Liver Pathology Chapter 5 PDF

LIVER PATHOLOGY PART 2 SON 2111 Professor Carrie H. Hall Chapter 5 -from Diane Kawamura  DIFFUSE HEPATOCELLULAR DISEASE Hepatocellular disease causes hepatocyte dysfunction and interferes with normal liver function. Effect of disease process on the whole live...

LIVER PATHOLOGY PART 2 SON 2111 Professor Carrie H. Hall Chapter 5 -from Diane Kawamura  DIFFUSE HEPATOCELLULAR DISEASE Hepatocellular disease causes hepatocyte dysfunction and interferes with normal liver function. Effect of disease process on the whole liver ranges from simple fatty changes to more severe hepatitis or progressive cirrhosis. Parenchymal disease process produces changes that can decrease but more commonly increase normal echo density and often affect liver’s size. As disease progresses, liver is generally more difficult to penetrate due to increased sound attenuation. Most common cause of acute liver failure in the United States is an overdose of acetaminophen, usually as a suicide attempt.  FATTY INFILTRATION AKA Steatosis is accumulation of triglycerides within hepatocytes Most common causes- metabolic syndrome (type 2 diabetes, Obesity) & alcohol abuse drugs, nutritional status, metabolic abnormalities, severe hepatitis Incidence is 30% in US Reversible, range from mild to severe SONOGRAPHIC FINDINGS: Increased echogenicity, decreased acoustic penetration, increased attenuation makes it hard to see the posterior liver and diaphragm FOCAL FATTY INFILTRATION: Focal regions of increased echogenicity within normal liver. Commonly seen at porta hepatis and FOCAL FATTY SPARING: Focal regions of normal liver within a fatty infiltrated liver. Sparred areas are seen as hypoechoic areas within a hyperechoic liver Sparred areas commonly seen adjacent to GB, in Porta hepatis, caudate lobe, and at liver margins  Focal fatty infiltration (arrows) FATTY INFILTRATION noted in right lobe. Two areas of focal fatty sparing (arrows) are seen in classic locations as hypoechoic, irregular shaped areas anterior to gallbladder and portal lack of visualization of internal vessels, Same patient: Lower frequency sector, liver is vein. marked difference in echogenicity between identified to diaphragm, and renal liver and kidney, and decreased sound parenchyma echoes are seen penetration limiting visualization of diaphragm.  GLYCOGEN STORAGE DISEASE GSD Autosomal recessive disorder Genetically acquired disorder= results in excess deposits of glycogen in the liver Patient usually has absence or deficiency of one of enzymes responsible for making or breaking down glycogen Associated with fatty infiltration and hepatic adenomas There are 11 different GSD’s Glycogen Storage Disease with Liver Cell Adenoma *GSD type 1- defect enzyme glucose-6-phosphatase- Transverse image in a man with known glycogen storage disease demonstrates originally known as “Von Gierke’s Disease” fatty infiltration of the liver and hypoechoic May cause hypoglycemia, abdominal distension, fatigue, and liver lesions consistent with liver cell adenomas (cursors). irritability.  HEPATITIS Inflammation of the liver from: infectious (viral, bacterial, fungal, parasitic organisms) or noninfectious (medications, toxins and autoimmune disorders) agents Can elevate ALT, AST, conjugated and unconjugated bilirubin Viral hepatitis may be mild or extensive and account for most cases - Route of transmission: Types A, B, C, D, and E account for 95% of all acute hepatitis cases. Hepatitis A: highly contagious liver infection caused by hepatitis A virus – FECAL/ORAL Hepatitis B: Serious liver infection caused by hepatitis B virus; preventable by vaccine- BLOOD/BODY FLUIDS Hepatitis C: Infection caused by virus that attacks liver and leads to inflammation- BLOOD /BODY FLUIDS Hepatitis C is often caused by sharing needles, before 1992 was spread through blood transfusions and organ transplant. HEP C is associated with chronic liver disease and is most frequent indication for liver transplantation  HEPATITIS Alcoholic hepatitis: Liver inflammation caused by excess alcohol consumption. Autoimmune hepatitis: Inflammation in liver occurs when immune system attacks liver. Viral hepatitis pathology: Liver cell injury, swelling, varying cellular degeneration, possible necrosis, an immune system response, and regeneration. Fulminant hepatitis pathology: Massive necrosis of liver parenchyma; decrease in liver size (acute yellow atrophy), sudden and severe onset leading to shock, coma, and possible rapid death from marked liver necrosis.  