Rubin’s Pathology6th Edition

2011

Contemporary neuroimaging techniques provide the first look at the “gross pathology” of a CNS lesion and constitute a rich source of information that can be utilized by the pathologist to formulate a refined differential diagnosis prior to surgical biopsy and tissue examination.

The Importance of Imaging Studies to the Pathologist Cannot be Stressed Enough!

Rubin’s Pathology7th Edition

2015

Go to the Operating RoomPeter C. BurgerAm J Surg Path 1988

1988

Go to the Operating RoomPeter C. BurgerAm J Surg Path 1988

“…the radiographs on display in the operating theater are as relevant to the work of the pathologist as they are to the neurosurgeon.”

1988

Importance of Knowing what the

Pre-operative MR Imaging Studies

Show

Importance of Pre-op Imaging

Biopsy (H&E)

Pre-operative MR Imaging

Pre-op MRI: coronal T1 post-contrast Biopsy (H&E)

Importance of Pre-op Imaging

Pre-op MRI: coronal T1 post-contrast Biopsy (H&E)

YIKES!Importance of Pre-op Imaging

Pre-op MRI: coronal T1 post-contrast Biopsy (H&E)

The biopsy was NOT representative!

Importance of Pre-op Imaging

Our patients are best served by a collegial Team Approach –

surgeon, oncologist, radiologist, pathologist

To be able to talk to the other team

members, you must be able to speak their

language!

Practical Neuroimaging

for the

Surgical Pathologist

Information Gained from MRI

Information Gained from MRI

Anatomic location of the lesion(s)

Information Gained from MRI

Anatomic location of the lesion(s)

Nature of interface of lesion border with brain parenchyma (sharp margin vs. diffuse infiltration)

Information Gained from MRI

Anatomic location of the lesion(s)

Nature of interface of lesion border with brain parenchyma (sharp margin vs. diffuse infiltration)

Presence or absence of contrast enhancement

Information Gained from MRI

Anatomic location of the lesion(s)

Nature of interface of lesion border with brain parenchyma (sharp margin vs. diffuse infiltration)

Presence or absence of contrast enhancement

If contrast-enhancing, pattern of enhancement

Patterns of Contrast Enhancement

Patterns of Contrast Enhancement

Smooth ring

Ragged ring

C-shaped ring

Solid, uniform

Cyst w/ nodule

Dark ring*

*T2, T2-FLAIR, GRE, SWI

Patterns of Contrast Enhancement

Smooth ring Abscess

Ragged ring GBM, Metastasis

C-shaped ring Demyelinating pseudotumor

Solid, uniform Meningioma, PCNSL

Cyst w/ nodule JPA, PXA, Ganglioglioma

Dark ring* Cavernoma, Abscess

*T2, T2-FLAIR, GRE, SWI

Patterns of Contrast Enhancement

Patterns of Contrast EnhancementAbscess Demyelinating

PseudotumorGBM

PCNSL CavernomaPXA

Magnetic Resonance Imaging

• Axial• Coronal• Sagittal

3 Planes of Section

Sagittal

CoronalAxial

Histopathology

•Hematoxylin & Eosin

1 “Work horse” Stain

MRI

•T1 without contrast (pre-contrast)

•T1 with contrast (post-contrast)

•T2

•T2-FLAIR (fluid attenuation inversion recovery)

4 “Work horse” Sequences

Magnetic Resonance Imaging

2 Simple Principles• On T2-weighted images, water (H20) is

hyperintense (bright, white)

• White matter is rich in myelin; myelin is a fat; thus, normal white matter contains lesswater than gray matter; thus, white matter is darker (hypointense) compared to gray matter on T2-weighted images

T2-weighted images

( H20 )

• Cerebrospinal fluid (CSF) is very bright (white, hyperintense)

• Gray matter, because it has more water, is brighter (hyperintense) compared to white matter

If the CSF is Bright (White, Hyperintense), it’s a T2-weighted

Sequence

• Cerebrospinal fluid (CSF) is dark (black, hypointense)

• Gray matter is darker (hypointense) compared to white matter on T1-weighted images

T1-weighted Images (T1WI)

Compare Cortex with White Matter

If Cortex is Brighter than White Matter: T2

If Cortex is Darker than White Matter: T1

(in an area of normal brain away from the lesion)

So… is it a T1? or a T2?

Whether or not a lesion exhibits contrast enhancement is assessed

only on T1-weighted sequences

(the contrast agent is gadolinium)

(compare T1-pre with T1-post)

Whether or not a lesion exhibits contrast enhancement is assessed

only on T1-weighted sequences

T1-pre

Whether or not a lesion exhibits contrast enhancement is assessed

only on T1-weighted sequences

T1-pre T1-post

Whether or not a lesion exhibits contrast enhancement is assessed

only on T1-weighted sequences

T1-pre T1-post T2

DO NOT CONFUSE T2 Brightness (Water: CSF, Edema) with Contrast

Enhancement !

