Peripheral (Intrahepatic) Cholangiocarcinoma

Published on 20/07/2015 by admin

Filed under Radiology

Last modified 22/04/2025

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 Most common type of CCA

image Well circumscribed, large, with lobulated margins
image Multicentricity, especially around main tumor
• Periductal-infiltrating CCA

image Grows along bile ducts and is elongated, spiculated, or branch-like
• Progressive, gradual, and concentric filling (centripetal) on delayed phase images

image Usually not isodense to vessels (unlike hemangioma)
• Substantial delayed enhancement (i.e., greater than that of liver parenchyma) is common (74%)

image Attributed to fibrous stroma in CCA
• ± capsular retraction (frequent), with parenchymal atrophy of liver segments peripheral to tumor
• Bile ducts will be dilated upstream from tumor

image Duct lining may be thickened and enhanced
image Rare with other types of hepatic tumors

TOP DIFFERENTIAL DIAGNOSES

• Hepatic metastases and lymphoma
• Hepatocellular carcinoma
• Focal confluent fibrosis

PATHOLOGY

• Based on growth characteristics

image Mass forming (exophytic/nodular); most common form
image Periductal infiltrating (sclerosing)
image Intraductal growing (polypoid/papillary)

CLINICAL ISSUES

• Only minority of cholangiocarcinomas are peripheral type
• Large size at presentation contributes to poor prognosis
image
(Left) Intrahepatic cholangiocarcinomas generally arise in noncirrhotic livers. This gross photograph shows a white-tan, firm, and distinct mass in a background of noncirrhotic liver. (Courtesy M. Yeh, MD, PhD.)

image
(Right) Desmoplastic stroma is a common finding in intrahepatic cholangiocarcinoma. (Courtesy M. Yeh, MD, PhD.)
image
(Left) Axial CECT of a 46-year-old woman with jaundice shows the portal vein image and bile ducts image encased and obstructed by the tumor image, accounting for the altered perfusion of the right hepatic lobe. Hepatic veins were encased as well, resulting in collateral blood vessels seen within the right lobe image.

image
(Right) Axial 10-minute delayed CECT in the same patient shows heterogeneous, persistent enhancement of the tumor image, a feature of cholangiocarcinoma (and other tumors with fibrous stroma).

TERMINOLOGY

Abbreviations

• Cholangiocarcinoma (CCA)

Synonyms

• Cholangiocellular carcinoma, intrahepatic cholangiocarcinoma

Definitions

• CCA: Adenocarcinoma arising from bile duct epithelium (cholangiocytes)
• Peripheral CCA: Tumor arising from intrahepatic bile ducts

IMAGING

General Features

• Best diagnostic clue

image Infiltrative hepatic mass with capsular retraction and delayed persistent enhancement (CECT and MR)
• Location

image Originates from interlobular bile ducts (i.e., bile ducts distal to 2nd order branches)
• Size

image Usually large (> 5 cm) at diagnosis
• Morphology

image Peripheral CCA is usually a mass-forming tumor

– Often has “satellite” nodules
• Key concepts

image Mass-forming CCA: Well circumscribed, large, with lobulated margins

– Multicentricity, especially around main tumor
image Periductal-infiltrating CCA: Grows along bile ducts and is elongated, spiculated, or branch-like
image Intraductal-growing CCA: Small, sessile, or polypoid

– Often spreading superficially along mucosal surface and resulting in multiple tumors (papillomatosis) along various segments of bile ducts

CT Findings

• NECT

image Well-defined, predominantly homogeneous, hypodense mass

– Lobular margins
– Hypodense satellite nodules (65% of CCAs)
– Punctate, stippled, chunky calcifications (18% of CCAs)
• CECT

image Mass-forming PCC

– Thin or thick rim-like enhancement frequently seen around periphery of tumor on arterial phase images
– Progressive, gradual, and concentric filling (centripetal) on delayed phase images

image Usually not isodense to vessels (unlike hemangioma)
– Substantial delayed enhancement (i.e., > that of liver parenchyma) is common (74%)

image Attributed to fibrous stroma in CCA
– Homogeneous or heterogeneous hyperattenuating enhancement

image Entire mass may be enhanced only on delayed-phase images
image May be only evidence of tumor
– ± capsular retraction (frequent), with parenchymal atrophy of liver segments peripheral to tumor
image Bile ducts will be dilated upstream from tumor

– May not be evident in very peripheral CCA
– Duct lining may be thickened and enhanced

image Rare for hepatic metastases or other hepatic primary tumors

MR Findings

• T1WI

image Heterogeneous hypointense mass
• T2WI

image Hyperintense periphery (cellular tumor) + large central hypointensity (fibrosis)
image Hyperintense foci in center may represent necrosis, mucin
• T1WI C+

image Central hypointense areas exhibit homogeneous, heterogeneous, or no enhancement

