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Assessment of a Liver Mass: What do you need to knowy

Arun J Sanyal, M.B.B.S., M.D.

Charles Caravati Professor of Medicine

Vi i i C lth U i itVirginia Commonwealth University

CONFLICTS: US PI for Gideon Trial sponsored by Bayer

What to do with a liver mass?

• What could it be?– differential diagnosis varies based on whether d e e t a d ag os s a es based o et e

cirrhosis is present• Which diagnoses are particularly lethal if

missed?– hepatocellular and other cancers– non-malignant lesions that can bleed

• What are you going to do when you find it?– curative therapies for liver cancer– resection for high risk lesions for bleed– stop birth control pills for specific lesions

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Differential diagnosis of liver mass

• Cirrhosis presentHepatocellular CA– Hepatocellular CA

– Dysplastic nodules

– Regenerative nodules

– Cholangiocarcinoma

– Scar tissue

– HemangiomaHemangioma

– Other lesions commonly seen in non-cirrhotic liver

Clinical considerations in the diagnosis of a liver mass in cirrhosis

• Is cirrhosis present?H/O chronic liver

• Risk factors for HCC:Age– H/O chronic liver

disease

– Evidence of underlying chronic liver disease e.g. elevated liver enzymes

F t f i h i

– Age

– Male gender

– Alcohol + other liver disease

– Insulin resistance

– Obesity– Features of cirrhosis:

• Low platelets

• Synthetic dysfunction

• Features of portal HTN

y

– Diabetes

– Elevated AFP

– HVPG > 10 mm Hg

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Evaluation of a liver mass

CIRRHOSIS

PRESENT ABSENT

> 2 CM 1-2 CM < 1 CM

Imaging features used to diagnose HCC

• Presence of a visible mass with or without involvement of blood vessels etc

• Changes seen over time after injection of an intravenous contrast agent

• Tissue characteristics based on its content

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Size matters

Type of lesion Mean sizeType of lesion Mean size (cm)

Regenerative nodule

Low grade dysplastic nodule

High grade dysplastic nodule

Well differentiated HCC

< 1

1

1.3

1 6Well differentiated HCC

Classic HCC

1.6

2.2

Matsui O. Clin Gastroenterol Hepatol 2005;3:S136–S140

Natural history of HCC development

Matsui et al, Clin Gastroenterol Hepatol 2005;3:S136-S140

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Phases of blood flow in the liver

Arterialpeak Venousliver

peak

washout

Pre-contrast

Portalvein

0 5-20 60-90 200-300

seconds

Hepaticartery

Hepatocellular cancer

Hepatic artery and portal vein supply lost

Arterial neovascularization

Early enhancement

Washout in venous/delayed phase

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Regenerative nodule

Main blood supply from portal vein

Mild arterial enhancement

Strong venous enhancement

HCC: CT scan imaging

Pre-contrast arterial venous

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Additional MRI features of HCC

Variable intensity on T1-image Hyperintensity on T2-image

Diffuse hepatocellular cancer

Bright lesion in T2 weighted image Arterial enhancement with malignantPortal vein thrombosis

Willat, et al. Radiology 2008;247:311-330

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Confluent scar vs tumor:progressive enhancement in scar

Imaging criteria for diagnosis of HCC

Finding Sensitivity Specificity

Arterial enhancement

Delayed washout

Delayed enhancing capsule

> 90%

80%

89%

80%

95%

96%

Bright lesion on T2 images

80% 95%

Multiple sources

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Utility of imaging modalities for diagnosis of HCC

Modality Sensitivity SpecificityModality Sensitivity Specificity

Conventional US

Contrast-enhanced US

CT scan

MRI

45-92%

60-90%

68%

81%

40-90%

> 90%

> 95%

> 95%

Multiple sources

ALWAYS ORDER CONTRAST IMAGING WITH TUMOR PROTOCOL

What you need to know about AFP

• Normally produced in the fetus-fetal equivalent of albuminequivalent of albumin

• Elevated levels occurs due to:– Neonatal period– Pregnancy– Pregnancy-related disorders (omphalocele)– Germ cell tumors (testes and ovary)– Hepatocellular carcinoma– Hepatic regenerative activity

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Alternate biomarkers

• AFP-L3 (lectin-bound AFP), descarboxylprothrombin(DCP), glypican-3

• Relevant only when AFP > 10 or < 200

• If AFP-L3 > 10%, then:

