Non–Contrast-Enhanced Computed Tomography of the Liver

The attenuation value of the normal liver typically varies between 54 and 60 Hounsfield units (HU), which is approximately 8 HU greater than that of the spleen, owing to glycogen and iron stores in the liver. Increased density may be seen in hemochromatosis, glycogen storage disease, Wilson disease, β-thalassemia, sickle cell disease, and with certain drugs (amiodarone, cisplatin). A false appearance of increased hepatic density may occur in anemia, in which the decreased attenuation of the blood pool gives the impression of increased hepatic density relative to the intrahepatic vessels. Decreased hepatic density most frequently is related to fatty infiltration of the liver or occasionally secondary to hepatic edema. Noncontrast CT is useful for detecting diffuse abnormalities, such as hemochromatosis or fatty infiltration (Figs. 16.11 and 16.12), in which the attenuation of the liver is increased (hemochromatosis) or decreased (fatty infiltration). Both of these processes may be obscured by the administration of intravascular contrast medium. Hemorrhage or faint calcifications also are better visualized on unenhanced CT (Fig. 16.13).

FIGURE 16.11 Nonenhanced computed tomography through the liver of a patient with hemochromatosis shows diffuse increased attenuation of the liver compared with the spleen.

FIGURE 16.12 Nonenhanced computed tomography through the liver of a patient with fatty infiltration shows low attenuation of the hepatic parenchyma compared with the hepatic blood vessels and liver capsule.

FIGURE 16.13 Unenhanced computed tomography reveals numerous calcifications in a patient with amyloid.

Hepatic neoplasms usually have a high water content, resulting in relative hypoattenuation compared with liver parenchyma. The portal veins and bile ducts also are of lower attenuation than liver parenchyma, and a vessel running vertically through a section may mimic a small tumor, leading to errors in diagnosis. On unenhanced studies, the attenuation difference between liver and tumor may be subtle and may require viewing at very narrow window widths to allow focal lesion detection, but much higher lesion-to-liver attenuation difference can be achieved by the administration of intravenous contrast medium (Tidebrant et al, 1990).

Contrast-Enhanced Computed Tomography of the Liver

The administration of an iodinated contrast agent serves many purposes in hepatic CT imaging, including improved lesion detection and characterization and better vascular mapping. Because a precise rate of injection is essential to image quality, a dedicated power injector is required. Different methods are commercially available to determine the time of maximal arterial enhancement for each patient, depending on factors such as cardiac function and state of hydration (Sica et al, 2000).

Lesion conspicuity is enhanced when there is maximal contrast between a lesion and the surrounding parenchyma. The liver receives 75% to 80% of its blood supply from the portal venous system and only 20% to 25% from the hepatic artery; however, the majority of liver tumors receive most of their blood supply from the hepatic arterial system (Honda et al, 1992). The noncirrhotic liver displays maximal contrast enhancement at approximately 70 seconds from the start of the intravenous administration of contrast medium. At this time, referred to as the portal venous phase of enhancement, maximal contrast between a liver lesion and the surrounding parenchyma is seen with clear delineation of the portal and hepatic veins. Routine evaluation of the liver should be performed using portal venous phase imaging.

The pattern of contrast enhancement also is important for lesion characterization. Certain lesions, such as focal nodular hyperplasia (FNH) and hemangiomata (discussed in greater detail later in this chapter), have specific patterns of enhancement on arterial phase and portal venous phase images. Hypervascular malignant neoplasms, such as HCC and metastatic neuroendocrine carcinoma, display prominent contrast enhancement and increased lesion conspicuity on the arterial phase images, but these lesions may become isodense to the remaining liver and and may be invisible on the portal venous phase images (Fig. 16.14). When HCC or neuroendocrine mestastases are suspected, arterial phase images should be acquired in addition to the routine portal venous phase images.

FIGURE 16.14 Arterial and portal venous phase images as part of a triphasic examination in a patient with metastatic renal cell carcinoma. A, Late arterial phase image reveals multiple hypervascular enhancing foci of metastatic renal cell carcinoma (arrows). B, Portal venous phase image at the same level does not reveal the numerous masses. The low-attenuation lesion represents a partially treated hypoattenuating metastasis.

Computed Tomographic Angiographic of the Liver

MDCT scanners can acquire high-resolution images (<1-mm slice thickness) of the aorta and hepatic arterial anatomy, referred to as early arterial phase images. The intravenous administration of contrast material is performed using a high injection rate of 4 to 5 mL/s to provide maximal contrast enhancement of the arteries, before opacification of the veins or abdominal organs. The same volume of intravenous contrast material is administered as that for routine abdominal CT. Water is administered as a negative contrast agent to facilitate three-dimensional postprocessing. Additional late arterial phase images can be obtained through the hepatic parenchyma in the same breath hold in patients with suspected hypervascular lesions. A major attribute of CT angiography is that it is performed as an adjunct to a routine CT scan. CT of the chest, abdomen, and pelvis can be performed during the same examination to allow for a staging examination in addition to vascular mapping.

Gross Morphology

Three scissurae interrupt the surface of the liver and help define its segmentation (see Chapter 1B). The interlobar fissure is an incomplete structure that defines the inferior separation between the right and the left liver; the scissura here is generally difficult to identify on axial CT, but its position may be estimated, because it is orientated in a vertical plane defined by the gallbladder fossa inferiorly (Fig. 16.16) and the middle hepatic vein superiorly. The gallbladder lies in the main interlobar scissura on the inferior surface of the liver. Three-dimensional reformatting of axial CT data provides a clear depiction of the interlobar scissura and its relationship to the hepatic segments (see Fig. 16.6).

FIGURE 16.16 Normal hepatic segmental and vascular anatomy on computed tomography. A, On cephalad sections, the three hepatic veins are seen to enter the inferior vena cava (ivc). B, The lines of the hepatic veins divide the liver into sectors. The right hepatic vein divides the right liver into anterior and posterior sectors; the middle hepatic vein separates the right from the left liver and represents the line of the interlobar scissura; the left hepatic vein separates segments II and III of the left lobe. C, Approaching the midpoint of the liver, the left portal vein (pvl) is seen. The fissure for the ligamentum venosum (arrows) divides the caudate lobe (c) from the left lateral segments. D, The next section shows the horizontal portion of the right portal vein (pvr). The fissure for the ligamentum teres is now seen (large arrows); this structure divides the lateral segments of the left liver from the caudate lobe (c), segment IV. E, On the last section, the gallbladder (GB) has come into view; a line drawn along the axis of the gallbladder to the IVC represents the inferior extent of the interlobar scissura. R, right hepatic vein; M, middle hepatic vein; L, left hepatic vein.

Slightly to the right of midline, toward the patient’s left side, the anteroinferior portion of the diaphragmatic surface of the liver is notched by the fissure for the ligamentum teres, or umbilical fissure, which defines the inferior border between the medial and lateral segments of the left liver. The ligamentum teres passes through this fissure and usually is surrounded by a small amount of fat. When the ligamentum teres passes out of the liver ventrally, it is located in the free edge of the falciform ligament. The third fissure is present at the point of contact between the lateral segments of the left hepatic lobe and the caudate lobe. This is the fissure for the ligamentum venosum, which is in continuity with the umbilical fissure.

Segmental Anatomy

The segmental anatomy of the liver is based on both the hepatic venous outflow and the inflow pedicles. A functional scheme that corresponds to the liver anatomy and is useful surgically has been described (Bismuth, 1982). The three main hepatic veins divide the liver into four sectors, each of which is independent in that it receives a separate portal venous and hepatic arterial supply and is drained by a separate bile duct. The middle hepatic vein divides the liver into a right and left liver. The right liver is divided into two sectors by the right hepatic vein, and the left liver is divided similarly by the left hepatic vein. Because axial CT readily shows the course of all three major hepatic veins on contrast-enhanced scans obtained near the diaphragm, the major hepatic sectors are easy to identify at this level. The inferior boundary between the anterior and posterior sectors of the right lobe has to be estimated by extrapolating the line of the right hepatic vein onto lower sections. An imaginary line drawn between the IVC and the gallbladder divides the right and left liver on caudal sections and corresponds to the line of the middle hepatic vein. Three-dimensional reformatting can assist in localization of the hepatic segments (see Fig. 16.6). The fissure for the ligamentum teres divides the medial and lateral segments of the left liver and corresponds to the line of the left hepatic vein. The anterior and posterior sectors of the right lobe are subdivided into inferior (V and VI) and superior (VIII and VII) segments. The right portal vein runs horizontally as it enters the right liver, and this level demarcates the anterior and posterior sectors.

Vascular Anatomy

In classic arterial anatomy (see Chapter 1B), the celiac axis gives rise to the common hepatic artery, which bifurcates into the proper hepatic artery and the gastroduodenal artery (see Fig. 16.3). The proper hepatic artery divides into the right and left branches before entering the liver, but the point at which the proper hepatic artery gives rise to the left and right hepatic arteries varies. Although classic arterial anatomy is the most common pattern seen, variant hepatic and celiac arterial anatomy has been reported in 55% of patients based on initial cadaveric dissections by Michels (1955). Many of these variants have significance for preoperative planning and surgical management. Preoperative knowledge of variant anatomy can assist in selection of treatment options and in surgical planning, and it facilitates surgical dissection and may help avoid iatrogenic injury (Figs. 16.17 and 16.18).

FIGURE 16.17 Three-dimensional volume-rendered computed tomographic angiogram reveals a replaced right hepatic artery (arrows) originating from the superior mesenteric artery. The right hepatic artery courses posterior to a stent in the common bile duct (arrowheads).

FIGURE 16.18 Three-dimensional volume-rendered computed tomographic angiogram reveals the right hepatic artery (solid arrow) originates from the celiac axis and courses posterior to the gastroduodenal artery (open arrow).

The portal vein originates at the junction of the splenic vein (SV) and superior mesenteric vein (SMV), immediately posterior to the neck of the pancreas. It courses toward the right and cephalad, as it enters the hepatoduodenal ligament. Within this ligament, the portal vein courses parallel to the proper hepatic artery, which lies on its anteromedial surface, and the common bile duct, which lies on its anterolateral surface. After entering the hepatic parenchyma, the portal vein branches to supply each portal sector (see Fig. 16.1A) and subsequently each segment. A spectrum of portal venous variants has been described, many of which have major implications for safe and efficacious hepatic resection and percutaneous hepatobiliary intervention. Covey and colleagues (2004) reported the presence of variant portal venous anatomy in 35% of a group of 200 patients studied. CT is ideally suited to display these variants, an awareness of which may help avoid iatrogenic injury (Fig. 16.19).

FIGURE 16.19 Variant portal venous anatomy. Thick-slab maximum intensity projection reveals that the portal venous branch perfusing the anterior sector of the right hepatic lobe (arrow) shares a common trunk with the left portal vein (arrowhead).

The hepatic veins course between the hepatic sectors and have a short extrahepatic course before joining the IVC (Blumgart et al, 2001). The right hepatic vein drains directly into the IVC, and the middle hepatic vein and left hepatic vein usually join before draining into the IVC. A variable number of retrohepatic veins drain from the posterior aspect of the liver into the IVC, and a large inferior right hepatic vein, referred to as an accessory right hepatic vein, may be present in some patients (see Fig. 16.1B).

