4/16/2018 1 Liver Lesions: How to Evaluate? Laura Kulik MD Professor of Medicine, Surgery and Interventional Radiology Northwestern University Finberg School of Medicine Disclosures • Consulting: BMS, Bayer, BTG, Eisai Malignant Lesions • Hepatocellular Carcinoma (HCC) • Intrahepatic Cholangiocarcinoma (ICCA) • Metastatic lesions • Hepatic Angiosarcoma • Hepatic Epithelioid Hemangioendothelioma (HEHE) Cirrhosis Unrelated to Cirrhosis Burden of Hepatocellular Carcinoma • Increased incidence • Peak incidence of HCV induced HCC in 2020 • In US rising faster than all other cancer except lung cancer • Main cause of death in patients with cirrhosis – 1/3 of cirrhotic pts. develop HCC over their lifetime • HCC is the indication for OLT in 15-50% of centers • DM is an independent risk factor for HCC – Males with BMI > 40 have a 5x increased mortality • Novel therapies are needed to treat HCC at various stages – 5-yr cause specific HCC survival: 3% 1975-1977 vs. 18% 1998-2007 – Attributed to diagnosis and treatment at earlier stage • 5-yr. OS: Localized 31% vs. 3% in metastatic Parkin DM et al. Int J Cancer 1999;80:827-41. World Health Organization; Sangiovanni A et al. Hepatology. 2006;43(6):1303-10; El-Serag HB et al. N Engl J Med 1999;340:745-50; Calle EE. NEJM 2003;348:1625-38. Altekruse SF et al. Hepatology 2012;55:476-82 www.cancer.org/cancer ; www.wcrf.org/cancer_statistics/world_cancer_statistics.php. Risk of HCC • Inflammation leading to scar tissue • Prospective study identified risk for HCC: – Platelet < 75,000 – > 55 y/o – + HCV – PT > 75% baseline 5 year risk of HCC: HCV cirrhosis 17% West; 30% East Hemochromatosis 21% HBV cirrhosis 10% West; 15% East ETOH cirrhosis 8 -12% Biliary cirrhosis 4% Liver stiffness α with risk of HCC El Serag et al Hepatology 2014 Singh S et al Clin Gastroenterol Hepatol 2013 2013 ;11(12):1573-84. Velazquez RF et al. Hepatology 2003;37:520-7. Diagnosis of HCC In Cirrhosis Arterial Enhancement Venous Washout
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Disclosures Liver Lesions: How to Evaluate? · 2020. 2. 10. · • Bright on T2-weighted images is helpful for confident diagnosis of hemangiomas. • Can mimic HCC; especially when
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4/16/2018
1
Liver Lesions: How to Evaluate?
Laura Kulik MD
Professor of Medicine, Surgery and Interventional Radiology
Northwestern University Finberg School of Medicine
Disclosures
• Consulting: BMS, Bayer, BTG, Eisai
Malignant Lesions
• Hepatocellular Carcinoma (HCC)
• Intrahepatic Cholangiocarcinoma (ICCA)
• Metastatic lesions
• Hepatic Angiosarcoma
• Hepatic Epithelioid Hemangioendothelioma
(HEHE)
Cirrhosis
Unrelated to Cirrhosis
Burden of Hepatocellular Carcinoma • Increased incidence
• Peak incidence of HCV induced HCC in 2020
• In US rising faster than all other cancer except lung cancer
• Main cause of death in patients with cirrhosis
– 1/3 of cirrhotic pts. develop HCC over their lifetime
• HCC is the indication for OLT in 15-50% of centers
• DM is an independent risk factor for HCC– Males with BMI > 40 have a 5x increased mortality
• Novel therapies are needed to treat HCC at various stages
– 5-yr cause specific HCC survival: 3% 1975-1977 vs. 18%1998-2007
– Attributed to diagnosis and treatment at earlier stage
• 5-yr. OS: Localized 31% vs. 3% in metastatic
Parkin DM et al. Int J Cancer 1999;80:827-41. World Health Organization; Sangiovanni A et al. Hepatology. 2006;43(6):1303-10;
El-Serag HB et al. N Engl J Med 1999;340:745-50; Calle EE. NEJM 2003;348:1625-38.Altekruse SF et al. Hepatology 2012;55:476-82
*Discrete ring along the lesion, margin that is thicker or of greater conspicuity than the ring along the margin of regenerative nodules✚Includes nodule in nodule
Mazzoferro et al N Engl J Med 1996;334(11):693-9. Onaca N. et al. Liver Transpl. 2009 Jun;15(6):574-80.