– sensitivity: 70%

– specificity: 63%

• If AFP-L3 > 35%, then:

i i i 33%– sensitivity: 33%

– specificity: 100%

Evaluation of a liver mass

CIRRHOSIS

PRESENT ABSENT

> 2 CM 1-2 CM < 1 CM

4 phase CT or MRI

Tumordiagnosed

p

2nd modalityimaging

Biopsy

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Similar findings on two modalities allow HCC diagnosis to be made with high specificity

N= 89Nodules 1 2 cm in size in cirrhotic subjects

Modality sensitivity specificity PPV NPV

CEUS

MRI

CEUS + MRI

62

52

33

96

93

100

97

94

100

55

50

42

Nodules 1-2 cm in size in cirrhotic subjects

Forner, et al, Hepatology 2008;47:97-104

Evaluation of a liver massCIRRHOSIS

PRESENT ABSENT

> 2 CM 1-2 CM < 1 CM

4 phase CT or MRI4 phase CT or MRI

Tumordiagnosed

2nd modalityimaging

Biopsy

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Very early HCC• < 1 cm

• Neo-arterialization absent or incomplete

none or poor arterial enhancement– none or poor arterial enhancement

– non-specific washout

Duct cellsat interface of tumorat interface of tumorare less and replaced by tumor cells

Park et al, Cancer 2007;109:915–923.

Small HCC: diagnosis with MRI

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Super-paramegnetic iron oxide (SPIO)-MRI

Fe is taken up by Kupffer cells and make the liver look darker and making the tumor which lacks Kupffer cells stand out as a bright signal

Macarini, et al. Radiol Med 2009;114:1267–1282

Malignant tumors grow faster than benign tumors

Doubling time

• Malignant tumors: Median doubling time 120-180 days

• Benign tumors: > 1 yr

Taouli, et al. J Comput Assist Tomogr 2005;29:425–429

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Dysplastic nodules

• Isointense on T1 and T2 like regenerative nodules

• Low grade dysplasia: retain portal vein supply

• High grade dysplasia: increasing arterial enhancement and decreased

h tvenous enhancement

• T2 image bright if infarcted

• Nodule within nodule

Benign nodule masquerading as cancer: arterial enhancement without washout

Pre contrast Arterial phase Venous phase Delayed phase

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CT-arteriography for diagnosis of very small or indeterminate nodules

Pattern Findings correlateg

I

II

III

Nodule not seen, arterial and venous supply intact

Nodule hypodense-indicating decrease in arterial supply

Partial Hyperdense area in a nodule (neoarterialization) + loss of portal supply

Low gradeDysplasia

High gradeDysplasia

Early HCC in a nodule

IV

( ) p pp y

Diffusely hyperdense lesion with loss of portal supply

Classic HCC

AASLD guideline for evaluation of HCC

Refer to a transplant center early

Hepatology 2011 Mar;53(3):1020-2

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Differential diagnosis of liver masses when cirrhosis is not present

• In non-cirrhotic liverHemangioma– Hemangioma

– Focal nodular hyperplasia

– Hepatic adenoma

– Nodular regenerative hyperplasia

– Focal fat deposition

– Cystic lesions

– Hepatocellular cancer

Differential diagnosis of incidentalomas

Hemangioma FNH adenoma

Age 30-50 20-40 All ages

Gender

symptoms

US

CT enhancement

MRI

RBC scintiscan uptake

Calcification

F>M

Very rare

Hyperechoic

+++

CSF intensity

yes

Yes

F>>M

Rare

Varied

Central scar

Liver intensity

no

No

F>M*

FNH

Varied

Capsule

Liver intensity

No

NoCalcification

Risk of HCC

Risk of rupture

Yes

No

low

No

No

low

No

Yes

Yes

* Male predominant in glycogen storage diseases (types I and III)Bahirwani and Reddy, Aliment Pharmacol Ther. 2008 Oct 15;28(8):953-65

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Hepatic adenoma

Risk factors for HCC• > 5 cm 5 cm• rising AFP

Bahirwani and Reddy, Aliment Pharmacol Ther 2008 Oct 15;28(8):953-65

Focal nodular hyperplasia

• central scar• takes up biliary contrast

• Tc-colloid uptakepresent due toKupffer cells

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Take home messages

• Clinical assessment:– background likelihood of chronic liver disease– use of birth control pills– symptom status

• Asymptomatic solid solitary masses:– evaluate with CT scan with correct protocol– assess diagnosis, risk of bleeding and cancer

M i i h ti bj t• Masses in cirrhotic subject:– US used mainly for screening– 4 phase CT or MRI for lesion seen on other imaging– worry about HCC and follow AASLD guidelines

THANK YOU FOR YOUR ATTENTION