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ImagingofNeuroendocrineTumors
and
Obstaclesto
Diagnosis
EricLiu,M.D.
VanderbiltNeuroendocrineCenter
DivisionofSurgicalOncologyandEndocrineSurgery
DepartmentofSurgery
Vanderbilt
University
Medical
Center
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Overview
BackgroundonNeuroendocrine
CrossSectional
Imaging
NuclearImaging
NewImagingTechniques
FollowupImaging
Choosingtherightimagingtechnique
Obstaclesto
Diagnosis
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Basicsof
Neuroendocrine
Cells
Foundinbronchial,gastroenteropancreatic
tract
Secretehormones
Serotonin
VIP Insulin Somatostatin
Gastrin Histamine
Glucagon
ExpressSOMATOSTATINRECEPTORS
Liu and Oberg, Endo Meta Clin N Am, 39(4):697-71, 2010
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Terminology Carcinoid
APUDoma IsletCellTumors
Neuroendocrinecarcinoma
Modlin et al, Hum Pathol 12:1440-51, 2004
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Definitions
Carcinoidslow growing tumor of the GI and bronchial tractsthat derives from enterochromaffin cells that
frequently secrete serotoninNeuroendocrine Tumorstumors derived from GI endocrine cells that can
secrete many hormonesInsulin glucagon gastrin VIP
Express somatostatin receptor
SiegfriedOberndorfer
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Incidence of neuroendocrine
tumors
2.55.0/100,000
inhabitants
Modlin, I. M. et al. J. Natl. Cancer Inst. 2008 100:1282-1289; doi:10.1093/ nci /d n275
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Incidence of neuroendocrine
tumors2.55.0/100000inhabitants
Modlin, I. M. et al. J. Natl. Cancer Inst. 2008 100:1282-1289; doi:10.1093/ nci /d n275
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GEPNET
~75%
Lung
Smallintestine
Rectum
Incidence of neuroendocrine
tumorsSurveillance,EpidemiologyandEndResults(SEER),USpopulation19742005
Yaoetal.,JCO,2005. Modlinetal.,LancetOncol.2008
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0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 12 24 36 48 60 72 84 96 108 120
Survivalprobability
Survival time (months)
1988-99 n=892 SEER data base. Median survival 37 mo
1973-87 n=787 SEER data base. Median survival 17 mo
1974-2004 SEER. Median survival 33 mo
Survivalof
patients
with
metastatic
carcinoid
Yaoetal.,JCO,2005.
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SurvivalChangesBasedonLocation
andDifferentiation
Well/ModeratelyDifferentiated PoorlyDifferentiated
Yaoetal,JCO,2005.
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ClinicalPresentations
Carcinoid:diarrhea,flushing,abdominal
cramping Insulinoma: WhipplesTriad
Glucagonoma: diabetes,anemia,diarrhea,
necrolyticmigratory
erythema
Gastrinoma(ZES):resistantulcers,abdominalpain,diarrhea
VIPoma(WDHA,
VMS):
watery
diarrhea,
hypokalemia,achlorhydria,vasodilation
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BiochemicalTesting
Hormonelevels
5HIAA
Gastrin
Insulin/C
peptide/Proinsulin Glucagon
VIP
Serotonin Andothers
Biomarkers
ChromograninA
ChromograninB
Pancreastatin
Neuronspecific
enolase
Ghrelin
PancreaticPolypeptide
SubstanceP
Andmore
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TheImportance
of
Imaging
Diagnosis
Incidentalfinding
Stagingformetastaticdisease
Determinationofresectability
Followup
Diseaseprogression
Symptomatology
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TheImportanceofImaging
Resectionofprimary7.4vs.4.0years;p
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PathologicalClassification
of
NETs
Histology WellDifferentiated Moderately Poorly
Appearance Uniform Pleomorphism
Prognosis Good Intermediate Poor
MitoticRate 10
Ki67 20%
Necrosis Absent Present
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Ultrasound LowCost
HighResolution
ExaminationoftheLiverandBiliary
USER DEPENDENT
Best when attached to an endoscope orbiopsy needle
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Imagefromhttp://www.hopkinscoloncancercenter.org
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Sundin etal,2009
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ComputedTomography
(CT)
Workhorse
Readilyavailable
Fast
CTAbdomen
liver
and
pancreas
protocol
