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Imaging of Melanoma

Metastases in the Brain


Jessica J. Kim, HMS III & Dr. Gillian Lieberman, M.D.
Harvard Medical School
Beth-Israel Deaconess Medical Center
May 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)

Lets discuss why we want to


learn about diagnostic imaging of
metastatic melanoma in the brain

Melanoma
Tumor of melanocytes

1A

4% of all dermatologic cancers, but


80% of all skin cancer deaths
619% in annual diagnoses, 165%
in annual mortality (1950-2000)

1B

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.

Melanoma: Metastasis

SITE
Lung
Liver
Brain
Bone
GI tract

CLINICALLY
18-36%
14-20%
12-20%
11-17%
1-7%

AUTOPSY
70-87%
54-77%
36-54%
23-49%
26-58%

Other sites: Heart, Pancreas, Adrenals, Kidney,


Thyroid

Donohoe (2010) UpToDate

Melanoma: Metastasis
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)

Sloan et al. (2009) Cancer Control; Eichler and Loeffler


(2007) Oncologist; Testori et al. (2009) Ann Oncol

Lets preview the menu of tests


and their use in brain
melanoma imaging

Imaging of Brain Metastases

Indications

1.

Neurologic symptoms in patients with known melanoma


Accurate prognosis and optimal palliative treatment
Re-staging
R/O brain metastases before initiating new chemotherapy

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

Mohr et al. (2009) Ann Oncol; Delbeke (1999) J Nuc Med; Donohoe (2010) UpToDate

Before we proceed, lets 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)

Interim Summary 1
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

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


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
2

Axial CT w/o contrast, 3/07


(Source for Fig. 2: PACS, BIDMC)

Patient AC

MRI was recommended for


further evaluation of intracranial masses

Patient AC: MRI 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/o contrast, 3/07

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


(Source for Fig. 3: PACS, BIDMC)

Patient AC: MRI 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

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

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


(Source for Fig. 4: PACS, BIDMC)

Patient AC: MRI 3/07


Nodular area in the right frontal lobe of heterogeneous hypo- and
iso-intensity extensive area of vasogenic edema
5

Predominant: T1 , T2
or , enhancing

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


(Source for Fig. 5 : PACS, BIDMC)

What do we make of these findings?


Lets study how melanoma brain
mets should appear on MRI

MRI of Brain Melanoma


Variable MR pattern dependent on melanin & hemorrhage!
1] Melanin (free radicals = paramagnetic)
T1 signal
Melanotic pattern
Amelanotic pattern

T2 signal

Key:
= hyperintensity
= hypointensity
= isointensity

2] Evolution of blood products if hemorrhagic metastasis


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

Mohr et al. (2009) Ann Oncol; Warakaulle & Anslow (2003) Clin Radiol; Escott (2001) RadioGraphics

MRI of Brain Melanoma: Companion


Patient 1, Classic Melanotic Melanoma
6A

6B

Axial T1-weighted MR w/o contrast

Axial T2-weighted MR w/o contrast

Hyperintense on T1, Hypointense on T2

(Source for Fig. 6: Escott (2001) RadioGraphics)

MRI of Brain Melanoma: Companion


Patient 2, Classic Amelanotic Melanoma
7A

7B

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)

Armed with this knowledge,


we can now go back to our
Patient AC

Patient AC: MRI 3/07


T1 signal
Melanotic pattern
Amelanotic pattern

T2 signal

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

Predominant: T1 , T2 or , enhancing
Suggest melanoma metastasis, predominantly with
melanin OR
blood products (likely early subacute)
surrounded by edema

DDx of Intracranial Lesions with


Increased Signal on T1

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

Colloid cyst of third ventricle


Craniopharyngioma
Rathkes cleft cyst
Atypical epidermoid

Acquired hepatocerebral degeneration


Wilsons disease

Melanin-containing lesions

Endocrine-metabolic disorders
Calcified neoplasms
Infections
Dural osteomas

Lesions with other mineral accumulation

Lipoma
Dermoid
Lipomatous meningioma

Calcified/ossified lesions

Protein-containing lesions

Fatty lesions

Melanoma metastases
Leptomeningeal melanosis

Miscellaneous

Ectopic neurohypophysis
Multiple sclerosis (chronic stage)
Neurofibromatosis type I
Cakirer et al. (2003) Curr Probl Diagn Radiol

Patient AC: MRI 4/10


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

Patient AC: MRI 4/10


8A

Axial T1 w/o contrast, 4/10

8B

Axial T1 w/ contrast, 4/10

8C

Axial T2 w/o contrast

Enhancing nodule in the right temporal lobe,


hyper-intense on T1 pre-GAD
(Source for Fig. 8: PACS, BIDMC)

Patient AC: MRI 4/10


9A

Axial T1 w/ contrast, 4/10

9B

Axial T1 w/o contrast, 4/10

Plan for patient AC:


Compassionate use of
ipilimumab for systemic
therapy
Small, punctate enhancing lesion in the
right posterior parietal lobe, iso-intense
on T1 pre-GAD
(Source for Fig. 9: PACS, BIDMC)

Interim Summary 2
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!

What about imaging


modalities other than MRI?
Lets briefly discuss
our patients PG and MO

Companion Patient 3, PG:


CT without Contrast
69 yo man with known malignant melanoma presents to the ED
following syncope, brief shaking movements in 4/10
10A

CT w/o contrast, 4/10

10B

CT w/o contrast, 4/10

Multiple hyperattenuating (hyperdense) lesions, ex. In the left


frontal lobe and right occipital lobe metastatic melanoma?
(Source for Fig. 10: PACS, BIDMC)

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

Majority = HIGH
attenuation
pre-contrast

(Source for Table:


McGann et al. (1991) Brit
J Radiol.)
McGann et al. (1991) Brit J Radiol

DDx of Hyperdense Intracranial


Lesions without Contrast

Meningioma
Lymphoma
GBM
Ependymoma
Colloid cyst
Craniopharyngioma
Germinoma
Hemorrhage
Metastatic tumors

Melanoma
Renal cell carcinoma
Choriocarcinoma
Thyroid carcinoma

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
11

FDG axial slice, 12/04

(Fig. 11 courtesy of Dr. Kevin Donohoe,


BIDMC)

CT axial slice, 12/04

Fused FDG/CT axial slice,


12/04

Avid uptake in the left medial occipital


lobe, hyperdense on CT C-

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
12A

Sagittal T1 w/ contrast, 12/04

12B

Axial T1 w/ contrast, 12/04

(Source for Fig.


12: PACS,BIDMC)

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


homogeneously enhancing; confirms PET/CT stereotactic radiosurgery

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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