Essentials in Oncologic Imaging

What Radiologists Need to Know

Liver: Primary, Metastases

Richard Baron, M.D.

University of Chicago
 Liver Malignancies
• Primary
– Hepatocellular Carcinoma (~85 – 90%)
– Cholangiocarcinoma (~5 – 10%)
– Rare tumors (Angiosarcoma, Lymphoma, Epithelioid
Hemangioendothelioma, others)

• Metastases
HCC without cirrhosis

Mosaic and capsule

 HCC in Cirrhosis
• 10 – 14% of advanced cirrhosis harbors HCC
• 25% of Hepatitis B/C patients develop HCC within
10 years
• Compare to risk of colon cancer in 50 y.o.:
< 1% prevalence, 7% lifetime incidence
 Screening Cirrhosis: 1329 patients
Peterson et al, Radiology, 2000

Patients %HCC

Alcohol 86 10%
B Hepatitis 22 27%
C Hepatitis 99 22%
B/C Hepatitis 22 18%
C Hep/Alcohol 22 18%
PBC 47 2%
PSC 31 0%
Other 99 8%

430 14% 59 pts

 Screening Cirrhosis: 1329 patients
Peterson et al, Radiology, 2000

Patients %HCC

Alcohol 86 10%
B Hepatitis 22 27%
C Hepatitis 99 22%
B/C Hepatitis 22 18%
C Hep/Alcohol 22 18%
PBC 47 2%
PSC 31 0%
Other 99 8%

430 14% 59 pts

 Pathogenesis of HCC:
Key Role of Dysplastic Nodules

• Regenerative Nodule
• Large Regenerative Nodule
• Dysplastic Nodule
• HCC (nodule-in-nodule)

• HCC
Dysplastic Nodules: MR

CT: ~ 10% Lim et al, BJR 2004

MR: 10 – 15% Krinsky, Radiology 2001

Dysplastic Nodules:
Low Grade
- Nuclear atypia is minimal
- Portal tracts present
High Grade
- High nuclear cytoplasmic ratio
- Rare mitotic figures
- Resistance to iron accumulation
-New vessels (nontriadal arteries) increase
-Portal flow to nodules decreases
 HCC
AP

PV
 HCC: Detection
Patient Lesion
Detection Detection Study

CT 67 – 73% 35% Peterson, 2000

MR 77% 37% Krinsky, 2001

MR 91% Bhartia, 2003

Dual Contrast

US ~ 50% ~ 35% multiple

 48 y.o. male, chronic hepatitis C
Solitary 2.5 cm lesion

AP PV EQ
 What would be next best step
To plan appropriate treatment?

A. Biopsy Lesion
B. Confirm with MR exam
C. Make Rx plans as HCC
D. F/U imaging in 3 - 6 mos.
HCC Dx: 2005 AASLD CRITERIA
> 20 mm Liver Lesion, chronic liver disease
AP
One imaging technique with typical HCC
(AP hypervascularity & EQ washout)
One imaging technique showing a mass with
AFP levels > 200 ng/ml

10-20 mm Two imaging techniques with PV

typical HCC (AP hypervascularity & washout

< 10 mm Repeat US every 3-6 months for 2 yrs

American Association for the Study of Liver Diseases

(AASLD) Practice Guideline. Hepatology 2005;42:1208 EQ
HCC Dx: 2010 AASLD CRITERIA
> 10 mm Liver Lesion, chronic liver disease
AP
One imaging technique with typical HCC
(AP hypervascularity & EQ washout)

< 10 mm
PV
Repeat US every 3-6 months for 2 years

American Association for the Study of Liver Diseases (AASLD)

Practice Guideline. Bruix and Sherman. Hepatology 2010 EQ
 Why is non biopsy Dx important?
2009

2011
01/22/2008 Value of Equilibrium Phase CT

Pre Early arterial Late arterial Portal Equilibrium

10/30/2007 Courtesy of M. Hori , Osaka

 ‘Peliotic HCC’