3 lesions, none > 3 cm
1 lesion < 5 cm
S. Cook ‘97
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Listing for Liver Transplant
HCC MELD Upgrade:
OLD NEW as of 10/08/15
Initial Score 22 Calculated MELD Score
Extension 1 25 Calculated MELD score
Extension 2 28 28
Extension 3 29 30
Extension 4 31 31
Extension 5 33 33
Extension 6+ 35 Cap of 34
6 mo. Waiting until HCC MELD upgrade applies
Native MELD-Na: 6-40
Limited Resource
End stage Liver disease HCC patients
Waiting list for liver transplant: 15,000-16,000
Liver transplants in 2016: 7841
Post Transplant Outcomes
DAAs Reduce Incident HCC
Kanwal et al. Gastroenterology 2017Kanwal et al. Gastroenterology 2017
Intrahepatic Cholangiocarcinoma• Poor outcomes
– 5-yr. OS < 5%– Increase in Incidence worldwide
• age-adjusted 0.32 per 100,000 to 0.85 per 100,000 over 30 yrs.
• Risk factor: Chronic biliary stasis/inflammation– PSC (present at younger age)– Intrahepatic stones– Liver flukes– HCV/HBV– Cirrhosis– Chemical exposure: thorium dioxide, dioxin, asbestos, and radon. – Congenital abnormalities of bile ducts (Caroli’s, choledochal cysts)– DM– ETOH/smoking
• Distinction between iCCA and HCC needed– Poor prognosis w/ ICCA w/ high recurrence rates
• Can distinguish from HCC on imaging
• No MELD upgrade due to reduced OS c/w HCC in OLT
16Rimola et al Hepatology 2009;50:791-798. Rana A et al. Curr Opin Gastroenterol.2012 May;28(3):258-65.
Hepatic Abscess• Most pyogenic: portal or biliary origin
• More common in right lobe, majority solitary
• Risk factors: DM, cirrhosis, immunocompromised, advanced age, PPI
• Imaging characteristics variable depending on stage of disease
• Can mimic a solid mass– Rim- like enhancement with central
non-enhancing area– Can have no non-enhancing areas– -Transient enhancement on arterial – PVT or HV thrombosis
• Clinical signs of infection are key: fever, chills, RUQ pain
• -50% + Blood culture
Mavilla MG et al. J of Clin Transplational Hepatol. 2016;4:158-68.
Benign Lesions in Cirrhosis
*Arterial phase nonhyperenhancing atypical nodules may be categorized as LR-2 at the discretion of the radiologist.
“Teaching Point: Note that hepatocellular adenoma and focal nodular hyperplasia, both of which are benign and are usually hyperenhancing during the arte- rial phase, are purposely omitted from the pro- vided list of differential diagnoses for LR-1 and LR-2, since these conditions rarely occur in cirrhotic livers”
MillianM et al. Int J Surg Case Rep. 2016; 28:165‐68.
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Hepatic Epithelioid Hemangioendothelioma(HEHE)
• Rare tumor: vascular origin
• Non specific sx: RUQ pain, wt loss, BCS, abnormal liver function
• Generally low to intermediate grade– More favorable prognosis than other hepatic malignancies
• Commonly middle age female, median age 41
• Stains: + for 1 of the following endothelial markers:– Factor VIII-related Ag, CD34, CD31– Negative for epithelial markers: cytokeratin and CEA: – MUST distinguish from adenocarcinoma or sarcoma
• Course: prolonged survival to rapidly progressive course
• Treatment:– Resection– OLT: >10 nodules or >4 involved hepatic segments– Anti VEGF therapy
Hepatic Epithelioid Hemangioendothelioma
Peripheral coalescing masses with capsular retraction
surgeon, interventional radiologist and pathologist
2016
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Hemangioma
• Most common benign liver lesion; 1-20% population
• Classic appearance: peripheral nodular enhancement with gradual central fill-in
• Bright on T2-weighted images is helpful for confident diagnosis of hemangiomas.
