Cholangio

Carcinoma
4 MARET 2023
DEFINISI
Cholangiocarcinoma (CCA) : keganasan yang heterogen yang muncul di
sistem empedu.
CCA dibagi menjadi tiga subtipe berdasar lokasi anatomi asal :
intrahepatik (iCCA), perihilar(pCCA) dan distal (dCCA) CCA

CCA : keganasan hati primer kedua yang paling umum setelah karsinoma
hepatoseluler (HCC). Sekitar 15% dari semua tumor hati primer dan 3%
dari kanker gastrointestinal

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 . On the basis of the anatomical site of origin, cholangiocarcinoma (CCA) is classified into intrahepatic CCA (iCCA), perihilar CCA (pCCA)
and distal CCA (dCCA). iCCA is defined as a malignancy located in the periphery of the second-order bile ducts, pCCA arises in the right and/or
left hepatic duct and/or at their junction, and dCCA involves the common bile duct (that is, the choledochus). Grossly, CCA can show three main
patterns of growth: mass-forming, periductal-infiltrating, and intraductal-growing. Mass-forming CCA is a mass lesion in the hepatic
parenchyma. Periductal-infiltrating iCCA grows inside the duct wall and spreads longitudinally along the wall. Intraductal-growing CCA is a
polypoid or papillary tumour growing towards the duct lumen
Up-to-Date Pathologic Classification and Molecular Characteristics of Intrahepatic Cholangiocarcinoma. Front. Med. 9:857140
 EPIDEMIOLOGI
Kejadian bervariasi dari 85 per 100.000 di timur laut Thailand (tertinggi di dunia)
sampai 0,4 per 100.000 di Kanada.
Variasi kejadian  perbedaan faktor risiko lokal dan predisposisi genetik
Kematian CCA : Laki-laki > Wanita ; Negara di Asia > Negara barat.

Khon Kaen
city
NAture RevIewS | GASTROENTEROLOgy & HEPATOLOgy volume 17 | September 2020 |
NAture RevIewS | GASTROENTEROLOgy & HEPATOLOgy volume 17 | September 2020 |
FAKTOR RISIKO
Risk factor Study type OR or RR from selected studies
OR 26.71 for iCCA
Choledochal cyst Meta-analysis
OR 34.94 for eCCA
OR 10.08 for iCCA
Choledocholithiasis Meta-analysis
OR 18.58 for eCCA
OR 3.38 for iCCA
Cholelithiasis Meta-analysis
OR 5.92 for eCCA
OR 1.75 for iCCA
Cholecystolithiasis Meta-analysis
OR 2.94 for eCCA
OR 38 for iCCA
Caroli disease Population-based study
OR 97 for eCCA
OR 22 for iCCA
Primary sclerosing cholangitis Population-based study
OR 41 for eCCA
OR 15.32 for iCCA
Cirrhosis Meta-analysis
OR 3.82 for eCCA
OR 4.57 for iCCA
Chronic hepatitis B Meta-analysis
OR 2.11 for eCCA
NAture RevIewS | GASTROENTEROLOgy & HEPATOLOgy volume 17 | September 2020 |
FAKTOR RISIKO
Risk factor Study type OR or RR from selected studies
OR 4.28 for iCCA
Chronic hepatitis C Meta-analysis
OR 1.98 for eCCA
Haemochromatosis Population-based study OR 2.1 for iCCA
OR 2.68 for iCCA
Inflammatory bowel disease Meta-analysis
OR 2.37 for eCCA
OR 2.7 for iCCA
Chronic pancreatitis Population-based study
OR 6.6 for eCCA
Liver fluke (Opisthorchis
Meta-analysis OR 5 iCCA > eCCA
viverrini, Clonorchis sinensis)
Type 2 diabetes mellitus Meta-analysis OR 5 iCCA > eCCA
OR 2.2 for iCCA
Nonalcoholic fatty liver disease Meta-analysis
OR 1.5 for eCCA
OR 1.14 for iCCA
Obesity Meta-analysis
OR 1.2 for eCCA

NAture RevIewS | GASTROENTEROLOgy & HEPATOLOgy volume 17 | September 2020 |

FAKTOR RISIKO
Risk factor Study type OR or RR from selected studies
OR 1.10 for iCCA
Hypertension Meta-analysis
OR 1.21 for eCCA
OR 3.15 for iCCA
Alcohol consumption Meta-analysis
OR 1.75 for eCCA
OR 1.25 for iCCA
Cigarette smoking Meta-analysis
OR 1.69 for eCCA
Environmental toxins

