Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jun 28;14(13):3156.
doi: 10.3390/cancers14133156.

Integrative Analysis of Intrahepatic Cholangiocarcinoma Subtypes for Improved Patient Stratification: Clinical, Pathological, and Radiological Considerations

Tiemo S Gerber  1 , Lukas Müller  2 , Fabian Bartsch  3 , Lisa-Katharina Gröger  3 , Mario Schindeldecker  1   4 , Dirk A Ridder  1 , Benjamin Goeppert  5 , Markus Möhler  6 , Christoph Dueber  2 , Hauke Lang  3 , Wilfried Roth  1 , Roman Kloeckner  2 , Beate K Straub  1
Affiliations

Integrative Analysis of Intrahepatic Cholangiocarcinoma Subtypes for Improved Patient Stratification: Clinical, Pathological, and Radiological Considerations

Tiemo S Gerber et al. Cancers (Basel). .

Abstract

Intrahepatic cholangiocarcinomas (iCCAs) may be subdivided into large and small duct types that differ in etiology, molecular alterations, therapy, and prognosis. Therefore, the optimal iCCA subtyping is crucial for the best possible patient outcome. In our study, we analyzed 148 small and 84 large duct iCCAs regarding their clinical, radiological, histological, and immunohistochemical features. Only 8% of small duct iCCAs, but 27% of large duct iCCAs, presented with initial jaundice. Ductal tumor growth pattern and biliary obstruction were significant radiological findings in 33% and 48% of large duct iCCAs, respectively. Biliary epithelial neoplasia and intraductal papillary neoplasms of the bile duct were detected exclusively in large duct type iCCAs. Other distinctive histological features were mucin formation and periductal-infiltrating growth pattern. Immunohistochemical staining against CK20, CA19-9, EMA, CD56, N-cadherin, and CRP could help distinguish between the subtypes. To summarize, correct subtyping of iCCA requires an interplay of several factors. While the diagnosis of a precursor lesion, evidence of mucin, or a periductal-infiltrating growth pattern indicates the diagnosis of a large duct type, in their absence, several other criteria of diagnosis need to be combined.

Keywords: adenocarcinoma; diagnostic imaging; large duct type; liver cancer; small duct type; subtyping.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure A1
Figure A1
Depicted are Venn’s diagrams of histological growth patterns of (a) small and (b) large duct type iCCA [45].
Figure 1
Figure 1
Radiological features of iCCAs. We differentiated two types of growth patterns: (A) mass-forming and (B) ductal-growing (in this case with an inserted biliary drainage). (C) Obstruction of bile ducts. Contrast agent behavior in the late arterial phase: (D) hypodense; (E) rim-enhanced; (F) hyperdense.
Figure 2
Figure 2
Histological distinction features of iCCA. (A) Adenocarcinoma forming solid sheets; (B) with cuboidal cells; (C) Infiltrative glands composed of prismatic cells. Different histological growth patterns of iCCA showing (D) a mass-forming (MF) tumor, (E) a tumor showing intraductal growth (IG), and (F) a tumor with periductal-infiltrating growth. Note the adjacent inconspicuous biliary epithelium (inlay; (E,F)). (G) Biliary intraepithelial neoplasia of low-grade and (H), 200X magnification) high-grade; (I) intraductal papillary neoplasm of the bile ducts. Different amounts of mucin: (J) little mucin with PAS-positivity showing in the inlaid picture; (K) moderate and (L) extensive amounts of mucin. (M) Lymphangioinvasion and (N) lymph node metastasis. (O) Perineural invasion.
Figure 3
Figure 3
Overall survival of patients according to different iCCA subtypes.
See this image and copyright information in PMC

References

    1. Bertuccio P., Malvezzi M., Carioli G., Hashim D., Boffetta P., El-Serag H.B., La Vecchia C., Negri E. Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma. J. Hepatol. 2019;71:104–114. doi: 10.1016/j.jhep.2019.03.013. - DOI - PubMed
    1. Rizvi S., Khan S.A., Hallemeier C.L., Kelley R.K., Gores G.J. Cholangiocarcinoma—Evolving concepts and therapeutic strategies. Nat. Rev. Clin. Oncol. 2018;15:95–111. doi: 10.1038/nrclinonc.2017.157. - DOI - PMC - PubMed
    1. Xing H., Tan B., Yang C., Zhang M. Incidence Trend and Competing Risk Analysis of Patients with Intrahepatic Cholangiocarcinoma: A Population-Based Study. Front. Med. 2022;9:846276. doi: 10.3389/fmed.2022.846276. - DOI - PMC - PubMed
    1. Lamarca A., Palmer D.H., Wasan H.S., Ross P.J., Ma Y.T., Arora A., Falk S., Gillmore R., Wadsley J., Patel K. ABC-06|A randomised phase III, multi-centre, open-label study of active symptom control (ASC) alone or ASC with oxaliplatin/5-FU chemotherapy (ASC + mFOLFOX) for patients (pts) with locally advanced/metastatic biliary tract cancers (ABC) previously-treated with cisplatin/gemcitabine (CisGem) chemotherapy. J. Clin. Oncol. 2019;37
    1. Massironi S., Pilla L., Elvevi A., Longarini R., Rossi R.E., Bidoli P., Invernizzi P. New and Emerging Systemic Therapeutic Options for Advanced Cholangiocarcinoma. Cells. 2020;9:688. doi: 10.3390/cells9030688. - DOI - PMC - PubMed

LinkOut - more resources