– Regions of fibrosis display enhancement (delayed) while those of coagulative necrosis and mucin show no enhancement
image Dynamic MR: Minimal or moderate rim enhancement and progressive and concentric filling with contrast material

– Intratumoral fibrous stroma displays marked or prolonged enhancement on delayed phase scans
– Some cases of PCC exhibiting little fibrosis may show early enhancement on dynamic studies
• MRA

image Displacement or encasement of adjacent vessels

Ultrasonographic Findings

• Grayscale ultrasound

image Mass-forming PCC: Homogeneous or heterogeneous mass with irregular borders and “satellite” nodules

– Hyperechoic (75%); iso- &/or hypoechoic (14%) mass
image Intrahepatic bile ducts of involved hepatic segment may contain calculi or intraductal mass (echogenic): Mucin is echo free

Angiographic Findings

• Avascular, hypo- or hypervascular mass
• Stretched, encased arteries (frequent); neovascularity in 50%; venous invasion (rarely)

Nuclear Medicine Findings

• Cold lesion on sulfur colloid scans
• May show uptake on gallium scan

Other Modality Findings

• ERCP/percutaneous transhepatic cholangiography

image Periductal-infiltrating CCA: Lumen of bile duct may be completely obstructed or string-like, severely narrowed bile duct may be seen
image Intraductal CCA: Biliary tree is dilated (partial obstruction) diffusely, segmentally, or aneurysmally

Imaging Recommendations

• Best imaging tool

image Multiphasic CT or MR to include delayed images
• Protocol advice

image Delayed contrast-enhanced images, obtained 5-20 minutes after contrast injection

DIFFERENTIAL DIAGNOSIS

Hepatic Metastases and Lymphoma

• Hepatic colorectal metastases

image Metastatic adenocarcinoma histologically similar to PCC, can mimic mass-forming PCC on imaging
• Usually less capsular retraction and biliary obstruction with metastases

Hepatocellular Carcinoma (HCC)

• Hypervascular on arterial phase, washout on portal venous and delayed phase CT
• “Satellite” lesions, venous invasion, and regional lymphadenopathy are common

image Obstruction of intrahepatic bile ducts is uncommon with HCC

Fibrolamellar HCC

• Large, lobulated, heterogeneous mass with central scar
• Delayed partial enhancement of fibrous scar and septa
• Calcification (scar), lymphadenopathy are common
• Usually occurs in adolescents and young adults

Focal Confluent Fibrosis

• Wedge-shaped zone of fibrosis often seen in advanced cirrhotic liver
• Also associated with capsular retraction, but without biliary obstruction

PATHOLOGY

General Features

• Associated abnormalities

image Associated with several etiological factors: Primary sclerosing cholangitis, bile stasis, recurrent pyogenic cholangitis, clonorchiasis, choledochal cyst

Staging, Grading, & Classification

• Based on growth characteristics

image Mass forming (exophytic/nodular)
image Periductal infiltrating (sclerosing)
image Intraductal growing (polypoid/papillary)

Gross Pathologic & Surgical Features

• Large, firm, white tumor with dense fibrosis, irregular margins, and capsular retraction

Microscopic Features

• 90% are adenocarcinomas (well to moderately differentiated)
• Tendency to spread between hepatocyte plates, along duct walls, and adjacent to nerves
• Mucin production + desmoplastic, fibrous stroma are often abundant
• Most mass-forming PCCs are poorly differentiated; most periductal infiltrating are well differentiated; most intraductal are papillary adenocarcinomas

CLINICAL ISSUES

Presentation

• Most common signs/symptoms

image Abdominal pain (84%), weight loss (77%), painless jaundice (28%), palpable mass (18%), fatigue
image Presents as large mass because tumor does not cause clinical symptoms in its early stages
• Clinical profile

image Lab data: ↑ serum level of CA19-9

– Moderate anemia, leukocytosis, mild ↑ AST and ALT, ↑ carcinoembryonic antigen
image Diagnosis: Suggested by imaging, confirmed by biopsy

Demographics

• Age

image 50-60 years, rarely occurring < 40 years
• Gender

image No gender bias
• Epidemiology

image 8-13% of cholangiocarcinomas are peripheral type
image Comprises 10-20% of primary liver malignancies

Natural History & Prognosis

• Tumoral spread

image Local extension along duct
image Local infiltration of liver substance
image Metastases to regional lymph nodes, peritoneum
• Vascular or lymphatic invasion
• Perineural invasion
• Prognosis: Poor; < 20% resectable; 30% 5-year survival

Treatment

• Surgical resection remains primary treatment
• Palliative: Biliary catheter drainage, biliary stenting
• Adjuvant: Radiation and chemotherapy
• Liver transplantation (not considered appropriate in most cases, high recurrence)

