Clinicopathological, radiologic, and molecular study of 23 combined hepatocellular-cholangiocarcinomas with stem cell features, cholangiolocellular type

cHCC‐CCA: Consensus terminology for primary liver carcinomas with both hepatocytic and cholangiocytic differentation

“…Whether intermediate cell carcinoma and CLC are best categorized within cHCC‐CCA, or as unique and separate entities, has yet to be fully determined. However, it is now recognized that stem/progenitor cell features and desmoplastic stromal alterations may be detected in many PLCs; thus, these features are no longer considered characteristic of unique, specific diagnostic subtypes of cHCC‐CCA.…”

“…With the promises of advances in the molecular biology of PLCs, and the development of more specialized therapeutics on the horizon, standardized nomenclature is critical for appropriate clinical-radiological-molecularpathological correlations. Thus, an international group of hepatic pathologists, radiologists, surgeons, and clinicians previously published in this area have worked to formulate proposed nomenclature for these heterogeneous carcinomas with the goals of (1) creating uniformity of histological approach for diagnostic and research purposes and (2) (10)(11)(12) has yet to be fully determined. However, it is now recognized that stem/progenitor cell features and desmoplastic stromal alterations may be detected in many PLCs; thus, these features are no longer considered characteristic of unique, specific diagnostic subtypes of cHCC-CCA.…”

A Review on the Update of Combined Hepatocellular Cholangiocarcinoma

“…27,29 In addition, CLC has a better prognosis than iCCA. 29,31 Therefore, CLC should be recognized as being different from HCC or iCCA. As of the 5th WHO classification, CLC is categorized as either cHCC-CCA or smallduct iCCA based on the presence of hepatocytic differentiation: if hepatocytic differentiation is present in CLC, it is categorized as cHCC-CCA.…”

“…Just as the histological aspects in cHCC-CCA vary, so does the molecular profile. 31,32,34,[36][37][38][39][40][41][42] Previous studies found that the genetics of cHCC-CCA were closer to iCCA than HCC. 42 However, the recent study performed by Joseph et al showed that the genetics of cHCC-CCA, classical type, are distinct from iCCA but similar to HCC, for example, alterations in TERT, TP53, cell cycle genes (CCND1, CCNE1, CDKN2A), receptor tyrosine kinase/Ras/PI3-kinase pathway genes (MET, ERBB2, KRAS, PTEN).…”

Intrahepatic cholangiocarcinoma: review and update

“…In the cirrhotic liver it was demonstrated that by contrast, enhanced MRI iCCAs showed constantly a lack of HCC hallmarks; however, by CT, this occurs only in large nodules (> 3 cm) [124][125][126] . Although, the HCC diagnosis belong from the demonstration of the typical contrast agent uptake, the identification of HCC with stem cell features (CK19+-HCC), combined HCC-CCA, cholangiolocellular carcinoma and bile duct mixed type iCCA, by imaging procedures, still remains an unsolved challenge [3,4,10,123,127,128] . Biopsy is, therefore, necessary after excluding HCC in cirrhosis, or in the context of a nodule in non-cirrhotic liver [3,129] .…”