Liver Tumors Jesse Civan, M.D. Medical Director, Jefferson Liver Tumor Center Differential Diagnosis Malignant Metastatic from non-hepatic primary Hepatocellular carcinoma Cholangiocarcinoma Biliary cystcarcinoma Lymphoma Epithelioid hemangioendothelioma Benign Hemangioma, focal nodular hyperplasia, adenoma Cyst, biliary cystadenoma, inflammatory pseudotumor, reactive lymphoid hyperplasia, granulomatous hepatitis Focal fat, focal fatty sparing, focal fibrosis, shunt 1
Context is Key How was liver lesion identified? Evaluation of vague abdominal symptoms Screening for HCC in patient known to be at risk Follow-up of known non-hepatic malignancy Completely incidental finding Hepatocellular Carcinoma Risk Factors: Cirrhosis of any etiology Chronic HBV Asian men age >40 Asian women age >50 African ancestry any age Screen with US every 6 months Liver mass lesion: assume HCC until proven otherwise 2
HCC Diagnosis is Radiographic Biopsy of HCC tumor associated with ~ 2.7% risk of seeding Silva et al, Gut 2008; 57: 1592-1596 3
Diagnosis: Safety of IV MRI Contrast Agents Nephrogenic Systemic Fibrosis (NSF): 1990s: preferential MRI over CT for advanced CKD 2000s: description of debilitating irreversible fibrotic skin condition Newer contrast agents (macrocyclic) associated with lower risk Don t allow radiologists to reflexively refuse contrast-enhanced MRI CEUS version of LI-RADS added in June 2016 Beware LI-RADS 5T LI-RADS 5T indicates treated HCC lesion LI-RADS 5T does not indicate successfully treated HCC lesion There are no validated radiographic criteria to reliably assess adequacy of treatment Treated lesions are assessed using descriptive language and impression should offer radiologist s opinion whether residual/recurrent viable tumor is present 4
1-year survival 3-year survival 5-year survival Within Milan 89% 75% 65% Beyond Milan 82% 65% 38% Refer early avoid disadvantaging patients as regards evolving policy on transplant prioritization HCC MELD exception 5
Hemangioma Most common benign liver tumor Prevalence likely ~ 1% to 20% Female predominance Not associated with OCP use or pregnancy Pathogenesis not well understood Hemangioma EASL Clinical Practice Guideline. J Hepatology 2016 6
Hemangioma Atypical features: Very small: flash-filling Large: thrombosis, sclerosis increased heterogeneity MRI >90% sensitive, >90% specific If MRI non-diagnostic can consider biopsy FNA: series of 36 FNA biopsies, one bleeding complication requiring transfusion (Taavitsainen et al Acta Radiologica 1990; 31:69) Core Bx: series of 51 biopsies with 18-gauge needle, zero serious complications (Helio & Stenwig Radiology 1997; 204:917) Hemangioma: Management Generally asymptomatic, even when large Do not spontaneously bleed Intervention generally not needed Routine radiographic surveillance not indicated (typical features) Oral contraceptive, pregnancy OK Kasabach-Merritt (giant hemangioma, consumptive coagulopathy): trans-arterial embolization 7
Focal Nodular Hyperplasia 2 nd most common benign tumor after hemangioma Prevalence likely ~ 0.5% to 3% Marked female predominance May be multiple No established link to oral contraceptives or pregnancy Polyclonal hyperplasia in response to abnormal artery Focal Nodular Hyperplasia Histology may mimic cirrhosis Nodules of hepatocytes Fibrous septa originating from central scar Dystrophic / aberrant arteries 8
Focal Nodular Hyperplasia Central Scar Bahirwani & Reddy. APT 2008; 28: 953 FNH: Management Intervention rarely indicated Resection if symptomatic Oral contraceptives, pregnancy OK EASL Clinical Practice Guideline. J Hepatology 2016 9
Hepatic Adenoma Fairly rare benign tumor Prevalence likely <0.01% Marked female predominance 10:1 Established link to oral contraceptives Linked in men to anabolic steroid use Link to obesity & metabolic syndrome Risk of spontaneous hemorrhage, malignant transformation 10
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Hepatocellular Adenoma: Molecular Classification Group Proportion Characteristics HNF-1 α Mutations Β-Catenin Mutations * 30% 40% Marked steatosis on histology Association with adenomatosis 10% - 20% Highest risk of malignant transformation Some may have inflammatory features Overrepresented in men Inflammatory 40% - 55% Inflammatory infiltrates on histology May have some steatosis Previously telangiectatic FNH Heterogeneous molecular pathway: JAK/STAT, IL6ST, FRK, GNAS Other 5% - 10% Not fitting above * Activating β-catenin mutations seen in many hepatocellular carcinomas 12
Features favoring HNF-1-α inactivated HCA Homogenous signal dropout on chemical shift images PPV 100% / NPV 95% Sensitivity 87% / Specificity 100% Only moderate arterial enhancement 13
Hepatocellular Adenoma: Management Withdraw OCPs, IUDs, anabolic steroids Intervention for adenoma >5 cm European guidelines: intervention for men even if <5 cm Conservative approach: monitor with MRI every 6-12 months Spontaneous hemorrhage: transarterial embolization Treat multiple HCA based on size of largest lesion ACG Clinical Practice Guideline. Am J Gastro 2014 EASL Clinical Practice Guideline. J Hepatology 2016 14
Conclusions Patient with HCC risk factor: HCC until proven otherwise Patient with likely HCC: early referral to transplant center Adenoma: intervention or follow-up required, evolving recommendations by gender & histology / molecular subtype Hemangioma, FNH: generally reassurance 15