Approach to Liver Lesions. Anjana A. Pillai, MD Associate Professor of Medicine Director, Liver Tumor Clinic The University of Chicago Medical Center

Approach to Liver Lesions Anjana A. Pillai, MD Associate Professor of Medicine Director, Liver Tumor Clinic The University of Chicago Medical Center

Objectives Identify common clinical features and imaging characteristics of benign and malignant liver masses Identify which benign lesions require further follow-up and management Review key imaging characteristics of hepatocellular carcinoma and cholangiocarcinoma

Three Categories of Liver Masses Benign lesions typically requiring no further imaging Benign lesions requiring further follow-up and management Malignant lesions requiring appropriate therapy Lewis, R. Clinical Approach to Liver Mass Lesions. In: Mayo Clin Gastro and Hep Board Review, Hauser SC, ed. 2015, 5 th ed, Ch 24: 252-264

How do I approach liver lesions? First thing is first - take a good history! Is there underlying liver disease? Is the patient symptomatic vs incidentally found? Is the lesion new? Is the lesion growing? Is the imaging study adequate? Then examine the patient! What did their physical exam tell me? Finally, ALWAYS, ALWAYS personally review the imaging

BENIGN LESIONS NOT REQUIRING FOLLOW-UP Simple liver cysts Cavernous hemangioma Focal Nodular Hyperplasia Focal fatty change (fat sparing) in liver Angiolipoma BENIGN LESIONS REQUIRING FOLLOW-UP Hepatic adenoma Pyogenic Liver Abscess Nodular Regenerative Hyperplasia Biliary Cystadenoma Inflammatory pseudotumor Granulomatous abscesses Amebic Liver abscess Echinococcal Cysts

Question #1 A 25 yo AA woman with long standing asthma was noted to have an incidentally found liver lesion on cuts from her CT chest. A dedicated MRI and CT with contrast of the abdomen described the lesion as a large 7 cm central arterially enhancing mass (extending into segment 7,8,4A and1) with fading/isoenhancement on venous phase with no wash out on delayed images. No definitive central scar noted. The liver appeared morphologically normal.

What is your next step in management? A. No further work-up needed B. Repeat imaging in 6-12 months C. Repeat imaging now with a different modality D. Biopsy the lesion E. Surgical resection

Liver Cysts Cysts are thin-walled structures lined by cuboidal bile duct epithelium and filled with isotonic fluid. Female predominance Can be solitary or multiple Often asymptomatic unless very large Often coexist with other mass lesions Prevalence increases with age Ultrasound best imaging modality Biopsy is not needed

Liver Cyst - US Anechoic = black Increased through transmission (white around it) Smooth with round margins No internal echoes No flow on doppler

Liver Cyst - CT <10 Hounsfield units Same density as water Don t change with contrast

Liver Cyst MRI Bright on T2 Dark on T1 No enhancement T2 MR T1 Portal venous phase

Case Presentation 55 yo Indian woman presents with dyspnea on exertion. She also notes new right sided abdominal pain/ache for the last 2-3 weeks which is persistent. Pain is worse when she lies on the right side. She has also noted early satiety and poor appetite for last few years but never sought treatment for this because she was able to maintain her weight for the most part. She has noticed progressive mild lower extremity edema for the last few years. No jaundice or dark colored urine. No fevers/chills. No recent travel. Labs: Viral hepatitis serologies negative. LFTs nl, Alb 4.2, Cr 0.7, WBC 2.9 H/H 11.8/35 platelets 138, MCV nl

Cavernous Hemangioma Extensive network of vascular spaces lined by endothelial cells and separated by thin, fibrous stroma Most common benign liver lesion Most common in women Often asymptomatic Do not undergo malignant transformation and rupture is very rare Can be multicentric in 30% of cases Only require intervention if symptomatic Biopsy not needed Kasabach-Merritt syndrome (DIC, thrombocytopenia, usu in infants)

Hemangioma - US Hyperechoic = bright Smooth, wellcircumscribed Homogenous

Hemangioma CT Peripheral discontinuous enhancement with gradual fill-in.

Bright T2 signal (as bright as CSF) Hemangioma MRI Peripheral discontinuous enhancement T2 MR Arterial phase MR with gradual fill-in. Portal venous phase MR Delayed phase MR

Case Presentation 65 yo Somalian man with no known liver disease presents with recent onset of abdominal discomfort, early satiety, 30 lb weight loss and lower extremity edema Labs unremarkable except for lowish albumin and mildly elevated INR Viral serologies negative Imaging showed Went to OR for resection with unremarkable post op course and resolution of symptoms

Focal Fat or Fat Sparing Usually occurs in obese patients or those with diabetes, heavy ETOH use or malnourished (chemotherapy) Focal fat can appear as a mass or alternatively an area of fat sparing can appear as a mass in the background of a fatty liver Asymptomatic Does not displace vessels or distort appearance of the liver Usually found near falciform ligament and around the gallbladder