CTNeckandChest
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ScanningProtocols
64
slice
MDCT
PancreasProtocol
Slices13mm
OralContrast(negativecontrast)
LateArterialPhase(25
30sec)
PancreaticPhase(40sec)
VenousPhase(7090sec)
BolusTracking
LiverProtocol
Slices3mm
OralContrast
Noncontrast
ArterialPhase(1525sec)
LateArterialPhase(2530sec)
Venous
Phase
(70
90
sec)
BolusTracking
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Sensitivityand
Specificity
of
CT
Sundin etal,2009
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Featuresof
NETs
on
CT
Mass
Relationshipto
structures
Calcifications
Lymphnode
metastases
LiverMetastases
Carcinomatosis
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RadiationExposure
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MagneticResonance
Imaging
SpecificOrganSystem
Liver Pancreas
Bones
Pelvis ContrastAgents
Gadolinium
EOVIST/PRIMAVIST MRCholangiogram
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MRProtocols
T1weighted(fatbright,waterdark)
T2weighted
(fat
dark,
water
bright)
ContrastEnhancedforvasculature
(Gadolinium) LiverParenchyma
Gadoxetate(Eovist/Primovist)
DuctalSystem
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Appearanceof
NET
on
MRI
T1lowsignal
T2high
signal
Goodforsmalllesions
Sundin etal,2009
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CTvs.
MRI
MRImaypickup~20%morelesions
Giesel etal,2011,Dromain,etal,2005
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FunctionalImaging
ColorPictures
Describe
Biology
Octreoscan 111InPentetreotide131
I/123
I
MIBG18FDGPET11CHTP
18
FDOPA68GaDOTATATE
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Octreoscan SinglePhotonEmissionTomography(SPECT)
ImagesSomatostatin
Receptor
Octreotidepeptidechelatedto111Indium
Inject185
222
MBq
FourHourScan
24hourscan
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Octreoscan
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Octreoscan
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Octreoscan
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Octreoscan
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Octreoscan
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Kwekeboom,etal,2009.
/
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metaiodobenzylguanidine
123/131IMIBG
Pheochromocytoma
Neuroblastoma
Paraganglioma
Sensitivity8288%
Specificity82
24%
Wisemanet
al,
2009
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FDGPET
Tends to accumulate in poorly differentiated tumors
Pasquali, World J Surg, 1998
Adamsetal,EJNM,1998
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11CHTP
PET
Orlefors etal,2005
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18
F
DOPA
PET
Koopmansetal,2008.
68Gallium DOTATATEPET
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Patientwastoldshehadonlytwolesionsby
CT,MRI,octreoscan
Otherpeptides:
DOTATATE
DOTATOC
DOTANOC
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Direct
Comparison
CT
vs.
MRI
vs.
SRS
Dromain etal,JCO,2005
21%betterthanCT
93%better
than
SRS
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STRONGSSTR2Staining
WEAKSSTR2Staining
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Direct
Comparison
CT
vs.
MR
vs.
PET
Giesel etal,EJR,2012.
CT ArterialPhase CT PortalPhase
MRIwithcontrast PET 68GaDOTATOC
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CT
vs.
MRI
Giesel etal,EJR,2012.
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Effective
Imaging
Modlin, 2007
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ChoosingtheRightImagingTechnique
CT resolution
MRI sensitivityinorgans
Ultrasound
biopsyOctreoscan SSTR/Distant
FDGPET
PDNEC
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Follow
up
Imaging EarlyStages: 36months
LateStages:
12
24
months
ChangesinTumorMarkers
Changesin
Symptoms
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Obstaclesin
the
diagnosis
for
the
clinician
Whatdo
these
markers
mean?
Whendoyoustartthehunt?
How
far
do
you
go? WhatifIcantfindit?
WhatifImissit?
Vinik etal,
2010
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GUIDELINESNORTHAMERICANNEUROENDOCRINETUMOR
SOCIETY(2010)
www.nanets.net
EUROPEANNEUROENDOCRINETUMORSOCIETY
(2009)
www.enets.org