Biliary Anatomy

The intrahepatic biliary tree branches in a fashion nearly identical to the portal system (Fig. 16.20; see Chapter 1B). The left and right hepatic ducts form the common hepatic duct, near the lateral margin of the main portal vein, near its junction with the right portal vein. The common hepatic duct continues inferiorly toward the left and posteriorly, and it maintains its anterolateral position with respect to the portal vein throughout its course within the hepatoduodenal ligament. It becomes retroperitoneal at the level of the head of the pancreas and occupies a position on the posterolateral surface of the pancreas, until it joins the pancreatic duct immediately before entering the ampulla of Vater. The confluence of the right and left hepatic ducts is often seen lying anterior to the portal venous confluence.

FIGURE 16.20 Contrast-enhanced computed tomography in a patient with a minimally dilated biliary system. A, The intrahepatic bile ducts are seen as branching, low-attenuation structures adjacent to the portal veins. At the porta hepatis, the hepatic artery (arrow) is seen to pass between the main portal vein (pv) and the common hepatic duct. B, A scan caudal to the porta hepatis shows the common hepatic duct and the cystic duct running adjacent to each other in the hepatoduodenal ligament (arrows). The hepatic artery (ha) is in a more medial position.

Visualization of the intrahepatic bile ducts with CT originally was considered to be evidence of biliary obstruction; but with newer scanners and thin collimation, peripheral bile ducts measuring 1 to 3 mm may be seen in normal subjects (Liddell et al, 1990). The common duct, which measures 3 to 6 mm in cross-sectional diameter, is seen as a circular structure of near-water density posterolateral to the head of the pancreas on a postcontrast scan. The CT diagnosis of biliary obstruction is based on the demonstration of dilated intrahepatic or extrahepatic bile ducts. Dilated intrahepatic ducts appear on CT as linear branching or circular structures of near-water density that enlarge as they approach the junction of the left and right hepatic ducts in the porta hepatis. The extrahepatic bile duct is considered unequivocally dilated if it is 9 mm or more in diameter; less than 7 mm is considered normal. High-resolution images and reformatting techniques allow for depiction of the biliary tree on CT that was once impossible (Fig. 16.21).

FIGURE 16.21 Coronal reformatted image of the confluence of the right (solid arrow) and left (open arrow) hepatic ducts reveals soft tissue thickening and enhancement along the common bile duct (arrowheads), reflecting recurrent gallbladder carcinoma in a patient after cholecystectomy. Note the bilobar intrahepatic biliary ductal dilation.

Although CT has proved to be accurate in establishing a diagnosis of biliary obstruction, a direct correlation between the caliber of the biliary tree and the presence of clinically significant obstruction has not been found. In patients with significant dilation of the biliary tree, in whom the obstruction is later relieved surgically or by spontaneous passage of a calculus, the bile duct may remain more dilated than normal for the remainder of the patient’s life. In such patients, the CT findings may falsely suggest the presence of biliary obstruction. Likewise, a normal-caliber bile duct can be observed in the presence of a surgically correctable cause of jaundice. Intermittently obstructing calculi and subtle strictures of the extrahepatic duct may be present when the overall duct caliber is normal. When a discrepancy exists between clinical or biochemical evidence and the CT findings, magnetic resonance cholangiopancreatography (MRCP) or direct cholangiography by the percutaneous or endoscopic route should be performed to resolve the problem.

CT can also help ascertain the cause of obstruction in many cases. Although abrupt termination of the extrahepatic duct suggests a malignant process, smooth and gradual tapering of bile ducts favors benign disease. The use of water as a negative oral contrast agent aids in identification of small distal bile duct calculi.

Cyst (See Chapter 69A, Chapter 69B, Chapter 79A, Chapter 79B )

Hepatic cysts are common and occurr in 2% to 7% of the population (Horton et al, 1999). Hepatic cysts may be either congenital or acquired. Congenital cysts are more common and are thought to be caused by a malformation of a bile duct that has lost its communication with the remainder of the biliary tree. Lined by a single layer of cuboidal or columnar epithelium that secretes fluid, the cyst fills with serous fluid (Blumgart et al, 2001). The acquired type of hepatic cyst is usually secondary to inflammation, trauma, or parasitic disease. Hepatic cysts typically are discovered incidentally and have no malignant potential.

At CT, a hepatic cyst is round or ovoid and sharply defined with an imperceptible wall; it shows water attenuation and does not enhance after administration of an intravenous contrast agent. Although small cysts do not affect the adjacent hepatic parenchyma, very large cysts may result in lobar atrophy with contralateral compensatory hypertrophy (Blumgart et al, 2001).

Multiple hepatic cysts may be associated with polycystic renal disease (Fig. 16.22) but may occur in the absence of renal cysts. Occasionally, patients may present with discomfort or biliary obstruction secondary to a large cyst (Fig. 16.23). In such cases, therapeutic intervention may be indicated.

FIGURE 16.22 Multiple simple hepatic cysts in a patient with polycystic kidneys.

FIGURE 16.23 Giant simple cyst arising in right lobe of liver. It is well circumscribed and has homogeneous, near-water attenuation.

Hemangioma

Hemangiomas (see Chapter 79A, Chapter 79B ) are the most benign solid tumors of the liver (Blumgart et al, 2001). The incidence of cavernous hemangiomata has been reported as 7% in an autopsy series (Karhunen, 1986). Cavernous hemangiomata may range in size from less than 1 cm to greater than 40 cm, referred to as giant hemangiomata (Blumgart et al, 2001). Hemangiomata usually are incidentally detected lesions seen in women (Horton et al, 1999).

Hemangiomata are composed of endothelium-lined vascular spaces separated by fibrous septa, and they derive their blood supply from the hepatic artery (Horton et al, 1999). On unenhanced CT, a hemangioma has low attenuation compared with the adjacent hepatic parenchyma. After the intravenous administration of contrast material, peripheral globular enhancement is seen on the arterial phase images. The attenuation of the peripheral nodules equals that of the aorta (Quinn & Benjamin, 1992), and venous phase images reveal centripetal enhancement to the center of the lesion (Leslie et al, 1995; Nelson & Chezmar, 1990). Because the peripheral, nodular, clumplike enhancement is seen best on arterial phase images, it is important to acquire images during this phase (Fig. 16.24).

FIGURE 16.24 Cavernous hemangioma of the right liver showing typical enhancement starting at the periphery of the lesion (A to C) and finally showing complete opacification (D).

Giant hemangiomata (>6 to 10 cm; Bouras et al, 1996; Mitsudo et al, 1995; Ros et al, 1987) have a heterogeneous appearance with a low-attenuation central scar on unenhanced CT. The low attenuation is attributed to thrombosis, hyalinization, and fibrosis (Ros et al, 1987). The typical early, peripheral, nodular, clumplike enhancement is observed on the arterial phase images, but giant hemangiomata often do not completely fill in with contrast material on delayed images (Fig. 16.25; Vilgrain et al, 2000).

FIGURE 16.25 A, Volume-rendered three-dimensional image of a giant hemangioma. The image is oriented such that the patient is facing forward, with the observer looking down from above. Note the peripheral nodular, clumplike enhancement (black arrow) and the central low-attenuation scar (white arrow). The hemangioma is in contact with the left hepatic vein (arrowhead) and with the inferior vena cava (IVC). B, Volume-rendered coronal image of the same patient. The giant hemangioma exerts mass effect on a long segment of the IVC (arrows), which is displaced to the left of midline. The right kidney (arrowhead) is displaced inferomedially by the mass. Resection was performed with a good result. (Courtesy L.H. Blumgart, MD.)

Most hemangiomata do not cause clinical symptoms. However, larger tumors are more likely to cause symptoms such as abdominal pain, increasing abdominal girth, early satiety, and nausea and vomiting (Blumgart et al, 2001). These symptoms are attributed to the rapid expansion of the tumor or thrombosis and infarction resulting in stretching or inflammation of the Glisson capsule (Blumgart et al, 2001). Large hemangiomata can lead to complications such as an inflammatory process manifested by low-grade fever, weight loss, abdominal pain, and elevated erythrocyte sedimentation rate (Takayasu et al, 1990). Other complications include Kasabach-Merritt syndrome, a coagulopathy with systemic fibrinolysis and thrombocytopenia (Maceyko & Camisa, 1991), intratumoral hemorrhage, spontaneous rupture resulting in hemoperitoneum (Vilgrain et al, 2000), and volvulus of a pedunculated hemangioma (Tran-Minh et al, 1991). Pain or secondary complications may necessitate surgical intervention. CT angiography can play an important role in delineating the arterial supply to these tumors, facilitating surgical enucleation or hepatic resection.

Focal Nodular Hyperplasia

FNH (see Chapter 79A, Chapter 79B ) is the second most common benign liver tumor, with a reported prevalence ranging from 0.9% (Nguyen et al, 1999) to 3% (Karhunen, 1986). FNH usually is incidentally detected when patients are scanned for other reasons (Carlson et al, 2000). With the increased use of CT and faster scan protocols, FNH is being detected more frequently (Carlson et al, 2000). FNH is more commonly seen in women, and it occurs in relatively young patients (Nguyen et al, 1999). At histopathologic analysis, classic FNH contains nodular hyperplastic parenchyma that is at least partially surrounded by fibrous septa and a central scar. The central scar contains fibrous connective tissue, cholangiolar proliferation with surrounding inflammatory infiltrates, and malformed vessels (Nguyen et al, 1999; Wanless et al, 1985).

On unenhanced CT, FNH has the same or slightly lower attenuation than the liver. When FNH has the same attenuation as the liver, the lesion may be invisible or may be detectable only because of the central, low-attenuation scar or mass effect on the adjacent structures (Carlson et al, 2000). The value of unenhanced images is to ensure the absence of intralesional hemorrhage, intratumoral fat, and calcifications, findings atypical of FNH (Carlson et al, 2000). During the early phases (arterial, early portal venous), the typical pattern of FNH is diffuse, immediate, homogeneous, hyperdense contrast enhancement. The prompt, diffuse arterial enhancement is due to the rich arterial supply. Rapid washout of contrast material is seen in the late portal venous phase and on delayed images, as lesions tend to become isodense to the liver on these views (Figs. 16.26 and 16.27; Carlson et al, 2000).

FIGURE 16.26 Focal nodular hyperplasia. A, Arterial phase image shows a well-circumscribed, brightly enhancing lesion in segment IV/V. B, During the portal phase, the lesion is isodense with liver parenchyma and cannot be identified.

FIGURE 16.27 Focal nodular hyperplasia. A, Contrast-enhanced computed tomographic image acquired in the late arterial phase reveals the arterial supply to a well-circumscribed hypervascular mass in the right hepatic lobe. B, Oblique coronal, volume-rendered three-dimensional reformatted image of the same patient reveals early venous drainage from the mass via a large vein (arrow) into the inferior vena cava (arrowhead). The major hepatic veins have not yet opacified with contrast material.

A central scar is thought to be present at histopathology in almost all cases of FNH, but on CT, scars are less frequently visualized, seen in approximately one third of patients (Shamsi et al, 1993; Welch et al, 1985). The central scar is usually hypodense to the liver on unenhanced and early contrast-enhanced images, and it displays gradual fill-in on the portal venous phase and delayed images owing to diffusion of contrast material into the myxomatous stroma.

