How to differentiate benign liver lesions

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Classical behavior of liver metastases (LM) How to differentiate benign liver lesions Frederik Vandenbroucke Radiologie en Medische Beeldvorming Universitair Ziekenhuis Brussel Erasmus Abdominal and Urogenital Module June 26st-29th, 2012 Almost always extrahepatic metastases Colon CA, carcinoid and HCC may present with metastases limited to the liver CT routinely used, MRI as problem solver Characteristics similar to the primary tumor: hypo- or hypervascular Incomplete and central progression of lesion enhancement Early ring enhancement Peripheral wash-out on delayed scans Margins can vary from well defined to ill defined Classical behavior of liver metastases (LM) Patterns: Doughnut Target Peripheral enhancement with hypoattenuating center: most common Homogeneous enhancement in small lesions Heterogeneous enhancement in large lesions Stays of high signal on b0 b600-b1000 with DWI TYPICAL MRI APPEARANCE Multiple and variable Moderately high SI on T2WI, low SI on T1WI Relaxation times between liver and cyst Hypovascular: thin vascular rim Hypervascular: NET, renal cell, breast, melanoma, thyroid Patterns: Doughnut, Target, Amorphous, Halo, Lightbulb Amorphous Halo Lightbulb

Liver nodules mimicking metastasic disease A. 1. Hemangioma 2. Focal Nodular Hyperplasia 3. Hepatocellular Adenoma 4. Nodular Regenerative Hyperplasia 5. Cyst 6. Biliary microhamartoma B. Secondary benign liver lesions 1. Abscess C. Hepatic Pseudolesions 1. Focal Steatosis, Focal spared Area in Fatty Liver 2. Inflammatory pseudotumor 3. Solitary Necrotic Nodule 4. Vascular disorders 1. Hemangioma Most common liver tumor (+/- 5%) Women (4-5:1) Increase in OCP, pregnancy and Estrogen Rx Asymptomatic in 85% Solitary (50-90%) Most <5cm Giant hemangioma > 10cm Mass effect Thought to arise from congential hamartomas Can also develop from dilatation of existing blood vessels in normal tissue 1. Hemangioma Path.: Composed of cavernous vascular spaces lined by a single layer of endothelium Supported by fibrous septa Varying degrees of thrombosis, sclerosis and calcification 1. Hemangioma 1. Hemangioma Signal intensity Homogeneously hyperintense on T2, no halo Mimicking metastases of a NET ("lightbulb" sign) Low SI on T1 Morphology Sharply circumscribed Lobulated Subcapsular (normal liver contour) Cystic areas Occasionally pedunculated Calcification in <10%, phlebolits Fibrotic areas Enhancement pattern Peripheral nodular enhancement (same attenuation as aorta) Progressive centripetal fill-in The clue is the contrast pooling (same SI as the vessels at the equilibrium phase images) Hyalinized hemangioma has internal fibrotic changes, does not fill up totally with contrast Capillary hemangiomas: uniform early enhancement Small hemangioma difficult to differentiate on portal venous phase CT: MRI is problem solver

2. Focal Nodular Hyperplasia = FNH 2 nd most common benign hepatic tumor 1-5% of population F>>> (5-17 :1) 3 rd to 5 th decade Incidental finding Rarely symptomatic Usually solitary Recent data shows that FNH is caused by a portal tract injury Formation and enlargement of arterial to venous shunts Local arterial hyperperfusion Oxidative stress Reaction from stellate cells to form central scar. Often other vascular lesions: adenoma, hemangioma, even HCC 2. Focal Nodular Hyperplasia = FNH Path: Hyperplasia of normal appearing hepatocytes Fibrous septae, which deviate the lesion into nodules Septae often merge centrally or eccentrically to form a scar (localized fibrosis) The scar and the septae usually contain 1 or more large arteries with fibromuscular hyperplasia The septae contain a variable number of proliferating bile ductules and inflammatory cells NO capsula Areas of necrosis or hemorrhage are very rare