Focal Fat - US Ultrasound Hyperechoic = bright

Focal Fat - CT Normal coursing of hepatic vessels through mass

Fat Sparing -CT

Focal Fat Sparing - MRI In-phase Out-of-phase

Focal Nodular Hyperplasia Non-malignant response to a congenital arterial malformation Female predominance Central scar (arterial malformation) is classic but not always seen Relationship to OCP controversial and no data that discontinuing OCPs helps Most are asymptomatic unless large and space-occupying (rare)

Focal Nodular Hyperplasia No potential for malignant transformation The term telangiectatic FNH is no longer used and are instead classified as adenoma inflammatory subtype which can have malignant potential Biopsy can be useful in differentiating from adenoma but both lesions may show benign appearing hepatocytes on FNA

FNH - US Varies: can be hypo/hyper or isoechoic Most hypoechoic except for central scar Color Doppler increased blood flow in central stellate scar

FNH - CT Hyperenhances in arterial phase Isoattenuating in venous phase Delayed phase fades out

FNH - MRI Hyperenhances in arterial phase Isoattenuating in venous phase

Hepatic Adenoma Characterized by sheets of hepatocytes separated by dilated sinusoids and supplied by naked arteries (no venous supply or bile ducts) 4 molecular subgroups: 1) HNF1A-inactivated adenoma 2) telangiectatic or inflammatory subtype 3) B-catenin activated adenomas 4) unclassified hepatocellular adenoma Present in women in the 3 rd and 4 th decade of life Associated with OCPs (can decrease in size after withdrawal, usu no change) relative risk of adenoma formation 2.5x greater if OCP use 3-5 yrs vs 1 yr; if 9 yrs, risk is 25x greater

Hepatic Adenoma Obesity and metabolic syndrome also increases risk (esp inflammatory subtype) Associated with MODY-3, glycogen storage disease 1A or 3 and androgenic hormone use Multiple adenomas more common in obese patients and in MODY -3 or glycogen storage disease Hepatic adenomatosis >10 adenomas Rupture also rare but occur in large adenomas (>5 cm)

Hepatic Adenoma Malignant transformation rare but seen in: Size >5 cm Male sex Positive B-catenin staining Surgical resection recommended for large adenomas (>5 cm), any size in men, B-catenin +, or unable to distinguish from well-diff HCC Adenomas in pregnant patients need to be monitored closely

Hepatic Adenoma - MRI Pre T2 Arterial Delayed

Is there imaging that can distinguish FNH from hepatic adenoma? Gadobenate dimenglumaine (Multihance) or gadoxetate disodium (Eovist): not taken up by adenomas but light up with FNH Why? Because adenomas have no bile ducts and do not light up in the hepatobiliary scan

Biliary Cystadenoma Composed of multiple cysts lined by cuboidal or columnar epithelium that resemble normal biliary epithelium Cystic neoplasms can be unilocular or multilocular More common in middle aged women Asymptomatic unless large Usually benign Can recur after excision Cannot differentiate from cystadenocarcinoma without surgical resection

Biliary Cystadenoma CT/MRI CT septae enhances with contrast MRI- Bright on T2

Liver Abscesses

Hepatic Abscess - US Heterogenous on US

Hepatic Abscess - MRI Bright on T2 Dark on T1 T1 portal venous phase - enhances

Echinococcal Cysts CT Portal venous phase Large solitary mass or multiple well-defined lesions with internal daughter cysts

Echinococcal Cysts MRI Bright on T2

Question #2: What is the most common malignant lesion seen in the liver? A. Hepatocellular carcinoma B. Cholangiocarinoma C. Metastases D. Lymphoma E. Cystadenoma

MALIGNANT LESIONS REQUIRING TREATMENT Liver Metastases Primary HCC Cholangiocarcinoma Mixed HCC/CCA Hemangioendotheliomas Epitheliod angiomyolipoma Mixed epithelial and stromal tumors Sarcomas

Case Presentation 29 yo woman becomes jaundiced after delivering her 3 rd child via C-section. Noted to have ALT 319 AST 171 TB 1.2 AP 353 One week later ALT 159 AST 137 TB 14.9 AP 356 Abdominal US shows multiple lesions throughout the liver with IH ductal dilatation CT abdomen shows central hepatic lesion measuring 6x6.3, similar density smaller lesions throughout the liver

Liver Metastases Hypoattenuating/hypovascular lesions on CT

Question #3 60 yo Egyptian man with genotype 4 HCV cirrhosis presents with new onset ascites and a new mass in the liver. Physical exam reveals mild temporal wasting, anicteric sclera, moderate abdominal distension with small reducible umbilical hernia, palpable spleen tip, mild lower extremity edema and palmar erythema Labs reveal TB 2, ALT 33 AST 30 alb 2.8 INR 1.6 platelets 55 AFP 249 MRI liver protocol shows a 4.5 cm mass in segment 6 with a pseudocapsule and a hyperenhancing right and main portal vein thrombus.

