Imaging Melanoma: Imaging Melanoma: Focus on Patient with Unsuspected Focus on Patient with Unsuspected

MetastasesMetastasesSasha Sasha GirouardGirouard, HMSIII, HMSIIIGillian Lieberman, MDGillian Lieberman, MD

April 16, 2010April 16, 2010

Our Patient: Clinical PresentationOur Patient: Clinical Presentation

48 year48 year--old woman complains of old woman complains of raised, itchy, nonraised, itchy, non--bleeding lesion bleeding lesion on her right chest, just inferior to on her right chest, just inferior to her clavicle, in September 2006 her clavicle, in September 2006

Lesion biopsied by dermatology in Lesion biopsied by dermatology in November 2006November 2006––

0.9 mm Clarks level IV melanoma 0.9 mm Clarks level IV melanoma with ulceration and two mitoses with with ulceration and two mitoses with per high powered fieldper high powered field

Referred to oncology and surgeryReferred to oncology and surgery

Wolff K, Johnson RA, "Section 12. Melanoma Precursors and Primary Cutaneous

Melanoma" (Chapter). Wolff K, Johnson RA: Fitzpatrick's Color Atlas & Synopsis of Clinical Dermatology, 6e: http://www.accessmedicine.com.ezp-

prod1.hul.harvard.edu/content.aspx?aID=5187071.

What should be done next?What should be done next?

Melanoma

In order to understand the next In order to understand the next steps for this patient’s steps for this patient’s

management, we must first gain management, we must first gain an appreciation for melanoma an appreciation for melanoma

and it’s staging.and it’s staging.

MelanomaMelanomaMost lethal skin cancerMost lethal skin cancer

Over the past 3 decades, there has been an increased Over the past 3 decades, there has been an increased rate of melanoma incidence, though 5 year survival rate rate of melanoma incidence, though 5 year survival rate has improved overallhas improved overall11

55thth

most common cancer in US for men; 6most common cancer in US for men; 6thth

most common most common cancer in US for womencancer in US for women22

Only 15.5% patients with metastatic melanoma survive for Only 15.5% patients with metastatic melanoma survive for 5 years; the 55 years; the 5--year survival rate for localized melanoma is year survival rate for localized melanoma is 99%99%11

Approximately 80% of melanomas are diagnosed at a Approximately 80% of melanomas are diagnosed at a localized stagelocalized stage22

TMN Staging TMN Staging SystemSystem

Staging dictates prognosis and treatment options

Staging also influences what imaging studies are chosen, but there is no clear algorithm to follow

Buzaid, Gershenwald, and Ross. Tumor node metastasis (TMN) staging system and other

prognostic factors in cutaneous

melanoma. UpToDate. Jan 2010.

Stage GroupingsStage Groupings

Stages I and IIStages I and II

--

localized localized primary melanomasprimary melanomas––

Stage I: low risk Stage I: low risk ––

Stage II: higher risk of Stage II: higher risk of reoccurrencereoccurrence

Stage IIIStage III

--

involvement of involvement of regional lymph nodes regional lymph nodes

Stage IVStage IV

--

distant distant metastasesmetastases

Buzaid, Gershenwald, and Ross. Tumor node metastasis (TMN) staging system and other prognostic factors in cutaneous

melanoma. UpToDate. Jan 2010.

We have now reviewed the We have now reviewed the staging of melanoma. Let us staging of melanoma. Let us

continue to discuss the clinical continue to discuss the clinical course of our index patient.course of our index patient.

Our Patient: Pathology ReportOur Patient: Pathology Report

Primary Tumor:Primary Tumor: T1b:T1b:

Melanoma Melanoma ≤≤

1.0 mm with 1.0 mm with ulceration.ulceration.

Regional Lymph Nodes:Regional Lymph Nodes: NX:NX:

Regional lymph Regional lymph nodes cannot be assessed.nodes cannot be assessed.

Distant metastasis:Distant metastasis: MX:MX:

Presence of distant Presence of distant metastasis cannot be assessed.metastasis cannot be assessed.

Lymph nodes and metastases have not been assessed Lymph nodes and metastases have not been assessed at this point. Let us begin with lymph node staging…at this point. Let us begin with lymph node staging…

LymphoscintigraphyLymphoscintigraphyNuclear medicine study in which a Nuclear medicine study in which a radioactive colloid and/or blue dye is radioactive colloid and/or blue dye is injected into the primary tumor site to injected into the primary tumor site to identify the sentinel lymph identify the sentinel lymph node(snode(s))

Gamma cameraGamma camera --

used to image nodes used to image nodes that take up tracer in nuclear medicine that take up tracer in nuclear medicine suite just prior to surgery. Radiologists suite just prior to surgery. Radiologists mark focal areas of tracer uptake on mark focal areas of tracer uptake on overlying skin.overlying skin.