2. Focal Nodular Hyperplasia = FNH Iso, hypo or hyper intense High signal of the scar on T2 2-10cm No capsula, fuzzy margin No Calcification Central stellate scar 65% of big FNH 35% of small FNH (<3cm) Homogeneous on all phases Very hypervascular on arterial phase Disappears on venous phase Delayed enhancement of scar Hepatobiliary agents: uptake and prolonged excretion (high SI) 3. Hepatocellular Adenoma: mixed group Rare, 7-12/100.000 Mostly in young women, associated with the use of contraceptive hormones (85%) Glycogen storage disease, anabolic steroids,... Decreases in hormone dosage have led to a decrease in incidence 70-80% solitary Rarely adenomatosis, >3 to dozens In a non-cirrhotic liver Rarely transform to carcinoma Large tumors (>5cm) may rupture and bleed Should be resected 3. Hepatocellular Adenoma: mixed group Path: Composed of hepatocytes in trabecular arrangement Nuclei are regular The cytoplasm may contain fat or glycogen Areas of hemorrhage and scars from previous necrosis may be present Lack of portal tracts May contain sinusoidal dilatation Seldom capsule NO bile ducts

3. Hepatocellular Adenoma: mixed group Depends on fat content Well defined, smooth, round Usually heterogeneous due to the fat, necrosis, hemorrage, calcifications If hemorrhagic Large size Heterogeneous Hemosiderin rings Hypervascular nature, may mimick HCC - hypervascular metastases Clue: No clear diffusion restriction 3. Hepatocellular Adenoma: RECENTLY DEVIDED INTO GROUPS ~ genotype: 1. Inflammatory HCA (= previously telangiectatic FNH)(40%): Women > men Sinusoidal dilatation Inflammatory infiltrates and dystrophic arteries Risk of HCC T1: iso-hyper T2: hyper Gd: intense in art., persists in portal and delayed 2. Hepatocyt Nuclear Factor 1 mutated type (30-35%): Only women Adenomatosis frequently Intracellular fat = steatosis T1: iso-hyper T2: iso slightly hyper Gd: moderate in art., iso in portal and delayed 3. Hepatocellular Adenoma: RECENTLY DEVIDED INTO GROUPS ~ genotype: 3. -catenin mutated type (10%): Men and women High risk of HCC May mimic HCC (wash-out) 4. Unclassified HCA (10%) Radiographics 2011;31:1529-1543 Hepatol Int 2008;2:316-321 liver biopsy 4. Nodular Regenerative Hyperplasia = Nodular transformation, Non-cirrhotic nodulation, Adenomatous hyperplasia Rare; 0,72% of autopsies Male = Female Hepatic parenchyma is transformed into small regenerative nodules Portal hypertension Secondary to altered blood flow Obstructive portal or hepatic veins Associated with clinical conditions: Malignancy, prothrombotic, rheumatological, idiopathic Common abnormal LFT (cholestatic), but no cirrhosis Survival is related to underlying disease Path.: Multiple hyperplastic parenchymal nodules Thickened liver-cell plates No or only slightly fibrosis ( cirrhosis)

4. Nodular Regenerative Hyperplasia Hypo on T2 Hyper- to isointense on T1 Multiple Small (1-4cm) Hypervascular homogeneous enhancement Unlike HCC, may take up and retain Gd-EOB-DTPA (=benign) Imaging studies are usually unable to provide definitive diagnosis as lesions are very small and difficult to differentiate from cirrhosis Definitive diagnosis is by biopsy 5. Cyst In utero intrahepatic duct formation defects ductules that lack connection from rest of the biliary tree dilate to form simple cysts Solitary in > 50% Polycystic disease Most < 5cm Can be confusing, if small, on CT scan (partial volume effect) 5. Cyst : water Bright on T2WI Smooth wall No septa No contrast uptake DWI bright on low b values and dark on high b values with high ADC (bright)