Adenoma

Hepatic adenoma (see Chapter 79A, Chapter 79B ) is an uncommon benign neoplasm usually discovered in women. A causative link has been described between the use of oral contraceptives and the development of hepatic adenomas (Blumgart et al, 2001). Other risk factors for the development of this neoplasm are androgen-containing steroids (Soe et al, 1992) and type I glycogen storage disease (Labrune et al, 1997). Adenomas are usually solitary but may be multiple in 30% of patients (Foster & Berman, 1977). A distinct entity referred to as liver adenomatosis, a term coined in 1985, refers to multiple (>10) adenomas in a patient without other known risk factors (Flejou et al, 1985).

Adenomas contain large plates of hepatocytes separated by dilated sinusoids perfused solely by peripheral arterial feeding vessels (adenomas lack a portal venous supply) under arterial pressure. Adenomas have poor connective tissue support, and the combination of poor connective tissue support and arterial pressure predisposes to hemorrhage. Multiple and large adenomas are more prone to spontaneous hemorrhage (Leese et al, 1988). Intracellular and intercellular lipids manifest as macroscopic fat within the tumor (Ichikawa et al, 2000).

The imaging appearance of adenomas parallels the histopathologic appearance. Unenhanced CT may be valuable in detecting the presence of intralesional hemorrhage or fat. Calcifications have been reported in 10% of lesions (Grazioli et al, 2000, 2001). Adenomas tend to be isoattenuating relative to normal liver on unenhanced CT and on portal venous phase images. Small adenomas usually enhance homogeneously in the arterial phase and are hyperattenuating to the liver (Grazioli et al, 2001). Larger adenomas are more heterogeneous in appearance than smaller lesions (Grazioli et al, 2001), presumably because of the presence of acute or prior hemorrhage. Peripheral enhancement reflects the presence of large subcapsular feeding vessels, with a resultant centripetal pattern of enhancement.

Biliary Hamartoma

Bile duct hamartoma (see Chapter 79A, Chapter 79B ), also known as von Meyenburg complex, is a common benign tumor composed of disorganized bile ducts and ductules with a fibrocollagenous stroma (Horton et al, 1999). The tumors usually range from 1 to 15 mm, do not communicate with the biliary tree, and are scattered throughout the liver (Wei et al, 1997). Bile duct hamartomas may be single, although they are often multiple (Blumgart et al, 2001), and they have a nonspecific imaging appearance such that they may be mistaken for metastases or microabscesses (Eisenberg et al, 1986; Lev-Toaff et al, 1995; Sada & Ramakrishna, 1994).

Bile Duct Adenoma

Bile duct adenomas are usually incidentally detected, benign, asymptomatic lesions (Welch et al, 1985). Bile duct adenomas are usually solitary and subcapsular, ranging in size from 1 mm to 1 cm. On unenhanced CT, a bile duct adenoma appears as a well-defined hypoattenuating or isoattenuating mass. Usually, little or no enhancement is seen after contrast administration. There is no specific imaging finding, however, and definitive diagnosis can be made only at histologic analysis (Horton et al, 1999).

Pyogenic Abscess

Recent surgery, biliary disease, diverticulitis, Crohn disease, and alcoholism all predispose to pyogenic hepatic abscess (see Chapter 66), commonly caused by Clostridium species and gram-negative bacteria such as Escherichia coli and Bacteroides, which enter the liver via the biliary tree or portal venous system (Mergo & Ros, 1997). Ascending cholangitis and portal phlebitis are the most common causes of pyogenic hepatic abscesses (Murphy et al, 1989).

As a result of the widespread use of broad-spectrum antibiotics, the clinical presentation and CT appearance vary widely (Halvorsen et al, 1984). Pyogenic hepatic abscesses may be classified as either microabscesses (<2 cm) or macroabscesses, larger confluent lesions. Microabscesses appear as small, well-defined, hypodense lesions on contrast-enhanced CT. They may be widely scattered or clustered with a tendency to coalesce (Jeffrey et al, 1988). Larger pyogenic abscesses range in appearance from unilocular cavities with smooth outer margins to highly complex and septated structures with internal debris and irregular contours. Most large pyogenic abscesses appear as a well-defined mass of low attenuation on unenhanced CT. The attenuation value of the abscess cavity depends on the age of the abscess; it becomes lower as the abscess matures. Gas bubbles may be seen if anaerobic bacteria are present, and the periphery and internal septa may enhance after contrast agent administration. Abscesses often have a thick wall, which enhances with contrast administration (Fig. 16.28). In addition, there may be hepatic enhancement peripheral to the enhancing wall, secondary to increased capillary permeability. This is referred to as the double-target sign (Mendez et al, 1994; Murphy et al, 1989).

FIGURE 16.28 Contrast-enhanced computed tomography of a pyogenic liver abscess shows enhancement of the walls and internal septa. A sympathetic right-sided pleural effusion is seen.

Fungal Abscesses

Fungal hepatic abscesses generally are disseminated microabscesses that occur in immunosuppressed patients. The most common fungal organism implicated is Candida albicans. Other fungal infections that cause microabscesses include cryptococcus, histoplasmosis, and mucormycosis. With contrast-enhanced CT, hepatic microabscesses appear as small, hypodense lesions ranging from several millimeters to 1.5 cm in size. A bull’s-eye appearance may be identified, with a small, high-attenuation focus centrally surrounded by a low-attenuation zone. Authors have reported significant increase in the sensitivity and lesion conspicuity using arterial phase CT, compared with portal venous phase CT, when evaluating liver lesions in immunocompromised patients suspected to have hepatosplenic fungal infections (Metser et al, 2005).

Echinococcus

In endemic areas, involvement of the liver by hydatid disease is a common finding. Echinococcus granulosus (see Chapter 68) presents with a large solitary mass or multiple well-defined cystic lesions, which often contain internal “daughter” cysts (Fig. 16.29). Coarse calcifications of the wall are present in 50% of patients (Fig. 16.30), and daughter cysts are identified in approximately 75% (de Diego Choliz et al, 1982; Murphy et al, 1989). Communication between the cysts and the biliary tree is found in approximately 25% of patients (de Diego Choliz et al, 1982), and frank rupture of cyst contents into the bile ducts occurs in 5% to 10%, accompanied by clinical features of cholangitis. In contrast, Echinococcus alveolaris infection resembles an infiltrating hepatic tumor clinically and radiographically with its irregular margins and heterogeneous density (Didier et al, 1985).

FIGURE 16.29 Contrast-enhanced axial computed tomography reveals a multiseptated echinococcal cyst in the right hepatic lobe. Note eccentric calcifications along the wall of one of the cysts (arrow).

FIGURE 16.30 Unenhanced computed tomography reveals a calcified rim of echinococcal cyst (arrow). Air within the cyst was from recent instrumentation.

Amebic Abscess (See Chapter 67)

The protozoan Entamoeba histolytica infects 10% of the world’s population. Hepatic abscess is the most common extraintestinal complication of amebiasis and occurs in approximately 8.5% of all patients with amebic infection (Ralls, 1998). On CT, amebic abscesses appear as well-defined masses of near-water attenuation with a thick enhancing rim. One or more internal septations may be present. A feature of amebic liver abscess that may aid in distinguishing it from other focal hepatic lesions is its tendency to extend beyond the surface of the liver (Radin et al, 1988). The CT findings are not specific, however, and serologic tests are necessary to confirm the diagnosis.

Fatty Infiltration

Fatty infiltration (see Chapter 65), as seen in patients on chemotherapy or in patients with systemic disorders, such as diabetes mellitus, cystic fibrosis, or malnourishment, results in a decrease in hepatic density. Mild degrees of fatty change may be subtle, unless liver density is compared carefully with the density of the spleen. The liver is normally 6 to 12 HU higher in attenuation than the spleen, and reversal of this relationship is the earliest CT indication of fatty infiltration. With more advanced changes, the hepatic parenchyma becomes less dense than the intrahepatic vessels. In most instances, fatty infiltration is diffuse and uniform (see Fig. 16.12), but a nonuniform, focal distribution also can occur and occasionally may mimic a mass (Fig. 16.31). Fatty infiltration should be suspected if blood vessels can be seen passing through the focal area in a normal pattern (Fig. 16.32).

FIGURE 16.31 Numerous foci of fatty infiltration. Contrast-enhanced computed tomography reveals numerous low-attenuation lesions in a patient with breast cancer. Note lack of mass effect or distortion of the hepatic vessels. Lesions were stable over time and were shown to represent focal fatty deposition on magnetic resonance imaging.

FIGURE 16.32 Focal fatty infiltration. A wedge-shaped area of low attenuation is visible in the right liver. The hepatic vessels pass through the area normally with no deviation.

An awareness of the common locations of focal fatty infiltration and focal fatty sparing is important, so as not to mistake these for tumor. Common locations for focal fatty infiltration include segment IV adjacent to the falciform ligament (Ohashi et al, 1995; Paulson et al, 1993) and around the gallbladder (Yoshimitsu et al, 1997). A common location for focal fatty sparing is in the posterior aspect of segment IV (Matsui et al, 1995; White et al, 1987) or along the gallbladder fossa. It has been suggested that areas of focal fatty sparing are due to aberrant venous drainage to the liver, because these areas do not receive portal venous flow from the main portal trunk (Gabata et al, 1997; Marchal et al, 1986; Matsui et al, 1995).

It has been shown that focal fatty sparing in a fatty infiltrated liver may occur secondary to a mass. This occurrence is presumably due to regionally decreased portal blood flow caused by compression of the adjacent portal venous branch distal to a mass. This fatty sparing can appear as wedge shaped, peripheral, segmental, or lobar, depending on the site of the portal venous compression (Grossholz et al, 1998).

Assessment for fatty infiltration is better performed with unenhanced CT than with contrast-enhanced CT, because factors such as the rate of contrast injection and timing of measurements significantly influence the optimal liver-to-spleen ratio threshold for diagnosing fatty liver. The required ratios are protocol specific, which limits the clinical usefulness of such measurements (Jacobs et al, 1998; Johnston et al, 1998). If it is unclear based on the CT findings whether an area of focal low attenuation represents a mass, magnetic resonance imaging (MRI) using opposed-phase gradient echo images may make a definitive diagnosis.

Cirrhosis (See Chapter 70A, Chapter 70B )

CT is capable of showing morphologic changes associated with advanced hepatic cirrhosis. Typical CT features are a nodular hepatic outline (in macronodular cirrhosis) caused by regenerative nodules of variable size, bands or regions of confluent fibrosis, relative atrophy of the right hepatic and quadrate lobes, and hypertrophy of the left lateral segment and caudate lobe (Fig. 16.33; Torres et al, 1986). Measurement of the transverse dimension of the caudate lobe compared with the adjacent right lobe provides an index of right hepatic lobe shrinkage and a relatively specific morphologic measurement of hepatic cirrhosis (Harbin et al, 1980). A caudate/right lobe ratio greater than 0.65, using the bifurcation of the main portal vein to divide the lobes provides 96% confidence in the diagnosis of cirrhosis. An MRI study suggested that using the right portal vein to set the lateral boundary of the caudate lobe when assessing the caudate/right lobe ratio was more accurate for diagnosing cirrhosis than using the main portal vein (Awaya et al, 2002). Evidence of coexistent portal hypertension is found with ascites, splenomegaly, and portal-systemic varices. MDCT combined with three-dimensional reformatting can help determine the extent of portosystemic collateral vessels, such as the left gastric vein, short gastric vein, esophageal and paraesophageal varices, splenorenal and gastrorenal shunts, and paraumbilical and abdominal wall veins (Kang et al, 2002).