DO NOT CONFUSE T2 Brightness (Water: CSF, Edema) with Contrast

Enhancement !

T1

DO NOT CONFUSE T2 Brightness (Water: CSF, Edema) with Contrast

Enhancement !

T1

DO NOT CONFUSE T2 Brightness (Water: CSF, Edema) with Contrast

Enhancement !

T1

The CSF in the subarachnoid space is BRIGHT, and the CORTEX IS BRIGHTER than the white matter, so it’s a T2 sequence!

T1 T2

DO NOT CONFUSE T2 Brightness (Water: CSF, Edema) with Contrast

Enhancement !

The CSF in the subarachnoid space is BRIGHT, and the CORTEX IS BRIGHTER than the white matter, so it’s a T2 sequence!

T1 T2 T1-post

DO NOT CONFUSE T2 Brightness (Water: CSF, Edema) with Contrast

Enhancement !

T1 without (pre) or with (post) contrast? Look for bright blood

vessels, choroid plexus

T1 without (pre) or with (post) contrast? Look for bright blood

vessels, choroid plexus

T1 pre T1 post

T1 without (pre) or with (post) contrast? Look for bright blood

vessels, choroid plexus

• Normal H20 (CSF) signal is suppressed; thus the ventricles and subarachnoid spaces are dark (black, hypointense)

• But… the gray matter is still brighter (hyperintense) compared to the white matter, so it is a T2-based sequence, not a T1 T2-FLAIR

What is a T2-FLAIR Image?

The Ventricles are Black:

Is it a T1? or a T2-FLAIR?

The Ventricles are Black:

Is it a T1? or a T2-FLAIR?

Compare Cortex with White Matter to Determine if the Scan

is a T1 or T2 weighted sequence!

The Ventricles are Black:

Is it a T1? or a T2-FLAIR?

The Ventricles are Black:

Is it a T1? or a T2-FLAIR?

T2-FLAIR T1-pre

The Ventricles are Black:

Is it a T1? or a T2-FLAIR?

T2-FLAIR T1-preT2

The Ventricles are Black:

Is it a T1? or a T2-FLAIR?

You see Abnormal Bright Signal!

You see Abnormal Bright Signal! Is it contrast enhancement on a T1 post, or

is it edema on a T2 or T2-FLAIR ???

You see Abnormal Bright Signal! Is it contrast enhancement on a T1 post, or

is it edema on a T2 or T2-FLAIR ???

You see Abnormal Bright Signal! Is it contrast enhancement on a T1 post, or

is it edema on a T2 or T2-FLAIR ???

The cortex is hyperintense to white matter, thus it’s a T2 sequence

You see Abnormal Bright Signal! Is it contrast enhancement on a T1 post, or

is it edema on a T2 or T2-FLAIR ???

The cortex is hyperintense to white matter, thus it’s a T2 sequence

The CSF is dark, thus it’s a T2-FLAIR

You see Abnormal Bright Signal! Is it contrast enhancement on a T1 post, or

is it edema on a T2 or T2-FLAIR ???

The cortex is hyperintense to white matter, thus it’s a T2 sequence

The CSF is dark, thus it’s a T2-FLAIR

It’s a T2-FLAIR, thus the bright signal is edema, not contrast enhancement!

Superior Sensitivity of T2 & T2-FLAIR compared to T1-post

T1-post

Do you see an obvious

lesion?

Superior Sensitivity of T2 & T2-FLAIR compared to T1-post

T2-FLAIR

Superior Sensitivity of T2 & T2-FLAIR compared to T1-post

T1-post

ADVANTAGE of T2-FLAIR over T2

ADVANTAGE of T2-FLAIR over T2

T2

Do you see an obvious

lesion?

ADVANTAGE of T2-FLAIR over T2

T2 T2-FLAIR

For a Quick Look: T2-FLAIRand T1-Post Contrast

For a Quick Look: T2-FLAIRand T1-Post Contrast

T2-FLAIR T1-POST

3 “Advanced” MR Imaging Sequences Relevant to Pathologic Diagnosis

DWI: Diffusion-Weighted Imaging

T2-GRE (Gradient Echo; T2*, “T2 Star”)

SWI: Susceptibility-Weighted Imaging

DWI: Diffusion-Weighted Imaging

“Restricted Diffusion” Bright on DWI - Dark on ADC map - Bright on T2-trace

• Acute Infarct (within 6 hrs. of stroke –7d)

• Pyogenic Abscess

• Epidermoid cyst

• Hypercellular tumors (PCNSL, PNET, etc)

