Cholangiocarcinoma

Todd M. Blodgett, MD

Alex Ryan, MD

Omar Almusa, MD

Key Facts

Terminology

Malignancy that arises from ductular epithelium of intrahepatic biliary tree, extrahepatic bile ducts

Imaging Findings

PET: Hypermetabolic activity corresponding to primary tumor in liver, extrahepatic metastatic disease
Ultrasound (US), CT, MR: For hilar lesions (Klatskin tumor), bile duct obstruction with small central mass
Extrahepatic tumors (87-92% of CC): Proximal, middle, distal ductal tumors
PET for staging distant metastases; characterizing peripheral CC
Delayed enhancement with increasing attenuation seen in up to 74% of lesions, usually ↑ CT sensitivity/specificity
Hilar CC: Low FDG activity with focal nodular or linear branching pattern

Top Differential Diagnoses

Hepatocellular Carcinoma (HCC)
Primary Sclerosing Cholangitis (PSC)
Focal Nodular Hyperplasia (FNH)
Cavernous Hemangioma
Pancreatic Carcinoma

Clinical Issues

Obstructive jaundice (90%)

Diagnostic Checklist

Ability of PET to detect distant metastases alters surgical management (reportedly up to 30% of cases)
PET sensitivity for distant mets 65-70%
PET sensitivity for regional or hepatoduodenal mets is approximately 13%

Graphic shows a typical Klatskin tumor

, which is cholangiocarcinoma near the bifurcation of the main right and left intrahepatic bile ducts.

Coronal PET (A), axial CT (B) and fused PET/CT (C) show focal intense activity in the portacaval region

of this patient with a history of cholangiocarcinoma.

TERMINOLOGY

Abbreviations and Synonyms

Cholangiocarcinoma (CC), Klatskin tumor, malignant bile duct tumor

Definitions

Malignancy that arises from ductular epithelium of intrahepatic biliary tree and extrahepatic bile ducts
- Note: Gallbladder cancer 9x more common than CC
Klatskin tumor: Perihilar cholangiocarcinoma involving bifurcation of hepatic duct; accounts for more than 70% of all bile duct cancers

IMAGING FINDINGS

General Features

Best diagnostic clue
- PET: Hypermetabolic activity corresponding to primary tumor in liver, extrahepatic metastatic disease
- Ultrasound, CT, MR: Bile duct obstruction w/small central mass suggests hilar lesion (Klatskin tumor)
Location
- Extrahepatic tumors (87-92% of CC): Proximal, middle, distal ductal tumors
- Extrahepatic tumor at bifurcation of proximal common hepatic duct = Klatskin tumor
- Intrahepatic tumors (8-13% of CC) arise from small ducts
- Nodular or papillary type is most common in distal duct and periampullary region
- Intrahepatic tumors have tendency for perineural spread, but spread to liver, peritoneum, lung is extremely rare
- Extrahepatic tumors spread to celiac nodes in ˜ 16% of cases
Size
- Peripheral lesions are usually larger, measuring 5-20 cm at presentation
- More central lesions (Klatskin) smaller at diagnosis
Morphology
- Variable
- Most intrahepatic CC present as mass, whereas 90% of extrahepatic CC reveal diffusely infiltrating growth pattern

Imaging Recommendations

Best imaging tool
- CT: Staging regional/distant metastases; similar to US for demonstrating ductal dilation, large mass lesions
- MRCP/ERCP: Sensitivity of 71-81% for detecting tumor in malignant stenoses, particularly central lesions
- PET for staging distant metastases and characterizing peripheral CC
- ERCP with brush cytology, DNA analysis, and serum analysis of CA 19-9 and CEA for initial workup
  - Have been shown to increase sensitivity significantly
  - Diagnosis of CC, especially in primary sclerosing cholangitis (PSC), may remain uncertain until invasive and aggressive approaches such as exploratory laparotomy provide biopsy
Protocol advice
- Delayed PET imaging at ˜ 120 minute time point shown to better discriminate tumor from inflammation
- Delayed imaging helps differentiate tumor from background liver activity

CT Findings

NECT
- Mass predominantly hypoattenuating with irregular margins
- Intrahepatic biliary duct (IHBD) dilation common with obstruction
- Larger peripheral lesions may be isodense with central low attenuation and scarring
  - Central and satellite lesions
- Hilar masses often not visible on NECT
  - IHBD dilation = clue
- Capsular retraction may reveal intrahepatic tumor
- Large common duct (extrahepatic) masses may be identified on NECT
CECT
- Solitary, small, well-demarcated tumors are difficult to differentiate from primary hepatocellular carcinoma (HCC)
- Arterial phase: Peripheral CC seen as intrahepatic mass showing early peripheral rim enhancement and progressive patchy central enhancement
- Portal phase: Portal vein invasion, ductal wall thickening with minimal enhancement, and portal lymphadenopathy
- Delayed phase
  - Enhancement with increasing attenuation seen in up to 74% of lesions, usually ↑ CT sensitivity/specificity
  - Persistent tumor enhancement due to fibrous stroma
- Low reported sensitivity for small hilar lesions (approximately 50%)
- Regional lymph node spread rarely detected (24-40% of cases)

Nuclear Medicine Findings

FDG PET
- Primary uses
  - Identification of new lesions
  - Evaluation of metabolic activity and associated malignancy
  - Characterization of response to neoadjuvant therapy
  - Detection of lesions in liver that are not suspected on US or MR in up to 50% of patients
- Peripheral CC: Intensely hypermetabolic activity, may be ring-shaped
- Hilar CC: Low activity with focal nodular or linear branching pattern
  - Lower FDG uptake may be related to tumor size or arrangement of fibrous stroma and mucin pool in tumor
  - Can be difficult to discriminate between extrahepatic tumor itself and FDG-accumulating lymph nodes in perihilar region
  - Extrahepatic CC may have low uptake due to loosely connected cell nests and poor detection with PET due to infrequency of evident mass formation
- PET sensitivity
  - 61-90% for primary CC
  - 85% for nodular CC
  - 18% for infiltrating CC
  - 65-70% for distant metastases
  - Only 13% for regional or hepatoduodenal mets
- False negatives are seen with mucinous adenocarcinomas (rare)
- False positives are seen due to foci of inflammation (e.g., intrahepatic stone)
  - Uptake likely to be seen along tract of biliary stents
- Primary sclerosing cholangitis (PSC)
  - PET can be used to discriminate between PSC with and without CC
  - Not reliable for early diagnosis of CC in patients with PSC
  - Liver in patients with PSC may have ↑ background signal than those of healthy control patients
PET/CT
- Allows better identification of non-FDG avid tumors & carcinomatosis and helps distinguish stent-related uptake from malignant disease
- Shown to change oncological management in up to 17% of patients
- No diagnostic advantage over CECT in detection of intrahepatic CC or primary tumor site of extrahepatic CC
- Generally cost-effective method, avoids unnecessary surgery
Hepatobiliary scintigraphy: Focal photopenic lesion
Tc-99m sulfur colloid: Focal photopenic lesion
Ga-67 scintigraphy: Variable Ga-67 uptake