The Incidental Focal Liver Lesion: Photon, Proton, or Needle?

Transcription

1 Concise Review The Incidental Focal Liver Lesion: Photon, Proton, or Needle? PABLO R. ROS 1 AND GARY L. DAVIS 2 The objective of this concise review is to offer practicing hepatologists a straightforward guide for elucidating a diagnosis in cases of focal liver lesions discovered incidentally by routine survey ultrasound or computed tomography (CT) of the abdomen. We will focus this discussion on the three major tools available to clinicians, namely: 1) photon, i.e., CT with its different variants of helical CT, CT arterial portography (CTAP), CT hepatic arteriography (CTHA), and intravenous CT angiography; 2) proton, i.e., magnetic resonance imaging (MRI) with breath-hold or fast imaging with or without nonspecific extracellular contrast agents or liverspecific contrast agents that use different hepatic functions for expression; and 3) needle, i.e., percutaneous biopsy in cases in which a confident imaging diagnosis cannot be achieved with the use of either photon- or proton-based imaging techniques. CLINICAL HISTORY AND PREVALENCE Ultrasound and CT scans are commonly performed as the first line of imaging studies in the evaluation of patients with abdominal complaints or conditions. It is not uncommon to discover incidental focal liver lesions. In many cases, these patients are referred to hepatologists for further workup. What to do next? The importance of a detailed history and physical examination in the assessment of a patient with a newly discovered liver lesion cannot be overemphasized. In many cases, the clinical presentation provides important clues to a specific diagnosis and suggests whether the condition might be benign or malignant. The patient s age, gender, history of malignancy (i.e., colorectal cancer) or chronic liver disease caused by alcohol or hepatitis, history of sclerosing cholangitis or other chronic biliary diseases, metabolic diseases (von Gierke s, tyrosmemia, etc.), current or past steroid use (e.g., oral contraceptives or anabolic steroids), prior exposure to thorium dioxide, occupational history, and travel are all factors that must be considered. Physical examination may reveal fever, a palpable mass, right upper quadrant tenderness, ascites, stigmata of cirrhosis, and so forth. Finally, a serological evaluation should look for Abbreviations: CT, computed tomography; CTAP, computed tomography arterial portography; CTHA, computed tomography hepatic arteriography; MRI, magnetic resonance imaging; FNH, focal nodular hyperplasia; DTPA, dimeglumine gadopentetate; DPDP, mangafodipir trisodium. From the 1 Division of Body Imaging, Department of Radiology, and 2 Section of Hepatobiliary Diseases, Department of Medicine, University of Florida College of Medicine, Gainesville, FL. Received January 5, 1998; accepted February 26, Address reprint requests to: Dr. Pablo Ros, Department of Radiology, Harvard Medical School/Brigham and Women s Hospital, 75 Francis Street, Boston, MA, Fax: (617) Copyright 1998 by the American Association for the Study of Liver Diseases /98/ $3.00/ evidence of chronic liver disease, particularly hepatitis, hematologic or hepatic infiltrative disease, or an elevation of tumor markers including -fetoprotein and CEA. Furthermore, from a practical standpoint, the differential diagnosis must consider the prevalence of specific focal liver lesions. In the adult, the most common focal liver lesions are cysts (easily diagnosed as such by ultrasound and CT), hemangioma, metastases, and hepatocellular carcinoma. The latter is most commonly seen in patients with underlying cirrhosis. The diagnosis of focal fatty infiltration has recently become more common because of improvement of imaging methods and may present as a pseudo-mass. PHOTON (CT) The recent advent of helical (spiral) CT has greatly improved the capabilities of this technique when applied to the liver. Although helical CT is currently used in assessing all parts of the human body, it is in the abdomen, and especially in the liver, where it is of particular value. CT scan with helical capabilities constitutes the majority of the units installed in North America since 1991, being available to the majority of hepatologists. Helical CT scans of the liver are non operator-dependent, but as it is in MRI, the imaging protocols must be well tailored to each particular unit and disease to be studied. Therefore, it is imperative to have different protocols for cirrhotic livers, primarily liver tumors, hypovascular metastasis, etc. Its ability to acquire images of the entire organ within a single breath-hold eliminates the problem of respiratory misregistration, thus allowing confident detection of subcentimeter lesions, and facilitating optimal contrast delivery. 1,2 The rapid scan time also allows helical CT to capture the liver during both the arterial phase (20-30 seconds after the beginning of contrast administration) and venous or portal phase of contrast perfusion (60-70 seconds after contrast administration). 3,4 The advantages of this ability are obvious. Biphasic helical CT has become the preferred imaging technique for assessing all primary neoplasms of the liver, because these derive their vascular supply from the hepatic artery and are therefore well outlined in the arterial phase. Likewise, hypervascular metastases, including those from carcinoid, islet cell tumors, melanoma, sarcomas, and thyroid and renal carcinomas, are well imaged in the arterial phase, appearing with higher attenuation than the liver. Many of these lesions may go undetected if only portal venous phase images are performed. 5,6 The arterial phase of helical CT is also helpful in assessing benign focal lesions. Hemangiomas present a characteristic appearance when peripheral globular feeders are seen in the arterial phase with the same attenuation as that of the aorta. This feature allows the characterization of hemangioma with almost the same certainty as MRI scanning with gadolinium, and has made other CT techniques obsolete, including delayed and single-level dynamic scans that have lower specificity for hemangioma than MRI or red blood cell scintigraphy. 7 During the arterial phase, focal nodular hyperplasia (FNH) may also demonstrate a characteristic punctate enhancement in the central scar. When present, this sign may be helpful in differentiating FNH from other benign and malignant masses. The venous or portal phase in helical CT scanning provides the optimal enhancement of the normal liver parenchyma, because it receives the bulk of its blood supply from the portal

