imaging of brain metastases from melanoma

Imaging of Melanoma Metastases in the Brain

Jessica J. Kim, HMS III & Dr. Gillian Lieberman, M.D. Harvard Medical School

Beth-Israel Deaconess Medical CenterMay 21, 2010

Overview

•

Melanoma–

Background–

Brain metastases: Epidemiology, Symptoms, Treatment

•

Menu of imaging modalities in brain melanoma

•

Case presentation–

Patient AC clinical history and imaging by MRI–

Variety of appearances of brain melanoma on MRI

•

Utility of alternative imaging modalities (CT, FDG-PET)

Let’s discuss why we want to learn about diagnostic imaging of metastatic melanoma in the brain

Melanoma•

Tumor of melanocytes

•

4% of all dermatologic cancers, but 80% of all skin cancer deaths

•

619% ↑

in annual diagnoses, 165% ↑ in annual mortality (1950-2000)

•

Metastasizes to virtually any organ unlike other skin cancers

•

Stage IV median survival < 1 yr (Source for Fig. 1A and B: Tsao

et al., 2004)

Miller and Mihm

(2006) NEJM; Tsao

et al. (2004) NEJM.

1A

1B

Melanoma: Metastasis

SITE

CLINICALLY

AUTOPSY•

Lung 18-36% 70-87%

• Liver 14-20% 54-77%

• Brain 12-20% 36-54%

• Bone 11-17% 23-49%

• GI tract 1-7% 26-58%

Other sites: Heart, Pancreas, Adrenals, Kidney, Thyroid

Donohoe

(2010) UpToDate

Melanoma: Metastasis

Sloan et al. (2009) Cancer Control; Eichler

and Loeffler

(2007) Oncologist; Testori

et al. (2009) Ann Oncol

•

3rd most common cause of brain metastases

•

Highest propensity to metastasize to the brain of all primary tumors in adults

•

Clinical features:–

Headaches & symptoms from increased pressure–

Focal neurologic deficits–

Seizures; cognitive impairment

“Given the recognized neurotropism of melanoma, neurological symptoms in a melanoma patient should prompt diagnostic imaging studies.” (Sloan et al., 2009)

Let’s preview the menu of tests and their use in brain melanoma imaging

Imaging of Brain Metastases

Mohr et al. (2009) Ann Oncol; Delbeke

(1999) J Nuc

Med; Donohoe

(2010) UpToDate

•

Indications –

Neurologic symptoms in patients with known melanoma–

Accurate prognosis and optimal palliative treatment –

Re-staging–

R/O brain metastases before initiating new chemotherapy

1.

MRI with contrast: Study of choice to assess melanoma in CNS!–

More sensitive than CT for detecting brain mets–

Detect spinal cord and leptomeningeal

involvement–

Detect associated hemorrhage or melanin –

Contraindications: non MRI-compatible objects in/on the patient

2.

CT: Patients with MRI contraindications; emergency setting; staging

3.

18FDG-PET/CT: Less sensitive for brain mets, but can be useful

Before we proceed, let’s get our eyes used to the normal brain anatomy on a few MRI images

(Source : Johnson & Becker. “The Whole Brain Atlas.”

http://www.med.harvard.edu/AANLIB/home.html)

We have:

1) Learned why diagnostic imaging of metastatic melanoma in the brain is important

2) Reviewed the menu of tests relevant for our discussion

3) Familiarized ourselves with a bit of normal brain anatomy

We are now ready to apply and expand our knowledge…

Interim Summary 1

Case Presentation Patient AC and Her Intractable

Melanoma Brain Mets

Patient AC

42 yo

female with history of metastatic melanoma, presented to ED in 3/07 with headache

2/07: Diagnosed with the first brain mets

from melanoma after experiencing severe headaches; underwent whole brain radiation; dexamethasone

wean to begin TMZ

1d prior to admission: Onset of “slight”

bifrontal

headaches

Day of admission: Worse headaches, pain 5-6/10

Neurologic ROS unremarkable

Patient AC

As the patient presented to the ED with acute headache, CT was first ordered to r/o

bleed

Patient AC: CT 3/07

Axial CT w/o contrast, 3/07

Multiple brain lesions, the largest mass in the right frontal lobe measuring 2.3 cm, iso-

to hyper-attenuating (isodense

to hyperdense), with extensive edema

(Source for Fig. 2: PACS, BIDMC)

2

Patient AC

MRI was recommended for further evaluation of intracranial masses

Patient AC: MRI 3/07

Sagittal

T1-weighted MR w/o contrast, 3/07 Axial T1-weighted MR w/o contrast, 3/07

Nodular area in the right frontal lobe of heterogeneous hyper-

and iso-intensity, surrounded by extensive area of vasogenic

edema


3A 3B


Sagittal

T1-weighted MR w/ contrast, 3/07 Axial T1-weighted MR w/ contrast, 3/07

Nodular area in the right frontal lobe measuring ~ 2.1 cm in diameter with diffuse heterogeneous enhancement after administration of Gadolinium-DTAP; surrounding edema non-enhancing


4A 4B


Axial T2-weighted MR w/o contrast, 3/07

Nodular area in the right frontal lobe of heterogeneous hypo-

and iso-intensity extensive area of vasogenic

edema

Predominant: T1 ↑, T2 ↔ or ↓, enhancing

(Source for Fig. 5 : PACS, BIDMC)

5

What do we make of these findings?

