A literature review of cholangiocarcinoma (CCA) with a focus on diagnostic challenges, classification, genomic profiling, and targeted therapy has been recently published in the Archives of Pathology and Laboratory Medicine.
CCA often presents with nonspecific symptoms as well as alterations in liver function tests which are not specific and not suggestive of malignancy, and most patients are diagnosed with advanced disease, the researchers noted.
Read more about CCA diagnosis
The microscopic morphology of CCA can be quite varied, ranging from well-differentiated gland-forming tumors to poorly differentiated adenocarcinoma. Therefore, the differentiation between intraductal CCA and benign glandular proliferations can prove to be challenging in some cases.
Intrahepatic CCA is classified into 2 gross subtypes: small duct type and large duct type, which are difficult to distinguish from hepatocellular carcinoma and extrahepatic CCA, respectively.
The presence of overlapping histological characteristics can make it difficult to diagnose CCA; important differential diagnoses include reactive ductal proliferations, bile duct adenomas, and metastatic adenocarcinoma.
Furthermore, markers commonly expressed in other gastrointestinal malignancies, such as CA19-19, CK stains are also present in CCA. Therefore, clinical and radiological characteristics should be taken into account in a personalized manner when attempting diagnosis.
Although there are currently no reliable biomarkers for CCA diagnosis, recent research has shown that doublecortin-like kinase 1 (DCLK1) is doubled in the serum and could potentially serve as a biomarker for CCA diagnosis in the future. Despite its low specificity, CA19-9 can be used to support diagnosis in certain clinical settings.
The implementation of gene profiling studies in recent years has led to the identification of commonly altered genes in CCA, such as BRAF, BAP1, TP53, and FGFR2. Profiling has led to CCA classification into several molecular subtypes with potential therapeutic and prognostic implications, as they not only identify possible therapeutic targets but also aid in understanding resistance to treatment.
“Advances in knowledge of the CCA mutational landscape now place this tumor squarely within the growing group of neoplasms for which patient outcome may be improved by routine molecular profiling,” the authors wrote.
Based on the current evidence, the authors recommend the consideration of tumor genomic analysis for patients with CCA when possible.
Gopal P, Robert ME, Zhang X. Cholangiocarcinoma: pathologic and molecular classification in the era of Precision Medicine. Arch Pathol Lab Med. Published online June 19, 2023. doi:10.5858/arpa.2022-0537-ra