Focal Lesions in the Cirrhotic Liver Michael P. Federle, MD Associate Chair for Education Department of Radiology Stanford University

Focal Lesions in the Cirrhotic Liver Cysts, hemangiomas, focal fat, confluent fibrosis Can usually be diagnosed accurately Hemangiomas shrink and become sclerosed in cirrhotic liver Often not identified in advanced cirrhosis Focal fat Key is out-of-phase MR (focal sign dropout) Brancatelli et al. Radiology 2001; 219: 69-74

Cysts + Regenerative Nodules (RN) NECT Enhancement Cysts Hypodense No RN Hyperdense Minimal

Cavernous Hemangioma Large ones have typical appearance Very intense on T2WI Nodular peripheral enhancement Smaller (“capillary”) hemangiomas May enhance homogeneously Can be confused with HCC Key is remaining isodense with vessels

Hemangioma in Cirrhotic Liver Shrinks to Fibrotic Scar 2 years later Only found a “scar” in explant

HCC? No! Cavernous Hemangioma Isodense to vessels

Focal Confluent Fibrosis Present in ~ 30% of advanced cirrhosis > 50% of PSC Most common in anterior + medial segments Usually wedge-shaped lesion 80% have focal volume loss Capsular retraction, crowded vessels Low density on NCCT Delayed persistent enhancement High intensity on T2 – MR Can simulate tumor Ohtomo et al. Radiology 1993; 188: 31-35 Krinsky et al. Radiology 2001; 219: 445-454

Confluent Hepatic Fibrosis (Focal Confluent Fibrosis) Present in ~ 30% of advanced cirrhosis > 50% of PSC Most common in anterior + medial segments Usually wedge-shaped lesion 80% have focal volume loss Capsular retraction, crowded vessels Low density on NCCT Delayed persistent enhancement High intensity on T2 – MR Can simulate tumor Federle: DI: Abdomen

Focal Confluent Fibrosis Note delayed enhancement

Confluent Hepatic Fibrosis

NC T1WI MRI Confluent Hepatic Fibrosis HAP delayed

T1 WI Confluent Hepatic Fibrosis T2 WI T1 PVP

Peripheral Wedge-shaped Lesion May appear central + round on axial section Examples: Focal confluent fibrosis THADs AP shunts

Focal Lesions in the Cirrhotic Liver Regenerative nodules (RN) Dysplastic nodules Hepatocellular carcinoma (HCC)

Evolution of (some) Cirrhotic Nodules (Sakamoto hypothesis, 1991) Regenerative Nodule Low Grade Dysplastic Nodule High Grade Dysplastic Nodule Well-Differentiated HCC Overt HCC (Moderately/Poorly Differentiated)

Regenerating Nodules Usually too small to detect by imaging May be surrounded by fibrotic septa May contain iron, copper Siderotic nodules Hyperdense on NCCT, disappear on HAP & PVP Hypointense on T2 MR, “bloom” on GRE Larger or vascular/enhancing RN Can not be distinguished from dysplastic nodule or HCC

Regenerating Nodules

NCCT Cirrhotic Nodules visible only on NCCT & GRE HAP PVP GRE

Regenerating Nodules T1 WI Best seen on T2 WI (hypointense, multiple)

NCCT Regenerating Nodules hyperdense only on NECT HAP PVP

Regenerating Nodules Importance of NCCT imaging Don’t call “hypervasc. HCC”

Regenerating Nodules 48 y/o man with cirrhosis Cavernous Hemangiomas

Also has HCC 48 y/o man with cirrhosis Must characterize lesions on all phases of CT or MR

Dysplastic Nodules “Adenomatous hyperplasia” (old term) Are premalignant Rarely diagnosed by US or CT MR – iso to hyperintense on T1 Hypo on T2 (opposite of HCC) Should not enhance much on HAP Diagnosed correctly 5 – 15% of cases Krinsky et al. Radiology 2001; 219: 445-454 Dodd et al. AJR 1999; 173: 1185 - 1192

T1WI T2WI Hyper on T1 Hypo on T2 (opposite of HCC) Dysplastic Nodules

Focal Nodule Large Hyper on NECT Minimal vascularity NECT HAP PVP

Focal Nodule Dysplastic Nodule T1WI-IP T1WI-OOP Bright on T1WI No signal loss on OOP (= not focal fat) Dark on T2 WI Minimal Vascularity HAP PVP Delayed T2WI Dysplastic Nodule

Focal Nodule (same patient) Hypoechoic mass US-guided Bx Confirmed dysplastic nodule Courtesy: Mitch Tublin MD UPMC

Hepatocellular Carcinoma (HCC) Heterogeneously hypervascular mass Washes out on delayed phase Invades veins (portal > hepatic) Federle: DI: Abdomen

HCC - Helical CT Main imaging tool in most institutions Must be multiphasic Arterial phase ~ 25 – 35 seconds Dual arterial, or test bolus is ideal Portal venous ~ 60 – 70 seconds Noncontrast Very helpful for RNs, cysts Delayed or equilibrium Useful (but hard to justify 4 phase imaging) Rapid injection (4 or 5 ml/sec); large volume (2 ml/kg; > 150 ml)