Let’s study how melanoma brain mets

should appear on MRI

MRI of Brain Melanoma

T1 signal T2 signalMelanotic

pattern ↑ ↓

Amelanotic

pattern ↓

/ ↔ ↑

1] Melanin (free radicals = paramagnetic)

2] Evolution of blood products if hemorrhagic metastasisT1 signal T2 signal Time Hgb

Hyperacute ↔ / ↓ ↑ < 24h Oxy-Hgb, intracellularAcute ↔ / ↓ ↓ 1-3d Deoxy-Hgb, intracellularEarly subacute ↑ ↓ > 3d Met-Hgb, intracellular

Late subacute ↑ ↑ > 7d Met-Hgb, extracellular

Chronic ↓ ↓ > 14d Ferritin

and hemosiderin, extracellular

Key:↑

= hyperintensity↓

= hypointensity↔ = isointensity

Mohr et al. (2009) Ann Oncol; Warakaulle

& Anslow

(2003) Clin

Radiol; Escott

(2001) RadioGraphics

Variable MR pattern dependent on melanin & hemorrhage!

MRI of Brain Melanoma: Companion Patient 1, Classic “Melanotic

Melanoma”

Axial T1-weighted MR w/o contrast Axial T2-weighted MR w/o contrastHyperintense

on T1, Hypointense

on T2(Source for Fig. 6: Escott

(2001) RadioGraphics)

6A 6B

MRI of Brain Melanoma: Companion Patient 2, Classic “Amelanotic

Melanoma”

Axial T1-weighted MR w/o contrast Axial T2-weighted MR w/o contrast

Hypointense

(or isointense) on T1, Hyper-

or iso-intense on T2(Source for Fig. 7: Escott

(2001) RadioGraphics)

7A 7B

Armed with this knowledge, we can now go back to our

Patient AC…

•

Predominant: T1 ↑, T2 ↓

or ↔, enhancing•

Suggest melanoma metastasis, predominantly with •

melanin OR

•

blood products (likely early subacute)•

surrounded by edema

Patient AC: MRI 3/07T1 signal T2 signal

Melanotic

pattern ↑ ↓

Amelanotic

pattern ↓

/ ↔ ↑

T1 signal

T2 signal

Time Hgb

Hyperacute ↔ /

↓ ↑ < 24h Oxy-Hgb, intracellular

Acute ↔ /

↓ ↓ 1-3d Deoxy-Hgb, intracellular

Early subacute ↑ ↓ > 3d Met-Hgb, intracellular

Late subacute ↑ ↑ > 7d Met-Hgb, extracellular

Chronic ↓ ↓ > 14d Ferritin

and hemosiderin, extracellular

•

Hemorrhagic lesions–

Infarcts–

Infections–

Intraparenchymal

hematoma–

Cortical contusions–

Diffuse axonal injuries–

Subarachnoid hemorrhage–

Vascular malformations and aneurysms associated with hemorrhage and/or thrombosis

–

Hemorrhagic primary tumors–

Hemorrhagic metastases•

Melanoma•

Renal cell carcinoma•

Choriocarcinoma•

Bronchogenic

carcinoma•

Thyroid carcinoma

•

Protein-containing lesions–

Colloid cyst of third ventricle–

Craniopharyngioma–

Rathke’s

cleft cyst–

Atypical epidermoid

DDx

of Intracranial Lesions with Increased Signal on T1

•

Fatty lesions–

Lipoma–

Dermoid–

Lipomatous

meningioma

•

Calcified/ossified lesions–

Endocrine-metabolic disorders–

Calcified neoplasms–

Infections–

Dural osteomas

•

Lesions with other mineral accumulation–

Acquired hepatocerebral

degeneration–

Wilson’s disease

•

Melanin-containing lesions–

Melanoma metastases–

Leptomeningeal

melanosis

•

Miscellaneous–

Ectopic neurohypophysis–

Multiple sclerosis (chronic stage)–

Neurofibromatosis type I

Cakirer

et al. (2003) Curr

Probl

Diagn

Radiol


4/07 –

4/10: Progressing brain mets; multiple radiosurgeries, radiotherapy, and chemotherapy

4/10•

45 yo, presents with severe bilateral “sharp”

headaches

•

Similar to headaches from prior metastatic disease•

Associated nausea


Axial T1 w/o contrast, 4/10 Axial T1 w/ contrast, 4/10 Axial T2 w/o contrast

Enhancing nodule in the right temporal lobe, hyper-intense on T1 pre-GAD


8A 8B 8C

Patient AC: MRI 4/10Axial T1 w/ contrast, 4/10 Axial T1 w/o contrast, 4/10

Small, punctate

enhancing lesion in the right posterior parietal lobe, iso-intense on T1 pre-GAD

Plan for patient AC: Compassionate use of ipilimumab

for systemic therapy


9A 9B

As we have learned from the multiple MR images, beware of atypical and various appearances of melanoma mets!

