Cholangiocarcinoma

Cholangiocarcinoma
Diagnosis in short
Cholangiocarcinoma. H&E stain.
Synonyms	bile duct carcinoma
LM	atypical cuboidal or columnar mucin producing cohesive cells (carcinoma) - usually gland forming (adenocarcinoma), classically with a dense fibrous (desmoplastic) stroma
LM DDx	metastatic carcinoma - esp. luminal GI tract, hepatocellular carcinoma
IHC	CK7 +ve, CK20 +ve/-ve, CK19 +ve, HepPar-1 -ve, AFP -ve, EMA +ve
Site	bile ducts (including pancreas, liver - see liver neoplasms)
Associated Dx	liver flukes (Clonorchis sinensis, Opisthorchis viverrini), Caroli disease, primary sclerosing cholangitis - esp. in ulcerative colitis
Signs	+/-jaundice
Prevalence	uncommon
Blood work	+/-findings of cholestasis
Prognosis	poor
Clin. DDx	other liver tumours - hepatocellular carcinoma, metastases
Treatment	surgical resection if possible

Cholangiocarcinoma is a malignant tumour that arise from the bile ducts and may been seen in the liver.

It is also known as bile duct carcinoma.

General

• Malignancy of the biliary tree.
• May be intrahepatic, i.e. intrahepatic cholangiocarcinoma (abbreviated ICC), or extrahepatic.

Epidemiology

• Rare - approximately 1/5 the incidence of HCC.
• More common among asians.

Risks:

• Infection - liver flukes (endemic to Southeast Asia):
  • Clonorchis sinensis (AKA Opisthorchis sinensis).
  • Opisthorchis viverrini.
• Caroli disease - rare congenital disease.
• Primary sclerosing cholangitis - may be assoc. with inflammatory bowel disease (IBD), esp. ulcerative colitis (UC).

Gross

• Classically one large mass - outline described as cauliflower-like.
  • May have satellite nodules.

Image

• 

  Cholangiocarcinoma. (WC)

Microscopic

Features:

• Usually an adenocarcinoma, i.e. gland forming with:
  • Cuboidal or columnar mucin producing cells, and
  • A dense fibrous (desmoplastic) stroma.

Notes:

• Biliary stents lead to reactive changes, these can be confused for malignancy. One must always check whether a biliary stent was in situ at time of biopsy.
• Usually abundant desmoplasia, ergo hard to get good, i.e. diagnositic, endoluminal brushing specimens.
• May have hyaline inclusions.

DDx:

• Metastatic adenocarcinoma.
  • Pancreatic adenocarcinoma.
• Fulminant hepatic necrosis.
  • Bile ducts usu. left behind... look like well-differentiated adenocarcinoma.
• Bile duct adenoma.
  • No necrosis, no mitotic activity, no significant nuclear pleomorphism.

Images

• 

  Cholangiocarcinoma - low mag. Shows the typical desmoplastic stroma. (WC/Nephron)

• 

  Cholangiocarcinoma - intermed. mag. (WC/Nephron)

• 

  Cholangiocarcinoma - high mag. Shows a normal portal triad adjacent to atypical glandular cells within the interlobular septum and obvious tumour. (WC/Nephron)

• 

  Cholangiocarcinoma - very high mag. (WC/Nephron)

Cholangiocarcinoma, intrahepatic, large duct type. Extremely unfortunate case arising in a pre-teenage girl. MRI showing multiple hepatic masses. Histologic images. A mass comprising often large ducts abuts uninvolved liver (Row 1 Left 40X). CK7 immunostain emphasizes large, often adjoining ducts (Row 1 Right 40X). Trichrome stain shows spread of tumor into scar with collagen deposition (Row 2 Left 100X). Reticulin stain emphasizes disorderly vertical and horizontal spread of bizarrely shaped acini (Row 2 Right 100X). PAS-D stain shows luminal mucin; note absence of red lining of outside of ducts seen in normal bile ducts/proliferating bile ductules (Row 3 Left 200X). Loss of polarity (varied orientation with respect to base of epithelium) and variable size and shape of nuclei are obvious (Row 3 Right 400X, high pixel image).

Cholangiocarcinoma, intrahepatic, small duct type. Middle aged man with jaundice. Small dark tumorous masses [arrows] irrupt scar (Row 1 Left 20X). Cribriforming (net like pattern) of gland in gland [arrow] without intervening stroma, which can be difficult to discern from reactive bile ducts at times (Row 1 Right 100X). A second focus shows, on the left, glands with disorderly spread, further explored, and in the middle, partly formed glands with necrosis, further explored, both diagnostic (Row 2 Left 100X). Note how some glands go up and down [red arrows] & others go right to left [black arrows] showing disorderly spread (Row 2 Right 400X). Note necrotic cell nuclei [red arrows] and incompletely formed glands [black arrows] (Row 4 Left 200X). Nuclear anaplasia is also able to be used for a definite diagnosis, but there is considerable nuclear variability in reactive bile duct proliferations, making it less facile than disorderly spread, incomplete glands, and necrotic nuclei (Row 3 Right 400X).

www:

• Cholangiocarcinoma & liver flukes - several images (upmc.edu).
• Cholangiocarcinoma - several images (upmc.edu).

IHC

Classic IHC pattern:

• CK7 +ve.
• CK20 +ve/-ve.
• HepPar-1 -ve.
• AFP -ve.

Others:

• CA125 +ve/-ve (30 +ve of 63 cases).

Note:

• MUC-1 is also known as EMA.

Hepatocellular carcinoma versus cholangiocarcinoma

ICC vs. HCC:

• ICC: CK19 (92.5%), MUC-1 (73.8%) +ve.
• HCC: HepPar-1 (85.6%), CD34 (87.8%) +ve.

HCC vs. ICC:

• TTF-1: ~90-100% +ve (cytoplasmic) in HCC vs. ~10% in cholangiocarcinoma.

Molecular

• Approx. 10% of the tumors carry a IDH-1 or IDH-2 hotspot mutation.
• FGFR2 gene fusions have been reported.

Sign out

MASS, PANCREAS, CORE BIOPSY:
- ADENOCARCINOMA, MODERATELY DIFFERENTIATED.

Note:

• On biopsy, it isn't possible to cleanly separate from pancreatic adenocarcinoma. Thus, it is better to stay vague.

Micro

The sections show an atypical gland-forming lesion (adenocarcinoma) in a fibrous background. This lesion is separate from the benign pancreatic glands that are present. The atypical glands are unequally spaced. Moderate-to-marked cytologic atypia is present. Mitotic activity is not readily apparent.

See also

• Liver neoplasms.