FIGURE 16.33 Cirrhosis. A, The liver has an irregular outline. B, The interlobar fissure, delineated by the gallbladder, is deviated toward the right as a result of atrophy of the right liver with hypertrophy of the left liver and the caudate lobe.

Budd-Chiari Syndrome

Budd-Chiari syndrome (see Chapter 77) is caused by chronic hepatic venous congestion secondary to obstruction to hepatic venous outflow. The CT appearance is characterized by hepatomegaly and ascites; the hepatic veins are either obliterated and not seen, or they contain thrombus (Fig. 16.34). Precontrast scans show decreased attenuation of hepatic parenchyma because of congestion; postcontrast scans show normal enhancement of the caudate lobe, which is hypertrophied in chronic cases, and patchy enhancement of the remainder of the liver (Vogelzang et al, 1987). Concomitant portal vein thrombosis is present in 20% of patients with Budd-Chiari syndrome. A similar CT appearance of the liver, with patchy enhancement, is seen in patients with congestive heart failure; in contrast to patients with true Budd-Chiari syndrome, these patients have patent and enlarged hepatic veins (Moulton et al, 1988).

FIGURE 16.34 A, Contrast-enhanced computed tomography (CT) in a patient with acute hepatic venous thrombosis leading to Budd-Chiari syndrome shows nonenhancement of the thrombosed hepatic veins. There also is patchy peripheral parenchymal enhancement. B, In a patient with chronic Budd-Chiari syndrome resulting from a congenital stricture of the intrahepatic inferior vena cava, enlargement of the caudate lobe (CL) and marked homogeneity of parenchymal enhancement are seen. Splenomegaly also is seen. C, Contrast-enhanced CT reveals mottled parenchymal enhancement and enlargement of the caudate lobe (arrows) in a patient with occlusion of the hepatic veins secondary to paroxysmal nocturnal hemoglobinuria.

Hepatic Infarction

Hepatic infarction is rare and implies compromise to the arterial and portal venous supply to a segment or lobe of the liver. CT findings include a well-defined, wedge-shaped area of low attenuation in segmental or subsegmental distribution, extending to the liver surface. After contrast administration, the affected zone is enhanced minimally; a peripheral, thin, subcapsular rim often contains enhancing hepatic tissue. Gas formation within sterile infarcts is a recognized finding and does not imply superimposed infection. A late complication of hepatic infarction is formation of bile lakes in the affected segments as a result of disruption of biliary radicles.

Hepatocellular Carcinoma

HCC (see Chapter 80) is the most common primary hepatic malignancy worldwide, with the highest incidence in Asia, Southeast Asia, and sub-Saharan Africa. Although less common in the West, the incidence of HCC in the United States has been increasing (Arakawa et al, 1986). The most significant risk factors include cirrhosis and hepatitis B and C viruses. Approximately 70% of HCCs develop in cirrhotic livers (Blumgart et al, 2001), and detection of HCC in the cirrhotic liver poses a great diagnostic challenge, because the hepatic parenchyma is distorted by nodular regeneration and fibrosis. In addition, there are alterations in arterial and portal venous blood flow. These changes can obscure malignant lesions and conversely can simulate disease (Baron & Peterson, 2001).

Regenerative nodules within the cirrhotic liver, especially large nodules (8 to 10 mm), are readily identifiable at CT, because they distort the hepatic contour. When these nodules contain iron, referred to as siderotic nodules, they have high attenuation on unenhanced CT. These nodules typically do not enhance during the arterial phase, and this is an important characteristic that differentiates regenerating nodules from dysplastic nodules and HCC. Regenerative nodules enhance homogeneously during the portal venous phase to the same degree that surrounding fibrotic tissue does and thus are not visible as distinct from the adjacent parenchyma (Baron & Peterson, 2001).

Dysplastic nodules contain cellular atypia and are precursors to frank HCC in some cases. Dysplastic nodules may contain nontriadal arterial flow pathologically, which distinguishes them from regenerative nodules. Dysplastic nodules typically do not display vivid arterial enhancement on CT but occasionally do enhance in this phase and may mimic HCC (Baron & Peterson, 2001).

The appearance of HCC on CT varies. Most small HCC nodules enhance on arterial phase images and display a washout of contrast material during the portal venous phase (Fig. 16.35). A few are hypovascular and are best seen in portal venous phase or equilibrium phase imaging. Larger lesions (>5 cm) tend to be heterogeneous with a mosaic pattern of enhancement (Stevens et al, 1996); they may be surrounded by a tumor capsule and may contain necrosis and fatty metamorphosis. Tumor can invade the portal or hepatic veins directly (Freeny et al, 1992), with enhancing tumor thrombus evident on CT (Figs. 16.36 and 16.37). Tumor extension into the bile duct, resulting in biliary obstruction, also can be seen on CT.

FIGURE 16.35 Arterial phase and portal venous phase images in a patient with multifocal hepatocellular carcinoma (HCC). A, Arterial phase images reveal numerous hypervascular masses (arrows) in a patient with multifocal HCC. B, Portal venous phase image reveals low-attenuation masses (arrows). C, Portal venous phase image reveals an exophytic heterogeneous mass reflecting an additional focus of HCC (arrow).

FIGURE 16.36 A, Contrast-enhanced computed tomography reveals an exophytic hepatocellular carcinoma (arrow) with tumor thrombus extending up the main portal vein (arrowheads). B, Coronal maximum intensity projection image in the same patient reveals extensive collateral venous flow (arrows) about the mass.

FIGURE 16.37 Hepatocellular carcinoma (HCC). Contrast-enhanced computed tomography reveals HCC involving segment I of the liver (arrow). Tumor thrombus extends into the inferior vena cava and right atrium (arrow).

Distortion of the liver related to the underlying cirrhosis can lead to abnormalities at CT that may be misinterpreted as HCC. A false-positive diagnosis of HCC was made on CT in 8% of 1329 patients with cirrhosis who were referred for hepatic transplantation in an experienced liver transplant center (Brancatelli et al, 2003). Benign lesions mistaken for HCC include focal confluent fibrosis, transient hepatic attenuation difference, flash-filling hemangiomata, peliosis, and benign regenerative nodules showing dysplastic change.

HCC may be predominantly intrahepatic or pedunculated, with a large exophytic component “hanging” off the liver (see Fig. 16.36A). This finding is evident on cross-sectional imaging and has implications for surgical resectability (Vauthey et al, 1995). Approximately 5% of HCCs are seen with spontaneous rupture and hemoperitoneum (Blumgart et al, 2001).

The appearance of HCC differs in cirrhotic and noncirrhotic livers. HCC in a cirrhotic liver commonly appears as multifocal small lesions, whereas HCC in a noncirrhotic liver is more typically a large, hypervascular solitary or dominant mass with small satellite nodules and central necrosis (Fig. 16.38; Brancatelli et al, 2002; Winston et al, 1999b). The pathogenesis of HCC differs in these two patient groups. HCC may arise de novo in an otherwise normal liver, whereas a multistep sequence of carcinogenesis has been described in patients with cirrhosis (Okuda et al, 1982). It has been shown that venous invasion by tumor is more common in cirrhotic patients than in patients without underlying liver disease (Smalley et al, 1988). Patients with minimal or no cirrhosis have a better prognosis after resection than patients with cirrhosis (Fong et al, 1999).

FIGURE 16.38 Hepatocellular carcinoma in a noncirrhotic liver.

Fibrolamellar Hepatocellular Carcinoma

Fibrolamellar HCC is a malignant hepatocellular tumor with distinct clinical, pathologic, and radiologic differences from HCC. Fibrolamellar carcinoma typically manifests as a large hepatic mass in adolescents or young adults with no evidence of cirrhosis, and it accounts for 1% to 9% of all HCCs (Berman et al, 1980; Craig et al, 1980; Goodman et al, 1985; Pinna et al, 1985). There are no known risk factors for the development of this lesion. The main diagnostic challenge is to distinguish it from FNH, a benign lesion occurring in the same age group.

On unenhanced CT scans, fibrolamellar carcinoma usually appears as a hypoattenuating, solitary mass with well-defined lobular margins (McLarney et al, 1999) and a central scar. Calcification, a finding used to help differentiate this lesion from FNH, has been reported in 35% to 55% of tumors (Brandt et al, 1988; Friedman et al, 1985; Soyer et al, 1991). During the arterial and portal phases of enhancement, the nonscar portion of the tumor enhances heterogeneously (McLarney et al, 1999). This heterogeneous enhancement is also an important imaging finding used to differentiate fibrolamellar HCC from FNH, which should display homogeneous arterial enhancement around a central scar. On delayed images, increasing homogeneity of the mass and occasional scar enhancement may simulate the appearance of FNH, underscoring the need to scan the liver during the arterial and portal venous phases. Although fibrolamellar HCC does not typically have a true capsule, the liver surrounding the mass may be compressed and may form a pseudocapsule (McLarney et al, 1999). Associated findings of vascular invasion, lymphadenopathy, or peritoneal implants strongly suggest fibrolamellar HCC.

Angiosarcoma

Risk factors for angiosarcoma of the liver include hemochromatosis, radiotherapy, and exposure to compounds such as polyvinyl chloride (PVC), arsenic, or Thorotrast. Angiosarcoma is a vascular hepatic neoplasm that appears as an infiltrating, brightly enhancing mass on CT (Silverman et al, 1983). High-attenuation thorium deposition may be seen in a patchy distribution in the liver, perihepatic lymph nodes, and spleen. Histologic “cavernous” angiosarcoma may enhance in a way similar to that of hemangioma, with the tumor becoming wholly or partly isodense with liver on delayed scanning (Itai & Teraoka, 1989; White et al, 1993).

Hepatic Lymphoma

Primary lymphoma of the liver is rare, but the liver is a common secondary site of lymphomatous involvement in patients with Hodgkin disease and non-Hodgkin lymphoma. At autopsy, hepatic involvement is seen in 50% of patients with non-Hodgkin lymphoma and in 60% of patients with Hodgkin disease. Approximately 6% to 20% of patients with Hodgkin disease have hepatic involvement at presentation (Castellino, 1982; Fishman et al, 1991; Sandrasegaran et al, 1994). Liver involvement usually is associated with lymph node disease and almost invariably is associated with splenic disease. The more extensive the splenic involvement, the greater the likelihood of hepatic involvement (Figs. 16.39 and 16.40).

FIGURE 16.39 Contrast-enhanced computed tomography reveals multiple hepatic masses in a patient with lymphomatous involvement of the liver and spleen. Note the low-attenuation mass in the spleen (arrow).

FIGURE 16.40 Large unifocal lymphomatous mass in the right hepatic lobe (arrow). Small splenic lesions are also seen.

On CT, hepatic involvement usually appears diffuse; discrete nodular lesions are seen in only 10% of cases. The sensitivity of CT in the detection of hepatic disease is low, presumably because liver involvement is diffuse. It is thought that extensive disease must be present before becoming apparent at imaging, and CT may reveal only hepatomegaly with no focal lesion. Diffuse or infiltrative forms of the disease result in irregular infiltration in the portal areas.

