cns imaging of metastatic melanomaeradiology.bidmc.harvard.edu/learninglab/central/mukherjee.pdf ·...

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CNS Imaging of Metastatic MelanomaCNS Imaging of Metastatic Melanoma

Sonali Mukherjee, Harvard Medical School Year IIISonali Mukherjee, Harvard Medical School Year IIIGillian Lieberman, MDGillian Lieberman, MD

May 2006Sonali Mukherjee, HMS IIIGillian Lieberman, MD

UpToDate 2006

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OutlineOutline

MelanomaMelanoma

BackgroundBackground

Epidemiology of CNS MetastasesEpidemiology of CNS Metastases

Imaging Modalities and Indications Imaging Modalities and Indications

ContrastContrast--enhanced MRI enhanced MRI

Melanin and Hemorrhage: The Diagnostic DilemmaMelanin and Hemorrhage: The Diagnostic Dilemma

Clinical Image ExamplesClinical Image Examples

Patient Presentation: Patient Presentation: A Tale of Two MetastasesA Tale of Two Metastases

SummarySummary

Sonali Mukherjee, HMS IIIGillian Lieberman, MD

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MelanomaMelanoma

Melanoma is a cancer of melanocytes, or melanin Melanoma is a cancer of melanocytes, or melanin producing cells derived from the neural crest.producing cells derived from the neural crest.

Projected lifetime risk of developing melanoma in the Projected lifetime risk of developing melanoma in the United States is 1/75.United States is 1/75.

Melanoma has widespread metastatic potential.Melanoma has widespread metastatic potential.

Preferential sites include:Preferential sites include:

Lymph nodesLymph nodes

LungLung

LiverLiver

BrainBrain

SpleenSpleen

KidneysKidneys

GI tractGI tract

Subcutaneous tissuesSubcutaneous tissues


http://rad.usuhs.mil/derm/lecture_notes/Images/melanoma.JPG

Malignant Melanoma

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Epidemiology of CNS Metastatic MelanomaEpidemiology of CNS Metastatic Melanoma

Melanoma metastasizes to the central nervous system Melanoma metastasizes to the central nervous system more frequently than any other malignancy.more frequently than any other malignancy.

Third most common cause of brain metastases in the US Third most common cause of brain metastases in the US (after lung and breast.)(after lung and breast.)

Average time between first diagnosis of cutaneous Average time between first diagnosis of cutaneous melanoma and CNS metastasis is 45 months.melanoma and CNS metastasis is 45 months.

1212--20% of patients present with their first metastasis to 20% of patients present with their first metastasis to the CNS.the CNS.

Brain metastasis is found in 50% of patients with widely Brain metastasis is found in 50% of patients with widely disseminated melanoma.disseminated melanoma.


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Treatment of CNS Metastatic Treatment of CNS Metastatic MelanomaMelanoma

Palliative treatment includesPalliative treatment includes

Surgical removal of lesionsSurgical removal of lesions

Tumor Tumor debulkingdebulking

Whole Brain Radiation TherapyWhole Brain Radiation Therapy

BiochemotherapyBiochemotherapy

Stereotactic Stereotactic RadiosurgeryRadiosurgery


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Imaging of CNS MetastasesImaging of CNS Metastases

IndicationsIndications

Neurologic symptomsNeurologic symptoms

R/O brain metastases prior to beginning some chemotherapy regimeR/O brain metastases prior to beginning some chemotherapy regimens ns (concern for brain toxicity.)(concern for brain toxicity.)

1818FDG PET CT is not appropriate for detecting metastasis because oFDG PET CT is not appropriate for detecting metastasis because of f the physiologic uptake of the physiologic uptake of 1818FDG by the brain. FDG by the brain.

Contrast Enhanced MRI studiesContrast Enhanced MRI studies recommended recommended

Identify CNS metastasis missed by CTIdentify CNS metastasis missed by CT

Examine metastatic involvement of the spinal cord and Examine metastatic involvement of the spinal cord and leptolepto--meningesmeninges..

Melanoma has a unique tendency to hemorrhage.Melanoma has a unique tendency to hemorrhage.

MR can document presence of blood, approximate age of hemorrhageMR can document presence of blood, approximate age of hemorrhage

Three categories of signal intensity patterns seen on MRI for Three categories of signal intensity patterns seen on MRI for metastatic melanoma to the brain.metastatic melanoma to the brain.


