The appearance of GB CA on CT depends upon the morphology of the tumor and extent of disease at the time of imaging [8]. GB CA can be divided into five subtypes based on gross morphologic appearance: papillary (best prognosis), nodular, flat, filling, and massive (most common) [7]. Papillary, nodular, and filling tumors share the same imaging feature of an enhancing soft tissue mass protruding into the normally low-density fluid attenuation lumen of the gallbladder (Fig. 2). Flat tumors may present as irregular thickening of the gallbladder wall without a discrete soft tissue mass or nodule (Fig. 3). Detection of wall thickening (>1 cm) with mural irregularity on CT raises the suspicion for malignancy [9]. A large mass that replaces the GB and adjacent liver parenchyma is an imaging feature of the massive type (Figs. 4 and 5). The mass may be iso- to hypoattenuating relative to the liver on the pre-contrast CT examination. The mass attenuation after intravenous contrast increases but may be heterogeneous owing to necrosis.

According to the American Joint Committee on Cancer (AJCC) for GB CA staging criteria, T1 tumor invades the lamina propria of muscle layer. T2 tumor invades the perimuscular connective tissue but does not extend beyond the serosa. T3 tumor perforates the serosa and directly invades the liver (<2 cm) or one other adjacent organ or structure, such as the bile duct, colon, duodenum, or pancreas. T4 tumor invades the liver (>2 cm), the main portal vein or hepatic artery, or multiple (two or more) adjacent organs and structures. Due to spatial resolution limitations, CT is not very useful for T-staging except to discriminate between T3 and T4 tumors. The sensitivity of CT to detect tumor extension is better when there is advanced disease (T4), approaching 100 % [10]. When the stage is T3, the sensitivity decreases to 65–79 % [10]. The addition of multiplanar reconstructions will improve the accuracy of T-staging of GB CA.

Direct extension to adjacent organs is the most common method of tumor spread. The gallbladder wall has a thin single muscle layer and a narrow lamina propria. The violation of the thin layers of the GB wall will result in liver extension, and lymphatic and vascular spread of disease. The liver is the organ most commonly involved by direct extension (65 % of cases), and tumors of the fundus and body of the gallbladder have a propensity to invade segments IVb and V at an early stage [4, 11, 12]. Hepatic invasion is demonstrated on contrast-enhanced CT as an irregular soft tissue mass disrupting the adjacent liver parenchyma, usually in segments IVb and V (Figs. 5, 6). Radical surgical resection (usually including excision of segments V and IVb) has been shown to improve survival in patients whose tumors are locally confined to the cystic fossa and adjacent hepatic parenchyma [7, 10].

The criterion for tumor extension to adjacent organs, bile ducts, or vessels is the disruption of fat planes between the tumor and the adjacent structures [13, 14] (Fig. 7). Anatomic structures in the hepatic hilum and in close proximity to the gallbladder can also be involved by direct tumor extension: the bile duct and the portal vein are commonly involved by direct tumor extension of GB CA [15]. Biliary dilatation secondary to GB CA can be seen by CT. This may be a result of tumor spread along the cystic duct or extrinsic mass effect from tumor infiltration or enlarged nodes. The colon and duodenum (Fig. 8) are also frequently involved, followed by the pancreas [15]. Extension into the hepatic flexure of the colon is shown on CT as infiltration of the normal low-density pericolonic fat by soft tissue with obliteration of vessels. Wall thickening with possible luminal narrowing and eventual obstruction may also occur (Fig. 9).

The assessment for nodal disease is important for accurate staging. The prevalence of lymphatic metastases in GB CA exceeds 70 % in some series [4, 13]. Lymphatic spread in GB CA occurs first to the cystic, pericholedochal, periportal, hepatic artery, and hepatoduodenal nodes (N1 nodes) (Figs. 10, 11). Disease can then spread to the celiac, superior mesenteric, and peripancreatic nodes, which comprise the N2 nodes (Fig. 12). Attention to the presence of suspicious interaortocaval, left para-aortic, and retropancreatic nodes is important because they may be regarded as distant nodal metastases. The CT detection of metastatic adenopathy will assist in the staging. Detection of nodal involvement on CT is based on size and internal imaging features of the nodes. Nodes >1 cm in short axis are likely malignant [15]. Nodes with a low-attenuation center indicating central necrosis are also likely to harbor metastatic disease [15]. Using the CT criteria for nodes larger than 1 cm, for the presence of malignancy, the sensitivity of CT in the detection of positive nodes in gallbladder cancer is 36 and 47 % for N1 and N2 nodes, respectively [16].

