The current classification of cholangiocarcinoma (CCA) may correlate with important histological and biochemical characteristics, according to a study recently published in the journal Expert Review of Molecular Diagnostics.

“In conclusion, a subclassification system on mucin production and immunohistochemical characterization is applicable in clinical practice, and the subtypes identified with this system present distinct clinicopathologic characteristics, prognostic outcomes, and FGFR2 rearrangements,” the authors wrote.

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This retrospective observational study included 106 patients previously diagnosed with intrahepatic CCA who also underwent surgical resection of the tumor in a single center in China. Most of the cases (n=61) were classified into the small duct category, followed by large (n=32), and intermediate (n=13) duct type. 

Regarding mucin production, 24 cases showcased diffuse mucin staining and 8 focal staining, all of which were from the large duct type. Moreover, S100P immunoreactivity was common among cases with large type CCA, with 18 cases scoring 4 points, 8 cases with 3 points, 5 cases with 2 points, and only 1 case with 1 point. 

Also, the large duct type exhibited higher levels of tumor markers in serum, increased vascular invasion, higher rates of lymph node metastasis, and, importantly, postoperative recurrence. 

Notably, unlike previous makers, cases that were positive for FGFR2 translocation rearrangement occurred exclusively in patients with small duct-type CCA. Similarly, IDH1/2 mutations were primarily present in small duct type cases.

These results become especially relevant when discussing treatment options. For example, pemigatinib, a drug that targets the FGFR2 rearrangement mutation, demonstrated excellent results, achieving tumor reduction in the 1 case that qualified for this drug. This, in turn, yields a valuable use for the CCA classification.

“Most importantly, we found that FGFR2 rearrangements only occurred in the small duct type ICC, which suggested that a substantial proportion of small type ICC might benefit from FGFR2-targeted treatment with pemigatinib,” the authors concluded.


Chen Y, Liu X, Huang L, et al. Clinicopathological, etiological, and molecular characteristics of intrahepatic cholangiocarcinoma subtypes classified by mucin production and immunohistochemical features. Expert Rev Mol Diagn. Published online April 23, 2022. doi:10.1080/14737159.2023.2205588