Intl ACGVGRAhn Liver Lesion

8/2/2023
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Moderator:
Zaigham Abbas, MBBS, FCPS, FRCP, FRCPI, FACP, FACG
American College of Gastroenterology

1
8/2/2023
ACG Virtual Grand Rounds

Join us for upcoming Virtual Grand Rounds!
Week 31 – Thursday, August 3, 2023

American College of Gastroenterology Guidelines Update:
Diagnosis and Management of Celiac Disease
Faculty: Benjamin Lebwohl, MD, MS
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Week 32 – Thursday, August 10, 2023

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8/2/2023
Practical Management of
Focal Liver Lesions in 2023
ACG International Grand Rounds

August 1, 2023
Joseph Ahn, MD, FACG

Professor of Medicine
Section Head of Hepatology
Oregon Health & Science University
Focal Liver Lesions (FLL) ~ Benign Liver Masses
Learning Objectives
Introduction
• Clinical Context
• Imaging
Characteristics
Management • DDx
Approach • When to Biopsy
• When to Resect
Case Review Not for Radiologists

But Clinicians
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Case 1- PCP referral
55 yo M with DM, obesity, abdominal pain
US- 4 cm solid hepatic mass
What are the next best steps?
Why?
Patients worry Providers worry

about having: about missing:
Cancer Cancer
Patient want to Providers worry

know about being
“What is it?” SUED
Nguyen, J Am Col Rad 2017;14:324

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Increase in Diagnoses of
Unsuspected Liver Lesions
1996 ---------------------------------------------------------------- 2010
- CTs tripled Increase in

- MRIs quadrupled Liver
- US doubled Lesions
- PET scans increased being
Discovered
CT Chest obtained for lung cancer screening
2.1% had incidental hepatobiliary findings JAMA 2012; 307
Practice Guideline
Marrero, Ahn, AJG 2014; 109: 1328
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More Guidelines
Management of incidental liver lesions on CT: A white paper of the ACR Incidental
Findings Committee. J Am Coll Radiol 2017;14(11):1429–37
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Overview
1. Introduction
2. Management approach
• Understand the Clinical Context
• Know your Differential Diagnosis
• Make Practical Management Decisions
3. Case review
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Clinical context
Study indication
• Incidental finding
– Most are asymptomatic
• Directed evaluation
– Elevated AFP
– Abdominal pain
– HCC surveillance
– Abnormal LFTs
– Weight loss
13
Clinical context
Risk Factors
• Chronic liver disease  HCC
• Viral hepatitis, NASH
• Cirrhosis
• Cancer history  Metastatic Cancer
• OCP, HRT, anabolic steroid exposure, PCOS, Glycogen storage disease
 Hepatocellular Adenoma
Rule of Thumb
< 1 cm ~ almost always benign in those without risk factors
Gore, JACR 2017
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Differential Diagnosis Stratification
Cirrhotic Non-Cirrhotic
• HCC • Metastatic tumor (>>> more
likely than primary liver
• HCC cancer)
• Hepatocellular adenoma
• HCC (HCA)
• Focal nodular hyperplasia
• Dysplastic Nodule (FNH)
• Macroregenerative Nodule • Hemangioma
• Cholangiocarcinoma
• Epithelioid Hemangioendothelioma
• Angiomyolipoma
• HCC
• Fibrolamellar HCC
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Distribution of Liver Masses
Courtesy of Dr. Mitch Shiffman
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Make Practical Decisions

Characteristics
• Solid vs.
Formulate the (Differential)
Cystic
• Single vs.
Diagnosis
Multiple
• Size Further Imaging Needed?
• Margin- Study Adequacy?
smooth vs.
irregular
• Location-
central vs.
Biopsy?
peripheral
• Growth Decisive referrals (MDLT,
• Contrast surgery, IR) vs.
Enhancement
Explicit (non) Monitoring Plans
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Ultrasound
Pros Cons
• No ionizing radiation
• Technique, Operator
• No contrast
dependent
• Safe in pediatric population, women of
child-bearing age • Limited if gas in abdomen
• Inexpensive • Limited in obese individuals
• Real-time images • Dome lesions are less well
• Dopplers can show blood flow
seen
• Widely available
• Good overall beginning study
Bad terms
Good Terms • Focal irregularity
• Hyperechoic
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CT
Pros Cons
• Detailed view of many types of tissues • Significant radiation
• Painless, noninvasive, accurate – Radiation dose: 10 mSv
• Fast, simple (usually < 5 min) – Background radiation dose received
• Guide for radiation therapy, needle biopsies over 3 years
• Arterial and portal venous phases may be • Contrast allergy risk
obtained to delineate blood supply of liver
masses, assesses thrombosis • Contrast renal risk
• More widely available and usually easier to • May need to repeat in multiphase because
schedule than MRI often single phase obtained in ED
Favorable Terms Bad terms