• Can mimic HCC; especially when small and lack centripetal enhancement “filling” in
– Larger lesions may show an avascular zone
– MUST distinguish from malignancy
• Predominant prevalence in woman• Female to male 3:1
• Size generally remains stable• Hormonal influence has been documented to increase size• Single or multiple: most solitary• Size varies from millimeters to 20 cm: most < 5 cm
– > 10 cm giant hemangioma
Hemangioma
Kim TK et al. Clinical and Molecular Hepatology 2015;21:326-43.
Sclerosing Hemangioma: fibrous replacement
T1 Arterial Portal
Hepatobiliary T2
T1 Early Arterial
Late Arterial T2
Typical Hemangioma
Management
• Biopsy not contraindicated if can not make Dx with imaging
– Must have normal parenchyma between the capsule and margin of hemangioma
– Biopsy 96% accurate
• Often asymptomatic; may increase in size over time
• Follow up is not required for typical hemangioma
• NO correlation with size and complication
• Pregnancy & OCP NOT contraindicated with stable, asymptomatic hemangioma
• Symptomatic or giant hemangioma uncommon; refer to multidisciplinary team
Hemangioma vs. ICCA
• Not seen with similar frequency in cirrhosis
– often shrink & become sclerosed in cirrhosis– generally not seen in advanced cirrhosis
– therefore follow up on lesions read as hemangioma
• Atypical hemangioma may represent an intrahepatic cholangiocarcinoma
• Hypothyroidism – 2° to high levels of enzyme activity
• Kasabach Meritt syndrome: consumptive coagulopathy, more common in > 5 cm– Breaches in EC integrity exposure of sub-endothelial collegen &
tissue factors• platelet aggregation (low platelets) and activation of coagulation
cascade– Reports of development of KMS w/ pregnancy in > 5 cm lesions
• Steroid resistant polymylagia rheumatica
• Hemobilia
• Rupture: large, peripherally located
• Innumerable hemaniomas– Associated with Osler Weber Rendu
Rare manifestations
Focal Nodular Hyperplasia (FNH)• 2ND most common benign hepatic lesion; in autopsy series prevalence 0.4 – 3%
• Contains bile ducts and Kuffer cells; distinguishing from adenoma
• Features:– More frequent in right lobe– 90% female– 80 - 95% solitary– Usually < 5 cm, only 3% > 10 cm
• generally stable in size but can see slow growth
• MRI is nearly 100% specific:– CEUS is more accurate than MRI in FNH <3 cm
• Congenital vascular anomaly:
• Associated with Osler Weber Rendu and hemangiomas
• Hallmark is central scar : Feeding artery- “corkscrew artery”– 15% no central scar present; generally in lesions < 3 cm– 20 – 30% multiple: more seen in pts. w/ vascular liver diseases, i.e. Budd-Chiari
syndrome, obliterative portal venopathy and congenital disorders
Livderatlas.org
Central scar
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Imaging Characteristic: FNH
Pre contrast 25s post contrast 40s post contrast
60s post contrast Delayed phase 10 min post contrast
FNH
• No evidence is pre-malignant lesion– Need to differentiate from fibrolamellar cancer
(calcified central scar seen in 55%)
• Management: conservative regardless of size if patient asymptomatic
– poor correlation between FNH & symptoms, so even with symptoms, treatment is rarely indicated.
Plates of hepatocytes 2-3 cells thick, no bile ducts
HCA
• Estrogen: dose dependent
• Obesity, steatosis, & metabolic syndrome, often multiple (incidence RISING)
• Anabolic androgenic steroids
• Imbalance of hormones: Klinefelter’s, PCOS
• Genetic syndromes:
• Familial adenomatous polyposis (associated with β-catenin)
• Glycogen storage disease: seen in 75% of pts. GSD 1a
– Guidelines: annual US age 0-10, biannual > 10
– Adenoma size/# decreases with optimal metabolic control of GSD
• Maturity onset DM
• Abnormalities of hepatic vasculature & intra hepatic shunt
Subtype Classification of Adenomas
EASL J of Hepatol 2016
Almost exclusively in females
Expression of serum amyloid A &CRP
MRI can identify HNF‐1 and inflammatory subtype with > 90% specificity
EASL Guidelines: Adenoma
Klompenhouwer AJ et al. BJS 2017;104:1695‐03.
