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Difference between revisions of "Cholangiocarcinoma"
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| LMDDx = [[metastatic carcinoma]] - esp. luminal GI tract, [[hepatocellular carcinoma]] | | LMDDx = [[metastatic carcinoma]] - esp. luminal GI tract, [[hepatocellular carcinoma]] | ||
| Stains = | | Stains = | ||
| IHC = CK7 +ve, CK20 +ve/-ve, CK19 +ve, HepPar-1 -ve, AFP -ve | | IHC = CK7 +ve, [[CK20]] +ve/-ve, [[CK19]] +ve, HepPar-1 -ve, [[AFP]] -ve, [[EMA]] +ve | ||
| EM = | | EM = | ||
| Molecular = | | Molecular = | ||
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==Gross== | ==Gross== | ||
*Classically one large mass - outline described as ''cauliflower-like''.<ref name=pmid18425077>{{Cite journal | last1 = Nakanishi | first1 = Y. | last2 = Zen | first2 = Y. | last3 = Kawakami | first3 = H. | last4 = Kubota | first4 = K. | last5 = Itoh | first5 = T. | last6 = Hirano | first6 = S. | last7 = Tanaka | first7 = E. | last8 = Nakanuma | first8 = Y. | last9 = Kondo | first9 = S. | title = Extrahepatic bile duct carcinoma with extensive intraepithelial spread: a clinicopathological study of 21 cases. | journal = Mod Pathol | volume = 21 | issue = 7 | pages = 807-16 | month = Jul | year = 2008 | doi = 10.1038/modpathol.2008.65 | PMID = 18425077 | URL = http://www.nature.com/modpathol/journal/v21/n7/full/modpathol200865a.html }}</ref> | *Classically one large mass - outline described as ''cauliflower-like''.<ref name=pmid18425077>{{Cite journal | last1 = Nakanishi | first1 = Y. | last2 = Zen | first2 = Y. | last3 = Kawakami | first3 = H. | last4 = Kubota | first4 = K. | last5 = Itoh | first5 = T. | last6 = Hirano | first6 = S. | last7 = Tanaka | first7 = E. | last8 = Nakanuma | first8 = Y. | last9 = Kondo | first9 = S. | title = Extrahepatic bile duct carcinoma with extensive intraepithelial spread: a clinicopathological study of 21 cases. | journal = Mod Pathol | volume = 21 | issue = 7 | pages = 807-16 | month = Jul | year = 2008 | doi = 10.1038/modpathol.2008.65 | PMID = 18425077 | URL = http://www.nature.com/modpathol/journal/v21/n7/full/modpathol200865a.html }}</ref> | ||
**May have satellite nodules. | **May have [[satellite nodules]]. | ||
===Image=== | ===Image=== | ||
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Image:Cholangiocarcinoma.png | Cholangiocarcinoma. (WC) | Image:Cholangiocarcinoma.png | Cholangiocarcinoma. (WC) | ||
</gallery> | </gallery> | ||
==Microscopic== | ==Microscopic== | ||
Features:<ref name=Ref_GLP609>{{Ref GLP|609}}</ref> | Features:<ref name=Ref_GLP609>{{Ref GLP|609}}</ref> | ||
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Image:Cholangiocarcinoma - very high mag.jpg | Cholangiocarcinoma - very high mag. (WC/Nephron) | Image:Cholangiocarcinoma - very high mag.jpg | Cholangiocarcinoma - very high mag. (WC/Nephron) | ||
</gallery> | </gallery> | ||
A [[File:1 CCA 1MRI.png| Cholangiocarcinoma, intrahepatic, large duct type.]] | |||
B [[File:2 CCA 1 680x512px.tif|Cholangiocarcinoma, intrahepatic, large duct type.]] | |||
<br> | |||
C [[File:3 CCA 1 680x512px.tif|Cholangiocarcinoma, intrahepatic, large duct type.]] | |||
D [[File:4 CCA 1 680x512px.tif|Cholangiocarcinoma, intrahepatic, large duct type.]] | |||
<br> | |||
E [[File:5 CCA 1 680x512px.tif|Cholangiocarcinoma, intrahepatic, large duct type.]] | |||
F [[File:6 CCA 1 680x512px.tif|Cholangiocarcinoma, intrahepatic, large duct type.]] | |||
<br> | |||
G [[File:7 CCA 1 1360x1024px.tif| Cholangiocarcinoma, intrahepatic, large duct type.]] | |||
Cholangiocarcinoma, intrahepatic, large duct type. Extremely unfortunate case arising in a pre-teenage girl. A. MRI showing multiple hepatic masses. B. A mass comprising often large ducts abuts uninvolved liver. C. CK7 immunostain emphasizes large, often adjoining ducts. D. Trichrome stain shows spread of tumor into scar with collagen deposition. E. Reticulin stain emphasizes disorderly vertical and horizontal spread of bizarrely shaped acini. F. PAS-D stain shows luminal mucin; note absence of red lining of outside of ducts seen in normal bile ducts/proliferating bile ductules. G. 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). | |||
