Case Scenario

A 36-year-old woman presents to the emergency room with hypotension, severe right upper quadrant (RUQ) abdominal pain, and one episode of emesis. She is in the second trimester of her first pregnancy, and her last prenatal note states that she was to be scheduled for an ultrasound study due to mildly elevated liver function tests and 3 to 4 days of right upper quadrant pain that worsens with lying on the right side. She had previously used oral contraceptives for approximately 20 years. She has a history of appendectomy performed approximately 3 weeks previously. An ultrasound study demonstrates a gravid uterus with a viable intrauterine pregnancy consistent with dates. During a focused assessment with sonography for trauma (FAST) examination, a liver mass is observed while imaging the hepatorenal recess. Upon arrival, vitals are T 99.0°F, HR 113, BP 104/54, RR 26, and SaO2 96%. She looks unwell and is mildly tender in the RUQ. Labs are pending.



Parenchymal lesions of the liver may be broadly grouped into neoplastic and non-neoplastic categories. Neoplastic lesions may be tumors, either benign or malignant; non-neoplastic lesions include hepatic cysts and abscesses. Many of these lesions are diagnosed after extensive multidisciplinary workup; however, certain diagnoses are associated with key imaging findings and may present acutely. For purposes of this section, we review three parenchymal lesions that may present for acute surgical evaluation in the emergency room: hepatic abscesses, symptomatic liver cysts, and ruptured hepatic adenoma.

Liver Abscess

Liver abscesses are the most common type of visceral abscess. Pyogenic abscesses account for nearly half of all visceral abscess, and more than 10% of all intra-abdominal abscesses in one large series.1 Historically, most pyogenic abscesses occurred after an intra-abdominal infection such as ruptured appendicitis; however, among patients with access to modern surgical and antibiotic therapy, the incidence of pyogenic abscess secondary to primary intra-abdominal infection has decreased. However, the overall incidence of pyogenic abscess has not decreased over the past 50 years, and may have increased.2 Notably, the patient population affected by hepatic abscess has changed dramatically, with increasing proportions of patients that are older, have underlying malignancy or immunocompromise, or have undergone biliary instrumentation. Ascending hepatic infection secondary to biliary obstruction is now increasingly common, particularly as the management of biliary tract pathology has grown increasingly sophisticated, and as endoscopic and percutaneous techniques within the diagnostic and therapeutic armamentarium have expanded. Risk factors for hepatic abscess include biliary or pancreatic disease and immunosuppressed states such as diabetes or transplantation.3

Hepatic Cysts

Simple cysts are uncommon before age 40. The female-to-male ratio is 1.5:1 for asymptomatic simple cysts at autopsy or on ultrasound, but 9:1 in symptomatic or complicated cysts. Parasitic echinococcal disease is relatively uncommon in the United States, but is more common in other parts of the world, particularly where humans live in close contact with definitive animal hosts, and is an important diagnostic consideration among patients who have migrated from such areas. Nonetheless, with the increasing incidence of abdominal imaging, prevalence of simple cysts has grown from 3% to 5% to 18%, and nonparasitic etiologies are the leading cause of hepatic cysts in almost every patient population.4

Hepatic Adenoma

Most hepatic tumors do not present acutely or require acute surgical intervention; however, an exception to this rule includes ruptured hepatic adenoma. Hepatic adenoma, an uncommon benign tumor of the liver, has an incidence as low as 0.1/10,000, but it is 300 to 400 times more prevalent in users of oral contraceptives.5 Additional risk factors for the development of hepatic adenoma include anabolic steroid use and the presence of thalassemia or glycogen storage disorders. In the latter case, adenomas may become clinically evident in pediatric patients in the second decade of life. Overall, there is a strong female preponderance, with most cases found in women between the second and the fifth decades of life.6 As the case scenario at the introduction to this chapter describes, rupture of hepatic adenoma is more common in patients with hepatic adenoma who are concurrent users of oral contraceptives.



Liver Abscess

Hepatic abscess often occurs when a favorable microenvironment characterized by local tissue destruction is seeded with bacteria, either via direct or hematogenous inoculation. Consequently, abscess may occur after hepatic blunt trauma (which is increasingly managed conservatively), after hepatic resection, or after ablative therapy for hepatic tumors. Infective sources for hepatic abscess may include distant sources such as dental procedures or endocarditis, or via ascending infection from obstruction in the biliary tree or after biliary instrumentation. Up to 50% of hepatic abscesses may have no identifiable source.7

Hepatic Cysts

Simple cysts of the liver do not communicate with the biliary tree and usually contain clear fluid. They are believed to be the result of excluded hyperplastic bile duct rests. Small cysts are surrounded by normal hepatic tissue, whereas large cysts can cause atrophy of the adjacent liver. Simple cysts are lined with secretory epithelia, and as such are classified as true cysts. Most simple cysts are unilocular, without septations, but fusion of multiloculated cystic disease may result in cysts with internal septations.7 An important diagnostic consideration in the case of multiloculated cystic disease is cystadenoma. Large cysts can cause compression of the biliary tree and resultant jaundice.