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Three SI patterns of CNS melanoma metastasisThree SI patterns of CNS melanoma metastasis

Melanotic Metastasis*Melanotic Metastasis*

Amelanotic MetastasisAmelanotic Metastasis

Metastasis w/ Hemorrhage Metastasis w/ Hemorrhage dependent on hemorrhagic progressiondependent on hemorrhagic progression


Signal on T1Signal on T1 Signal on T2Signal on T2

= increased signal intensity= increased signal intensity

= decreased signal intensity= decreased signal intensity

* 10% of the tumor cells must have melanin* 10% of the tumor cells must have melaninin order for the MRI to show this signal pattern.in order for the MRI to show this signal pattern.

KeyKey

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Metastasis with hemorrhage: Metastasis with hemorrhage: The diagnostic dilemmaThe diagnostic dilemma

STAGESTAGE T1T1 T2T2 TIME FRAMETIME FRAME STATE OF HGBSTATE OF HGB

HyperacuteHyperacute < 12 hrs< 12 hrs IC oxyIC oxy--HGBHGB

AcuteAcute 11--3 d3 d IC IC deoxydeoxy--HGBHGB

Early Early subacutesubacute 33--7 d7 d IC metIC met--HGBHGB

Late Late subacutesubacute 44--7 d to 1 mo7 d to 1 mo EC metEC met--HGBHGB

Chronic hemorrhageChronic hemorrhage 1 mo to yrs1 mo to yrs HemosiderinHemosiderin


= = isoiso to hypoto hypo--intenseintense = Hyper= Hyper--intenseintense = Hypo= Hypo--intenseintense

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Metastasis with Hemorrhage: Metastasis with Hemorrhage: The diagnostic dilemmaThe diagnostic dilemma

How do you differentiate melanin in a tumor from a How do you differentiate melanin in a tumor from a simple hematoma?simple hematoma?

Heterogeneous SI patternsHeterogeneous SI patterns

(indicates multiple stages of hematoma aging.)(indicates multiple stages of hematoma aging.)

Slower evolution of the hemorrhagic tumor Slower evolution of the hemorrhagic tumor

Reduced, absent, or irregular Reduced, absent, or irregular hemosiderinhemosiderin--laden rim laden rim

Persistent edema in the Persistent edema in the subacutesubacute and chronic stages.and chronic stages.

(acute simple hematomas only have transient edema.)(acute simple hematomas only have transient edema.)

Administer contrast!Administer contrast!


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LetLet’’s look at some images to illustrate s look at some images to illustrate these three categories of MR signal these three categories of MR signal intensity patterns in CNS metastatic intensity patterns in CNS metastatic

melanoma.melanoma.


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Melanotic Pattern: T1 weighted imageMelanotic Pattern: T1 weighted image


http://radiographics.rsnajnls.org/cgi/content/figsonly/21/3/625http://radiographics.rsnajnls.org/cgi/content/figsonly/21/3/625

Companion Patient #1:Companion Patient #1:54 y.o. male w/ 54 y.o. male w/ hxhx of acral of acral lentiginous melanoma of lentiginous melanoma of the distal thumbthe distal thumb

Melanotic melanoma Melanotic melanoma appears as homogeneous, appears as homogeneous, wellwell--circumscribed, circumscribed, hyperintensehyperintense nodules on T1 nodules on T1 images.images.

Axial T1Axial T1--weighted MR w/o contrastweighted MR w/o contrast

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Melanotic Pattern: T2 weighted imageMelanotic Pattern: T2 weighted image


http://radiographics.rsnajnls.org/cgi/content/figsonly/21/3/625http://radiographics.rsnajnls.org/cgi/content/figsonly/21/3/625Axial T2Axial T2--weighted MR w/o contrastweighted MR w/o contrast

Companion Patient #1Companion Patient #1Same axial slice as Same axial slice as previous T1previous T1--weighted weighted imageimage

Nodules are Nodules are hypointensehypointense on on T2T2--weighted image, weighted image, surrounded by areas of surrounded by areas of edemaedema

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Amelanotic pattern: T1 weighted imagesAmelanotic pattern: T1 weighted images


http://radiographics.rsnajnls.org/cgi/content/figsonly/21/3/625http://radiographics.rsnajnls.org/cgi/content/figsonly/21/3/625

Companion Patient #2:Companion Patient #2:40 year old male with metastatic melanoma40 year old male with metastatic melanoma

Axial T1Axial T1--weighted MR w/o contrastweighted MR w/o contrast Axial T2Axial T2--weighted MR w/o contrast weighted MR w/o contrast

Amelanotic melanoma metastasis appears as wellAmelanotic melanoma metastasis appears as well--circumscribed nodules with circumscribed nodules with hypointensehypointense signal on T1, and signal on T1, and hyperintensehyperintense signal on T2.signal on T2.