Thorotrast (banned 1969) Retrospective study RR >300

1,2-Dichloropropane Retrospective study RR 15

OR 4.8 for iCCA
Asbestos Case–control study
OR 2.1 for eCCA
OR 1.1–1.7 for iCCA
Asbestos Case–control study
No association with eCCA

NAture RevIewS | GASTROENTEROLOgy & HEPATOLOgy volume 17 | September 2020 |

PATOLOGI CHOLANGIO
CARCINOMA
• CCA dapat didahului oleh lesi pra-invasif.
Biliary Intraepithelial Neoplasia (BIN)  invisible gross
Intraductal Papillary Neoplasm of the Bile Duct  grossly seen

• Secara histologis, mayoritas pCCA dan dCCA adalah adenokarsinoma

penghasil musin atau tumor papiler. Sedangkan iCCA memiliki
beberapa varian histologis.

Up-to-Date Pathologic Classification and Molecular Characteristics of Intrahepatic Cholangiocarcinoma. Front. Med. 9:857140
 PATOLOGI CHOLANGIO
CARCINOMA

Intraductal Papillary Neoplasm

of the Bile Duct  grossly seen

Intraductal Papillary Neoplasm of Bile Duct: Updated Clinicopathological

Characteristics and Molecular and Genetic Alterations. J. Clin. Med. 2020, 9, 3991
PATOLOGI CHOLANGIO
CARCINOMA
CCA merupakan tumor yang heterogen secara molekuler, sel asal
dan patogenesis
Secara gross : iCCA menunjukkan tiga pola pertumbuhan :
massforming, periductal-infiltrating, and intraductal growing.
pCCA dan dCCA : nodul tumor sclerosis atau tumor intraductal

Up-to-Date Pathologic Classification and Molecular Characteristics of Intrahepatic Cholangiocarcinoma. Front. Med. 9:857140
PATOLOGI CHOLANGIO
CARCINOMA

pCCA dan dCCA : nodul tumor sclerosis atau tumor intraductal

Surgical Case Reports volume 3, Article number: 110 (2017) Scientific Reports volume 8, Article number: 10826 (2018) 

 PATOLOGI CHOLANGIO
CARCINOMA
iCCA histological classification based on the size of the affected duct :

1. Small bile duct iCCA : a small-sized tubular or cuboid adenocarcinoma with

nodular growth invading the liver parenchyma, and with no or minimal mucin
production.

2. Large bile duct iCCA arises in large intrahepatic bile ducts and comprises
mucin-producing columnar tumour cells arranged in a large duct or papillary
architecture

Up-to-Date Pathologic Classification and Molecular Characteristics of Intrahepatic Cholangiocarcinoma. Front. Med. 9:857140
 GEJALA KLINIS CHOLANGIO
CARCINOMA
Awal penyakit : asymptomatic
Stadium lanjut : painless Jaundice terutama pada pCCA – dCCA. Sedangkan iCCA
lebih lambat jaundice,
Biliaryitchy (gatal
cancer: ESMOyang tidakPractice
Clinical membaik denganfor
Guidelines antihistamin)
diagnosis, treatment and follow-up
Klinis Abdomen : Tidak teraba massa, kecuali pada dCCA teraba gall bladder (hydrop)
Seringkali datang dengan cholangitis (demam, jaundice, nyeri perut, lekositosis)

Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
DIAGNOSIS CHOLANGIO
CARCINOMA
• Diagnosis pasti : Histopatology (Sulit). Tidak perlu pada pasien yang direncanakan operasi.
Histopatologi : ERCP biopsy (Spy glass), ERCP brush citology (sensitifitas 60%), EUS FNAB,
FNAB percutan
• Pencitraan : MRI atau CT Scan

• Tumor marker : Carbohydrate antigen (CA) 19-9 . CA19-9 meningkat pada 85% pasien
CholangioCa. Sensitivitas 40-70%, spesifisitas 50-80%

International Journal of Gastrointestinal Intervention 8(4):155-159

 Diagnosis Banding Cholangio Carcinoma
• Lesi jinak : IgG4 cholangiopathy

• iCCA harus dibedakan dari HCC dan tumor metastasis adenocarcinoma (kolon,
paru) dengan bantuan Imunohistokimia (IHK)

• iCCA mix HCC

Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
TATALAKSANA CHOLANGIO
CARCINOMA
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TERIMA
KASIH
4 MARET 2023