HEPATITIS Acute Hepatitis “Starry Night” or Periportal Cuffing Hypoechoic liver Liver enlarged Transverse image in a patient with acute Hyperechoic portal vein walls hepatitis demonstrating vessels seen as linear bands extending out to the periphery Chronic Hepatitis of the liver. Hyperechoic liver Small liver Decreased echogenicity of portal vein walls Sagittal image through liver and right kidney demonstrating decreased liver echogenicity and increased delineation of portal triad echoes secondary to edematous changes from acute hepatitis. This is “starry night” sign.  CIRRHOSIS General term for a diffuse process that destroys normal liver lobule architecture. Initial changes cause liver enlargement but continued insult results in hepatic atrophy > resulting in blood coagulopathy > hepatic enchaphalophathy > and portal hypertension. CAUSES: Hepatitis C Alcoholism was once the major cause of cirrhosis in US- but Hep C is now nations leading cause of both chronic hepatitis and cirrhosis (www.emedicine.com) Alcoholic liver disease Non-alcoholic fatty liver disease (NAFLD) Non-alcoholic Steatohepatitis (NASH) Hepatitis B MISC CAUSES: Autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, hemochromatosis (iron deposition, Wilson disease (copper deposition), drug-induced liver disease, venous outflow disease (Budd-Chiari), right sides heart failure/tricuspid regurgitation  CIRRHOSIS LIVER FUNCTION TESTS Increased liver function tests associated with cirrhosis AST (SGOT) ALT (SGPT) GGT LDH (lactate dehydrogenase) Conjugated bilirubin  Secondary findings of CIRRHOSIS cirrhosis should be SONOGRAPHIC FINDINGS documented and can include: Hepatomegaly (ACUTE) Portal hypertension Liver Atrophy (CHRONIC) Splenomegaly Caudate lobe enlargement Varices Collaterals Surface lobe enlargement – regenerative nodules Ascites Fatty infiltration – increased echogenicity Internal textural changes ranging from fine to coarse and from hypoechoic to hyperechoic; Loss of delineation of intrahepatic vasculature Common collaterals or varices include: Changes related to portal hypertension Recanalization of the Increased incidence of Hepatocellular Cancer paraumbilical vein coming off of the left portal vein Esophageal varices Splenic varices Splenorenal shunt CIRRHOSIS Sagittal: Level of IVC, enlarged caudate lobe (CL) associated with advanced cirrhosis. Caudate lobe enlargement is thought to be from alterations in portal blood flow to liver secondary to venous compression by fibrosis and regenerative nodules. Ascites Sagittal: Image of cirrhotic liver demonstrates multiple hypoechoic areas that are compatible with regenerating nodules.  Sonogram on another patient with a biopsy-proven HCC (double arrows) visualizes a regenerating nodule (single arrow). High frequency linear array image of a patient with mild cirrhosis. Notice nodularity of parenchyma and slight irregularity of capsule (arrow). Patient presents with elevated AFP and cirrhosis. Arrow is pointing to a biopsy-proven HCC.  Color Doppler image demonstrates reversed flow (hepatofugal) in main portal vein and hepatopetal flow of the hepatic artery Splenomegaly CIRRHOSIS A sagittal image demonstrating multiple cystic areas superior to aorta compatible with esophageal varices. These areas are filled in with color Doppler. Image of spectral Doppler of main portal vein demonstrates hepatofugal flow. Q Cirrhosis R S Q. Sagittal image of left upper quadrant showing a recanalized umbilical vein (arrows). R. Color Doppler image of same image as in Q showing flow toward the skin surface. S. Same image locations as in R now with a spectral Doppler signal showing that flow is venous. T. A color Doppler image following the recanalized umbilical vein under skin to level of umbilicus. T.  