• Without washout • Nodular liver
• Peripheral enhancement • Delayed rim enhancement
• Hypoenhancing • Enlarging mass
• Central scar
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Best- if you ask Radiologists

MRI Worst- if you ask Patients
Pros Cons
• Clear, detailed images • Not as widely available
• More sequences/data • Cost
• Enhanced soft tissue contrast
• Longer exam time
• Very few allergies to gadolinium • Need for breath-holding
contrast • Claustrophobia risk
• No radiation • Undetected metallic implant may affect
• Can obtain MR Elastography magnetic field
concomitantly • Nephrogenic systemic fibrosis
Favorable Terms (similar to CT) Bad terms (similar to CT)
Gore, JACR 2017; 14: 1429
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Contrast Enhanced Ultrasound (CEUS)

Pros Cons
• Similar to Ultrasound
• Similar to Ultrasound
• Microbubble contrast agent-ok in renal
failure, cirrhosis • Technique, Operator
• Incorporation into LIRADs in 2018 dependent
• Limited in obesity, steatosis
• Consider when CT, MRI are • Needs target lesion within 10
indeterminate, not available, or not
obtainable cm of transducer
• Limited availability
Good Terms Bad terms

• Hyperechoic
• Focal irregularity
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Practical Pearls
Get prior imaging for comparison
Talk to your Radiologist

Better yet- look at the imaging with them
Ask- “What scan do you recommend?”
Know your contrast agents
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Contrast Agents
• Anuric, on dialysis- CT IVC ok, contrast MRI avoid
• ACR Manual Classification of Gadolinium-Based
Agents Relative to Nephrogenic Systemic Fibrosis
Zhang, Frontiers in Oncol 2022
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Practical Biopsy Approach

• Early Biopsy if:
• Equivocal imaging
• Cannot exclude malignancy
• Consider concomitant assessment of uninvolved parenchyma for
fibrosis/cirrhosis
• Know when NOT to Biopsy:
• Obvious diagnosis by imaging
• Most FLL have characteristic MRI/CT to obviate Bx
• Risks
• Biopsy- bleeding, pain, seeding, false negative
• No biopsy- uncertainty, ongoing imaging
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Practical Diagnostic Approach

Obtain CT or MRI
Marrero, Ahn, AJG 2014; 109: 1328
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Practical Diagnostic Approach
Yataco, AJG 2021; 116:855
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Practical Challenges
Don’t Miss Malignancy!
• Metastatic disease
• HCC
• CCA
Recognize Benign Lesions!

• Simple Cysts Deal with
• Hemangioma
• FNH Indeterminates!
• Perfusion, focal fat
When to Stop Imaging?

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Practical Management
•Repeat imaging
• (Often done when unsure of what to do)
•MDLT, Surgical, IR referral
• Uncertainty
• Symptomatic
• First, exclude other causes of symptoms
• Growing
• Bleeding
• Size > 5 cm
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Case 1- Follow-up
55 yo M with DM, obesity, abdominal pain

US- 4 cm mass
MRI- 3.6 cm hemangioma

No biopsy, no referral out, no long term monitoring;
Workup for other causes of pain
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Hepatic
Hemangioma
(HH)
• Solid
• Solitary in 70-90%
• Size usually < 5 cm
• Asymptomatic- incidental
finding
• Nonspecific abdominal
discomfort
• No association with chronic
liver disease
• Most common benign FLL
Rungsinaporn, J Med Thai 2008
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Hepatic Hemangioma
• MRI or CT to confirm Dx
• Peripheral early enhancement  Centripetal fill-in (large HH may not fill in centrally)
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Hepatic Hemangioma
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Hepatic Hemangioma
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SMALL HEMANGIOMA (< 1.5 CM)