Hepatic Metastases (See Chapter 81A, Chapter 81B, Chapter 81C )

The liver provides a fertile soil for metastases, not only because of its dual blood supply from systemic and portal systems, but also because of humoral factors that promote cell growth. The liver is second only to regional lymph nodes as a site of metastatic disease. The CT appearance of metastases varies and depends on the size and vascularity of the tumor, the degree of necrosis, and the CT technique used (see Technique section). Borders may be sharp, poorly defined, or nodular; the shape may be round, ovoid, or irregular. Attenuation is usually lower than that of surrounding hepatic parenchyma on unenhanced CT. Intravenous contrast enhancement increases the sensitivity of lesion detection.

Scanning during the appropriate phase of enhancement (arterial, portal, delayed) increases detection even further (see Technique section). Peripheral ring enhancement occurs in metastases, but this is usually not appreciated in hypovascular metastases, which have low attenuation compared with surrounding, intensely enhancing hepatic parenchyma during portal phase scanning. Hypervascular metastases may be obscured during the portal phase and are most clearly visualized during the arterial phase (see Fig. 16.14). Metastases from mucinous carcinomas tend to contain punctate or amorphous calcification. Cystic metastases can be distinguished from benign simple cysts, because the former often contain mural nodules, fluid-fluid levels, or septations. Differentiation of multiple hepatic metastases from multifocal HCC may be difficult, but metastases rarely protrude prominently from the liver surface, a feature that is commonly seen with HCC.

The appearance of metastases may change in response to treatment. Lesions may appear of lower attenuation as they undergo necrosis (Figs. 16.41 and 16.42). Hepatic metastases from gastrointestinal stromal tumors (GISTs) that respond to imatinib mesylate become near cystic on contrast-enhanced CT. These metastases may resemble cyts, but they display a slightly higher HU (Chen et al, 2002). Therefore when evaluating the liver at CT in a patient with a history of GIST, it is very important to know whether the patient has undergone treatment; comparison with pretreatment images becomes essential. Metastases may result in focal biliary ductal dilation secondary to compression or invasion of the adjacent bile duct (Fig. 16.43).

FIGURE 16.41 Metastatic colon cancer. A, Before treatment. B, After treatment.

FIGURE 16.42 Contrast-enhanced computed tomography in a patient with metastatic gastrointestinal stromal tumor. A, Before treatment, heterogeneous solid enhancing masses are seen in the right and left hepatic lobes (arrows). B, After treatment, lesions have lower attenuation and appear more cystic (arrows).

FIGURE 16.43 Contrast-enhanced computed tomography in a patient with metastatic colorectal cancer reveals infiltrative tumor invading the bile duct (arrowheads). Note the resultant biliary dilation (long arrow).

Gallstones

CT is inferior to ultrasound for detection of gallstones, but it may reveal unsuspected gallstones during studies performed for other reasons. Visualized gallstones are calcified or of lower attenuation than the surrounding bile because of a high cholesterol content. Stones that are missed on CT are mixed cholesterol stones that are isodense with bile.

Cholecystitis (See Chapter 31)

CT should not be used as a screening technique for the detection of acute cholecystitis, but occasionally, patients with cholecystitis who display a confusing clinical picture may undergo CT examination before the precise nature of the disease is clear. Gallbladder distension, wall thickening, and gallstones are often present in acute cholecystitis, but these are nonspecific signs that occur in most patients with chronic cholecystitis. The presence of ill-defined pericholecystic lucency within the hepatic parenchyma adjacent to the gallbladder suggests gallbladder inflammation (Fig. 16.46). Intramural edema within the gallbladder wall may be seen in acute cholecystitis and is a useful sign in an appropriate clinical setting, but it also can be seen in patients with ascites or hypoalbuminemia. The attenuation of the gallbladder bile is usually increased, and extremely high attenuation is seen in patients with hemorrhagic cholecystitis, a rare complication.

FIGURE 16.46 Acute cholecystitis. computed tomography shows a distended, thick-walled gallbladder with pericholecystic fluid. No gallstones are seen.

Although many of the CT findings in uncomplicated acute cholecystitis are nonspecific, CT is valuable when complications such as pericholecystic abscess, emphysematous cholecystitis, or gallbladder perforation are present, and CT can identify patients in need of emergency surgery. CT findings most specific for acute gangrenous cholecystitis are gas in the gallbladder wall or lumen, intraluminal membranes, irregular gallbladder wall enhancement, and pericholecystic abscess (Bennett et al, 2002).

Mirizzi Syndrome

Mirizzi syndrome is an uncommon condition in which the common hepatic duct is obstructed because of stones impacted in or extruded from a Hartmann pouch or cystic duct. Cholecystobiliary and cholecystoenteric fistulae are common complications. It is clinically important to recognize the diagnosis before surgery, because failure to appreciate the extraluminal obstructing process results in unrewarding exploration of the common duct and persistent obstruction. The typical CT features of Mirizzi syndrome are dilation of the biliary system above the level of the neck of the gallbladder with a normal system below. CT reveals a gallstone impacted in a cystic duct or gallbladder neck, and the stone usually appears eccentrically located relative to the bile duct. An irregular cavity with surrounding edema and inflammation may be seen adjacent to the gallbladder neck (Fig. 16.47). Because not all of the findings may be present on CT, direct cholangiography or MRI cholangiopancreatography can be obtained to document the nature of the obstruction and the presence or absence of a biliary fistula.

FIGURE 16.47 Mirrizi syndrome. A, Contrast-enhanced computed tomography reveals a large calcified gallstone associated with gallbladder wall thickening and extensive pericholecystic inflammatory change (arrowheads). B, Extensive inflammatory change surrounds the internal biliary stent (arrow).

Choledocholithiasis (See Chapters 35 to 37)

The insensitivity of sonography in detecting choledocholithiasis has been well documented, with a reported detection rate of 18% to 22%, whereas CT has a detection rate of 76% (Baron, 1987). Meticulous attention must be paid to technique, and when a change in duct caliber is detected, thin collimation scans should be performed through the transition area to detect the calculus. The only reliable indicator of choledocholithiasis is the presence of dense intraluminal calcification, or a target sign, which is due to a halo of bile surrounding the higher density stone. Calcified stones lying within an obstructed duct present no challenge to the radiologist. Most errors in diagnosis are due to cholesterol stones, which may blend imperceptibly with the surrounding bile. Errors of diagnosis also occur when choledocholithiasis occurs without ductal dilation, which occurs in about one third of patients with choledocholithiasis.

Intrahepatic calculi (see Chapter 39) are rare in Western countries but most frequently occur in association with iatrogenic bile duct strictures (Fig. 16.48). CT is of little value when stones are small and noncalcified and bile duct dilation is minimal or absent. Intrahepatic choledocholithiasis may give a bizarre appearance, owing to segmental or subsegmental biliary radicles filled with calculi. In Asian patients with recurrent pyogenic cholangitis, who subsequently form bile pigment stones, the debris filling the biliary system generally has higher attenuation than normal bile. Marked bile duct dilation is present, and often the larger intrahepatic ducts are dilated without side-branch dilation. Eccentric and diffuse extrahepatic bile duct wall thickening is usually seen (Schulte et al, 1990).

FIGURE 16.48 Intrahepatic cholelithiasis. Intrahepatic duct dilation is seen after recurrent anastomotic stricture formation at a hepaticojejunostomy. Several laminated, noncalcified calculi can be seen within the dilated ductal system.

Gallbladder Carcinoma

Gallbladder carcinoma (see Chapter 49) is the sixth most common gastrointestinal malignancy in the United States. Risk factors include female gender, age, postmenopausal status, and cigarette smoking (Khan et al, 1999). Gallstones are present in 74% to 92% of patients with gallbladder carcinoma and represent another well-established risk factor (Lowenfels et al, 1985; Nagorney & McPherson, 1988). Porcelain gallbladder, a term used to describe calcification within the gallbladder wall, places a patient at increased risk for gallbladder carcinoma. Older studies suggested that 10% to 25% of patients with a porcelain gallbladder develop gallbladder carcinoma (Berk et al, 1973), but more recent reports indicate that the risk may be lower and related to the type of calcification (lower risk with complete calcification of the entire wall compared with selective calcification; Stephen & Berger, 2001; Kim et al, 2009). Most patients with gallbladder carcinoma are diagnosed with advanced disease. Early-stage gallbladder carcinoma typically is detected incidentally because of inflammation related to coexistent cholelithiasis or cholecystitis. In 1% of patients undergoing cholecystectomy for cholelithiasis, gallbladder carcinoma is discovered incidentally (Wanebo & Vezeridis, 1993).

The CT imaging appearances of gallbladder carcinoma include a mass replacing the gallbladder (seen in 40% to 65% of patients), focal or diffuse gallbladder wall thickening (seen in 20% to 30%; Fig. 16.49), and an intraluminal polypoid mass (seen in 15% to 25%; Fig. 16.50) (Franquet et al, 1991; Lane et al, 1989; Yeh, 1979; Yum & Fink, 1980). Additional imaging findings associated with gallbladder carcinoma reflect the pattern of disease spread. The most common mode by which gallbladder carcinoma spreads is direct invasion into the adjacent organs. Direct tumor invasion is enhanced by the thin gallbladder wall, which contains only a single muscle layer. The perimuscular connective tissue of the gallbladder is continuous with the interlobular connective tissue of the liver, facilitating the direct spread of tumor into the hepatic parenchyma (Henson et al, 1992). The liver is the organ most frequently invaded, followed by the colon, duodenum, and pancreas (Sons et al, 1985).

FIGURE 16.49 Contrast-enhanced computed tomography reveals focal gallbladder wall thickening (arrows) in a patient with gallbladder cancer.

FIGURE 16.50 Gallbladder carcinoma. The gallbladder is distended and contains calcified stones. Nodular soft tissue emanates from the gallbladder wall into the lumen (arrow).

The gallbladder lies in the intersegmental plane between segments IVb and V (see Fig. 16.6), and tumors of the gallbladder fundus may invade directly into these segments at an early stage (Blumgart et al, 2001). Air may be seen within the gallbladder lumen if tumor results in a fistula to the transverse colon or duodenum. Tumors involving the infundibulum or cystic duct may invade directly and obstruct the common bile duct or portal vein, precluding surgical resection (Blumgart et al, 2001). Associated biliary dilation resuting from infiltrative tumor along the cystic duct to the extrahepatic bile duct, lymphadenopathy compressing the bile duct, or intraductal spread of tumor is apparent on CT (Levy et al, 2001). Tumor growth through the gallbladder wall away from the liver results in peritoneal carcinomatosis.

Laparoscopic cholecystectomy has become increasingly accepted as a treatment for symptomatic uncomplicated cholelithiasis (Southern Surgeon’s Club, 1991), and approximately 15% to 30% of gallbladder carcinomas are detected incidentally at microscopic review of cholecystectomy specimens (Clair et al, 1993). A serious potential complication of laparoscopic cholecystectomy is the inadvertent dissemination of unsuspected gallbladder carcinoma (Winston et al, 1999a). Wibbenmeyer and colleagues (1995) reported that gallbladder carcinoma recurs more rapidly after laparoscopic cholecystectomy than after open cholecystectomy. Tumor can recur in the laparoscopic port tracks, even if surgical resection of the port sites is performed at subsequent hepatic resection for attempted cure. Recurrent tumor may appear as a mass along the anterior abdominal wall with extension into the subjacent omental fat (Fig. 16.51; Winston et al, 1999a). These observations underscore the need to correctly identify findings suggestive of gallbladder carcinoma on preoperative imaging when elective laparoscopic cholecystectomy is planned.