Gamma probeGamma probe ––

hand held probe used hand held probe used during surgery to redetect focal areas of during surgery to redetect focal areas of tracer uptake.tracer uptake.

False negative rate: 5% or lessFalse negative rate: 5% or less3,43,4Neoprobe. Model 1017 14mm Detector Probe. http://www.neoprobe.com/detector.asp

. Accessed April 14, 2010

Dugdale, David C. Nuclear Scan. Medline Plus. ADAM, Inc. http://www.nlm.nih.gov/medlineplus/ency/imagepages/19100.ht

m. . Accessed April 14, 2010

Gamma Camera

Gamma Probe

Our Patient: Sentinel Lymph Nodes Our Patient: Sentinel Lymph Nodes on on LymphoscintigraphyLymphoscintigraphy

PACS, BIDMC

Two foci of tracer uptake in the right axilla

PACS, BIDMC

Lymphoscintigraphy, Frontal View Lymphoscintigraphy, Lateral View

Our Patient: Staging Course Our Patient: Staging Course December 2006December 2006

Patient underwent wide excision of her right Patient underwent wide excision of her right chest melanoma with concurrent right chest melanoma with concurrent right axillaryaxillary

sentinel lymph node samplingsentinel lymph node sampling

Pathology Report: No evidence of melanoma in Pathology Report: No evidence of melanoma in two examined lymph nodestwo examined lymph nodes

Stage 1BStage 1B

Patient had 6 month followPatient had 6 month follow--up skin checks with up skin checks with dermatologistdermatologist

Our Patient: ReOur Patient: Re--Presentation Presentation April 2010April 2010

Patient presents to outside hospital 4 Patient presents to outside hospital 4 years later, complaining of 4 months of years later, complaining of 4 months of progressive dyspnea, progressive dyspnea, dysphagiadysphagia, and , and intermittent palpitationsintermittent palpitations

What imaging tests would you do?What imaging tests would you do?((Hint: where do her symptoms anatomically localize to)Hint: where do her symptoms anatomically localize to)

Our Patient: Lung Nodule and Our Patient: Lung Nodule and MediastinalMediastinal AdenopathyAdenopathy

on Chest Radiographon Chest Radiograph

1.1.

Right tracheal deviationRight tracheal deviation2.2.

Right Right paratrachealparatracheal

abnormal soft tissue abnormal soft tissue density density

3.3.

Splayed carina, and Splayed carina, and subcarinalsubcarinal

soft tissue soft tissue fullnessfullness

4.4.

Full R Full R hilumhilum5.5.

Pulmonary nodulePulmonary nodule

PACS, BIDMC

Chest Radiograph, AP Frontal View

Our Patient: Lung Nodules and Our Patient: Lung Nodules and MediastinalMediastinal Mass on CTMass on CT

Findings:1.

Two round nodules in R lung field2.

Mediastinal

mass 3.

Bilateral pleural effusions4.

Parenchymal

opacities in right middle lobe, likely subpleural

atelectasis

PACS, BIDMCPACS, BIDMC

Chest CT with contrast, Axial View, Lung Window Chest CT with contrast, Axial View, Lung Window

While the most likely etiology of While the most likely etiology of our patient’s lung nodules is our patient’s lung nodules is metastatic melanoma, let us metastatic melanoma, let us

break from the case to review break from the case to review the different diagnosis (the different diagnosis (ddxddx) of ) of

multiple lung nodules.multiple lung nodules.

DdxDdx

Multiple Lung NodulesMultiple Lung NodulesMalignancyMalignancy––

Metastatic NeoplasmMetastatic Neoplasm––

NonNon--Hodgkin’s lymphomaHodgkin’s lymphoma––

Karposi’sKarposi’s

sarcoma in HIV+sarcoma in HIV+

InfectionInfection––

AbscessesAbscesses––

Septic emboliSeptic emboli––

Fungal infectionFungal infection

InflammationInflammation––

AmyloidosisAmyloidosis––

SarcoidosisSarcoidosis––

Wegner’s Wegner’s granulomatosisgranulomatosis––

Rheumatoid arthritisRheumatoid arthritis––

LymphomatoidLymphomatoid

granulomatosisgranulomatosis

PneumoconiosiesPneumoconiosies––

SilicosisSilicosis––

Coal workers Coal workers pneumoconiosispneumoconiosis

Pulmonary AVMsPulmonary AVMs

Our Patient: Additional StagingOur Patient: Additional Staging

TransbronchialTransbronchial

needle aspiration of lung needle aspiration of lung nodule was performed using nodule was performed using endobronchialendobronchial

ultrasoundultrasound

Tissue and cytology was positive for Tissue and cytology was positive for metastatic malignant melanomametastatic malignant melanoma