Restricted diffusion: Abscess

DWI

DWI: Diffusion-Weighted Imaging

Restricted diffusion: Abscess

DWI ADC Map

DWI: Diffusion-Weighted Imaging

T2-GRE (T2*): Gradient Echo

Useful for detecting:

• Blood products

• Iron

• Calcium all appear hypointense (dark, black)

Cavernous Malformation

T2-GRE (T2*): Gradient Echo

SWI: Susceptibility-Weighted

Useful for detecting:

• Blood products

• Iron

• Calcium

• Small Veins

all appear hypointense (dark, black)

SWI: Susceptibility-Weighted

Useful for detecting:

• Blood products

• Iron

• Calcium

• Small Veins

Shifting Gears

Differential Diagnosisbased on

Preoperative Imaging

POP

QUIZ!

Circumscribed Intraventricular Mass Lesion

• Choroid plexus papilloma• Atypical choroid plexus papilloma• Choroid plexus carcinoma• Choroid plexus meningioma• Choroid plexus xanthogranuloma• Ependymoma• Subependymoma• Subependymal giant cell astrocytoma• Central neurocytoma• Solitary metastasis to the choroid

plexus (especially renal cell carcinoma)

Circumscribed Intraventricular Mass Lesion

Circumscribed Cyst with

Enhancing Nodule in the Cerebellum

• Pilocytic astrocytoma• Hemangioblastoma• Cystic metastasis

Circumscribed Cyst with

Enhancing Nodule in the Cerebellum

Circumscribed Cyst with

Enhancing Nodule in the Cerebellum

in a 5yo Child

Circumscribed Cyst with

Enhancing Nodule in the Cerebellum

in a 5yo Child

• Pilocytic astrocytoma

Circumscribed Cyst with

Enhancing Nodule in the Cerebellum

in a 56yo Man

Circumscribed Cyst with

Enhancing Nodule in the Cerebellum

in a 56yo Man

• Hemangioblastoma• Cystic metastasis

Circumscribed Intraventricular Mass Lesion in the Lateral Ventricle Atrium (choroid plexus: glomus choroideum)

Circumscribed Intraventricular Mass Lesion in the Lateral Ventricle Atrium (choroid plexus: glomus choroideum)

Choroid plexus meningioma MORE LIKELY

Circumscribed Intraventricular Mass Lesion in the Lateral Ventricle Atrium (choroid plexus: glomus choroideum)

Choroid plexus meningioma MORE LIKELY

Central neurocytoma LESS LIKELY

Sellar / Suprasellar Mass

Sellar / Suprasellar Mass• Pituitary adenoma• Pituitary adenoma• Pituitary adenoma• Pituitary adenoma• Pituitary adenoma• Pituitary adenoma• Pituitary adenoma

• Craniopharyngioma• Granular cell tumor• Pituicytoma• Spindle cell

oncocytoma• Etc.

Sellar / Suprasellar Mass

Diffuse Lesion

• Diffuse glioma

Diffuse Lesion

T1 T2-FLAIRT2 T1-Post

T1 - hypointenseT2 and T2-FLAIR – hyperintense – extends into cortical gray up to pial surface when invasion is presentT1-post - no enhancement

Diffuse Glioma – ImagingGrades II & III

Not Just Histologic - Radiologic Too!

“Blurring” of the Gray-White Junction

Rubin’s Pathology, 6th Ed, 2011

T2-Hyperintense Diffuse Lesion: “Blurring of the Gray-White Junction” Secondary to Diffuse Glioma Infiltration of the Cortex

Ring Enhancing (Rim Enhancing) Mass

Smooth ring

Ring Enhancing (Rim Enhancing) Mass

• Abscess

Smooth ring

Ring Enhancing (Rim Enhancing) Mass

• Abscess• Glioblastoma• Metastasis

Smooth ring

Ring Enhancing (Rim Enhancing) Mass

Pineal Region Mass

• Germinoma

Pineal Region Mass

• Germinoma• PPT

Pineal Region Mass

• Germinoma• PPT• Meningioma

Pineal Region Mass

• Germinoma• PPT• Meningioma• CPP

Pineal Region Mass

• Germinoma• PPT• Meningioma• CPP• Ependymoma

Pineal Region Mass

• Germinoma• PPT• Meningioma• CPP• Ependymoma• PTPR

Pineal Region Mass

• Germinoma• PPT• Meningioma• CPP• Ependymoma• PTPR• Metastasis

Pineal Region Mass

Diffuse Enlargement of the

Pons

Diffuse Enlargement of the

Pons• DIPG

Diffuse Enlargement of the

Pons• DIPG

(diffuse intrinsic pontine glioma)