Hepatic Adenoma

Hepatic adenomas are not a single clinical entity, but rather a group of entities that arise via different biologic mechanisms. These include an inflammatory subtype that may be related to sustained activation of the Jak-Stat pathway and activation of inflammatory mediators including IL6; these tumors tend to demonstrate peliosis (multiple cyst-like, blood-filled cavities). Another subtype may be related to mutations in hepatocyte-nuclear factor 1-α (HNF1-α). These tumors typically demonstrate fatty infiltration. A third subtype is thought to arise from β-catenin mutations and Wnt pathway activation; notably, this subtype does not have pathognomonic imaging findings, and has the highest potential for malignant transformation.8 Adenomas are vascularized only by the hepatic arterial system, e.g., they do not receive a portal venous supply. Consequently, they are under slightly higher pressure in comparison to other hepatic segments. Additionally, they have decreased connective tissue support, also increasing the likelihood that they may rupture. Regardless of the subtype, the clinical presentation is the same.



In general, symptomatic parenchymal lesions of the liver present with right upper quadrant abdominal pain and fullness. Fever may be present, and the history of waxing and waning fever is often associated with an infectious process such as hepatic abscess. As such, symptoms may be insidious if the liver abscess develops in a delayed fashion, or may be associated with the primary illness. Fever and abdominal pain usually lead to radiologic examination resulting in the visualization of hepatic abscesses. In retrospect, nonspecific symptoms including myalgia, malaise, vomiting, anorexia, and weight loss may have been present for weeks prior to diagnosis. Jaundice, bacteremia, leukocytosis, and abnormal liver functions tests are common but variable. Shock may be present, especially if the underlying cause of the liver abscess has not previously been treated.

Small hepatic cysts are commonly identified incidentally on imaging, and do not require intervention unless they are symptomatic. Large cysts, on the other hand, may cause abdominal discomfort, pain, or nausea. Compression of adjacent abdominal or thoracic structures such as the stomach, biliary tree, diaphragm, or even the heart may cause symptoms such as early satiety, jaundice, breathing difficulty, or cardiac symptoms. Complications such as hemorrhage, infection, or torsion are rarely seen with small cysts.

As is the case with cystic liver disease, most hepatic adenomas are asymptomatic and never come to clinical attention. Asymptomatic adenomas are often found in the context of ultrasound examination performed for a different indication, such as a workup for elevated liver function tests. Large adenomas (>5 cm), however, are more likely to cause mild persistent right upper quadrant pain and are more likely to bleed spontaneously. This presentation may be dramatic, with hypotension, peritonitis, anorexia, nausea, emesis, and fever. Hyperestrogenic states, such as pregnancy or oral contraceptive use, are associated with a greater likelihood of rupture of hepatic adenoma. Adenomas >5 cm are also more likely to rupture.



The differential diagnosis of parenchymal liver lesions is complex. However, certain broad principles apply. Lesions may be classified on an anatomic basis, i.e., solid, cystic, or complex. Further, these may be divided into neoplastic, which may be benign or malignant; infectious, which may be parasitic or nonparasitic; and non-neoplastic/noninfectious causes. Solid lesions, which may be benign or malignant, include focal nodular hyperplasia, adenoma, hepatocellular carcinoma, metastatic lesions, and other causes. Non-neoplastic, infectious sources include abscess secondary to bacterial, fungal, or amebic etiologies. Cystic lesions of the liver may be differentiated as being congenital or acquired, neoplastic or non-neoplastic, or parasitic or nonparasitic.

In some cases, parenchymal liver lesions may present with fever, hypotension, and even shock-like symptoms. Prior to obtaining imaging studies, the differential diagnosis in these cases is the same as the differential diagnosis of any intra-abdominal processes presenting with peritoneal signs, hypotension, and shock. As such it is quite broad, but would include perforated ulcer, severe acute pancreatitis, cholangitis, septic cholecystitis, perforated diverticulitis, and splenic rupture. After a parenchymal liver lesion is identified, differential diagnosis proceeds as above (Tables 17–1, 17–2, and 17–3).

