Liver Nodules

I. Problem/Condition.

Liver nodules are commonly detected in both the inpatient and outpatient settings and can represent a spectrum of potential disease states.

II. Diagnostic Approach.

A. What is the differential diagnosis for this problem?

The differential diagnosis for liver nodules is broad and can be broken down into malignant and non-malignant causes.

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Malignant etiologies include metastatic lesions (including from colon and pancreatic cancers) as well as primary hepatocellular carcinoma. Hepatocellular carcinoma is more likely to present as a single liver nodule in a background of chronic liver disease, while metastatic cancer classically presents as multiple nodules.

Non-malignant causes of liver nodules include cysts (simple cysts and multiple cysts typically associated with polycystic kidney disease), hepatic adenomas, focal nodular hyperplasia (FNH), hemangiomas, regenerative nodules, and various infections, including bacterial liver abscesses and infections secondary to Echinococcus and Entamoeba histolytica.

B. Describe a diagnostic approach/method to the patient with this problem.

First, consider the clinical presentation of the patient to determine how to proceed with diagnostic workup. Clues from the patient’s history and features on imaging can suggest the etiology of the patient’s liver nodule(s).

With more patients undergoing diagnostic imaging, you will encounter patients with incidentally discovered liver nodules that may not require further inpatient work up as they are not related to the patient’s acute presentation. In this scenario, it is imperative to recommend follow up with the patient’s primary provider for consideration of further evaluation.

1. Historical information important in the diagnosis of this problem.

Patients should be asked about a prior history of or risk factors for chronic liver disease, including alcohol or intravenous drug use. Patients should also be questioned about a personal history of malignancy and whether they are up to date on age-appropriate cancer screening. A travel history, particularly for travel outside of the United States and to tropical climates, is also important, as this may increase risk for Entamoeba histolytica and Echinooccus infections. Because there is a risk of Echinococcus infection in those who raise sheep or swine, an employment or exposure history can be informative.

A complete medication list, including estrogens or oral contraceptives, should also be obtained as hepatic adenomas are associated with estrogen use. Hepatic adenomas are also associated with glycogen storage disorders, so a personal or family history of this may be important.

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

An examination of the skin for signs of chronic liver disease, including spider angiomas and palmar erythema, may inform you of the risk for hepatocellular carcinoma. Signs of systemic infection, such as splinter hemorrhages, may indicate endocarditis or lead you to suspect a liver abscess. Signs of shock should raise suspicion for ruptured hepatic adenoma with intraperitoneal hemorrhage or ruptured hepatic abscess with peritonitis.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

The etiology of a majority of liver lesions will be ascertained from contrast-enhanced imaging, usually by computed tomography (CT) or magnetic resonance imaging (MRI). Malignant metastatic lesions are generally multiple, and imaging may detect a primary tumor within the abdomen; if a known primary tumor is not seen or known, biopsy of a liver lesion with the aid of imaging-guidance is usually possible for histologic diagnosis to determine the primary cancer. However, hepatocellular carcinoma can frequently be diagnosed by characteristics on imaging and generally does not require biopsy confirmation (see hepatocellular carcinoma).

As for laboratory studies, liver transaminases, alkaline phosphatase, and bilirubin levels are not necessarily helpful to determine an etiology for the liver nodule. Alpha-fetoprotein may be elevated in patients with hepatocellular carcinoma (see hepatocellular carcinoma). Serologic testing for Echinococcus and Entamoeba histolytica is available, and both of these entities may be associated with leukocytosis with or without eosinophilia.

To diagnose hepatic adenoma or FNH, there is no specific laboratory testing available and biopsy is not recommended due to risk of bleeding.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

Each of the diagnoses above will be made by a combination of clinical information and laboratory and imaging data.

Metastatic malignancy is diagnosed by percutaneous biopsy, usually accomplished with imaging guidance. Hepatocellular carcinoma is discussed elsewhere (see hepatocellular carcinoma).

Non-malignant causes of liver nodules are increasingly diagnosed by imaging characteristics alone (i.e., simple cysts, hepatic adenomas, FNH, and hemangiomas). If liver abscess is suspected, aspiration should be pursued (see liver abscess).

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

Sulfur colloid imaging is not generally informative. Liver scintigraphy is also typically not needed for diagnosis as ultrasound and CT have superseded this imaging modality.

If Entamoeba histolytica liver abscess is suspected, stool testing for amoebas can be falsely negative.

III. Management while the Diagnostic Process is Proceeding.

A. Management of Clinical Problem Liver Nodules.

Individual patient management will depend on the etiology of the liver nodules. Management of metastatic liver lesions will depend on the primary malignancy. Management of hepatocellular carcinoma is discussed elsewhere (see hepatocellular carcinoma). Simple cysts and hemangiomas may not need any further monitoring or can be tracked over time with repeat imaging.

Emergent management of ruptured hepatic adenomas with resultant intraperitoneal hemorrhage will include placement of sufficient vascular access, volume resuscitation, and likely transfusion of packed red blood cells. Patients with small, asymptomatic hepatic adenomas who are taking oral contraceptives should consider discontinuing this medication and should be counseled about avoiding pregnancy. If hepatic adenoma is symptomatic or >5 centimeters in size, the patient should be referred to a surgeon for evaluation for resection.

Echinococcal cysts and pyogenic liver abscesses may also rupture causing peritonitis and septic shock, which should be managed initially with adequate resuscitation and supportive care. Treatment of liver abscess is discussed elsewhere (see liver abscess). Echinococcal cysts may be treated with percutaneous aspiration-injection-reaspiration (PAIR technique), drug therapy (benzimidazole or albendazole), or surgical resection, though the latter is becoming less common due to percutaneous options.

Amebic liver abscess due to Entamoeba histolytica is treated with metronidazole 500 to 750 mg three times daily for 7-10 days. If Echinococcus or Entamoeba histolytica infection is confirmed, consultation with an Infectious Disease specialist is recommended.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem.

Care must be taken during evaluation to pursue histologic diagnosis only when necessary to avoid complications from the procedure, such as bleeding, as well as seeding of the percutaneous needle track, as may occur in hepatocellular carcinoma.

IV. What's the evidence?

Di Bisceglie, AM, Friedman, LS, Keeffe, EB. “Hepatic Tumors”. . 2004.

Panzer, RJ, Black, ER, Bridley, DR, Tape, TG, Panzer, RJ. “Hepatic Metastases”. . 1999.

Igbal, N, Saleem, M. “Hepatic hemangioma: a review”. . vol. 93. 1997. pp. 48-50.

Bonder, A, Afdhal, N. “Evaluation of liver lesions”. . vol. 16. 2012. pp. 271-83.

Nunnari, G, Pinzone, MR. “Hepatic echinococcus: clinical and therapeutic aspects”. . vol. 18. 2012. pp. 1448-58.