PORTAL HYPERTENSION Surgical techniques to lower portal Most common cause is cirrhosis and destruction of liver cells pressure: Normal vein pressure is 5-10mmHg which is higher than Portacaval shunt’ Splenorenal normal inferior vena cava pressure. shunt/Linton shunt With fibrosis resulting in resistance to liver profusion portal Distal splenorenal vein pressure increases shunt/Warren shunt Portal vein diameter > 13mm suggest portal hypertension TIPS Portal hypertension is asymptomatic- patients usually present with upper GI hemorrhage due to rupture of esophageal varices that extend from right and left gastric (coronary) veins that are branches of the portal vein Secondary signs portal Clinical Signs Portal hypertension: Hypertension: Splenomegaly Hematemesis Ascites Hepatic encephalopathy Portal systemic venous Caput medusa (dilated abd wall collaterals veins)  HEPATOFUGAL FLOW PV Caput Medusa Sign Collaterals formation Paraumbilical v. /recanalized umbilical vein Physical signs of Gastroesphophageal collaterals: vein Dilated veins on anterior abd Splenorenal varices wall Intestinal varices Caput Medusa- tortuous Rectal varices collateral around umbilicus (hemorrhoids) Hemmorrhoids Venous collateral- left Ascites-fluid wave portal vein  BUDD-CHIARI SYNDROME Hepatic vein obstruction, Possible IVC involvement Patients presents with signs associated portal hypertension- ascites, hepatomegaly, splenomegaly. Allthough Non–specific clinical triad sign is ascites, hepatomegaly and abdominal pain Causes: Often idiopathic (approx. 50% cases) Congenital causes: IVC membranous obstruction, hepatic vein stenosis or hypoplasia, Hypercoagulable states: Polycythemia vera, paroxysmal nocturnal hemoglobinuria, Factor V Leiden deficiency, Protein C & S deficiency, Antithrombin III deficiency, Antiphospholipid antibody syndrome, Sickle cell disease, Oral contraceptives Infections Pregnancy/Postpartum Tumors: Hepatocellular carcinoma, renal cell carcinoma, adrenal carcinoma  BUDD-CHIARI SYNDROME Clinically significant: Generally requires occlusion of at least two hepatic veins. Sonographic findings depend on degree of venous obstruction and underlying cause. Hepatic veins: not visible, narrow, or reversed flow. Gray-scale imaging may show hypertrophy of caudate lobe as liver directs its venous blood to caudate lobe due to direct venous drainage into IVC. Color Doppler may demonstrate enlarged caudate veins draining into IVC.  LIVER CYSTS Classified as congenital or acquired. Congenital cysts: True hepatic cysts Categorized as simple cysts or related to hereditary disorders such as polycystic liver disease. Result from developmental anomalies in formation of intrahepatic bile ductules, proper involution of these ductules, or both. Incidence increases with age. Acquired cystic lesions: Categorized and result from traumatic (hematoma, biloma), parasitic (echinococcal), or inflammatory (abscess).  Sagittal image of right lobe of liver LIVER CYSTS showing multiple cysts compatible with polycystic liver disease. Patient also had cysts in their kidneys Congenital liver cysts. A. Congenital liver cysts (arrows) in an asymptomatic patient. The classic signs of a simple cyst are seen including enhancement. B. A simple cyst in the left lobe showing enhancement and a reverberation artifact (arrow). Anechoic Thin walled Acoustic enhancement A B  ECHINOCOCCAL CYST AKA-HYDATID DISEASE(ACQUIRED CYST) Most common caused by Taenia echinococcus or Echinococcus granulosus—parasitic tapeworm. If larvae invaginate and develop, they become encysted and generations of daughter cysts develop. Original unilocular-looking cyst is eventually filled in by multiple cysts of varying size. Sonographic appearance depends on course of larval maturation—possibilities include: (1) solitary cyst with possible mural or shell-like calcification; (2) mother cyst containing internal, peripherally placed daughter cysts; (3) fluid collections with septa—honeycomb appearance; (4) solid-looking cysts, with or without calcification. “Cyst within a cyst” or a “water-lily sign” is detachment of endocyst membrane which result in floating membranes within pericyst that mimic appearance of a water lily Do a Casoniskin test – look for