TABLE 17–1Causes of Liver Abscess Classified by Anatomic Route of Bacterial Spread

TABLE 17–2Differential Diagnosis of Hepatic Cysts, Classified by Frequency

TABLE 17–3Differential Diagnosis of Solid Parenchymal Liver Lesions



Workup of the patient should proceed expeditiously with targeted laboratory and imaging studies. In the acute phase, ultrasound is a very useful modality, as in our clinical scenario. In the stabilized patient, computed tomography (CT) scan is useful, particularly a triple-phase hepatic imaging protocol. However, it should not be overlooked that in the modern emergency department, the CT scan is often the first imaging study to be obtained. In such cases, ultrasound may not provide additional diagnostic utility. In certain cases, such as in hepatic abscess, ultrasound may be a useful modality to follow interval change in the abscess, and to evaluate the success of percutaneous drainage.

In the stable patient, magnetic resonance imaging (MRI) may be a useful modality in specific situations, i.e., to differentiate adenoma from other intrahepatic lesions. Other considerations, such as body habitus, resource availability, and particular features of clinical presentation, such as concurrent pregnancy, may influence the type of imaging obtained.




For hepatic abscess, ultrasound is less sensitive than CT scan (75%–95%) but may be useful to delineate biliary tract or pancreatic pathology such as ductal dilatation, gallstones, and pancreatic masses.4 Abscesses themselves vary in appearance, and may be heterogeneous or homogeneous hypoechoic or hyperechoic areas within the liver. Debris, internal septations, and echogenic foci representing air may be present.

Hepatic adenoma on ultrasound studies is usually visualized as a well-delineated, heterogeneous hepatic mass. Areas of hyperechoicity may correspond to areas of increased fat and glycogen content, whereas areas of hypoechoicity may signal hemorrhagic collections. Doppler imaging may demonstrate arterial flow, but does not typically add much to the diagnosis. In the case of ruptured adenoma, FAST examination may reveal free fluid in the hepatorenal, splenorenal, and suprapubic windows, corresponding to hemorrhage.

On ultrasound, simple cysts may be circular or ovoid and anechoic, with sharp, smooth borders. A well-defined interface between the tissue and the fluid is with strong posterior wall echoes. Simple cysts usually lack septa, which are typically findings of cystadenomas (Table 17–4 and Figures 17–1, 17–2, and 17–3).

TABLE 17–4Ultrasound Findings in Parenchymal Liver Lesion

Figure 17–1

Ultrasound demonstrates a large right-lobe liver abscess, denoted by the calipers. Note the heterogeneity and multiple septations.

Figure 17–2

Right upper quadrant ultrasound in a patient who presented with jaundice and was found to have a large cyst compressing the common bile duct. Note the sharp borders of the anechoic cyst.

Figure 17–3

Right upper quadrant ultrasound in a patient who presented with jaundice and was found to have a large cyst compressing the common bile duct. Note the sharp borders of the anechoic cyst.

CT Scan

Triple-phase CT should be performed to evaluate parenchymal lesions of the liver. Fluid collection in the liver parenchyma with surrounding edema is the hallmark of liver abscess on CT. With the administration of IV contrast, CT scan has 95% sensitivity, and peripheral enhancement of the abscess wall is diagnostic. Adjacent signs of inflammation may also be present, for example, colonic or duodenal thickening, fat stranding, and adjacent free fluid, elevation of the right hemidiaphragm, right-sided pleural effusion, or right basilar infiltrate.

In the evaluation of cysts, multiple cysts may create artifacts and shadowing on ultrasound, which is not a problem with CT scanning. CT allows for visualization of the entire liver, and may help better define the number and location of cysts in patients with multicystic disease. Administration of IV contrast can better define vascular anatomy with relation to the cysts, including possible compression by the cyst. CT can measure fluid density and evidence of hemorrhage.

On plain, unenhanced CT imaging, most adenomas are isodense. Particularly with rupture, or if the adenoma is large, heterogeneous appearance may be appreciated, which can be due to areas of hemorrhage. Contrast administration may demonstrate that the lesion enhances during the arterial phase, demonstrating hypervascularity and heterogeneity, but this enhancement will typically be lost on the portal venous phase, as the adenoma does not receive portal venous blood supply. Additionally, CT scan will demonstrate hemoperitoneum in the case of ruptured hepatic adenoma (Table 17–5 and Figures 17–4, 17–5, 17–6, 17–7, 17–8, 17–9, and 17–10).

TABLE 17–5CT Scan Findings in Parenchymal Liver Lesions

Figure 17–4

Axial CT scan demonstrating a heterogeneous right-lobe liver abscess (bracket) in a patient with ampullary stenosis and a common bile duct stricture.

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Dec 30, 2018 | Posted by in UROLOGY | Comments Off on LIVER PATHOLOGY
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