FIGURE 16.51 Contrast-enhanced computed tomography in a patient who had previously undergone laparoscopic cholecystectomy. The enhancing mass (arrow) within the anterior abdominal wall reflects recurrent gallbladder carcinoma within a laparoscopic port tract.

Cholangiocarcinoma

Cholangiocarcinoma (see Chapter 50A, Chapter 50B, Chapter 50C, Chapter 50D ) is an adenocarcinoma that arises from bile duct epithelium. Conditions that place patients at increased risk for developing cholangiocarcinoma include clonorchiasis, hepatolithiasis, choledochal cyst, Caroli disease, hepatitis C viral infection, and primary sclerosing cholangitis (Sherlock & Dooley, 1997). Cholangiocarcinoma usually is classified as either intrahepatic or extrahepatic, and intrahepatic cholangiocarcinoma is classified further as either hilar or peripheral in location; these three types of cholangiocarcinoma—peripheral, hilar, and extrahepatic—are often regarded as distinct clinical and radiologic entities (Han et al, 2002), although this classification scheme is controversial. The Liver Cancer Study Group of Japan (1997) categorized intrahepatic cholangiocarcinoma into three types based on the macroscopic appearance: mass forming, periductal infiltrating, and intraductal.

The hepatic hilus is the most common location of cholangiocarcinoma, occurring in 40% to 60% of patients (Burke et al, 1998; Nagorney et al, 1993; Nakeeb et al, 1996). Tumors involving the distal bile duct account for 20% to 30% of all cholangiocarcinomas, and approximately 10% of cholangiocarcinomas arise peripherally within the intrahepatic biliary tree (Berdah et al, 1996; Chu et al, 1997; Harrison et al, 1998).

Hilar Cholangiocarcinoma.

Cholangiocarcinoma can arise anywhere in the biliary tree, but tumors involving the biliary confluence, termed hilar cholangiocarcinoma, are the most common; these are further broken down into infiltrating, exophytic, and polypoid types. Infiltrating hilar cholangiocarcinoma is the most common type, accounting for more than 70% of cases (Fig. 16.52); such tumors usually are seen as focal thickening of the duct wall with obliteration of the lumen (Han et al, 2002). Exophytic cholangiocarcinoma appears as a mass showing peripheral rim enhancement; its appearance is similar to peripheral cholangiocarcinoma. The polypoid type of hilar cholangiocarcinoma appears as an intraductal soft-tissue mass that expands the duct lumen; this type of tumor may be mulifocal within the biliary tree, and it involves the intrahepatic and extrahepatic bile ducts (Han et al, 2002).

FIGURE 16.52 Hilar cholangiocarcinoma. A, Axial contrast-enhanced computed tomography (CT) reveals an infiltrative, low-attenuation tumor (arrow) surrounding an internal biliary stent (arrowhead), resulting in bilobar intrahepatic biliary duct dilation. B, Axial contrast-enhanced CT reveals confluent tumor (large arrows) encasing a replaced right hepatic artery (small arrow), which originates from the superior mesenteric artery. Despite the biliary stent, intrahepatic biliary duct dilation is evident. C, Oblique axial maximum intensity projection image reveals narrowing of the right portal vein (large arrow) secondary to infiltrative tumor. Bilobar intrahepatic biliary ductal dilation is evident (smaller arrows).

Generally, long-term survival is possible only with an en bloc resection of the liver and the extrahepatic biliary ducts (Jarnagin & Winston, 2005). Jarnagin and colleagues (2001) proposed a staging system for hilar cholangiocarcinoma that predicts resectability, likelihood of metastatic disease, and survival. Preoperative imaging should focus on addressing factors that determine resectability. Four crucial components of resectability are 1) level and extent of tumor within the biliary tree, 2) vascular invasion, 3) hepatic lobar atrophy, and 4) distant metastatic disease.

High-resolution MDCT in combination with interactive image viewing in cine mode using PACS has enhanced the radiologist’s ability to address these issues (see Fig. 16.52). It is possible to trace the individual dilated bile ducts to determine the point or points of obstruction (Fig. 16.53). Zandrino and colleagues (2002) reported that multislice CT performed without a cholangiographic contrast agent correctly identified the cause of biliary obstruction in 31 (86%) of 36 patients.

FIGURE 16.53 Cholangiocarcinoma. Contrast-enhanced computed tomography reveals bilobar central intrahepatic biliary duct dilation as a result of an obstructing enhancing mass at the hepatic hilus (arrow).

One feature of cholangiocarcinoma is subepithelial spread of tumor along the duct wall and periductal tissues, and significant tumor may extend beneath an intact epithelial lining. For this reason, radiologic studies may underestimate the full extent of tumor. This possibility emphasizes the need for frozen section analysis of duct margins (see Fig. 16.52; Jarnagin & Winston, 2005).

Tumor extent along the hepatic arteries can be identified with CT angiography. Lobar atrophy, also apparent on CT, is an important finding in patients with cholangiocarcinoma. Atrophy is a major factor in the proposed clinical T-stage criteria, and it affects resectability. Although long-standing obstruction of the ipsilateral bile duct may cause moderate atrophy, associated portal venous obstruction causes rapid and severe atrophy of the affected lobe (Fig. 16.54; Jarnagin & Winston, 2005). Atrophy also is important to recognize at imaging when biliary decompression is planned. Drainage of an atrophic lobe does not relieve jaundice and is not indicated, unless it is done as treatment for biliary sepsis (Jarnagin & Winston, 2005).

FIGURE 16.54 Infiltrative hilar cholangiocarcinoma. Reformatted oblique axial image with dilated bile ducts appearing bright. The infiltrative mass (long arrow) in the left hepatic lobe resulted in left-sided intrahepatic biliary ductal dilation (short arrows). Tumor extends along the central portion of the right portal vein with mild atrophy of the left lobe.

Peripheral Cholangiocarcinoma.

The most common type of intrahepatic cholangiocarcinoma is mass-forming peripheral cholangiocarcinoma. On contrast-enhanced CT, peripheral cholangiocarcinoma appears as a low-attenuation mass with peripheral rim enhancement (Fig. 16.55), and it is associated with focal dilation of the intrahepatic bile ducts around the mass. Contrast enhancement of the mass is often seen on the delayed images (Keogan et al, 1997; Lacomis et al, 1997; Valls et al, 2000). This delayed enhancement is likely due to the increased stromal fibrosis seen within these tumors (Valls et al, 2000).

FIGURE 16.55 Late arterial phase and portal venous phase images of a patient with a peripheral cholangiocarcinoma. A, Late arterial phase image reveals peripheral enhancement of a heterogeneous mass in the right hepatic lobe (arrows). B, Portal venous phase image reveals heterogeneous enhancement of the central portion of the mass.

Biliary Cystadenoma and Cystadenocarcinoma

Biliary cystadenomas (see Chapter 48) are uncommon benign cystic lesions that occur predominantly in middle-aged women between 42 and 55 years (Ishak et al, 1977). Although benign, these lesions may recur after excision and have the potential to develop into biliary cystadenocarcinomas. Cystadenomas are most often intrahepatic (83%), but they may also occur within the extrahepatic bile ducts (13%) or gallbladder (0.02%) (Devaney et al, 1994).

CT shows cystadenomas to be multiloculated cystic lesions with internal septations; only rarely are they unilocular (Fig. 16.56). Calcifications may be present within the wall of the cyst or within the septa, and septa may enhance with intravenous contrast media (Fig. 16.57). The attenuation of the cyst fluid depends on the content of the fluid, which may be hemorrhagic, mucinous, proteinaceous, or bilious (Buetow et al, 1995). Tumor nodules and papillary projections extending into the cyst typically enhance with intravenous contrast medium. No specific imaging feature permits reliable differentiation of biliary cystadenoma from biliary cystadenocarcinoma (Buetow et al, 1995a).

FIGURE 16.56 Biliary cystadenoma. Contrast-enhanced computed tomography reveals a large cystic mass with a very subtle internal septation (curved arrows).

FIGURE 16.57 Recurrent biliary cystadenoma after resection. A multiloculated cystic lesion is seen at the resection margin containing enhancing septa and calcification.

Pancreatic Adenocarcinoma

Pancreatic adenocarcinoma (see Chapter 58A) is the fourth most common cause of death from malignancy (Kim et al, 2004a) and is often discovered at an advanced and inoperable stage. Operative mortality and morbidity rates of 2.8% and 40%, respectively (Wagner et al, 2004), underscore the need for preoperative evaluation to select the subgroup of patients who may be candidates for curative resection.

A recent report describes a new scoring system for tumor invasion that looks at both the length and degree of circumferential encasement of the peripancreatic arteries and veins to determine resectability, using data obtained from 16-slice scanners (Klauss et al, 2008). This score evaluates the length of tumor contact and circumferential extent of tumor involving the SMV, splenic vein, portal vein, aorta, celiac trunk, hepatic artery, splenic artery, and SMA. Veins were also assessed for contour deformations. The authors of this study reported sensitivity and specificity of 89% and 99% for vascular invasion and a sensitivity of 94% and specificity of 89% for the evaluation of resectability.

Pancreatic ducts represent only 4% of the pancreatic tissue but are the source of 90% of pancreatic malignancies (Cubilla & Fitzgerald, 1975; Morohoshi et al, 1983). Adenocarcinoma is the most common form of pancreatic cancer, and it occurs in later life. The clinical presentation depends on the location within the gland; cancers within the pancreatic tail are clinically silent and may not show up until metastasis is widespread, but cancers within the pancreatic head or periampullary region tend to show up earlier, with biliary obstruction a common sign in 50% of patients.

Pancreatic adenocarcinoma appears as a low-attenuation mass, often deforming the contour of the pancreas with secondary signs depending on the tumor location (Figs. 16.61 and 16.62). A mass in the pancreatic head is more commonly associated with biliary or pancreatic ductal dilation. The pancreas proximal to the obstruction is often atrophic, a secondary and often early indication of the tumor site.

FIGURE 16.61 Low-attenuation mass (arrow) in the head of the pancreas.

FIGURE 16.62 Dilated pancreatic duct (arrow) secondary to carcinoma in the head of the pancreas.

Knowledge of vascular involvement or encasement is crucial to preoperative evaluation of the pancreas, because involvement of the superior mesenteric artery or vein, common hepatic artery, or celiac axis generally precludes operative resection for cure. Involvement of the main portal vein is not a contraindication to surgery, because a portion of the main portal vein may be resected and reanastomosed proximal to the jejunal branches (Chae et al, 2003; Lygidakis et al, 2004; Nakao et al, 2004; Yoshimi et al, 2003). Kitagawa and colleagues (2008) reviewed patterns of spread of adenocarcinoma of the pancreatic head and found specific patterns, depending upon the origin of the cancer from the dorsal or ventral pancreatic anlagen on an embryologic basis. Tumors confined to the ventral pancreas had metastases along the SMA and peripancreatic nodes, whereas tumors that arose from the dorsal pancreas domain metastasized to the common hepatic artery, hepatoduodenal ligament, and the peripancreatic nodes. Tumors that extended into both domains metastasized widely.