2 1184 ROS AND DAVIS HEPATOLOGY May 1998 FIG. 1. Biphasic (arterial and portal phases) helical CT in a patient with carcinoid metastases. (A) Arterial phase demonstrates multiple lesions in the liver (arrows) that are with brighter attenuation compared with the normal parenchyma. (B) In the venous phase, the carcinoid metastases are either less conspicuous than in the arterial phase or nonvisible. This case demonstrates the importance of arterial phase scanning in patients with hypervascular tumors. circulation. Therefore, the conspicuousness of the lesion is generally greatest during peak parenchymal enhancement (about 60 seconds after the beginning of bolus injection). 8 Portal phase scanning should be performed in all cases in which arterial phase scanning is obtained, because it demonstrates the venous phase of all primary neoplasms and of hypervascular metastases. Its major role, however, is in the detection of hypovascular metastases that will appear hypoattenuated in relation to the brighter normal liver parenchyma. Therefore, the portal venous phase is helpful in cases of suspected metastases from gastrointestinal adenocarcinomas (colon, pancreas, stomach). Portal phase helical CT has been

3 HEPATOLOGY Vol. 27, No. 5, 1998 ROS AND DAVIS 1185 shown to have a sensitivity higher than 90% for the detection of hepatic metastases greater than l cm in size, comparing favorably with CTAP. 9 CTAP AND CTHA CTAP and CTHA are two methods of angiographically assisted CT scan. CTAP has a high sensitivity for detection of small lesions, exceeding that of any other nonsurgical technique. 10 This has made it the method of choice to evaluate patients before hepatic resection. However, a major problem in the interpretation for CTAP and CTHA is the presence of nontumorous perfusion defects resulting from laminar flow in the portal vein, aberrant vascular supply, and/or improper technique. 11 Furthermore, there is recent evidence to suggest that MRI of the liver with ferumoxides (a reticuloendothelial system (RES)-based liver-specific contrast agent) is equally as sensitive as CTAP (see below). 12 Therefore, in many centers including our own, CTAP has been practically abandoned in favor of ferumoxides-enhanced MRI. A third method of angiographically assisted CT uses standard CT scanning performed 7 to 14 days after the selective angiographic delivery of iodized oil (lipiodol). 13 This technique is primarily used in the detection of hepatocellular carcinoma, because lipiodol is retained in hepatocellular carcinoma nodules in cirrhotic livers. 14 INTRAVENOUS CT ANGIOGRAPHY A spin-off of helical CT scanning is three-dimensional CT arteriography, in which intravenous contrast material is injected peripherally before scanning. This technique has been suggested as a substitute for conventional hepatic angiography. 15 Intravenous CT angiography is likely to gain favor as these specialized helical CT work stations become more commonplace, because it costs less and is better tolerated than conventional selective arteriography. Threedimensional display of hepatic venous anatomy is also being evaluated, but it has yet to find a routine application because it is not currently able to superimpose parenchymal tumors on the three-dimensional display of the hepatic venous anatomy. 16 PROTON (MRI) Recent advances in MRI hardware now provide the opportunity to perform single breath-hold T 1 -weighted images and respiratory-triggered T 2 -weighted images. In addition, the development of surface coils specifically designed for the abdomen allows far higher signal-to-noise images than images produced by standard body coils. 17 The development of breath-hold imaging techniques allows current hardware to scan the entire liver while the patient suspends a single respiratory cycle. This advance has virtually eliminated the motion artifacts that previously limited the sensitivity and application of MRI for the liver, and has given photon imaging an important role in the diagnosis of focal liver lesions. In fact, the use of conventional T 1 - and T 2 -weighted imaging of the liver has been largely supplanted by breath-hold T 1 -weighted images and fast (or turbo) spin-echo T 2 -weighted images. The latter technique can be further enhanced by breath-holding, a method referred to as HASTE (half Fourier acquisition single shot turbo spin-echo) sequences, which produces incredibly crisp T 2 - weighted images of the liver that are very sensitive for focal hepatic lesions, especially cysts or hemangiomas. Breath-hold pulsing sequences are offered by all major MRI manufacturers and are