Hematogenous metastases of GB CA occur most commonly to the liver. They appear as multifocal areas of low attenuation in relation to the adjacent hepatic parenchyma, usually with a peripheral rim of contrast enhancement (Fig. 13). Metastases to other organs, such as the lungs, osseous structures, kidneys, adrenals, and brain, occur less frequently.

GB CA spread into the peritoneum is also common. The imaging features of peritoneal deposits are discrete nodules and fat stranding of the low-attenuation peritoneal fat (Figs. 11, 14). The detection of peritoneal disease may be challenging [11].

Resectability of GB CA depends on multiple factors. In the assessment of resectability, MSCT has been found to be an accurate technique to determine resectability of GB CA when factors such as vascular invasion, adjacent organ invasion, and metastases are considered [17].

There are several conditions that may mimic GB CA on imaging studies, such as acute and chronic cholecystitis, adenomyomatosis, and polyps. Gallstones and GB CA may coexist, making differentiation more problematic (Fig. 15). Enhancement of the liver parenchyma adjacent to the cystic fossa has been reported in acute cholecystitis and should not be misjudged as a focal hepatic lesion. Also, tumors arising in the neck of the gallbladder not uncommonly may cause obstruction of the cystic duct and present clinically as acute cholecystitis.

Imaging features of adenomyomatosis on CT include focal or diffuse cystic-appearing thickening of the gallbladder wall (Fig. 16) [18]. Although it is not possible to reliably differentiate GB CA from this condition in all cases, the presence of cystic-appearing spaces in the thickened gallbladder wall allows the diagnosis of adenomyomatosis to be made with reasonable confidence [18].

Cholesterol polyps may be single or multiple and represent approximately 50 % of all polypoid lesions in the gallbladder; they have no malignant potential [19]. Cholesterol polyps may be rarely apparent on contrast-enhanced scans due to vascularity within the polyp (Fig. 17).

There are other benign tumors that are reported in the literature that may involve the gallbladder and biliary tract. For example, adenoma of the gallbladder is found in approximately 0.5 % of cholecystectomy specimens. Only a small proportion of gallbladder adenomas progress to carcinomas. With contrast-enhanced CT, gallbladder adenoma presents as an enhancing intraluminal soft tissue mass or nodule that may be iso- or hypoattenuating relative to the liver [12].

CT is used to monitor patients following treatment for GB CA. After therapy, careful assessment should be made not only for evidence of residual disease, but also for any evidence of complications from therapy. A nonenhancing fluid collection may be seen at the resection margin after surgery (Fig. 18). This fluid collection usually decreases in size after 3–6 months but may never completely disappear. If a catheter is left in the surgical bed, small pockets of air may be present and not necessarily imply infection. Increasing amounts of fluid and gas, development of a thick rim of peripheral enhancement, and progressive stranding of the adjacent fat are signs of abscess formation (Fig. 19). Differentiating an abscess from a postoperative seroma or hematoma requires correlation with clinical suspicion and can be challenging during the perioperative period.

Normal postsurgical findings such as infiltration of the peritoneal fat in the operative bed and focal areas of fat necrosis should not be misinterpreted as recurrent disease. The degree of soft tissue attenuation that increases in size 3–6 months following surgery is concerning for peritoneal metastasis and needs to be followed closely on subsequent imaging studies (Fig. 20). Careful attention to the detection of soft tissue nodules at the resection margin in the liver, at the tract of previous drainage catheters, at the laparoscopic ports tracts, and at the abdominal wall wound is essential for the detection of residual disease and peritoneal metastasis (Fig. 21) [13].