T1 AP AP PV

T2 PV EQ 2 hr
AP PV EQ
Small (10-20 mm) Enhancing CT/MR Nodules
• O’Malley et al (Am J. Gastro 2005): 28% HCC
– Doubling time – 6 mos.
• Jeong et al (AJR, 2002): 13% HCC

• Most small enhancing nodules are not HCC

• Delay, washout characteristics helpful in characterizing
• Multimodality imaging & Follow-up imaging essential
 HCC: MRI signal intensities

AP EQ Delay T1 T2 DWI
Enhancing Nodule: Value of T2 characteristics

AP EQ
OP T1 F/U OP T1 “Nodule
2007 f/u 2007 in
Nodule”
Evolution

IP T1 OP T1

2008
Evolution Dysplastic Nodule to HCC
2005

T2 T1

2006 2007
 Hypovascular Nodules

10 – 15% of small HCC are hypovascular

60% of small hypoattenuating nodules

transformed to enhancing vascular lesions
(Takayasu et al, AJR, 2006)
AP PV

2008

AP EQ

2009
 Diagnosis of Small Nodules
Forner et al, Hepatology, 2007

Serially followed cirrhotic patients for 3 yrs

89 patients developed NEW nodule

60 HCC, 1 cholangiocarcinoma
28 benign nodules (regenerative/dysplastic
predominate)

24/89 nodules = hypovascular (only 2/24 = HCC)

 STAGING HCC: TNM based
T1 Solitary Tumor
T2 Solitary Tumor with microvascular invasion,
OR multiple tumor (< 3 cm);
T3 Multiple tumors > 3cm,
OR tumor involving a major venous branch
T4 Tumor(s) with direct invasion of
adjacent organs other than gallbladder

N1 Regional lymph node metastasis

M1 Distant Metastasis
STAGING HCC: TNM based
I T1 Solitary
N0 Tumor M0
II T2 Multiple
N0tumor (< 3 cm);
M0
IIIA T3 N0 M0
IIIB T4 N0 M0
IIIC Any T N1 M0
IV Any T Any N M1
Extrahepatic HCC: 148 of 403 patients (37%)

Lungs 55%
Lymph Nodes 53%
Regional 41%
Distant 12%
Bone 28%
Adrenal 11%
Peritoneum 11%
Brain 2%
All other sites 7%

Ferris et al, Radiology, 2000

48 y.o. male, chronic hepatitis C
3 lesions; Largest = 3 cm

AP PV EQ
 To evaluate for possible liver transplantation,
which is next best step ?

A. Biopsy largest lesion

B. F/U in 3 mos to show stability
C. Proceed to transplantation list
without further steps
D. Patient is not candidate for
transplantation
Liver Transplantation
• UNOS HCC MELD score upgrade to
22 (15% mortality in 3 mos)

• Milan criteria:
– Single tumor 2 – 5.0 cm

– Multifocal tumor (3 nodules,

<3 cm each)

– No extrahepatic spread or
macrovascular invasion

Mazzaferro et al. N Engl J Med 1996;334:693-699.

 False Positive CT Diagnosis
HYPERVASCULAR HYPOVASCULAR

Reg/Dysplastic Nodules Focal Fibrosis

Focal Fibrosis Reg Nodules (and
Peliosis infarcted nodules)
A-P Shunting/THAD Fibrosed Hemangiomas
 False Positive CT Diagnosis
HYPERVASCULAR HYPOVASCULAR

Reg/Dysplastic Nodules Focal Fibrosis

Focal Fibrosis Reg Nodules (and
Peliosis infarcted nodules)
A-P Shunting/THAD Fibrosed Hemangiomas
 Summary of key issues in HCC
• Very common in chronic liver
disease
• Detection difficult despite claims
in literature
• US/CT/MRI can all be used as
screening tools, but require
optimizing techniques
• Liver transplantation often only
real cure option
• Radiology assessment/reports
are critical to determining patient
treatment options
• Wording, number and exact size
of lesions (to decimal point) in
radiology reports have dramatic
impact on care
 In imaging Hepatic Cholangiocarcinoma, which of
the following is true?