Early findings of pancreatic cancer may be extremely subtle and difficult to detect. In a study at the Mayo Clinic in Rochester, Minnesota, 62 scans obtained before the histologic diagnosis of pancreatic cancer in 28 patients were retrospectively reviewed by two radiologists. Half of the scans obtained before diagnosis showed findings that were interpreted as definite or suspicious for pancreatic carcinoma 2 to 6 months and 6 to 18 months before diagnosis (Gangi et al, 2004). Pancreatic duct dilation and cutoff were early findings. A limitation of this study is that it was a retrospective review of scans obtained between August 1994 and June 2001. Current techniques of thin-section, high-resolution scanning during optimal pancreatic enhancement should improve detection of small lesions. More commonly, pancreatic cancer is detected at an advanced stage, associated with arterial vascular encasement or invasion, venous involvement, peripancreatic adenopathy, hepatic metastases, or ascites (Figs. 16.63 and 16.64). Local arterial encasement or venous occlusion or both preclude resection for attempted cure. Centers with a high volume of pancreatic surgery do a partial resection of the portal vein and primary reanastomosis, but this mandates a cuff of remaining normal portal vein proximal to the first jejunal branch (Chae et al, 2003; Yoshimi et al, 2003). Three-dimensional workstations permit visualization of vascular involvement in coronal and sagittal planes and permit three-dimensional reconstructions using maximum intensity projections or volume rendering (Prokesch, 2003; Tamm & Charnsangavej, 2001; Tamm et al, 2001). Curved multiplanar reformatted images can offer a superb display of pancreatic anatomy and demonstration of adjacent vascular encasement (Vargas et al, 2004, Gong et al, 2004).

FIGURE 16.63 Pancreatic cancer with vascular encasement. A, Cancer in the body of the pancreas tracks posteriorly to encase the celiac axis, proximal hepatic artery (black arrowhead), and splenic artery (white arrowhead). B, Curved multiplanar reconstruction showing the mass (arrow) in the body of the pancreas. C, Coronal volume-rendered image shows a mass in the body of the pancreas occluding the splenic vein (arrowhead) and encasing celiac axis branches (arrows). D, Sagittal volume-rendered image shows mass encasing the celiac axis (arrow).

FIGURE 16.64 Large pancreatic mass with vascular encasement and collateral vessels. A, Mass in the body and tail of the pancreas encases the celiac artery and its branches. B, Coronal volume-rendered image shows the pancreatic mass and encasement of the celiac and superior mesenteric arteries (arrows) by tumor. C, Coronal volume-rendered image shows extensive collateral vessels in the abdomen from encasement of the splenic vein by pancreatic cancer.

Neuroendocrine Cancer of the Pancreas

Neuroendocrine cancer of the pancreas arises predominantly from the islets of Langerhans and may arise in a sporadic fashion or in patients with multiple endocrine neoplasia type I (MEN-I). Pancreatic neuroendocrine tumors generally have a much more favorable prognosis than pancreatic adenocarcinoma. Presentation is diverse and often depends on the presence of hormonal activity and its associated symptoms (Kulke, 2003). Hormonally active tumors may present earlier and are generally smaller than non–hormonally active tumors.

The CT and MR appearances of endocrine tumors of the pancreas according to the World Health Organization (WHO) classification was reviewed recently (Rha et al, 2007). Masses are often hypervascular on imaging and may be associated with liver or nodal metastases or both (Fig. 16.65). Careful attention to detail is required, particularly for imaging of the hormonally active tumors, which may be small hypervascular masses that often require dedicated thin-section pancreatic protocols for initial detection (Gouya et al, 2003). Arterial phase imaging is necessary to detect masses that otherwise may be isodense on the portal venous phase of imaging (Fig. 16.66). Insulinomas are the most common type of functioning islet cell tumor of the pancreas and are generally extremely hypervascular. Routine follow-up of these patients is best assessed with triphasic scans of the liver to detect masses that may become isodense on portal phase imaging.

FIGURE 16.65 Pancreatic neuroendocrine cancer/hypervascular mass (arrow) on the portal venous phase.

FIGURE 16.66 Islet cell tumor. A, Arterial phase scan shows hypervascular liver metastasis from islet cell cancer of the pancreas. B, Arterial phase scan shows hypervascular islet cell cancer of the pancreas (arrow). C, Liver metastasis from islet cell cancer of the pancreas is a lower attenuation than hepatic parenchyma on portal venous phase.

In a retrospective review of 50 patients with neuroendocrine cancer (Chu et al, 2002), median survival was 40 months, with overall 1-, 2-, and 5-year survival rates of 84%, 69%, and 36%, respectively. Long-term survival of these patients was related to surgical resection of the primary tumor, absence of liver metastases, metachronous liver metastases, and aggressive treatment of liver metastases using surgery, intrahepatic chemotherapy, or chemoembolization. A German review of 254 patients with neuroendocrine tumors showed 29% to be of pancreatic origin. The 5-year survival from the time of initial diagnosis for this subgroup of patients with pancreatic tumors was 43%. A smaller sized primary tumor (<2 cm) and histologic grading as low-grade malignant were associated with a longer survival (Pape et al, 2004).

Cystic Pancreatic Neoplasms

Cystic pancreatic neoplasms (see Chapter 57) represent a spectrum of disease that includes both benign and malignant entities. Distinguishing benign neoplasms from pancreatic pseudocysts can be difficult, and serial imaging may be necessary to evaluate for stability (Allen et al, 2003; Visser et al, 2004). Included in this group of neoplasms are serous cystadenomas, lymphoepithelial cysts and cystic neuroendocrine tumors, and pseudocysts. Mucinous cystic neoplasms have malignant potential and may present a challenge to distinguish from other benign pancreatic cysts.

Intraductal Papillary Mucinous Neoplasm.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a spectrum of disease, ranging from benign to malignant and characterized overall by improved survival compared with pancreatic adenocarcinoma. There is a greater male/female predominance, with a reported 57% of patients male in the Johns Hopkins experience (Sohn et al, 2004) and a 2.2 : 1 male/female predominance in a reported Japanese experience (Kimura et al, 1996). The tumor is classified into that of main pancreatic duct, branch duct, or mixed involvement (Bassi et al, 2000; Nagasaka & Nakashima, 2001; Nakamura et al, 2002; Tanaka, 2004; Tan et al, 2009; Ogawa et al, 2008; Freeman, 2008). A review of surgical experience of 136 IPMNs from Johns Hopkins (Sohn et al, 2004) found 62% to be benign, and the remaining 38% had IPMNs with associated invasive cancers. The most common presenting symptoms are abdominal pain, weight loss, and nausea and vomiting; patients with invasive IPMNs also may be seen with jaundice.

IPMNs may occur in any portion of the gland. Branch-type neoplasms are most commonly benign, whereas the main duct and mixed types are frequently malignant (Tanaka, 2004; Tan et al, 2009). Multiplanar reformatted images may prove invaluable in the discrimination of branch-type IPMN from main-duct type (Takada et al, 2005). They are cystically dilated ducts that connect to the remainder of the ductal system, lined by flat or papillary mucinous or oncocytic epithelium with or without a component of invasive adenocarcinoma, and they are recognized as identifiable cystic structures of at least 1 cm radiographically or at surgery (Fig. 16.67). Careful attention to radiographic technique, including thin-section imaging with rapid injection of intravenous contrast medium, is crucial to detect these often small masses. Appropriate timing of scanning with the administration of contrast medium is designed to scan the pancreas during the pancreatogram phase, when pancreatic parenchyma is maximally enhanced, which maximizes contrast differences between the cystic mass and the enhanced pancreas. Location of the mass within the pancreatic head (Fig. 16.68) may compress the common bile duct with resulting dilation of the intrahepatic bile ducts. Invasive adenocarcinoma may be found at pathologic examination and has been reported to correlate most closely with the presence of mural nodules and pancreatic duct dilation of 7 mm or greater (Sugiyama et al, 2003; Kawamoto et al, 2005; Fig. 16.69). D’Onofrio and colleagues (2009) reported a case of an 8-mm undifferentiated pancreatic adenocarcinoma that had a desmoplastic reaction on an adjacent pancreatic duct, which was dilated and mimicked an IPMN. Intraductal papillary mucinous tumors have a high reported incidence of associated extrapancreatic synchronous and metachronous malignancies of 23.6% to 32%, especially colorectal carcinoma (Sugiyama & Atomi, 1999), and a high incidence of associated pancreatic malignancies (Yamaguchi et al, 2002).

FIGURE 16.67 Intraductal papillary mucinous tumor of the pancreatic head (arrow).

FIGURE 16.68 Intraductal papillary mucinous tumor (arrow) of the pancreatic head with invasive adenocarcinoma at pathologic examination; note associated biliary ductal dilation.

FIGURE 16.69 Intraductal papillary mucinous neoplasm. A to D, Diffuse involvement of the main (white arrows) and branch (black arrows) pancreatic ducts with invasive adenocarcinoma. B, No evidence of vascular encasement is found, as shown on the normal-appearing portal vein (arrows), and none was found at surgery or at pathologic examination.

Serous Cystadenomas.

Often discovered incidentally on abdominal CT scans performed for other indications, pancreatic serous cystadenomas are slow-growing tumors with a 2 : 1 female/male predominance. These tumors present at a mean age of 63 years versus 54 years for mucinous cystadenomas/carcinomas. Symptoms include vague abdominal pain or back pain. Other symptoms—including nausea, weight loss, and vomiting—are less common. Initially, these tumors were called microcystic adenomas, a term that has fallen into disfavor because of reported macrocystic tumors (Anderson & Scheiman, 2002).

Serous cystadenomas generally are surrounded by a fibrous capsule and contain numerous tiny cysts, which are sometimes so small that the cystic nature is difficult to appreciate, because it is below the limits of CT resolution. In these instances, ultrasound or MRI may reveal the cystic nature more clearly. Cyst sizes may vary from 1 mm to 2 cm, but occasionally cysts several centimeters in size may be encountered; differentiation from mucinous cystic neoplasms may therefore be difficult (Warshaw et al, 1990; Visser et al, 2008; Chaudhari et al, 2007; Kim et al, 2006). A central stellate scar, when present, is helpful to make the diagnosis. MRI may be useful to visualize the cystic nature when CT findings are equivocal (Allen et al, 2003; Sahani et al, 2002; Visser et al, 2004). Because of their slow-growing nature and vague symptoms in only 50% of patients, these masses may be quite large at the time of discovery (Figs. 16.70 and 16.71).

FIGURE 16.70 Computed tomography showing low-attenuation pancreatic serous cystadenoma in the pancreatic tail (arrow) and hepatic hemangioma.

FIGURE 16.71 Serous cystadenoma of the pancreatic head shown in the portal phase.

Mucinous Cystic Neoplasms.

Mucinous cystic adenomas of the pancreas often present a mixed picture pathologically, including benign mucin-producing epithelium, dysplasia, carcinoma in situ, and tissue invasion. No imaging criteria permit differentiation of benign from malignant tumors, and all mucinous cystic tumors should be considered malignant or premalignant and should be excised completely (Sarr et al, 2000; Visser et al, 2004; Wilentz et al, 2000).