1) They can adhere to OR deviate from the typical “melanotic

and amelanotic”

patterns.

2) They can be subtle and small OR easily discernible.

3) They may or may not hemorrhage.

4) They can be stable OR rapidly growing!

Interim Summary 2

What about imaging modalities other than MRI?

Let’s briefly discuss our patients PG and MO…

Companion Patient 3, PG: CT without Contrast

Multiple hyperattenuating

(hyperdense) lesions, ex. In the left frontal lobe and right occipital lobe metastatic melanoma?


10A 10BCT w/o contrast, 4/10 CT w/o contrast, 4/10

69 yo

man with known malignant melanoma presents to the ED following syncope, brief shaking movements in 4/10

Expected CT of Brain Melanoma

•

Variety of appearances on CT! –

Single or multiple–

Small, large, or both–

Hyper-dense, iso-dense, hypo-dense, or mixed pre-contrast

McGann

et al. (1991) Brit J Radiol

(Source for Table: McGann

et al. (1991) Brit J Radiol.)

Majority = HIGH attenuationpre-contrast

•

Meningioma•

Lymphoma

•

GBM•

Ependymoma

•

Colloid cyst•

Craniopharyngioma

•

Germinoma•

Hemorrhage

•

Metastatic tumors–

Melanoma–

Renal cell carcinoma–

Choriocarcinoma–

Thyroid carcinoma

DDx

of Hyperdense

Intracranial Lesions without Contrast

Cakirer

et al. (2003) Curr

Probl

Diagn

Radiol

Companion Patient 3, PG: CT without Contrast

•

Patient PG has a pacemaker + renal insufficiency no f/u

on MRI or CT C+

•

Patient PG was scheduled for whole brain cranial irradiation

•

Remember, CT w/o contrast offers only limited evaluation for melanoma brain mets

Companion Patient 4, MO: FDG-PET/CT

58 yo

woman with history of metastatic melanoma (pulmonary and liver lesions) re-staged on FDG-PET 12/04

Avid uptake in the left medial occipital lobe, hyperdense

on CT C-

FDG axial slice, 12/04 Fused FDG/CT axial slice, 12/04

CT axial slice, 12/04

(Fig. 11 courtesy of Dr. Kevin Donohoe, BIDMC)

11

Companion Patient 4, MO: DDx

for Increased Signal on PET

•

Infection•

Inflammation

•

Neoplasm•

Beware of physiologic uptake (brain, myocardium, exercising muscle, thymus in children and post-chemo patients, thyroid in patients with thyroid disease, etc)

Delbeke

(1999) J Nucl

Med

Companion Patient 4, MO: FDG-PET/CT

Given the PET finding, MRI w/ contrast indicated

Round, well-circumscribed mass in the left occipital lobe, hyperintense

and homogeneously enhancing; confirms PET/CT stereotactic radiosurgery

(Source for Fig. 12: PACS,BIDMC)

Sagittal

T1 w/ contrast, 12/04 Axial T1 w/ contrast, 12/0412A 12B

FDG-PET for Brain Melanoma Mets

•

Less sensitive for detection of mets

in the brain due to high background FDG accumulation in the cortex

•

CAN detect new metabolically active lesions: f/u

using conventional imaging methods

•

CAN be useful to w/u

lesions identified in MRI: Recurrence (avid) versus radiation necrosis effects (non-avid)

Delbeke

(1999) J Nucl

Med; Kumar & Alavi

(2005) Curr

Opin

Oncol

Summary

1.

Radiologic imaging of melanoma metastases to the brain is clinically important

2.

MRI with contrast enhancement is the imaging modality of choice for brain metastases of melanoma, and we saw multiple examples in our patient AC

3.

Metastatic melanoma lesions in the brain have a variety of appearances due to hemorrhage and melanin: Beware!

4.

While MRI is the preferred test, CT and FDG-PET/CT have their uses in melanoma imaging in the brain: Remember when and why these imaging modalities can be useful

Acknowledgements

•

Gillian Lieberman, MD•

Kevin Donohoe, MD

•

Neel Madan, MD•

Johannes Roedl, MD

•

Maria Levantakis

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D (1999). Oncological

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imaging of brain metastases from melanoma

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