HEMANGIOMA • May not show globular peripheral
SIZE VERSUS enhancement
IMAGING
GIANT HEMANGIOMA ( > 10 CM)
FINDINGS
• May not progress to uniform enhancement
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Hepatic Hemangioma Management
Avoid No No
contraindication to contraindication to
Biopsy OCP pregnancy
Intervene ONLY Monitoring

No Routine If symptoms, NOT
Intervention growth,
hemorrhage indicated
Marrero, AJG 2014; 109: 1328
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Case 2- Oncology referral
55 yo F with breast cancer and FMH CRC
US- multiple nonspecific lesions in liver

CT- multiple hypovascular lesions
throughout the liver
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Metastatic
Cancer
• Solid
• Usually multiple
• Hypovascular
• Colorectal
• Lung
• Pancreatic
• Hypervascular
• Melanoma
• Renal cell carcinoma
• Neuroendocrine tumor
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Metastatic Cancer
Most commonly involved site in
GI tract cancer metastases
Most frequent site of blood-born metastases
irrespective of whether the primary is drained
by the systemic or portal veins
Involved in ~ 1/3 of all cancers

Including up to 50% of stomach, breast, lung, colon cancers
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Diffuse Metastases
to the Liver
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Metastatic Cancer can Mimic HH
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Case 2- Follow-up
55 yo F with breast cancer and FMH CRC
Colonoscopy negative
US-guided biopsy of the FLL  breast cancer mets
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Case 3- OB referral
26 yo F, prior OCPs + HCA
US- 3.5 cm lesion in R lobe

Gallbladder sludge; LFTs normal
42

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Hepatocellular Adenoma (HCA)

Hepatocytes arranged in cords
(no vessels, bile ducts)
43
Hepatocellula
r Adenoma
• Solid
• Size- usually < 5 cm
• Incidental in 12-25%
• Asymptomatic vs. Chronic
RUQ pain
• Rupture
• Multiple (Usually > 10) ~

Hepatic adenomatosis
44

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Hepatocellular
Adenoma (HCA)
• RF- OCP (30-40x risk),
anabolic steroids, Glycogen storage
diseases
• (Association with NAFLD)
• Potential rapid growth in pregnancy
• Risk of hemorrhage with growth, trauma
• Malignant potential (5-10%)
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Hepatocellular Adenoma- Intra-lesion

Hemorrhage
Risk- Subcapsular location, size, long duration of OCP
46

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Hepatocellular Adenoma
47
CT with IV contrast MR T1 Early arterial

enhancement
48

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Hepatocellular Adenoma Subtypes

8 subtypes, but 3 important ones
MRI can ID Inflammatory & HNF in up to 80% of cases.
Name % Histology Characteristics

HNF-1 alpha 30-40 Steatosis Rare HCC risk
(+ OCP association)
Inflammatory 40-55 Steatosis, inflammatory Very rare HCC risk
infiltrates (+ BMI, ETOH assoc)
B-Catenin 10-20 + B-catenin staining Increased HCC risk
immunohistochemical (Men, anabolics)
Nault, Gastro 2017; 152:880
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• Biopsy only in inconclusive cases
• Discontinue OCP, anabolic steroids, Wt loss- may regress (6 mo f/u)

• Pregnancy NOT contraindicated if < 5 cm
• > 5 cm, symptomatic, ♂, increase in size (20-25%), B-catenin 

resection > TA embolization (nonsurgical candidates)
• HCA should be monitored q 6 mo for 1-2 years then annually depending
on stability, growth pattern
Marrero, AJG 2014; 109: 1328
EASL PG 2016
Klompenhouwer, AJG 2019; 114:1292
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HCA & Pregnancy- AASLD Guidance 2021
Sarkar, Hep 2021
51
Hepatocellular Adenoma Regression with OCP

withdrawal
Kompenhouwer, AJG 2019
52

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Hepatic
Adenomatosis
• Glycogen Storage Disease
• Associated with fatty liver &
obesity
• Bx largest one (all tend to be

same subtype)
• Higher risk of complications

• But liver transplant not
routinely recommended for
multiple or unresectable HCA
53
Case 3- Follow-up
26 yo F with small HCA-