therefore currently available for clinical use. These are not research sequences, and therefore hepatologists have access to them routinely. MR CONTRAST AGENTS The ability to detect and characterize lesions with unenhanced breath-hold T 1 - and T 2 -weighted images is highly dependent on the difference in signal intensity between the lesion and the normal liver. Therefore, several contrast agents have been developed that increase this difference in signal, and thereby improve the sensitivity and specificity of MRI. Gadolinium dimeglumine gadopentetate (DTPA), was the first MR contrast agent. It has an extracellular distribution and behaves in a manner very similar to iodine in CT. However, gadolinium-dtpa has a much smaller risk of allergic reactions and lacks the nephrotoxicity potential of iodine. Therefore, MRI with gadolinium provide for CT scanning for the characterization of focal liver lesions in patients with severe iodine allergies and/or poor renal function. A major indication for gadolinium-enhanced MRI is the diagnosis of hemangioma. Gadolinium-enhanced MR images have 100% specificity and 95% accuracy in this context when the typical enhancement pattern of peripheral hypertense nodules followed by progressive centripedal enhancement is seen. 18 Ferumoxides are the first organ-specific contrast agents to become available since the development of the iminodiacetic acid radionuclides in the 1960s. 19 Ferumoxides are dextrancovered iron oxide particles that are administered by slow peripheral infusion, phagocytized by Kupffer cells, and eventually excreted. Ferumoxides are negative contrast agents with predominant T 2 effect. Thus, there is marked decrease of the signal intensity of the normal liver, as well as of tumors containing functioning Kupffer cells (such as FNH) or focal fatty liver. Furthermore, it results in improved contrast-tonoise, signal-to-noise, and lesion-to-liver contrast ratios in T 2 -weighted images. In the United States, clinical trials of this agent, ferumoxide-enhanced scans, identified additional lesions in 27% of the cases compared with unenhanced MRI and 40% of cases compared with contrast-enhanced CT. 19 Ferumoxides have been used to characterize FNH with excellent success. 20 There have been several recent reports indicating the superiority of ferumoxides-enhanced MRI over helical CT, gadolinium-enhanced MRI, and CTAP for the detection of metastases and hepatocellular carcinoma in cirrhotic patients. However, there is some debate over the applicability of ferumoxides in patients with cirrhosis, because there may be less uptake of the agents due to reduced phagocytic capabilities of Kupffer cells. 21,22 Ferumoxides are not helpful in the evaluation of hemangioma or abscess. Ferumoxides are very safe, with only a small percentage of minor reactions that subside after stopping the infusion of contrast. A unique adverse event is back pain. Another category of liver-specific MR contrast agents depends on hepatocyte function. These hepatobiliary contrast agents are similar iminodiacetic acid derivative radionuclides in that they are removed from the blood by hepatocytes and secreted in bile. Several gadolinium chelates with lipophilic ligands have been produced, including gadolinium- BOPTA and gadolinium-ebo-dtpa. Another biliary agent

4 1186 ROS AND DAVIS HEPATOLOGY May 1998 FIG. 2. CTAP versus ferumoxidesenhanced MRI in a patient with colon cancer metastases. (A) CTAP before resection in this patient demonstrates two clear peripheral defects (arrows). The inferior vena cava (arrows) has no contrast within it because all the contrast material is delivered via a catheter (curved arrow), enhancing the liver via the portal vein. (B) Breath-hold T 2 image post-ferumoxides administration demonstrates clearly not only the two definite metastases seen in the CTAP, but also a third metastases that was felt to correspond to an artifact by CTAP. Note the sharp borders of the three liver metastases as well as its relation to the major hepatic vessels (portal vein and inferior vena cava) that appear very bright because of the presence of flowing blood. recently approved for use in the United States is manganese mangafodipir trisodium (DPDP). Its affinity for hepatocytes and excretion pathways is not yet well understood, although the similarity between DPDP and vitamin B 6 suggests that Mn-DPDP exploits the vitamin B 6 pathway of uptake into hepatocytes. 23 All hepatobiliary agents are positive T 1 - weighted contrast agents increasing the signal intensity of normal liver and of neoplasms with quasi-normal hepatocyte