A [[File:1 cholangio 2 680x512px.tif| Cholangiocarcinoma, intrahepatic, small duct type.]] | |||
B [[File:2 cholangio 2 680x512px.tif| Cholangiocarcinoma, intrahepatic, small duct type.]] | |||
<br> | |||
C [[File:3 cholangio 2 680x512px.tif|Cholangiocarcinoma, intrahepatic, small duct type.]] | |||
D [[File:4 cholangio 2 680x512px.tif|Cholangiocarcinoma, intrahepatic, small duct type.]] | |||
<br> | |||
E [[File:5 cholangio 2 680x512px.tif|Cholangiocarcinoma, intrahepatic, small duct type.]] | |||
F [[File:6 cholangio 2 680x512px.tif|Cholangiocarcinoma, intrahepatic, small duct type.]] | |||
Cholangiocarcinoma, intrahepatic, small duct type. Middle aged man with jaundice. A. Small dark tumorous masses [arrows] irrupt scar. B. Cribriforming (net like pattern) of gland in gland [arrow] without intervening stroma, which can be difficult to discern from reactive bile ducts at times. C. 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. D. Note how some glands go up and down [red arrows] & others go right to left [black arrows] showing disorderly spread. E. Note necrotic cell nuclei [red arrows] and incompletely formed glands [black arrows]. F. 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. | |||
A [[File:1 Cholangio 4 680x512px.tif| Cholangiocarcinoma with associated abscess]] | |||
B [[File:2 Cholangio 4 680x512px.tif| Cholangiocarcinoma with associated abscess]] | |||
<br> | |||
C [[File:3 Cholangio 4 680x512px.tif| Cholangiocarcinoma with associated abscess]] | |||
D [[File:4 Cholangio 4 680x512px.tif| Cholangiocarcinoma with associated abscess]] | |||
<br> | |||
E [[File:5 Cholangio 4 680x512px.tif| Cholangiocarcinoma with associated abscess]] | |||
F [[File:6 Cholangio 4 680x512px.tif| Cholangiocarcinoma with associated abscess]] | |||
Cholangiocarcinoma, intrahepatic, with associated abscess. A. Aberrant spaces (arrows) contrast with the scar to the regions left and, at right, hemosiderin laden macrophages amid granulation tissue . B. Disorderly spreading glands (black arrows) associated with atypical single cells (cyan arrows) have nuclei that contrast with those of the normal bile duct (blue arrow) with its associated artery (green arrow). C. PAS without diastase shows disorderly spreading, aberrantly shaped glands at left (arrows) and red degenerated hepatocytes to right. D. PAS with diastase shows proliferating bile ducts to left, one with highly aberrant nuclei (black arrow), highly atypical cells at middle (green arrows) with sometimes incomplete (cyan arrows) acini, and normal liver at right (blue arrow). E. CK7 immunostain shows proliferating glands at left and a disorderly spread of single cells and cell groups at right, amid hepatocytes. F. CK7 immunostain at higher power shows the stained cells have aberrant nuclei. | |||
A [[File: 6_16572554904132_sl 1.png|Cholangiocarcinoma, poorly differentiated]] | |||
B [[File: 6_16572554904132_sl 2.png|Cholangiocarcinoma, poorly differentiated]] | |||
<br> | |||
C [[File: 6_16572554904132_sl 3.png|Cholangiocarcinoma, poorly differentiated]] | |||
D [[File: 6_16572554904132_sl 4.png|Cholangiocarcinoma, poorly differentiated]] | |||
<br> | |||
E [[File: 6_16572554904132_sl 5.png|Cholangiocarcinoma, poorly differentiated]] | |||
Cholangiocarcinnoma, intrahepatic, in a 72 year old man, poorly differentiated. A. Multiple cancerous foci strew otherwise unremarkable liver. B. Low cuboidal glands fuse and spread, with desmoplasia (green arrows points to slightly blue sttroma) and indian files (blue arrows). C. Aberrant single cells and cell clusters are present, with very little apparent cytoplasm, with extremely variable nuclei, with black and sometimes bubbly chromatin. Note close approximation raising possibility of molding (arrows). D. A mucicarmine stain, even when negative, can highlight the epithelial grouping of the nuclei by virtue of the slightly pink stroma. E. CK7 immunostain shows mostly groups, but also demarcates isolated cancer cells amid scar. Tumor was negative for p40, CK20 CDX2, TTF1, PAX8. | |||