anti-echinococcus antibodies  ECHINOCOCCAL CYST D D. Patient from Kenya presented with RUQ pain and hepatomegaly. Sonography E demonstrated a large cyst with daughter cysts compatible with an echinococcal cyst. E. Another patient with an echinococcal cyst that is solid and has rim calcifications that is typically seen in inactive cysts  ACQUIRED CYST HEMATOMAS A B A. Transverse of liver in a patient 1-hour post liver core biopsy. Patient complained of abdominal pain and sonography demonstrated a fresh hematoma at biopsy site (calipers). B. Transverse of patient in left lateral decubitus position 4 hours post a blind liver biopsy. Sonogram revealed a subcapsular hematoma (calipers). Note crescent-shaped hypoechoic region anterior to liver parenchyma. The bright white line (arrow) is Glisson capsule.  LIVER ABSCESSES 3 FORMS OF LIVER ABCESSES PYOGENIC ABSCESS- (BACTERIAL) AMEBIC ABSESS FUNGAL ABSCESS  PYOGENIC ABSCESS 80% of cases Escherichia coli most common organism Biliary tract is most common source Pyogenic enter via portal vein or hepatic artery Right lobe is more affected than left lobe SONOGRAPHIC FINDINGS: Complex mass, irregular walls Gas Reverberation artifact A large liver abscess in a patient with SYMPTOMS: cholecystitis. RUQ pain Sagittal scan of patient with debris-filled pyogenic Leukocytosis liver abscess (A). Note acoustic enhancement Fever (arrow) that helped differentiate this from a solid mass. Elevated LFT’s *MUST aspirate to confirm diagnosis Hepatic Abscess C D Pyogenic Abscess C. Patient presented with pain, fever, and history of diverticulitis. Sonogram shows complex collection in the left liver lobe compatible with an abscess. Power Doppler demonstrated increased flow around the abscess. D. Multiple gas-forming pyogenic liver abscesses in a patient with a history of diabetes. Notice bright white reflectors (arrows) compatible with gas. This type of abscess is associated with a high mortality rate. Copyright © 2018 Wolters Kluwer All Rights Reserved  AMEBIC ABSCESS Occurs when parasite reaches liver usually via the portal vein Often from contaminated food and/water Most common extraintestinal complication of amoebic dysentery Occurs almost exclusively in Immigrants or travelers Symptoms usually occur 8-12 weeks after travel date SYMPTOMS & FINDINGS: RUQ pain- hepatomegaly Diarrhea *Aspiration Fever may be Leukocytosis required to Elevated LFT’s Diagnose SONOGRAPHIC FINDINGS: In the right liver lobe (RLL), a 4.5-cm Round hypoechoic / complex mass complex cystic mass (M) is detected in Usually in right lobe liver around dome a woman who lived for a time in Indonesia. Continuous with the liver capsule , acoustic enhancement  SCHISTOSOMIASIS One of the most common parasitic infections in humans Contaminated water with immature worms can penetrate skin and travel via lymphatics and bloodstream to the mesenteric veins. Common parasitic infection in Africa, Asia, Indonesia, China, Japan, South America, and Mediterranean. It is major cause of PORTAL HYPERTENSION & can cause PERIPORTAL FIBROSIS 30-year-old woman with right back pain. SONOGRAPHIC FINDINGS: A calcification noted on a noncontrast abdominal radiograph and patient referred for renal sonography evaluation. Occluded intrahepatic portal veins Sagittal (A) and transverse (B) sonograms of liver advanced periportal fibrosis—provides Thickening of portal vein walls the “turtle back” sonographic appearance (arrows). Secondary signs- splenomegaly, ascites, esophageal variceal bleeding, portosystemic collaterals  HIV-AIDS – INFECTIOUS PROCESSES Human Immunodeficiency Virus- Acquired Immunodeficiency Syndrome Pneumocystis jiroveci (formerly Pneumocystis carinii) is the most common opportunistic infection in HIV-infected persons. Majority of AIDS-infected people eventually develop Pneumocystis pneumonia. Highly active antiretroviral therapy (HAART)- has dramatically decreased the complications associated with HIV- increasing the importance of prompt diagnosis Complications of HIV-AIDS Tuberculosis (TB) most common opportunistic infection w HIV Cytomegalovirus (common herpes virus) Candidiasis- common fungal infection Cryptococcal Meningitis- common central