Intrahepatic cholangiocarcinoma: pathogenesis, current staging, and radiological findings
Authors: Mohammed Saleh, Mayur Virarkar, Vlad Bura, Raul Valenzuela, Sanaz Javadi, Janio Szklaruk & Priya Bhosale
Journal: Abdominal Radiology, 2020 May 16
DOI: 10.1007/s00261-020-02559-7
Dr. Adriana Mirela Călin-Vainak, ESGAR Social Media Advocate and member of the Education Committee, Affidea Cluj-Napoca/RO
Dr. Vlad Bura, 4th year radiology resident, University Hospital, Cluj-Napoca/RO
Cholangiocarcinoma, the second most common primary liver malignancy following hepatocellular carcinoma (HCC), represents approximately 3% of gastrointestinal tumors. It comprises a heterogeneous group of malignancies emerging anywhere between the canals of Hering to the main bile duct: intrahepatic-cholangiocarcinoma (ICC) – from proximal bile ducts to the hepatic duct bifurcation, and extrahepatic-cholangiocarcinoma (ECC) – from the bifurcation to the main bile duct. Although ICC’s comprise only 10-20% of cholangiocarcinomas, its incidence is rising as compared to ECCs, according to World Health Organization databases and other national registries.
Imaging plays an important role not only for diagnosis and staging of ICC, but also for management and treatment guidance. In this comprehensive article, the authors discuss epidemiology, genetics, pathogenesis, clinical presentation, multimodal imaging features, staging, treatment options and management of ICC.
The risk factors for ICC are not so well defined as for HCC. However, factors that promote malignant transformation of premalignant conditions (e.g. biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct) have been linked to ICC development: liver flukes, chronic biliary and liver diseases, and lifestyle-related aspects causing chronic inflammation and cholestasis.
The clinical picture is nonspecific – abdominal pain – leading to its late diagnosis and fatal outcome (5y-survival as low as 10%). Unlike ECC, ICC rarely causes jaundice and is often asymptomatic. More than 50% of ICCs are unresectable by the time of diagnosis. A fortunate situation is that of cirrhotic patients undergoing HCC-screening, when ICCs can be incidentally depicted.
ICC rarely causes alteration of liver function tests; thus, initial evaluation mostly relies on imaging alone. The use of CA 19-9 tumor marker (>100U/ml) may be a useful addition for the differential diagnosis of ICC, although its sensitivity and specificity vary among the available literature. It is more useful for radical resection assessment and treatment monitoring.
The role of different imaging modalities in diagnosis, staging and post-treatment follow-up of ICC is largely discussed within the review. As ICC causes nonspecific abdominal symptoms, it may be firstly evaluated by US, but US-features are non-specific. Except for small tumors, CEUS may help differentiate ICC from HCC, mostly based on arterial-phase hyperenhancement pattern (homogeneous for HCC, heterogeneous or peripheral rim for ICC). The most common imaging modality for detection, diagnosis and staging of ICC is CT. Typical behavior of ICC on CT includes: irregular margins, capsular retraction, early rim hyperenhancement (arterial phase) and delayed central enhancement (portal and delayed phases).
At MRI, the enhancement pattern of ICC most commonly resembles the one seen at CT. However, different enhancement patterns exist, carry different prognoses and are better depicted at MRI. Additionally, DWI target appearance of the tumor has a diagnostic sensitivity and specificity as high as 80% and 99%, respectively. MRI is also very helpful to determine treatment response in unresectable cases (post-radiotherapy/TACE): treatment-responsive tumors have not been showing significant size decrease, but rather continuous ADC increase on serial MRI. Due to higher spatial resolution, CT is the modality used for surgical planning – resectability is assessed with greater accuracy than at MRI. CT is also preferred for assessing distant metastasis – most commonly peritoneal, pulmonary and osseous. With the advantage of assessing tumors’ metabolic activity, PET-CT can be more accurate than CT for distant metastasis detection (including lymph node metastasis), possibly altering management for up to 25% of ICC patients.
A separate staging system for ICC was only introduced in 2010 within the 7th edition of the AJCC cancer staging manual, proving to be more prognosis-predictive than the previously used model, extrapolated from HCC patients’ analysis. The 8th edition of AJCC’s manual (2017), also has some additions reflecting prognostic value, briefly and clearly discussed.
Treatment options closely depend on imaging staging and are briefly reviewed. Post-treatment recurrence, a frequent complication of ICC, is usually evaluated using CT. Recurrent lesions often have the same imaging features as the pre-treatment tumor. When recurrent disease is difficult to discern from post-operative changes on CT, DWI-MRI can help. Post-operative changes exhibit higher ADC values, while low ADC indicates recurrence.
Diagnosis and management of patients with ICC represent a major challenge in oncology. This review is of valuable importance for abdominal radiologists and trainees, as appropriate imaging diagnosis and staging are crucial for treatment planning and management of ICC patients.
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Dr Vlad Bura is a 4th-year radiology resident at the County Clinical Emergency Hospital in Cluj-Napoca, Romania. His main fields of interest are abdominal and urogenital radiology, and more recently, pediatric radiology. He is an active ESGAR member and has attended Junior ESGAR Summer School in Portugal in 2018. Dr Bura has also been actively involved in clinical imaging research, and he has contributed as a co-author in projects leading to conference presentations, awards and publications. In 2019, he applied and participated in ESOR Visiting Scholarship Programme in Oncologic Imaging; he closely worked with doctors Evis Sala and Tristan Barrett from Addenbrooke's Hospital at Cambridge University, UK, where he recently got a position as a Clinical Research Fellow.
Comments may be sent to vlad.t.bura@gmail.com