Non surgical candidates: Embolization or ablation depending on size
Bx proven β-catenin(irrespective of size)
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EASL Guidelines: Adenoma
Non surgical candidates: Embolization or ablation depending on size
EASL J Hep 2016
HCA:Resection after 6 Months?
• Retrospective study: 194 pts. (194 female) with HCA > 5 cm
Surveillance N= 86
Treatment N = 108
‐Higher BMI (P=0.029)-Smaller baseline HCA (P<0.001)-Centrally located (P<0.001)-Multiple lesions (P=0.001)
‐87% Resection-8.3% TAE-4.6% RFA
- Time-to-event analysis:- -HCA measured at 4 time points: Time of DX, 6 mo., 12 mo., last available scan- n=118 n=108 n=79 n=68
Klompenhouwer AJ et al. BJS 2017;104:1695‐03.
Regression with Time
Regression to ≤ 5 cm, by baseline diameter Regression to ≤ 5 cm, by HCA subtype
58.5% showed regression to < 5 cm after a median of 104 wks.
• 6-month cut-off for assessment of regression of HCA > 5 cm is too early• In females with typical, non-β-catenin HCA could be prolonged to 12 mo. Irrespective of baseline size.
Pregnancy with HCA
• Not discouraged in lesions < 5 cm
• In pregnancy follow with US q 6-12 wks.
– In lesions < 5 cm, not exophytic or growing, no data to support C- section over vaginal delivery
– For growing lesions embolization can be considered
– Prior to 24 wks., surgery may be preferred, especially if peripheral lesion to avoid radiation & IV contrast
Hepatobiliary Agents in MRI
• 2 different hepatobiliary agents:
– gadobenate dimeglumine (Gd-BOPTA)
– gadoxetic acid (Gd-EOB)
• Benefits:
– Can help distinguish FNH vs. Adenoma
– May be used to help suggest diagnosis of small HCC w/o washout
– Helpful detecting metastatic disease
• Concerns:
– Approved at lower dose, so may have less robust arterial phase
– Reported to induce transient hypoxemia
– Need long enough delayed phase to capture biliary excretion
Korean J Radiol. 2011 Jul-Aug; 12(4): 403–415.
Facilitates uptake of hepatobiliary agent
FNH & Adenoma
T2 ADC T1
Arterial Phase Venous Phase Hepatobilary Phase
Albiin N. et al Current Medical Imaging Review 2012;8:107-16.
FNHadenoma
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Simple Hepatic Cyst
• No communication with biliary tree
• 1% of autopsy
• More common – right lobe– in female; large cysts almost exclusively in female
> 50
• Generally no septations– Hemorrhage can cause appearance of septa
• No treatment for asymptomatic cysts– Laproscopic unroofing symptomatic cysts
• Monitor large cysts > 4 cm for growth for stability
• Symptoms or increase in size raises concern for cystadenoma/cystadenocarcinoma
Regev et al. J Am Coll Surg 2001; 193:36
Cystadenoma/Cystadenocarcinoma
• Cystadenoma– More common in females– Present with abdominal
fullness/anorexia– Malignant transformation in
15%– Treatment: enuclueation
• Cystadenmacarcinoma– Generally in elderly– Treatment : formal resection– Better prognosis than CCA
Regev et al. J Am Coll Surg 2001; 193:36.Normal CEA < 3 ng/ml Normal CA19-9 < 33 U/LKoffron A et al Surgery 2004; 136(4):926-36.
Conclusion• The presence of cirrhosis or chronic liver disease is important when
a liver lesion is identified
– increased risk of HCC
• Surveillance for HCC has improved outcomes due to identification of early HCC and curative options
– Liver biopsy is not needed to make a diagnosis of HCC
• Distinguishing HCC from other malignant lesions is crucial
• Most benign liver lesions can be managed conservatively
• Key radiographic features can help distinguish the various benign lesions