nervous system infection Toxoplasmosis- infection caused by parasite- spread primarily by cats Cryptosporidiosis- infection caused by intestinal parasite -often in animals Kaposi’s sarcoma- tumor blood vessels walls, rare in people not infected with HIV, usually appears pinl, purple red lesions on skin, mouth Lymphomas- most common early sign is painless swelling lymph nodes (neck, armpit, groin) Kidney disease- (HIVAN) HIV-associated nephropathy- inflammation of glomerulus, may show as larger than normal kidneys by ultrasound  HIV-AIDS RELATED LIVER Longitudinal sonogram through liver in a HIV-positive patient reveals small focal calcifications. Although this pattern can be seen in patients with disseminated P. jiroveci, other infectious processes in HIV patients Sagittal scan of right liver lobe reveals may also produce this pattern. This multiple tiny focal calcifications (starry patient had hepatic tuberculosis. sky). This pattern is highly suggestive of, but not definitive for, disseminated Pneumocystis infection, which this patient did have.  FUNGAL INFECTION / ABSCESS CANDIDIASIS Mycotic (fungal) infection of the blood that results in small abscesses in the liver Appearance can change over course of disease process “wheel within a wheel”- is a lesion with a peripheral hypoechoic zone, an inner echogenic wheel and a hypoechoic center- this is earliest stage of fingal Fungal Infection—Candidiasis: infection and most recognizable Microabscesses Outer hypoechoic wheel is fibrosis surrounding the Multiple small, hypoechoic masses, inner echogenic wheel “bulls eye”-oflesion inflammatory cells appears like thisand a “wheels within wheels” seen in an central hypoechoic when the area of necrosis hypoechoic center calcifies immunocompromised patient “uniformly hypoechoic focus”- most receiving high-dose chemotherapy. common presentation of lesion Patient presented with fever. Although metastatic disease could have “echogenic focus”- calcification is the similar appearance, rapid appearance scar formation-seen in late process of of multiple masses between short-term imaging sessions and patient’s clinical disease presentation was more indicative of a fungal infection/candidiasis.  CAVERNOUS HEMANGIOMAS Most common benign liver tumor and occurs in up to 4% of general population. Usually incidental finding and often asymptomatic Multiple vascular channels lined with endothelium – the multiple interfaces give the mass its hyperechoic appearance SONOGRAPHIC FINDINGS: Hyperechoic Posterior enhancement May enlarge with pregnancy and estrogen intake May appear hypoechoic within background of fatty liver Usually no color flow within Contrasted enhanced imaging demonstrates centripetal flow  FOCAL NODULAR HYPERPLASIA (FNH) 2nd most common benign liver mass Lacks normal hepatic architecture Arterial supply is from hepatic artery and venous drainage is into hepatic veins No portal venous branch More common in women in reproductive years SONOGRAPHIC FINDINGS: Incidental finding on a female patient Solid mass with varying echogenicity referred to sonography to evaluate for Solitary lesion 80-95% gallstones. The FNH mass (arrow) is slightly compressing the patient’s IVC. Central fibrous scar Note central scar in middle of mass. Often right lobe or lt lateral segment “Stealth lesion” isoechoic lesions and produce a mass effect displacing intrahepatic blood vessels Patient referred for possible palpable mass. This FNH was more isoechoic and harder to delineate. The borders are marked by Xs and the arrow points to the central scar.  HEPATIC ADENOMA OR (LCA) LIVER CELL ADENOMA Occur mostly in women of childbearing age Strongly associated with use oral contraceptives & other estrogens Clinical symptoms vary; can be asymptomatic. Patient may present with pain due to tumor Hemorrhage Can be associated with glycogen storage disease Surgical resection is recommended due to risk of malignant transformation SONOGRAPHIC FINDINGS: Arrow points to an adenoma on a patient who encapsulated, well-circumscribed, hyperechoic mass with presented with vague RUQ discomfort. hypoechoic halo; may also appear hypoechoic or isoechoic *Color Doppler image showing the vascularity of relative to normal liver parenchyma. the mass. The vessels gave the mass a halo effect on gray scale. On color Doppler: increased vasculature with flow in center of the lesion as well as flow around the periphery.  