A. Contrast washout key to diagnosis

B. Most lesions show homogeneous
retention of contrast material
C. Usually vascular lesions with
marked arterial enhancement
D. Can range from near water density
to densely solid lesions
 Cholangiocarcinoma
• Gross pathologic structure ~ 10%
– Annular, constricting Intrahepatic

– Infiltrative and expanding

– Intraluminal, polypoid
• Underlying histologic stroma
– Fibrous versus glandular stroma
• Locations
– Intrahepatic, Proximal CBD, Distal
• Associations: PSC, Choledochal cysts; infections,
chemical toxins
Spectrum of Cholangiocarcinoma Pathology

Fibrous Stroma Glandular Stroma

Mixed Stroma
 Cholangiocarcinoma:
Fibrous Stroma

+C EQ

+C EQ
Cholangiocarcinoma: Glandular Stroma
Cholangiocarcinoma: Contrast Enhancement
 STAGING Chol CA: TNM based
T1 Solitary Tumor
T2 Solitary Tumor with microvascular invasion,
OR multiple tumor (< 5 cm);
T3 Multiple tumors > 5cm,
OR tumor involving a major venous branch
T4 Tumor(s) with direct invasion of
adjacent organs other than gallbladder

N1 Regional lymph node metastasis

M1 Distant Metastasis
 Treatment and Staging Impact
Surgery is only cure possibility

Imaging role preparing for resection:

Exclude AdenoCa metastasis from unknown primary

Poor prognosis: Multiple nodules; bi-lobar disease;

vascular invasion; positive lymph nodes
Difficult surgery: Central lesions; chronic liver disease

Surgery offered to potentially resectable patients regardless of stage

Value of Delay Equilibrium Phase
 Liver Metastases
• Most common liver malignancy
• Generally variable, noncharacteristic features
Does not meet classic benign dx (cyst,
hemangioma, or FNH) with known primary tumor

• Site of origin can occasionally be suggested

 Liver Metastases
• Hypovascular (colon, lung, pancreas, many others)
• Hypervascular (renal, islet cell, breast, thyroid, sarcomas)
• Ca++ in mucinous tumors (colon, ovary)
• Change over time in appropriate setting
Significance of Small (<1.0 – 1.5 cm) Hepatic Lesions

Recon thickness 10 mm 7.5 mm 5.0 mm 2.5 mm

No. Lesions 90 112 137 167

Weg, et. al., Radiology, 1998

2,978 Cancer Patients

378 Small Lesions
44 Considered Metastases on Follow-Up
Schwartz et al., Radiology, 1999
58 year old breast cancer patient
CT T2 Gd
Biliary Hamartomas
Colon Ca Islet Cell Ca
AP DWI

AP EQ
Liver Specific Contrast Agents

T1 PV Gd +C EQ

T2 DWI
Carcinoid Metastasis

T2 AP PV EQ

Prior CT F/U CT
 Cystic Metastases

Key findings:
− thick, irregular rind
− mural nodule
− fluid-debris level

Sarcomas (and GIST)

Mucin Producing Tumors
Ovarian, colon, mucinous pancreas
Post Treatment Necrosis
GIST Mets
 GIST

6 month follow-up
 Choi Criteria: GIST
J. Clin Oncol 2007; 25:1753-1759

Complete Disappearance of all lesions

Response No new lesions
Partial Size of 10% OR tumor density > 15% on CT
Response
Stable Size of < 30% or of < 20%
Disease
Progressive > 20% increase in sum of target lesions diameters
Disease
Liver Tumors: Practical Summary
• Understanding the clinical setting is essential
– Chronic Liver Disease
– Presence of other primary tumor and type

• Optimizing imaging and contrast techniques

– Vary with underlying type of tumor suspected

• Regular communications and interactions with

oncologists/hepatologists/surgeons is essential