What is the next step in this patient s management? A. Liver transplant evaluation B. Biopsy of lesion C. Microwave ablation/radiofrequency ablation D. Sorafenib E. Surgical resection

HCC Always consider HCC if lesion present in cirrhotic or chronic HBV patient Male predominance Biopsy not required for diagnosis (risk of seeding) HCC is supplied by the hepatic artery Classic HCC: enhances in the arterial phase and washes out in portal venous and delayed phase, often has pseudocapsule Treatment options: liver transplant (Milan criteria), resection (small percentage), liver directed therapy (RFA/MWA/TACE/TARE/SBRT), systemic chemo Patients with cirrhosis or chronic HBV 6 month surveillance AFP not sensitive or specific (~40% of HCC does not secrete AFP)

HCC - US Heterogenous on US

HCC - MRI Enhances in arterial phase Washes out in portal venous/delayed phase

HCC - MRI Enhances in arterial phase Washes out in portal venous/delayed phase 20 sec 180 sec

Multifocal HCC - MRI Enhances in arterial phase Washes out in portal venous/delayed phase 20 sec 180 sec

Imaging Characteristics of HCC FINDING CT MRI Arterial hyperenhancement X X Delayed washout X X T2 bright signal Intralesional fat X X

Question #4 A 42 yo Korean physician is seen in the local ER with painless jaundice. Upon pressing him further he has noted a loss of appetite, fatigue and 10 lb weight loss in the last 3 months. He otherwise feels well. Does not smoke. Has a glass of wine with dinner most nights. CT scan of the abdomen reveals a 2.5 cm lesion at the bifurcation of the R/L hepatic ducts with upstream L sided ductal dilatation Physical exam reveals healthy appearing man with scleral icterus but otherwise unremarkable exam Labs reveal TB 4.2, ALT 45 AST 30 alb 3.2 INR 1.1 platelets 255 AFP 24 CA 19-9 548 CT guided biopsy of the lesion reveals a well-differentiated cholangiocarcinoma ERCP reveals a mass at the bifurcation with upstream ductal dilatation with stent placement. Brushings + adenocarcinoma

Question #4: Which of the following precludes this man s transplant candidacy? A. Diagnosis of cholangiocarcinoma B. Size of lesion C. Location of lesion D. CT guided biopsy E. Alcohol use

Cholangiocarcinoma Arise from bile duct epithelium; pathology reveals adenoca Risk factors include PSC (most common in W. countries), liver fluke (Asia), choledochal and cystic disorders Most have no known risk factors and present with advanced disease (painless jaundice and biliary obstruction) Classified as intra- or extra-hepatic CA 19-9 usually elevated (>100 ~65-75% sensitive and 85-95% specific) 60-70% tumors occur at bifurcation of the CHD, 20-30% extrahepatic and 5-15% intrahepatic

Cholangiocarcinoma Pain is usually a constant, dull ache in the right upper quadrant Resection and liver transplantation are options for early stage disease; otherwise systemic chemotherapy Most present in late stages with dismal prognosis

Mayo protocol for cholangiocarcinoma for Liver Transplantation

Cholangiocarcinoma Imaging Characteristics HYPOechoic on US HYPOenhancing (or minimal enhancement) on arterial phase with delayed or progressive HYPERenhancement in venous phase on CT HYPOintense on T1, HYPERintense on T2, peripheral contrast enhancement that progresses into the venous phase on MRI, similar to CT

Cholangiocarcinoma HYPOenhancement Delayed HYPERenhancement Arterial phase Delayed phase

Cholangiocarcinoma Arterial phase Delayed phase Delayed phase

Case Presentation 41 yo woman with no history of chronic liver disease began to experience right sided abdominal pain after the birth of her 3 rd child An abdominal US showed 10 cm mass in liver A dedicated MRI liver showed multiple masses throughout the liver, largest being 10 cm in right inferior lobe TB 0.3 ALT 9 AST 57 AP 152 CA 19-9 64 Biopsy of lesion shows adenocarcinoma

Case Presentation Arterial phase Venous phase

Take Home Points Be cognizant of the quality of the imaging study and phases available Most lesions can be diagnosed with proper imaging and biopsy is infrequently needed Many benign lesions are found incidentally and are not the cause of symptomatology Always error on serial monitoring if lesion is indeterminate and not clearly benign Distinction between FNH and adenoma is not always clear and biopsy may be beneficial Always suspect HCC in a patient with cirrhosis or chronic hepatitis B Early stage cholangiocarcinoma can be treated successfully with liver transplant and knowing criteria can be life saving!