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.[1]
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.[2]
- More common among asians.
Risks:
- Infection - liver flukes (endemic to Southeast Asia):
- Caroli disease - rare congenital disease.[6]
- 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.[7]
- May have satellite nodules.
Image
Cholangiocarcinoma. (WC)
Microscopic
Features:[8]
- 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,[9] these can be confused for malignancy. One must always check whether a biliary stent was in situ at time of biopsy.[10]
- Usually abundant desmoplasia, ergo hard to get good, i.e. diagnositic, endoluminal brushing specimens.[11]
- May have hyaline inclusions.[12]
DDx:
- Metastatic 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:[13]
Others:
Note:
- MUC-1 is also known as EMA.
Hepatocellular carcinoma versus cholangiocarcinoma
ICC vs. HCC:[15]
HCC vs. ICC:[16]
- 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.[17]
- FGFR2 gene fusions have been reported.[18]
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
References
- ↑ URL: http://www.cancer.org/cancer/bileductcancer/detailedguide/bile-duct-cancer-what-is-bile-duct-cancer. Access on: 23 May 2013.
- ↑ Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 608. ISBN 978-0443066573.
- ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 926. ISBN 0-7216-0187-1.
- ↑ Park, do H.; Son, HY. (Apr 2008). "Images in clinical medicine. Clonorchis sinensis.". N Engl J Med 358 (16): e18. doi:10.1056/NEJMicm054461. PMID 18420495.
- ↑ de Martel C, Plummer M, Franceschi S (March 2010). "Cholangiocarcinoma: Descriptive epidemiology and risk factors". Gastroenterol Clin Biol. doi:10.1016/j.gcb.2010.01.008. PMID 20202771.
- ↑ Ananthakrishnan AN, Saeian K (April 2007). "Caroli's disease: identification and treatment strategy". Curr Gastroenterol Rep 9 (2): 151–5. PMID 17418061.
- ↑ Nakanishi, Y.; Zen, Y.; Kawakami, H.; Kubota, K.; Itoh, T.; Hirano, S.; Tanaka, E.; Nakanuma, Y. et al. (Jul 2008). "Extrahepatic bile duct carcinoma with extensive intraepithelial spread: a clinicopathological study of 21 cases.". Mod Pathol 21 (7): 807-16. doi:10.1038/modpathol.2008.65. PMID 18425077.
- ↑ Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 609. ISBN 978-0443066573.
- ↑ Carrasco, CH; Wallace, S; Charnsangavej, C; Richli, W; Wright, KC; Fanning, T; Gianturco, C (Dec 1985). "Expandable biliary endoprosthesis: an experimental study.". AJR Am J Roentgenol 145 (6): 1279-81. PMID 3877438.
- ↑ STC. 2 October 2009.
- ↑ 11.0 11.1 STC. 6 December 2010.
- ↑ Aishima, S.; Fujita, N.; Mano, Y.; Iguchi, T.; Taketomi, A.; Maehara, Y.; Oda, Y.; Tsuneyoshi, M. (Sep 2010). "p62+ Hyaline inclusions in intrahepatic cholangiocarcinoma associated with viral hepatitis or alcoholic liver disease.". Am J Clin Pathol 134 (3): 457-65. doi:10.1309/AJCP53YVVJCNDZIR. PMID 20716803.
- ↑ Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 609. ISBN 978-0443066573.
- ↑ Higashi, M.; Yamada, N.; Yokoyama, S.; Kitamoto, S.; Tabata, K.; Koriyama, C.; Batra, SK.; Yonezawa, S. (2012). "Pathobiological implications of MUC16/CA125 expression in intrahepatic cholangiocarcinoma-mass forming type.". Pathobiology 79 (2): 101-6. doi:10.1159/000335164. PMID 22286058.
- ↑ [Evaluation of immunohistochemical markers for differential diagnosis of hepatocellular carcinoma from intrahepatic cholangiocarcinoma] Dong H, Cong WL, Zhu ZZ, Wang B, Xian ZH, Yu H. Zhonghua Zhong Liu Za Zhi. 2008 Sep;30(9):702-5. Chinese. PMID 19173916.
- ↑ Lei JY, Bourne PA, diSant'Agnese PA, Huang J (April 2006). "Cytoplasmic staining of TTF-1 in the differential diagnosis of hepatocellular carcinoma vs cholangiocarcinoma and metastatic carcinoma of the liver". Am. J. Clin. Pathol. 125 (4): 519–25. doi:10.1309/59TN-EFAL-UL5W-J94M. PMID 16627262.
- ↑ Wang, P.; Dong, Q.; Zhang, C.; Kuan, PF.; Liu, Y.; Jeck, WR.; Andersen, JB.; Jiang, W. et al. (Jun 2013). "Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas.". Oncogene 32 (25): 3091-100. doi:10.1038/onc.2012.315. PMID 22824796.
- ↑ Wu, YM.; Su, F.; Kalyana-Sundaram, S.; Khazanov, N.; Ateeq, B.; Cao, X.; Lonigro, RJ.; Vats, P. et al. (Jun 2013). "Identification of targetable FGFR gene fusions in diverse cancers.". Cancer Discov 3 (6): 636-47. doi:10.1158/2159-8290.CD-13-0050. PMID 23558953.