Let us now turn our attention to the Let us now turn our attention to the mediastinalmediastinal mass seen on imaging…mass seen on imaging…

Brief Anatomy Review of MediastinumBrief Anatomy Review of Mediastinum

4 4 SubcompartmentsSubcompartments::

Superior:Superior:

upper trachea, upper trachea, brachiocephalicbrachiocephalic

vessels, vessels,

thyroid, upper esophagusthyroid, upper esophagusAnteriorAnterior::

thymus, germ cellsthymus, germ cells

MiddleMiddle::

heart, great vessels, heart, great vessels, pericardium, lower tracheapericardium, lower tracheaPosterior:Posterior:

esophagus, esophagus,

descending aorta, descending aorta, azygousazygous system, system, sympathethicsympathethic

chain, chain,

dorsal root ganglia, thoracic dorsal root ganglia, thoracic ducts ducts

Anterior Mediastinum. http://en.academic.ru/dic.nsf/enwiki/3722111.

Accessed April 15,

2010.

DdxDdx

MediastinalMediastinal

MassMassDdxDdx

mediastinalmediastinal

mass may be based on mass may be based on

subcompartmentsubcompartment::––

Superior:Superior:

upper tracheal mass, thyroid mass, upper tracheal mass, thyroid mass,

Zenker’sZenker’s

diverticulumdiverticulum––

Middle:Middle:

pericardial tumors/cysts, vascular pericardial tumors/cysts, vascular

lesions, lesions, bronchogenicbronchogenic

tumors/cyststumors/cysts––

Posterior:Posterior:

esophageal dilation/masses, esophageal dilation/masses,

varicesvarices, thoracic duct cysts/, thoracic duct cysts/chylomaschylomas, , ganglion series tumorsganglion series tumors

Our Patient: Our Patient: MediastinalMediastinal

Mass on CTMass on CT

PACS, BIDMC

Chest CT with contrast, Axial Views, Mediastinal Window

Findings:

Mediastinal adenopathy, coalescing together to appear as lobulated

mass

Impingement of adenopathy

upon left atrium and inferior pulmonary veins

Our Patient: Our Patient: MediastinalMediastinal

MassMass

Our patient has Our patient has adenopathyadenopathy, which is not , which is not specific to any specific to any mediastinalmediastinal

subcompartmentsubcompartment

Remember:Remember: the following may be found in the following may be found in anyany mediastinalmediastinal

subcompartmentsubcompartment::

––

AdenopathyAdenopathy––

HemangiomaHemangioma

––

LymphangiomaLymphangioma––

Connective tissue tumorsConnective tissue tumors

––

Vascular lesionsVascular lesions

Our Patient: Summary of Clinical Our Patient: Summary of Clinical CourseCourse

48 year old woman presents with localized melanoma on 48 year old woman presents with localized melanoma on her right chest. She has wide excision of the lesion and her right chest. She has wide excision of the lesion and sentinel lymph nodes are removed. Lymph node pathology sentinel lymph nodes are removed. Lymph node pathology report is negative for melanoma.report is negative for melanoma.

Patient returns 4 years later with Patient returns 4 years later with dysphagiadysphagia, , dyspneadyspnea, and , and palpitations, and is found on chest radiograph and CT to palpitations, and is found on chest radiograph and CT to have 2 lung nodules in her right lung and have 2 lung nodules in her right lung and mediastinalmediastinal

adenopathyadenopathy, compressing her trachea, esophagus, and , compressing her trachea, esophagus, and pulmonary veins.pulmonary veins.

Where else might our patient have metastases?Where else might our patient have metastases?

Melanoma MetastasesMelanoma MetastasesMelanoma has a high potential for metastasisMelanoma has a high potential for metastasisCommon sites of metastases, in descending order of frequencyCommon sites of metastases, in descending order of frequency55

––

Skin, subcutaneous tissues, and nodesSkin, subcutaneous tissues, and nodes––

LungsLungs––

LiverLiver––

BrainBrain––

BoneBone––

GI tractGI tract––

Heart Heart ––

PancreasPancreas––

AdrenalsAdrenals––

KidneyKidney––

ThyroidThyroid

How can we survey the body to detect or rule out How can we survey the body to detect or rule out all of these sites of metastasis?all of these sites of metastasis?