6. Biliary microhamartoma (Von Meyenburg Complexes) 60-70% male Prevalence ranges from 0.7 to 2.8% on autopsy series Usually asymptomatic Path.: Fibrous stroma Contains irregular duct-like structures Ducts are dilated Benign malformations of the intrahepatic bile ducts Primitive and aberrant bile ducts Cystic dilatation of bile ducts 6. Biliary microhamartoma (Von Meyenburg Complexes) High SI on T2 Well-defined focal collections of varying degrees, usually less than 5mm No enhancement Can be confused with liver metastases, microabscesses, liver cysts, Caroli s disease and biliary adenoma Primary tumors causing cystic liver metastases are usually colorectal CA, melanoma, carcinoid, breast CA, renal cell CA and ovarian CA Secondary benign liver lesions 1. Abscess RUQ pain, malaise, weakness, anorexia, fever Inflammatory tests 80% pyogenic Often associated with pelvic abscess or with cholangitis Secondary benign liver lesions 1. Abscess High SI on T2 (dd cyst) Heterogeneous Multiseptated Clustered satellite lesions Rim enhancement DWI: Differentiate from cystic or necrotic tumors Filled with pus with a high viscosity and cellularity: decreased ADC Decreased ADC-values mimicking necrotic metastases but decreases in the central part ( mets in the peripheral solid part) Segmental perfusion disorders at the late arterial CE imaging phase

Hepatic Pseudolesions 1. Focal Steatosis, Focal spared Area in Fatty Liver Combination of in-phase and out-of-phase GRE imaging to detect steatosis with the aid of the chemical shift technique If severe: can be high SI on T1 and T2 Characteristic location: gallbladder, falciform ligament, periportal Lack of mass effect Branches of the hepatic and portal veins traverse it without change in their course Normal liver contour Well demarcated Same contrast behaviour as normal hepatic tissue No changes on DWI

Hepatic Pseudolesions 2. Inflammatory pseudotumor (IPT) A rare benign lesion that shows regression over the course of a month on repeated imaging modalities Reason for surgical resection in many cases Consist of a fibrous stroma and an inflammatory cell infiltrate Etiology in the liver remains doubtful, although infection, biliary obstruction, chronic cholangitis and primary sclerosing cholangitis have been suggested Hepatic Pseudolesions 2. Inflammatory pseudotumor (IPT) Variable Appears as a well-defined mass and has a resemblance to malignancy on imaging Early arterial enhancement (active inflammation) and increased contrast retention (chronic inflammation due to fibrosis) Clue to DD with metastasis: DWI with high b-values: low SI ( mets high) Hepatic Pseudolesions 3. Solitary Necrotic Nodule Solitary Necrotic Nodule of the liver is an uncommon lesion, which despite its name, may be multiple It may represent the end-stage of a range of benign lesions such as larval infestation, sclerosed hemangioma or (post-surgical, post-radiation) trauma Differentiation by means of CT/MRI between these nodules and hepatic metastases remains very difficult or impossible. PET scan (DWI?) may aid in the diagnosis

Hepatic Pseudolesions 4. Vascular disorders Can mimic hypervascular metastases Frequently in cirrhotic liver Typically not round No diffusion restriction CONCLUSION Things to consider: Cirrhotic or Non cirrhotic Symptomatic or Incidentally detected History of Hepatitis, PSC, or malignancy Age, gender, OCP s Travel history GENDER Female HCA (almost always) FNH (overwhelming predominance) Hemangioma (predominantly) Male HCC Abscess AGE 30 s FNH, HCA 40 s FNH, Abscess 50 s Cyst, Hemangioma, LM, Abscess 60 s Cyst, LM, HCC CLINICAL FACTORS Symptomatic Asymptomatic HCC Hemangioma HCA Cyst LM FNH Abscess

CONCLUSION Biopsy provides definitive diagnosis, but not always required Thanks For Your Attention Follow up imaging for small benign appearing lesions in patient without risk factors for HCC Special thanks to Ann Hoorens (Pathology UZ Brussel) Bart Op de Beeck (Radiology UZ Antwerpen)