Intrahepatic cholangiocarcinoma (ICC), also called peripheral cholangiocellular carcinoma, is a primary malignant tumor arising from intrahepatic bile duct epithelium. It is thought to arise from the secondary bile duct or proximal branches of the intrahepatic bile ducts. ICC accounts for 8 % of all cholangiocarcinomas [20]. The estimated annual incidence in the United States is 1 per 100,000 persons. ICC is the second most common intrahepatic primary liver cancer (7–10 %), with HCC being first [21]. Mixed tumors of cholangiocarcinoma and hepatocellular carcinoma components may be seen in approximately 2–6 % of primary malignant liver tumors, called combined HCC-ICC (cHCC-ICC) [22]. ICC occurs most commonly in the 6th and 7th decades with male-to-female predominance of 3:2. The incidence and age-adjusted mortality have increased in the last 3 decades [23]. The 5-year survival is <10 % and approaches 0 % when there are intrahepatic metastases. Surgery offers the best outcome [24]. The risk factors for ICC are shared with other cholangiocarcinomas [25].

The clinical symptoms of ICC are nonspecific. Patients can present with general malaise and discomfort, weight loss, abdominal pain, or nausea [26]. In contrast to ECC, jaundice due to biliary obstruction is not a common finding, and ICC typically presents with signs and symptoms associated with a large mass in the liver. On physical examination, an enlarged liver may be detected. In contrast to patients with HCC, patients do not present with ascites, cirrhosis, or portal hypertension. Some cases present with an incidental liver mass, and imaging studies or endoscopic evaluation are performed searching for a possible primary GI cancer.

Laboratory abnormalities include elevation of CA 19-9 and carcinoembryonic antigen (CEA); this is also seen in ECC [26]. The bilirubin level is usually normal. α-Fetoprotein (AFP), frequently elevated in patients with HCC, is usually normal in ICC. In combined tumors of HCC-ICC pathology, there will be elevated α-fetoprotein and modestly elevated CA19-9 versus elevation of AFP alone for HCC and CA19-9 for ICC [22].

Computed tomography plays a key role in the clinical evaluation of patients with ICC. The availability and short scan duration makes CT the main diagnostic tool in oncologic imaging, including patients with ICC. The CT protocol for a patient with a liver mass is a multiphasic examination. The liver protocol consists of pre-contrast and postcontrast images obtained during the late arterial, portal venous, and excretory phases of contrast administration. 150 ml of intravenous iodinated contrast is injected at a rate of 5 ml/s. SmartPrep^® (GE Healthcare, Milwaukee) is used for contrast bolus tracking, monitoring the aorta at the level of the celiac artery until 100 Hounsfield units is obtained; this takes roughly 20 s. Dynamic imaging through the liver in the late arterial phase is then obtained at 13 s postthreshold. Portal venous phase imaging is then obtained after 60 s, and delayed images through the liver are obtained at 90 s. The images are obtained at 5 mm and reconstructed at 2.5 mm for each phase of contrast administration.

There are three macroscopic presentations of ICC described by the Liver Cancer Study Group: mass-forming (MF), periductal-infiltrating (PD), and intraductal (ID) types [27]. A fourth group has been created to combine tumors that exhibit mixed characteristics, for example, MF + PD. The MF and the combination types are the most common (70 % of cases).

On the pre-contrast images, ICC presents as a large, hypoattenuating mass with lobular or irregular margins (Fig. 22a). During the late arterial phase of contrast administration, commonly there is minimal to no peripheral enhancement of the tumor (Fig. 22b). On the portal venous phase, the enhancement will continue in a centripetal fashion and continue to progress on the delayed and excretory phases of contrast (Fig. 22c). The delayed enhancement in ICC is due to the presence of a dense fibrous stroma, which retains contrast over time [28] (Fig. 22d). This enhancement pattern is distinct from other common liver malignancies such as, HCC or hypervascular metastases (e.g., neuroendocrine carcinoma). However, ICC can also present with arterial enhancement similar to other hypervascular tumors of the liver (Fig. 23). Associated findings include peripheral ill-defined calcification due to mucin production in 18 % and capsular retraction due to desmoplastic response (Fig. 24) [29, 30]. The differential diagnosis includes metastasis from the GI tract. Features that will suggest the diagnosis of ICC include a large single mass, the absence of a primary GI tumor, and the absence of multiple nodules.