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A Tale of Two MetastasesA Tale of Two Metastases:: A Patient PresentationA Patient Presentation


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CC: aphasia, RCC: aphasia, R--sided blurry visionsided blurry vision

KR is a 35 year old male with a history of metastatic melanoma wKR is a 35 year old male with a history of metastatic melanoma who ho presented in 2005 with two acute episodes of presented in 2005 with two acute episodes of expressive aphasiaexpressive aphasia and and rightright-- sided blurry visionsided blurry vision..

Difficulty saying the word Difficulty saying the word ““TAXTAX”” (said (said ““PAXPAX”” w/ a w/ a ““PP””.).)

Patient saw a blurry blue line in his right visual field.Patient saw a blurry blue line in his right visual field.

Episodes lasted 10Episodes lasted 10--15 minutes each, occurred three days apart. Symptoms 15 minutes each, occurred three days apart. Symptoms spontaneously resolved. spontaneously resolved.

Neurologic ROS was o/w negative.Neurologic ROS was o/w negative.

Head MR w/ and w/o contrast was performed after second episode.Head MR w/ and w/o contrast was performed after second episode.


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Patient KR: Metastasis #1 Patient KR: Metastasis #1 Left parietal metastasis with hemorrhageLeft parietal metastasis with hemorrhage

Sagittal T1-weighted MR w/o contrast

Nodular area of heterogeneous hypo- and iso-intensity surrounded by a ring of well-circumscribed hyperintensity.

Axial T1-weighted MR w/o contrast


PACS, BIDMCPACS, BIDMC

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Patient KR: Metastasis #1Patient KR: Metastasis #1

Sagittal T1-weighted MR with contrast

Rim enhancement is seen with administration of Gadolinium-DTAP.Focal specks of hyperintensity noted centrally.

Axial T1-weighted MR with contrast



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Axial T2-weighted MR w/o contrast


Fairly homogeneous, nodular central hypointense signal

Focal specks of hyperintense signal centrally

Surrounding area of homogeneous, hyperintense signal extending centrifugally that follows the shape of the gyri, not seen on T1!


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Hemorrhagic lesion with heterogeneous signal intensity.Hemorrhagic lesion with heterogeneous signal intensity.

Identified three probable hemorrhagic stagesIdentified three probable hemorrhagic stages

Acute (Predominant)Acute (Predominant)

Early Early subacutesubacute vs. melaninvs. melanin

Late Late subacutesubacute vs. vs. amelanoticamelanotic

Surrounded by persistent edemaSurrounded by persistent edema

Diagnostically appears to be a hemorrhagic tumor.Diagnostically appears to be a hemorrhagic tumor.

Given history and radiology findings, likely metastatic melanoma to the brain.


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Two days later, Patient KR underwent a Two days later, Patient KR underwent a craniotomy for removal of the craniotomy for removal of the

hemorrhagic left parietal metastasis.hemorrhagic left parietal metastasis.

A Head MR was obtained A Head MR was obtained 24 hours s/p surgery.24 hours s/p surgery.


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Patient KR s/p surgeryPatient KR s/p surgery


Axial T1Axial T1--weighted MR with contrastweighted MR with contrast Coronal T1Coronal T1--weighted MR with contrastweighted MR with contrast

Note the resection site, the subdural hematoma along the left Note the resection site, the subdural hematoma along the left hemisphere, and the posthemisphere, and the post--surgical effects on the skull.surgical effects on the skull.


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Differential Diagnosis for Hemorrhage in the BrainDifferential Diagnosis for Hemorrhage in the Brain

NeoplasmNeoplasm

Primary Primary

MetastasisMetastasis

AVMAVM

Hemorrhagic venous infarction Hemorrhagic venous infarction

Hypertensive vascular diseaseHypertensive vascular disease

Stroke (Hemorrhagic) Stroke (Hemorrhagic)

Trauma to head Trauma to head

Aneurysm, Berry vs. InfectiousAneurysm, Berry vs. Infectious


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Differential Diagnosis for Hemorrhagic Metastasis Differential Diagnosis for Hemorrhagic Metastasis in the Brainin the Brain (M A T C H)(M A T C H)

M M elanomaelanoma

A A naplasticnaplastic lung carcinomalung carcinoma

T T hyroidhyroid carcinomacarcinoma

C C horiocarcinomahoriocarcinoma

H H ypernephromaypernephroma..