HEPATIC LIPOMA Extremely rare fatty tumors Hepatic lipomas and angiomyolipomas associated with - Tuberous sclerosis (congenital familial disease) SONOGRAPHIC FINDINGS: Hyperechoic mass Propagation speed artifact* Decreased speed of sound in fat (1450 m/s) results in prolonged sound return time Objects posterior to the fatty mass will be placed farther away from transducer Broken diaphragm CT can confirm fatty nature of mass Hyperechoic liver masses: Hepatic lipoma Hemangioma Echogenic metastasis Focal fatty infiltration  HEPATOCELLULAR CARCINOMA SONOGRAPHIC (HCC) FINDINGS: Variable appearance Most hypoechoic AKA- Hepatoma Color Doppler shows Most common primary malignancy of liver chaotic internal vasculature Occurs predominantly in patients with underlying chronic liver disease & cirrhosis Clinical symptoms: 5th most common CA worldwide Weight loss Occurs in 10-25% patients with Cirrhosis in US Nausea & vomiting RUQ pain Commonly invade venous structures – portal veins, hepatic veins and Pruritus IVC Splenomegaly Unusual before age 40- most common sixth decade life Palpable mass Associated with increase Hepatomegaly Treatments: Jaundice hepatic resection AFP * most significant Ascites transcatheter arterial AST (SGOT) chemoembolization percutaneous ethanol injection ALT (SGPT) radiofrequency ablation cryoablation liver transplant.  Color box outlines a large infiltrative HCC. Power Doppler shows small tortuous vessels inside the mass. 61-year-old male, abnormal 62-year-old woman, abnormal LFTs, normal AFP. LFTs. Hypoechoic mass Hyperechoic mass later (between calipers). Post scan, biopsied and confirmed HCC. AFT drawn was elevated. Ultrasound-guided biopsy confirmed mass was HCC. 48-year-old man, history of alcohol abuse, and cirrhosis. 6 cm heterogeneous mass seen in right posterior lobe of the liver (Xs) with another mass pressing into IVC which mimicked a clot. AFP elevated. Ultrasound-guided biopsy confirmed HCC.  LABS METASTATIC DISEASE LFT values can be normal: AST, ALT may be elevated. ALP and bilirubin After lymph nodes, liver is the most common site for metastases from elevated with biliary cancers arising in other areas. obstruction. Metastatic liver tumors incidence—18 to 20 times more common than AFP is typically not HCC. elevated in liver Most common primary cancers contributing to metastatic liver disease are: metastatic disease. Gallbladder, colon, stomach, pancreas, kidney, ovaries, breast, and lung. Liver is vulnerable to metastases because of large blood volume and large reserve of lymphatic drainage. ≈40% of patients with cancer have liver metastases. Easily established in liver due to its dual blood supply and factors that promote cell growth Common Sonographic Findings: Due to nonspecific Hyperechoic metastases- Gastrointestinal tract sonographic appearance of Hypoechoic metastases- Lymphoma mets- ultrasound- Bulls eye or Target metastases- Lung guided biopsy is needed to Calcified metastases- mucinous adenocarcinoma of determine primary colon tissue diagnosis Cystic metastases- leiomyosarcoma  “Bull’s-eye” lesions—echogenic center with a hypoechoic rim. Patient also had unexpected finding of liver metastases with a lung primary. This patient was jaundiced and was referred for a biliary ultrasound. The sonography examination showed unexpected findings of infiltrative liver mets. This patient was discovered to have a left renal cell carcinoma. Multiple hyperechoic metastatic liver lesions seen in patients with a pancreatic primary. 58-year-old man referred for RUQ pain. Diagnosis of pancreatic head cancer with liver metastases was unexpected. Hypoechoic lesions in this patient with lymphoma.  HEPATOBLASTOMA Rare malignant tumor in infant or child Most often occur prior to age 2 Hepatomegaly Calcifications may be present Elevated AFP Associated with Beckwith-Wiedemann syndrome Familial adenomatous polyposis Associated lung metastases and portal vein invasion