Pregnancy is not generally contraindicated
US- 3.5 cm lesion in R lobe
MRI- suggests steatotic, HNF-1 alpha subtype
Asymptomatic HCA < 5 cm, can be observed
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Case 4- Urgent Care Referral
37 yo M with anxiety, RUQ pain

AST 80, ALT 40, TB 1, + ETOH
US- 5 cm lesion in R lobe
CT- enhancing lesion with central scar
55
Focal Nodular
Hyperplasia
(FNH)
• Solid
• Size usually < 5 cm
• May increase in size over time
• Asymptomatic- incidental finding
• Nonspecific abdominal
discomfort- poor correlation with
symptoms
• No association with OCP, chronic liver
disease
• NO malignant potential
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A B
Focal Nodular • Well defined unencapsulated mass in a

non-cirrhotic background liver.
Hyperplasia • There is a central scar, from which fibrous
septa radiate outward and separate the lesion
Pathology into small lobules.
57
Focal Nodular Hyperplasia

• UNENHANCED
• UNIFORM, LOW DENSITY MASS
• LOWER DENSITY CENTRAL SCAR IN 1/3
• SMALL SIZE IN FNH, LARGER ( > 2 CM) IN FIBROLAMELLAR CARCINOMA
• FIBROLAMELLAR CA HAS FIBROTIC CENTRAL SCAR WHICH OFTEN CALCIFIES
• THE CENTRAL SCAR OF FNH RARELY CALCIFIES
• ENHANCED
• RAPID INCREASE IN DENSITY
• HOMOGENEOUS ENHANCEMENT
• LESS DENSE CENTRAL SCAR BECOMES VISIBLE
• ENHANCEMENT OF CENTRAL SCAR MAY BE DETECTABLE
• ENHANCEMENT MAY ALSO OCCUR IN FIBROLAMELLAR CARCINOMA
• IN PORTAL PHASE LESION BECOMES ISODENSE WITH THE LIVER
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Focal Nodular • HYPERVASCULAR TUMOR

• CENTRIFUGAL “SPOKE WHEEL” VASCULAR PATTERN IN 2/3
Hyperplasia
• LARGE PERIPHERAL VESSELS PENETRATE MASS
• DIVIDE INTO SMALLER RADIATING VESSELS IN THE MASS
• CAPILLARY PHASE
Angiography
• UNIFORM BLUSH, NO AVASCULAR AREAS
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Arterial Hepatic Delayed
Focal • MRI > CT to confirm Dx

• Homogeneous enhancement, central non-enhancing scar, pseudocapsule
nodular • MRI most sensitive

• Biopsy not routinely indicated unless can’t distinguish b/w HCA, HCC
hyperplasia
Marrero, AJG 2014; 109: 1328
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Focal Nodular Hyperplasia

• Pregnancy and OCP not contraindicated
• No intervention for asymptomatic FNH

• Slight incidental increase in size is NOT concern
• Resection can be considered for symptoms, uncertain diagnosis
• Stop monitoring for stable, asymptomatic FNH
Marrero, AJG 2014; 109: 1328

EASL PG 2016
Sarkar, Hepatology 2021
61
Lesions with Central

Scars
• COMMON
• FOCAL NODULAR HYPERPLASIA
• HEMANGIOMA
• UNCOMMON
• FIBROLAMELLAR CARCINOMA
• CHOLANGIOCARCINOMA
• HEPATIC METASTASES
• HEPATOCELLULAR CARCINOMA
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FIBROLAMELLAR
HEPATOMA
GROSS SPECIMEN
63
Case 4- Follow-up
47 yo M with RUQ Pain
MRI- FNH
ETOH rehabilitation
Surgical resection NOT recommended at this time
Monitor in 6 mo
64

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Case 5- General Surgery Referral
34 yo M with anorexia, chills, RUQ pain
CT prelim report- “multiple liver cysts”
65
Cystic Liver Lesion- Differential Diagnosis
Polycystic Liver
Simple Hepatic Cyst Hepatic Abscess
Disease
Intraductal Papillary Intraductal Papillary

