Cholangiolocellular Carcinoma With "Ductal Plate Malformation" Pattern May Be Characterized by ARID1A Genetic Alterations.

Cholangiolocellular carcinoma (CLC) is a unique subtype of primary liver carcinoma, which sometimes coexists with hepatocellular carcinoma (HCC), cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma (cHCC-CCA). "Ductal plate malformation" (DPM)-pattern of primary liver carcinoma, which resembles biliary lesions in Caroli disease and von Meyenburg complex, is sometimes associated with CLC. We examined genetic alterations of hTERT promoter (hTERT), IDH1 or 2 (IDH1/2), KRAS, ARID1A, PBRM1, ARID2, BAP1, p53 and their association with histologic features such as proportion of CLC and DPM-pattern in 77 patients with primary liver carcinoma diagnosed as cHCC-CCA or CLC. Primary liver carcinomas were histologically subdivided into 29 CLC-predominant (CLC component >80%), 31 with CLC (5% to 80%) and 17 without CLC (<5%). CLC-predominant group was characterized by older age, male-predominant and smaller tumor size. Genetic alterations were detected in hTERT (25%), ARID1A (21%), PBRM1 (20%), ARID2 (3%), BAP1 (1%), p53 (46%), KRAS (5%), and IDH1/2 (8%). ARID1A alteration was more frequent in CLC-predominant group, compared with other groups (P<0.05) and was correlated with the degree of DPM-pattern (P<0.01). Alterations of hTERT and p53 were less frequent in CLC-predominant group compared with "with CLC group" (P<0.05). hTERT mutation was less frequent in carcinomas with DPM-pattern (P<0.01). PBRM1 alteration was more frequent in CLC with focal HCC subgroup and without CLC group compared with other groups (P<0.05). CLC may be a distinct subgroup of primary liver carcinoma, which is different from cHCC-CCA, based on clinicopathologic and genetic alterations. ARID1A alterations may characterize CLC with DPM-pattern and could be a diagnostic immunohistochemical marker for small CLCs with DPM-pattern.