Mucinous cystic adenomas are found more frequently in women (9 : 1 predominance) and are frequently within the body and tail of the pancreas. In a series of 52 female patients with pathologically proven mucinous cystic tumors (Procacci et al, 2001), the most highly associated features of malignancy were a thick wall (>2 mm), septations, and calcification in the wall or within septations (Fig. 16.72).

FIGURE 16.72 Mucinous cystadenocarcinoma. A, Contrast-enhanced computed tomography (CT) shows thick-walled cystic mass with punctate mural calcification. B, Contrast-enhanced CT shows thick-walled cystic mass with mural ulceration.

Other Cystic Pancreatic Masses.

Cystic masses may also be secondary to degeneration of previously solid masses. Neuroendocrine cancers may become necrotic and present with cystic degeneration (Fig. 16.73). Mucinous tumors may invade adjacent structures and present as cystic masses (Fig. 16.74).

FIGURE 16.73 Pancreatic neuroendocrine neoplasm with cystic degeneration in the portal venous phase.

FIGURE 16.74 Intraductal papillary mucinous tumor with invasive mucinous adenocarcinoma. A, Large multicystic tumor extends into the papilla. B, Computed tomography shows that the mass also invades into the duodenum and stomach.

Metastatic Disease to the Pancreas (See Chapter 60)

A pathology review (Adsay et al, 2004) of surgical and autopsy cases showed the most common primary malignancies metastatic to the pancreas were lung carcinomas, gastrointestinal carcinomas, and lymphomas. These are usually found in patients with widely disseminated disease. As at other sites in the body, pancreatic lymphoma tends not to occlude vessels but to encase them. This is a major distinguishing feature useful for diagnosis (Fig. 16.75). Detection of metastatic disease to the pancreas requires a high index of suspicion, because primary pancreatic carcinomas of ductal origin are far more common. When clinical suspicion is present, the study can be tailored to optimize the likelihood of detection. In a patient with renal carcinoma, hypervascular metastases to the pancreas may be detected on routine scanning or triphasic examination (Fig. 16.76).

FIGURE 16.75 Lymphoma of the pancreas. Note absence of vascular narrowing.

FIGURE 16.76 Renal cell carcinoma metastatic to pancreas. A, Computed tomographic angiogram of the pancreas shows hypervascular pancreatic metastases (arrows) from renal carcinoma. B, Portal venous phase imaging shows far fewer masses.

Solid and Papillary Epithelial Neoplasm of the Pancreas

Solid and papillary epithelial neoplasm (SPEN) of the pancreas is a rare tumor with a low malignant potential (Madan et al, 2004). SPEN has a reported incidence of 0.13% to 2.7% of all pancreatic malignancies and is most commonly encountered in the first three decades of life (Crawford, 1998; Cubilla & Fitzgerald, 1980; Lam et al, 1999), although the reported age range is 8 to 72 years with a mean age of 27 years. Female/male predominance is 9.5 : 1 (Mao et al, 1995), and these tumors are more common in nonwhites. Patients with malignant SPEN are often older and more often male (Lam et al, 1999). In a review of patients with pathologically proven SPENs, presenting complaints included abdominal pain, palpable mass, dyspepsia with bloating, and early satiety (Buetow et al, 1996; Yoon et al, 2001). Typically, laboratory findings are normal, with no elevation of tumor markers or serum amylase.

On CT, these tumors may have varied findings. They are often large and may have internal hemorrhage or cystic degeneration. Calcification is common (Fig. 16.77), but internal septations are not characteristic for this tumor (Buetow et al, 1996; West & Brady-West, 2000). Although this tumor is of low malignant potential, patients should be followed, because late metastases can occur.

FIGURE 16.77 Papillary epithelial neoplasm of the pancreas with calcification: portal venous phase.

Acinar Cell Carcinoma of the Pancreas

Acinar cell carcinoma is predominantly a tumor of the elderly man, with peak incidence in the 60s and many more men affected than women. Accounting for approximately 1% of all pancreatic tumors, acinar cell carcinoma of the pancreas is defined as a carcinoma of the exocrine pancreas exhibiting pancreatic enzyme production by the neoplastic cells (Cubilla & Fitzgerald, 1975; Morohoshi et al, 1983). They have a characteristic microscopic appearance of a relatively circumscribed periphery and minimal desmoplastic stroma within the tumor, with cells arranged in nests and cords. The tumor is most common in the head, neck, and uncinate process of the pancreas but may arise in any portion of the gland (Holen et al, 2002; Klimstra et al, 1992). Initial symptoms include abdominal pain or fullness, postprandial vomiting, and jaundice. Some patients may be asymptomatic, and the mass may be detected incidentally. Serum tumor markers may be normal, or there may be mild elevation of serum α-fetoprotein, carcinoembryonic antigen (CEA), and CA19-9.

CT features include a well-defined tumor with a thin, enhancing capsule and central necrosis, which may contain areas of internal calcification (Fig. 16.78). Such calcification may be a useful feature in distinguishing this entity, because only 2% of ductal adenocarcinomas and 22% of nonfunctioning islet cell tumors contain calcification (Buetow et al, 1995b; Eelkema et al, 1984). In a more recent series (Chiou et al, 2004), tumor diameters ranged from 3.3 to 18 cm, with an overall mean size of 7.2 cm. Most of these tumors were hypodense with respect to normal pancreatic parenchyma, although some showed hypervascular enhancement on the early arterial phase, some of which persisted into the portal venous phase.

FIGURE 16.78 Acinar pancreatic cancer (arrow).

Pancreatitis (See Chapter 54, Chapter 55A, Chapter 55B )

The most common cystic mass of the pancreas is not a malignancy but rather a complication of acute or chronic pancreatitis. Fluid collections occur in approximately 50% of patients with moderate to severe pancreatitis. Of these, approximately 50% resolve spontaneously within 6 weeks (Baron & Morgan, 1997; Byrne et al, 2002), and 10% to 15% may progress to pseudocyst formation after developing a capsule. Pseudocyst formation is more common in patients with chronic pancreatitis and may occur in 20% to 40% of these patients.

Common causes of pancreatitis include alcohol, gallstones, idiopathic hypertriglyceridemia, drugs, pancreas divisum, trauma, and endoscopic retrograde cholangiopancreatography (Baron & Morgan, 1997). Clinical presentation includes nausea, vomiting, and epigastric pain. Serum amylase, frequently used to monitor pancreatitis, may be normal in acute pancreatitis and elevated in nonpancreatitic conditions. Elevation of the serum lipase may support the diagnosis of acute pancreatitis.

Mild acute pancreatitis may appear on CT scan as enlargement of the pancreas with loss of definition of the borders of the pancreas. Depending on the part of the pancreas involved, there may be thickening of the right or left anterior pararenal fascia or diffuse thickening of adjacent fascial planes (Figs. 16.79 and 16.80). Acute fluid collections associated with pancreatitis are enzyme-rich collections, which lack a defined wall.

FIGURE 16.79 Pancreatitis involving the body and tail of the pancreas. Note the loss of fat planes to the spleen and in the left anterior pararenal space.

FIGURE 16.80 Severe pancreatitis obliterates tissue planes in a patient after gastrectomy.

Pancreatic fluid collections may present as an acute fluid collection interspersed with pancreatic parenchyma without a defined wall. The fluid collection may be well circumscribed, or it may infiltrate throughout the pancreas and retroperitoneum; this may dissect retroperitoneal planes and resolve spontaneously 50% of the time. An acute pseudocyst is defined as a collection of pancreatic juice confined by a nonepithelialized wall of granulation tissue that occurs as a result of acute pancreatitis (Baron & Morgan, 1997) and requires at least 4 weeks to form (Fig. 16.81). It is characterized by the presence of a well-defined wall and may contain internal septations.

FIGURE 16.81 Pancreatic pseudocyst in portal venous phase. The patient also has adenopathy from an islet cell tumor.

Lymphoplasmacytic Pancreatitis

Lymphoplasmacytic pancreatitis, also known as autoimmune pancreatitis (Kawaguchi et al, 1991; Kim KP et al, 2004; Yoshida et al, 1995), was first described as a “primary inflammatory sclerosis of the pancreas” (Sarles et al, 1961). It is characterized by a mixed inflammatory infiltrate centered around pancreatic ducts and ductules, combined with obliterative phlebitis (Hardacre et al, 2003). The clinical presentation can be identical to that of pancreatic adenocarcinoma, with abdominal pain, jaundice, weight loss, and elevated levels of CEA or CA19-9. Elevation of pancreatic enzymes is not a prominent feature of this entity, with mild elevation in serum amylase or lipase levels most commonly reported. Elevated levels of IgG and hypergammaglobulinemia are reported in 37% to 76% of patients with autoimmune pancreatitis (Kim et al, 2004b). Patients may also present with fluctuating obstructive jaundice without pain (Kamisawa et al, 2007).

Imaging features of this disease include diffuse or focal enlargement of the pancreas without pancreatic calcification or peripancreatic inflammation, often with nonvisualization of the pancreatic duct and associated with a low-attenuation rim around the pancreas (Fig. 16.82). Imaging also may show thickening of the wall of the common bile duct and gallbladder wall (Kawamoto et al, 2004; Takahashi et al, 2008), which pathologically is due to diffuse lymphoplasmacytic infiltration and fibrosis (Kloppel et al, 2003). Distinguishing lymphoplasmacytic pancreatitis from adenocarcinoma is important, because lymphoplasmacytic pancreatitis responds to oral steroid administration. Distinguishing focal lymphoplasmacytic pancreatitis with localized stenosis of the main pancreatic duct and associated pancreatic duct dilation from pancreatic carcinoma is often not possible, however, and the diagnosis is made only at laparotomy. A multifocal form of autoimmune pancreatitis has also been reported (Kajiwara et al, 2008).

FIGURE 16.82 Lymphoplasmacytic pancreatitis causing diffuse pancreatic enlargement.

Groove Pancreatitis

Groove pancreatitis affects the groove between the pancreatic head, duodenum, and the common bile duct and was first described by Becker and named by Stolte and colleagues (Becker, 1973; Stolte et al, 1982). This can be extremely difficult to distinguish from groove pancreatic carcinoma, as patients are seen initially with abdominal pain and vomiting secondary to duodenal stenosis. This represents chronic pancreatitis that occurs with a platelike mass between the head of the pancreas and the duodenum, and it may cause intrahepatic and extrahepatic biliary duct dilation. Duodenal stenosis may be associated with wall thickening and cystlike lesions in the duodenal wall or in the groove area (Gabata et al, 2003; Lauffer et al, 1999; Triantopoulou et al, 2009; Fig. 16.83). Pancreatic duct dilation is much less common than bile duct dilation, and distinguishing groove pancreatitis from groove pancreatic carcinoma is done from a biopsy.

FIGURE 16.83 Groove pancreatitis. Images A to D show paraampullary duodenal wall cysts with extension to the pancreas along with cystic dilation of the pancreatic duct. At pathologic examination, no malignancy was found. The duodenal wall showed fibrosis and chronic inflammation, and the adjacent pancreas showed focal chronic pancreatitis. The gallbladder showed changes of chronic cholecystitis.