Menu of Imaging Tests for Menu of Imaging Tests for Metastatic MelanomaMetastatic Melanoma

LymphoscintigraphyLymphoscintigraphyPlain RadiographsPlain RadiographsCT TorsoCT TorsoMRI BrainMRI BrainUltrasonographyUltrasonographyPET and PET/CTPET and PET/CTBone ScanBone Scan

Our Patient: OutcomeOur Patient: OutcomeCT of abdomen/pelvis: negative for evidence of CT of abdomen/pelvis: negative for evidence of metastatic melanoma metastatic melanoma

MRI head w/ and w/out contrast: negative for MRI head w/ and w/out contrast: negative for evidence of metastatic melanomaevidence of metastatic melanoma

Stage IV Stage IV

Currently receiving palliative radiation to Currently receiving palliative radiation to mediastinummediastinum

One imaging study which our One imaging study which our patient did not receive during her patient did not receive during her

clinical course, but is very sensitive clinical course, but is very sensitive in detecting areas of metastasis, is in detecting areas of metastasis, is

the PET scan.the PET scan.

PET and PET/CTPET and PET/CTPhysiological imaging technique versus anatomical imagingPhysiological imaging technique versus anatomical imaging

Uses glucose labeled with 18Uses glucose labeled with 18--fluorine, called fluorine, called fluorodeoxyglucosefluorodeoxyglucose

or FDG, which emits positrons that are or FDG, which emits positrons that are

detected by crystals and converted to light signalsdetected by crystals and converted to light signals

Tumor cells take up FDG because they are metabolically activeTumor cells take up FDG because they are metabolically active

Areas of inflammation and tissue repair are also sites of FDG Areas of inflammation and tissue repair are also sites of FDG accumulationaccumulation

PET/CT PET/CT ––

combines physiologic and anatomic imagingcombines physiologic and anatomic imaging

––

has been shown to be superior to PET alone for detection of has been shown to be superior to PET alone for detection of metastasesmetastases66

PET and PET/CTPET and PET/CT

Useful for:Useful for:–– Detection of metastases in patients with Detection of metastases in patients with

Stage III disease Stage III disease –– To instruct surgeryTo instruct surgery–– Detection of extent of disease in Detection of extent of disease in

patients eligible for adjuvant interferon patients eligible for adjuvant interferon therapy prior to initiation of therapytherapy prior to initiation of therapy

Companion Patient #1: Liver and Companion Patient #1: Liver and Pelvic Metastases on PET Pelvic Metastases on PET

Courtesy Kevin Donohoe, MD

FDG PET, Anterior View

Findings:Findings:Focal areas of Focal areas of increased uptake increased uptake in the in the liverliver, and , and pelvispelvis

Companion Patient #1: Companion Patient #1: Liver Metastasis on PET/CTLiver Metastasis on PET/CT

Courtesy Kevin Donohoe, MD

PET attenuated corrected, Axial View

CT w/out contrast, Axial View

CT & PET fusion, Axial View

Focal area of increased uptake in left lobe of liver

Companion Patient #1: Companion Patient #1: Pelvic Metastasis on PET/CTPelvic Metastasis on PET/CT

Courtesy Kevin Donohoe, MD

PET attenuated corrected, Axial View

CT w/out contrast, Axial View

CT & PET fusion, Axial View

Focal area of increased uptake in right pelvis

Take Home PointsTake Home PointsMelanoma has a high potential for metastatic Melanoma has a high potential for metastatic spreadspread

Imaging studies are helpful in staging Imaging studies are helpful in staging melanoma, surgical planning, melanoma, surgical planning, intraoperativeintraoperative

management, and postmanagement, and post--treatment followtreatment follow--upup

The use of imaging studies in melanoma needs The use of imaging studies in melanoma needs further evaluation, as current evidence does not further evaluation, as current evidence does not support any particular protocol for their use and support any particular protocol for their use and study benefits are not clearstudy benefits are not clear77

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AcknowledgementsAcknowledgements

KrithicaKrithica

KaliannanKaliannan, MD, MDKevin Kevin DonohoeDonohoe, MD, MDMaiMai--LanLan

Ho, MDHo, MD

Maria Maria LevantakisLevantakisGillian Lieberman, MD Gillian Lieberman, MD