Multiple Lesions

• Metastasis

Multiple Lesions

• Metastasis• Multiple

abscesses

Multiple Lesions

• Metastasis• Multiple

abscesses

Multiple Lesions

• Tumor Predisposition Syndrome (multiple primary tumors)

• Multiple vascular malformations

Multiple Lesions

• Multiple vascular malformations

• Multiple parasites (eg, cysticercosis)

Multiple Lesions

• Multiple vascular malformations

• Multiple parasites (eg, cysticercosis)

Multiple Lesions

• Multicentric glioma

Ring Enhancing Mass

Ring Enhancing Mass

Ragged ring

Ring Enhancing Mass

Ragged ring

• Glioblastoma• Metastasis

Ring Enhancing Mass

Ragged ring

• Glioblastoma• Metastasis

• Abscess

Uniformly Enhancing Periventricular Masses

PCNSL

PCNSL(primary CNS large B-cell lymphoma)

Dura-Based Mass

•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma

Dura-Based Mass

•SFT/HPC Family Tumor

•Plasmacytoma

•Granulocytic Sarcoma (Chloroma)

•Dural Marginal Zone (MALT-like) B-cell lymphoma

•Solitary metastasis

•Calcifying pseudotumor (fibro-osseous lesion)

• Inflammatory pseudotumor

• Idiopathic hypertrophic pachymeningitis

•Sarcoidosis

•Rosai-Dorfman Disease

•Castleman Disease

•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma•Meningioma

Dura-Based Mass

The Pathologist as a Physician

Putting it all together…

Case StudyPutting it all together…

HistoryA 30-year old woman presented with complaint of headache.

MR imaging studies showed a non-enhancing multicystic left frontal lobe lesion.

History

Open biopsy was performed at the local community hospital.

The H&E slides were outsourced to a reference lab, where a diagnosis of “low-grade diffuse astrocytoma” was rendered, with recommendation that additional molecular signature studies be performed (testing not available at the reference laboratory).

History

Subsequent immunohistochemical and FISH testing at 3 different reference and university laboratories showed:Ki67 index: <1%1p/19q intact (negative for codeletion)

History

The last university lab recommended that additional molecular testing for diffuse glioma-associated biomarkers be performed by chromosome microarray.

History

Based on the outsourced report data from the 3 reference laboratories, the final community hospital diagnosis was:

Diffuse Astrocytoma, NOS (IDH status was never determined, despite the use of 3 outside laboratories)

WHO Grade II

History

SRS (stereotactic radiosurgery) was administered to the residual portion of the lesion

History

SRS (stereotactic radiosurgery) was administered to the residual portion of the lesion

The patient received 3 cycles of temozolomide (Temodar)

History

SRS (stereotactic radiosurgery) was administered to the residual portion of the lesion

The patient received 3 cycles of temozolomide (Temodar)

Temodar treatment was subsequently discontinued secondary to side effects

History

Surveillance MR imaging showed no effect of the SRS or 3 cycles of chemotherapy on the residual lesion; the patient was told there were no further treatment options.

History

Patient self-referred to MDACC for a second opinion on treatment options.

History

As part of standard MDACC procedure, the referring institution biopsy slides, all reference lab reports, and

the preoperative MR imaging studies were obtained for review.

History

As part of standard MDACC procedure, the referring institution biopsy slides, all reference lab reports, and

the preoperative MR imaging studies were obtained for review.

This represented the first time in the patient’s clinical

evaluation that a single physician, the Pathologist, had assembled and reviewed all of the relevant clinical information (including, critically, the preoperative MR imaging studies).

Food for Thought

Food for Thought

Two things evolving over the last two decades have transformed surgical pathology and the surgical pathologist.

Food for Thought

Two things evolving over the last two decades have transformed surgical pathology and the surgical pathologist.

• The Advent of Genomic Pathology

Food for Thought

Two things evolving over the last two decades have transformed surgical pathology and the surgical pathologist.

• The Advent of Genomic Pathology

• The Electronic Medical Record

Food for Thought

For the first time in the history of our Specialty

Food for Thought

For the first time in the history of our Specialty the Pathologist is the FIRST MEMBER of the Clinical Team

Food for Thought

For the first time in the history of our Specialty the Pathologist is the FIRST MEMBER of the Clinical Team to have all of the Critical Information needed to render an Integrated Diagnosis

Food for Thought

For the first time in the history of our Specialty the Pathologist is the FIRST MEMBER of the Clinical Team to have all of the Critical Information needed to render an Integrated Diagnosis upon which everything is based.

Team Approach to Patient Care - the

Standard of

Excellence

Weekly Multidisciplinary MDACC Neuropathology Case Conference

25-30 attendees, including neuroradiologists, neurosurgeons, neuro-oncologists

2018

Thank You!

gfuller@mdanderson.org