www: | www: | ||
*[http://path.upmc.edu/cases/case296.html Cholangiocarcinoma & liver flukes - several images (upmc.edu)]. | *[http://path.upmc.edu/cases/case296.html Cholangiocarcinoma & liver flukes - several images (upmc.edu)]. | ||
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==IHC== | ==IHC== | ||
Classic IHC pattern:<ref>{{Ref GLP|609}}</ref> | Classic IHC pattern:<ref>{{Ref GLP|609}}</ref> | ||
*CK7 +ve. | *[[CK7]] +ve. | ||
*CK20 +ve/-ve. | *[[CK20]] +ve/-ve. | ||
*HepPar-1 -ve. | *HepPar-1 -ve. | ||
*AFP -ve.<ref name=stc6dec2010>STC. 6 December 2010.</ref> | *[[AFP]] -ve.<ref name=stc6dec2010>STC. 6 December 2010.</ref> | ||
Others: | |||
*[[CA125]] +ve/-ve (30 +ve of 63 cases<ref name=pmid22286058>{{Cite journal | last1 = Higashi | first1 = M. | last2 = Yamada | first2 = N. | last3 = Yokoyama | first3 = S. | last4 = Kitamoto | first4 = S. | last5 = Tabata | first5 = K. | last6 = Koriyama | first6 = C. | last7 = Batra | first7 = SK. | last8 = Yonezawa | first8 = S. | title = Pathobiological implications of MUC16/CA125 expression in intrahepatic cholangiocarcinoma-mass forming type. | journal = Pathobiology | volume = 79 | issue = 2 | pages = 101-6 | month = | year = 2012 | doi = 10.1159/000335164 | PMID = 22286058 }}</ref>). | |||
Note: | |||
*''MUC-1'' is also known as ''[[EMA]]''. | |||
===Hepatocellular carcinoma versus cholangiocarcinoma=== | |||
ICC vs. HCC:<ref name=pmid19173916>[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.</ref> | ICC vs. HCC:<ref name=pmid19173916>[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.</ref> | ||
*ICC: CK19 (92.5%), MUC-1 (73.8%) +ve. | *ICC: [[CK19]] (92.5%), [[MUC-1]] (73.8%) +ve. | ||
*HCC: HepPar-1 (85.6%), CD34 (87.8%) +ve. | *HCC: HepPar-1 (85.6%), CD34 (87.8%) +ve. | ||
HCC vs. ICC:<ref name=pmid16627262>{{cite journal |author=Lei JY, Bourne PA, diSant'Agnese PA, Huang J |title=Cytoplasmic staining of TTF-1 in the differential diagnosis of hepatocellular carcinoma vs cholangiocarcinoma and metastatic carcinoma of the liver |journal=Am. J. Clin. Pathol. |volume=125 |issue=4 |pages=519–25 |year=2006 |month=April |pmid=16627262 |doi=10.1309/59TN-EFAL-UL5W-J94M |url=}}</ref> | HCC vs. ICC:<ref name=pmid16627262>{{cite journal |author=Lei JY, Bourne PA, diSant'Agnese PA, Huang J |title=Cytoplasmic staining of TTF-1 in the differential diagnosis of hepatocellular carcinoma vs cholangiocarcinoma and metastatic carcinoma of the liver |journal=Am. J. Clin. Pathol. |volume=125 |issue=4 |pages=519–25 |year=2006 |month=April |pmid=16627262 |doi=10.1309/59TN-EFAL-UL5W-J94M |url=}}</ref> | ||
*TTF-1: ~90-100% +ve (cytoplasmic) in HCC vs. ~10% in cholangiocarcinoma. | *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.<ref>{{Cite journal | last1 = Wang | first1 = P. | last2 = Dong | first2 = Q. | last3 = Zhang | first3 = C. | last4 = Kuan | first4 = PF. | last5 = Liu | first5 = Y. | last6 = Jeck | first6 = WR. | last7 = Andersen | first7 = JB. | last8 = Jiang | first8 = W. | last9 = Savich | first9 = GL. | title = Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas. | journal = Oncogene | volume = 32 | issue = 25 | pages = 3091-100 | month = Jun | year = 2013 | doi = 10.1038/onc.2012.315 | PMID = 22824796 }}</ref> | |||
*FGFR2 gene fusions have been reported.<ref>{{Cite journal | last1 = Wu | first1 = YM. | last2 = Su | first2 = F. | last3 = Kalyana-Sundaram | first3 = S. | last4 = Khazanov | first4 = N. | last5 = Ateeq | first5 = B. | last6 = Cao | first6 = X. | last7 = Lonigro | first7 = RJ. | last8 = Vats | first8 = P. | last9 = Wang | first9 = R. | title = Identification of targetable FGFR gene fusions in diverse cancers. | journal = Cancer Discov | volume = 3 | issue = 6 | pages = 636-47 | month = Jun | year = 2013 | doi = 10.1158/2159-8290.CD-13-0050 | PMID = 23558953 }}</ref> | |||
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