DIAGNOSTIC CHECKLIST

Consider

• Hepatocellular-cholangiocarcinoma should be considered when hepatic tumor has features of both HCC and CCA
• Delayed tumoral contrast enhancement is typical but not specific feature of peripheral CCA

image Can be seen in other adenocarcinoma metastases and in confluent fibrosis

Image Interpretation Pearls

• In suspected cholangiocarcinoma (e.g., history of primary sclerosing cholangitis, or mass with capsular retraction, biliary obstruction) obtain delayed enhanced scans
image
(Left) Axial CECT in arterial phase of a 55-year-old woman with jaundice shows multifocal masses with continuous peripheral ring enhancement image.

image
(Right) The portal venous phase in the same patient shows little enhancement of the tumors image. The intrahepatic bile ducts are dilated image, and the left lobe of the liver is atrophic. Parenchymal atrophy of liver segments affected by peripheral cholangiocarcinoma is common and may be evident as lobar atrophy or capsular retraction.
image
(Left) Axial T1WI C+ MR in hepatic parenchymal phase shows a large but subtle, heterogeneous mass image. Capsular retraction image is also noted. This tumor showed persistent enhancement on 10-minute delayed images.

image
(Right) Axial T2WI MR shows mild hyperintensity within a hepatic mass image. Dilated intrahepatic ducts image are noted upstream from the mass. This is a typical feature of cholangiocarcinoma but may be seen with other tumors.
image
(Left) Axial CT in the arterial phase shows a large mass image with heterogeneous minimal enhancement. Hepatic capsular retraction image is a prominent feature of this cholangiocarcinoma.

image
(Right) Axial CT of the same patient shows heterogeneous enhancement on this portal venous phase image. Several “satellite” lesions were present (not shown). The intrahepatic bile ducts are dilated image, and there is marked retraction of the liver capsule image.
image
(Left) In an 80-year-old man with jaundice, axial CECT in the portal venous phase of enhancement shows a large mass image filling much of the right lobe of the liver. The mass obstructs central bile ducts, causing dilation of the peripheral intrahepatic ducts image.

image
(Right) In the same patient, the mass image encases the portal vein image. The delayed set of images (not shown) showed some persistent enhancement in some parts of the tumor and no washout.
image
(Left) Coronal reformatted CT of the same patient shows the mass image with dilation of intrahepatic bile ducts image. The CT findings are typical, but not diagnostic, of cholangiocarcinoma.

image
(Right) Coronal reformatted CT image of the same patient shows additional “satellite” tumor nodules image, a common feature of intrahepatic cholangiocarcinoma. The term “peripheral” cholangiocarcinoma seems to be a misnomer in cases such as this, but it implies that the tumor arose from intrahepatic bile ducts.
image
(Left) Axial T2WI FS MR of a 79-year-old woman with recurrent pyogenic cholangitis shows massive dilation of intrahepatic bile ducts image with stones and pus within the dependent ducts image. Marked ductal dilation plus lobar atrophy of the left lobe are caused by an obstructing mass image.

image
(Right) Axial contrast-enhanced T1WI MR section of the same patient shows the heterogeneously enhancing mass image and the intrahepatic ductal dilation. Cholangiocarcinoma was confirmed at left hepatic resection.
image
(Left) Axial NECT of a 67-year-old woman shows a homogeneous hypodense mass image with porta hepatic lymphadenopathy image.

image
(Right) Axial CECT image of the same patient shows heterogeneous enhancement of the mass, but not as having the nodular, peripheral pattern, isodense with blood vessels, which would have been characteristic of hemangioma.
image
(Left) CECT image of the same patient shows heterogeneous enhancement of the mass. The enlarged nodes image have the same enhancement pattern as the intrahepatic cholangiocarcinoma, indicating nodal metastases.

image
(Right) Axial CECT in delayed phase of the same patient shows foci of hyperdense persistent enhancement image, but the lesion does not fill in from the periphery as would be expected of a hemangioma.
image
(Left) Axial CECT in portal venous phase shows a heterogeneous infiltrative mass with intrahepatic biliary obstruction image and volume loss with capsular retraction image.

image
(Right) Axial CECT in the delayed phase of the same patient shows increased and persistent enhancement of the tumor image due to its fibrous stroma. Other tumor foci have the “target” pattern of enhancement image of other types of adenocarcinomas.
image
Axial CECT shows a heterogeneous infiltrative mass causing intrahepatic biliary obstruction.

image
Catheter cholangiogram shows long segmental stenosis of the left main bile duct with occlusion of multiple side branches and dilatation of the peripheral biliary ducts from intrahepatic cholangiocarcinoma.
image
Axial T1WI C+ GRE MR shows a large hepatic mass with ring-enhancing components image along with low-intensity, nonenhancing (fibrotic/necrotic) areas.
image
Axial T2WI MR scarcely shows a right hepatic lobe mass, although the absence of normal ducts and vessels within the mass is a clue.

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