The PD type accounts for approximately 15–20 % of cases [27, 31]. This tumor pattern presents as a proximal ductal dilation without a discrete mass or as periductal soft tissue in the noncontrast CT. On the arterial phase, minimal ductal wall or periductal soft tissue enhancement is observed [32]. In the portal venous phase, more intense enhancement is seen in the ductal wall and periductal soft tissues [27]. These tumors have a higher incidence of satellite nodules and also of nodal metastases. The differential diagnosis of this type includes benign strictures. The presence of portal vein obliteration and lymph node involvement is more suggestive of a malignant etiology.

The ID type of ICC accounts for approximately 5 % of cases [27, 31]. This pattern of ICC is considered similar to the intraductal papillary mucinous neoplasm (IPMN) of the pancreas and has the best prognosis [33]. On noncontrast CT, a dilated duct with or without a mass >1 cm can be seen. On the arterial and portal venous phases, a hypoattenuating mass or a hyperattenuating duct may be seen [34]. The differential diagnosis of a high-attenuation ID mass includes stone, tumor such as HCC or metastatic disease, or stricture with debris. ID HCC will usually have the typical pattern of HCC enhancement, being slightly less hypoattenuating on the noncontrast images and showing marked enhancement on arterial phase and washout on the portal venous images [35].

Mixed HCC and ICC tumors (cHCC-ICC) can present as large, solitary tumors with irregular margins [22]. The contrast enhancement pattern is dependent on the percentage of each tumor. An HCC pattern will present with intense arterial enhancement. It may be very difficult to predict prospectively whether the mass represents HCC or ICC. On noncontrast CT there is a large hypoattenuating tumor. During the arterial phase, the HCC portion will enhance avidly, while the ICC portion may stay hypodense. At the portal venous phase, the enhancing portion representing HCC will wash out and the portion representing ICC continues to enhance. On the delayed phase, the HCC component is hypoattenuating, and the ICC portion is homogeneously enhancing (Fig. 25).

Mass-forming ICC and cHCC-ICC are staged according to the AJCC hepatocellular carcinoma system [21, 36]. The discriminating factors for T-staging are tumor size, satellite nodules, vascular invasion, and extra-capsular extension. Any solitary tumor without vascular invasion, regardless of size, is classified as T1. A T2 tumor is defined as solitary tumors with vascular invasion or multiple tumors none larger than 5 cm. T3 tumors are classified as multiple masses larger than 5 cm or with major vascular invasion of a major branch of the portal or hepatic veins. A T4 lesion is defined as a tumor that demonstrates direct invasion to adjacent organs other than the GB or in the setting of perforation to the visceral peritoneum [37].

Similar to HCC, ICC has a propensity to encase and even invade branches of portal veins and hepatic arteries through direct extension [34] (Figs. 26, 27). There can be wedge-shaped enhancement of the liver surrounding the tumor due to arterial supply as a result of portal vein encasement [35] (Fig. 28). Biliary ductal dilation and gallbladder involvement due to direct extension of the tumor into the gallbladder fossa can also be seen (Figs. 29, 30).

Lymph node status is an important prognostic indicator. The radiologic evaluation of lymph nodes is based on size, morphology, and location. Helpful clues for metastatic lymph nodes include size >1 cm, low-density center due to necrosis, or delayed enhancement. Nodes located near the primary tumor are likely to be malignant, even if they measure <1 cm in minimum diameter. A round node is also more likely to be malignant than an oval node. CT has a high negative predictive value but a low positive predictive value for lymph node involvement [38].

Nodes along the hepatic hilum are a common site of central tumor spread. Central ICC typically spreads into the hepatoduodenal ligament first, and then into the para-aortic nodes, retropancreatic nodes, and common hepatic artery nodes, in that order. Diaphragmatic nodes in the anterior, posterior, or middle diaphragmatic nodal stations, as well as, para-cardiac and lesser curvature nodes may be considered as N1 nodes for ICC that are located near the dome and in the left lobe of the liver [39] (Fig. 31). The nodal disease defines N1 and N2 nodes as regional or distant nodal spread of disease, respectively. Examples of N1 are perihepatic, periportal, portocaval, and periceliac nodes (Figs. 32, 33). Common distant lymph node involvement includes mediastinum and retroperitoneal para-aortic nodes (Fig. 33).