Parasitic Neoplasm of Bile Carcinoma of Bile
Cyst Ducts ~ Biliary Ducts- Biliary
Cystadenoma Cystadenocarcinoma
66

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Simple
hepatic cyst
• Incidental, asymptomatic
• Common (up to 15%)
• F:M- 5:1
• Rare complications- pain,
infection, hemorrhage
• Imaging  fluid filled lesion

• No or minimal septations
• No fenestrations
• No irregular walls
• No calcifications
67
Polycystic Liver Disease
68

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PCLD
EASL 2022
69
MRI CT
• History of F, Pain
Hepatic Abscess • Inc WBC, BCx+, Stool Cx+
• Rx- Antibiotics, drainage
70

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Intraductal Papillary Neoplasm of Bile Ducts (IPNs)

~ Biliary cystadenoma, cystadenocarcinoma
• Complexity
= Septations, Fenestration,
Calcification, irregularity of walls
• No routine aspiration
• Limited sensitivity
• ? Dissemination risk
• Can’t differentiate by imaging
• Surgical consultation
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Case 5- Follow up
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Entamoeba
Histolytica Cyst
• CT- hypoechoic masses with
peripheral enhancing rim
• E. histolytic antibody +
• Treatment
• Metronidazole 750 mg
TID x 10 days
• Cure rate > 90%
• Imaging guided
aspiration
73
FLL- common consultation

Know the DDx  Make the Dx
HH, HCA, FNH, Cysts
Risks of Bx and NOT Bx
Reassurance in clearly benign cases=
Stop Imaging
Don’t miss HCC, Mets
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Joseph Ahn, MD, MS, MBA

Professor of Medicine
Section Head of Hepatology
Oregon Health & Science University
75
Questions?
Zaigham Abbas, MBBS, FCPS, FRCP, FRCPI, FACP, FACG
Joseph Ahn, MD, MS, MBA, FACG
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8/2/2023
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8/2/2023

Participating in the Webinar

Type your questions here so that the moderator

A handout with the slides and room to take notes can

American College of Gastroenterology

ACG Virtual Grand Rounds

Week 31 – Thursday, August 3, 2023

Week 32 – Thursday, August 10, 2023

Visit gi.org/ACGVGR to Register

American College of Gastroenterology

ACG International Grand Rounds

Joseph Ahn, MD, FACG

Focal Liver Lesions (FLL) ~ Benign Liver Masses

Case Review Not for Radiologists

American College of Gastroenterology

Case 1- PCP referral

55 yo M with DM, obesity, abdominal pain

US- 4 cm solid hepatic mass

What are the next best steps?

Patients worry Providers worry

Patient want to Providers worry

Nguyen, J Am Col Rad 2017;14:324

American College of Gastroenterology

1996 ---------------------------------------------------------------- 2010

- CTs tripled Increase in

Marrero, Ahn, AJG 2014; 109: 1328

American College of Gastroenterology

American College of Gastroenterology

American College of Gastroenterology

Differential Diagnosis Stratification

Distribution of Liver Masses

Courtesy of Dr. Mitch Shiffman

American College of Gastroenterology

Make Practical Decisions

American College of Gastroenterology

Favorable Terms Bad terms

Best- if you ask Radiologists

Favorable Terms (similar to CT) Bad terms (similar to CT)

Gore, JACR 2017; 14: 1429

American College of Gastroenterology

Contrast Enhanced Ultrasound (CEUS)

Good Terms Bad terms

Get prior imaging for comparison

Talk to your Radiologist

Know your contrast agents

American College of Gastroenterology

Zhang, Frontiers in Oncol 2022

Practical Biopsy Approach

American College of Gastroenterology

Practical Diagnostic Approach

Marrero, Ahn, AJG 2014; 109: 1328

Practical Diagnostic Approach

Yataco, AJG 2021; 116:855

American College of Gastroenterology

Recognize Benign Lesions!

When to Stop Imaging?

American College of Gastroenterology

55 yo M with DM, obesity, abdominal pain

MRI- 3.6 cm hemangioma