HCC - Helical CT Allows detection and characterization of most masses > 2 cm diameter Accurately reflects morphology and hemodynamics of tumor Small, well differentiated HCC Still have portal venous supply Often hypo – to isodense on NC + HAP Hypodense on PVP Capsule, fat common in well-differentiated Most HCC (Best seen as hyperdense on HAP)

HCC within Dysplastic Nodule “nodule-in-nodule” pattern (each component has typical features)

NC PVP Typical HCC screening CT chronic Hep C isodense on NC + PVP HAP

Simplified Approach to Liver Hemodynamics increased dysplasia = more arterial, less portal 100 % arterial supply 80 % 60 40 20 % venous supply Normal RN Dysplastic Nodule Well-diff HCC Mod-diff HCC

HCC moderately differentiated best on HAP “washes out” on PVP NC HAP PVP

HCC - only or best seen on HAP

NC HCC with capsule HAP PVP

HCC well-differentiated HAP HCC well-differentiated best on PVP PVP

HCC Mod Differentiated Best on HAP

Small HCC only seen on HAP & MR HAP PVP

T1 NC T1 HAP Small HCC T2 WI T1 PVP

HCC small tumor PV invasion Tumor Thrombus: Contiguity w tumor Expansion of lumen Enhancing thrombus

HCC: Other Features Lesion with Focal fat in cirrhotic liver = HCC NECT HCC: Other Features Focal fat Calcifications NECT HAP PVP Lesion with Focal fat in cirrhotic liver = HCC

Nodular Lesions in Cirrhosis CT MR NC HAP PVP Delay T1 HAP PVP T2 Regenerative Nodule  or   or   or  Dysplastic Nodule  or   or   or   or   or  Well-diff HCC  or   or     or   or   or   Mod-diff HCC  or   or   or    or    or   = not seen (isodense, isointense)  = hyperdense (-intense) to liver  = hypointense (-intense) to liver

HCC - Helical CT Accuracy Good for large tumors Challenging in screening population (asymptomatic, normal tumor markers) We miss (false + and neg) small HCCs (<2cm) frequently However, we usually (> 95%, UPMC data) accurately guide Rx Decision for follow-up, ablation, TACE, transplantation

HCC - Helical CT Accuracy Multidetector CT and dual arterial phase imaging Sensitivity (86%), positive pred value (92%) Mean size of HCC (22 mm) Much better results than other reports Murakami et al. Radiology 2001; 218: 763-767

HCC - MR Accuracy Variable intensity of HCC on T1 MR 35% hyper -, 25% iso-, 40 % hypo Hyperintense often well-differentiated, contain fat Almost always hyperintense on T2 MR Must have multiphasic study after bolus of Gd-DTPA Most HCC are hypervascular/intense on HAP

HCC - MR Accuracy Best studies with good reference standard (OLT, explantation) in screening population Detect HCC in 50 – 65% of patients Detect 35 – 50% of HCC tumors Miss many tumors  20 mm Hard to distinguish some RNs and dysplastic nodules Krinsky et al. Radiology 2001; 219: 445-454

HCC - Helical CT Pitfalls THAD (transient hep. attenuation differences) Small peripheral wedge-shaped Ignore, usually due to AP shunt or aberrant veins Larger segmental or lobar Often due to tumor occlusion of portal vein Arterioportal shunt Common in cirrhosis Usually benign if small, peripheral, non-spherical, isodense on PVP, visible vessels into + out

HAP Lobar “THAD” HCC obstructing RPV PVP PVP

AP Shunt no tumor resolved spontaneously

AP Shunt ? Post-biopsy visible vessels

AP Shunt spontaneous

AP Shunts + Hemangioma Shunts disappeared Hemangioma stable 3 yrs

AP Shunt in Cirrhosis Early draining vein Small AP shunts are common, often resolve Don’t be too aggressive with Dx or Rx

HCC - Helical CT vs MR Comparable performance MR preference Contrast allergy Known steatosis CT preference Ascites, unstable, tachypneic patient Both are evolving and improving (but often performed/interpreted poorly)

Tumor Markers for HCC Pitt Experience with 430 transplant recipients Excluding 2 patients with HCC + markedly AFP No significant difference in serum AFP in HCC, non-HCC groups AFP often normal in small HCC AFP often elevated in flare of hepatitis Peterson et al. Radiology 2000; 217: 743-749

Screening Recommendation for Known Cirrhosis AFP and PIVKA II – every 3 months Ultrasonography – every 3 or 4 months CT or MR – every 12 months (for chronic hepatitis without cirrhosis, extend intervals) (for high clinical suspicion or indeterminate lesion, shorten interval)

Summary US, CT, MR all useful in evaluation of cirrhosis Large and symptomatic HCCs are easily detected and staged Small HCCs in a screening population are more challenging Some overlap in appearance of regenerative + dysplastic nodules + HCC

Summary Optimal CT + MR techniques are key Must include multiple phases, rapid bolus contrast administration Image-guided Bx and angiography often necessary