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3 months later, during a 3 months later, during a followfollow--up head MR study on up head MR study on

Patient KRPatient KR……


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Patient KR: Metastasis #2Patient KR: Metastasis #2 Right Right parietoparieto--occipital metastasis with hemorrhageoccipital metastasis with hemorrhageSagittal T1-weighted MR with contrast Axial T1-weighted MR with contrast



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

Note the worsening edema, the decreasing central intensity, and the incomplete ring of hypointensity on the later image



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Metastasis #2Metastasis #2

Lesion w/ heterogeneous SI, mostly Lesion w/ heterogeneous SI, mostly hyperintensehyperintense on both T1 and T2, on both T1 and T2, indicating a late indicating a late subacutesubacute hemorrhage.hemorrhage.

Decreasing SI on T2 indicates that the hemorrhage is beginning tDecreasing SI on T2 indicates that the hemorrhage is beginning to progress o progress into a chronic stage.into a chronic stage.

Incomplete ring of Incomplete ring of hemosiderinhemosiderin noted.noted.

Edema is significantly worsened on subsequent MR.Edema is significantly worsened on subsequent MR.

Hemorrhage is evolving slowly.Hemorrhage is evolving slowly.

Lesion represents hemorrhage into a tumor that is not resolving.


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Two months later, Two months later, after experimental chemotherapy with after experimental chemotherapy with

oral oral temozolamidetemozolamide……


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Patient KR: Metastasis #2 has decreased in size Patient KR: Metastasis #2 has decreased in size and the edema has resolved.and the edema has resolved.

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



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SummarySummary

Imaging of CNS metastatic melanoma is an important clinical Imaging of CNS metastatic melanoma is an important clinical problem. problem.

Contrast enhanced MRI is the preferred modality for imaging CNS Contrast enhanced MRI is the preferred modality for imaging CNS metastatic melanoma. metastatic melanoma.

Recognize three different intensity patterns: Recognize three different intensity patterns:

MelanoticMelanotic

AmelanoticAmelanotic

Metastasis with hemorrhage Metastasis with hemorrhage

Melanoma is common: you will take care of these patients, Melanoma is common: you will take care of these patients, regardless of your field of medicine! regardless of your field of medicine!


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AcknowledgementsAcknowledgements

Larry Larry BarbarasBarbaras, webmaster , webmaster

Gillian Lieberman, MDGillian Lieberman, MD

AtifAtif ZaheerZaheer, MD , MD

Pamela Lepkowski Pamela Lepkowski


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ReferencesReferences

Au et al. CNS Melanoma. http://www.emedicine.com/neuro/topic660.htm . eMedicine. Viewed May 15, 2006.

Donohoe, K. Imaging studies in melanoma. http://utdol.com/utd/content/topic.do?topicKey=skin_can/8257&type=A&selectedTitle=11~65. Up To Date. Viewed May 15, 2006.

Bradley, W. et al., ed. Reeder and Felson’s Gamuts in Radiology: Comprehensive Lists of Roentgen Differential Diagnosis. 4th ed. Springer-Verlag. NY. 2003.

Edelman and Hesselnick. Clinical MRI. W.B. Saunders Co. Philadelphia. 1990.

Escott, E. A Variety of Appearances of Malignant Melanoma in the Head: A Review. Radiographics. 21: 625-639. 2001. (http://radiographics.rsnajnls.org/cgi/content/figsonly/21/3/625)

Latchaw, R. MR and CT Imaging of the Head, Neck, and Spine. Mosby-Year Book, Inc. St. Louis. 1991.

Malignant Melanoma: Chapter 22. Recommendations for Cross-Sectional Imaging in Cancer Management. March 2006.

Middleton et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol. 2000 Jan;18(1):158-66.

Parizel et al. Intracranial hemorrhage: principles of CT and MR interpretation. Eur. Radiol. 11: 1770-1783. 2001.

Pomeranz et al. Craniospinal MRI. W.B. Saunders Co. 1989

Sidhu et al. Neuradiology Case of the Week. http://www.urmc.rochester.edu/smd/Rad/neurocases/Neurocase72.htm. Viewed May 16, 2006.


http://www.emedicine.com/neuro/topic660.htm . Viewed May 15

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Remember your Remember your ABCDsABCDs……Sonali Mukherjee, HMS IIIGillian Lieberman, MD

WomenWomen’’s Health: Skin Cancer. s Health: Skin Cancer. http://www.southeastmissourihospital.com/health/adult/women/skinhttp://www.southeastmissourihospital.com/health/adult/women/skincaus.htmcaus.htm

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