5 HEPATOLOGY Vol. 27, No. 5, 1998 ROS AND DAVIS 1187 FIG. 3. Liver metastases ferumoxides-enhanced MRI versus CT. (A) In this patient with known colon cancer, helical portal phase CT was read normal. (B) MRI post iron oxide administration demonstrates clearly a lesion in the liver (arrow). The lesion is very conspicuous and well delimited with clear margins. Retrospectively, a faint area of low attenuation was seen in the CT. function, such as FNH, hepatic adenoma, and well-differentiated hepatocellular carcinoma. Dysplastic nodules in cirrhosis also enhance with DPDP. 24 Metastases, hemangiomas, and cholangiocarcinoma do not have hepatocyte function and therefore do not enhance, although DPDP may occasionally produce early rim enhancement of metastases because of compressed hepatic tissue. This peripheral enhancement or halo sign may be seen with either hepatobiliary or reticulo-

6 1188 ROS AND DAVIS HEPATOLOGY May 1998 FIG. 4. Helical CT versus MR enhanced with a hepatobiliary-specific contrast agent (gadolinium-b OPTA). (A) Portal phase helical scan demonstrates few lesions in the right lobe of the liver in this patient with metastatic disease. (B) After gadolinium- BOPTA administration, there are many more metastases identified throughout the liver, making this patient unresectable. endothelial system agents and helps to characterize focal lesions as malignant. 25,26 Peripheral enhancement is not seen with benign lesions such as cysts of hemangiomas. NEEDLE (BIOPSY) Biopsy is often the final step for confirming the diagnosis in cases of focal liver lesions. However, because imaging guidance now allows almost any focal liver lesion to be successfully biopsied, it is important to consider its necessity and use this resource appropriately. In most cases, biopsy should not be used if the lesion has already been confidently characterized by imaging studies or must be approached surgically. In the latter case, the intermediate step of biopsy is usually superfluous.

7 HEPATOLOGY Vol. 27, No. 5, 1998 ROS AND DAVIS 1189 FIG. 5. Use of iron oxide particles to characterize FNH. (A) T 2 - weighted image demonstrates an illdefined lesion in the right lobe of the liver (arrows). (B) After iron oxide particle administration, there is marked uptake within the lesion, indicating active Kupffer cells. When positive uptake is coupled with marked decrease in signal intensity, the diagnosis of FNH can be confidently made. In general, ultrasound is the preferred method for biopsy guidance for hepatic lesions. Its real-time nature and ease of performance make ultrasound-guided biopsies practical, fast, and cost-effective. CT guidance should be reserved for lesions not detected by ultrasound or if there is interpositioned bowel that makes visualization difficult (e.g., Chilaiditi syndrome or ventral hernias). Rarely, a lesion can only be detected by MR. Such lesions may be biopsied under MR guidance using appropriate non-ferromagnetic needles or, if available, open magnets that allow ease of access to the abdomen. CONCLUSION State-of-the-art CT and MR, in combination with the clinical evaluation, provide the hepatologist with powerful tools that are invaluable in assessing the focal liver lesion. These techniques are perhaps most valuable in characterizing

8 1190 ROS AND DAVIS HEPATOLOGY May 1998 nonsurgical lesions such as cysts, hemangiomas, FNH, focal fatty liver, and abscess. Cysts are best characterized with ultrasound or CT. Hemangioma can be diagnosed with assurance by enhanced helical CT or MRI with gadolinium enhancement. FNH cannot always be characterized with confidence unless the distinctive pattern of arterial enhancement is seen by helical CT or gadolinium-enhanced dynamic MRI. Ferumoxides may help in identifying FNH if there is significant reticuloendothelial system activity in the tumor. Focal fatty liver can be diagnosed by MRI, with or without administration of ferumoxides or a hepatobiliary agent. Finally, the clinical suspicion of a hepatic abscess can be confirmed by identifying peripheral enhancement on helical CT or dynamic gadolinium-enhanced MRI. All other neoplasms, either benign or malignant, primary or metastatic, are usually surgical in nature and should be removed if resection is feasible. 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