Genetic, Clinicopathological, and Radiological Features of Intrahepatic Cholangiocarcinoma with Ductal Plate Malformation Pattern - PubMed (original) (raw)
. 2022 Jul 15;16(4):613-624.
doi: 10.5009/gnl210174. Epub 2021 Nov 23.
Affiliations
- PMID: 34810298
- PMCID: PMC9289835
- DOI: 10.5009/gnl210174
Genetic, Clinicopathological, and Radiological Features of Intrahepatic Cholangiocarcinoma with Ductal Plate Malformation Pattern
Taek Chung et al. Gut Liver. 2022.
Abstract
Background/aims: Intrahepatic cholangiocarcinoma (iCCA) with a ductal plate malformation (DPM) pattern is a recently recognized rare variant. The genomic profile of iCCA with DPM pattern needs to be elucidated.
Methods: Cases of iCCA with DPM pattern were retrospectively reviewed based on the medical records, pathology slides, and magnetic resonance imaging (MRI) reports collected between 2010 to 2019 at a single center. Massive parallel sequencing was performed for >500 cancer-related genes.
Results: From a total of 175 iCCAs, five (2.9%) cases of iCCA with DPM pattern were identified. All cases were of the small duct type, and background liver revealed chronic B viral or alcoholic hepatitis. Three iCCAs with DPM pattern harbored MRI features favoring the diagnosis of hepatocellular carcinoma, whereas nonspecific imaging features were observed in two cases. All patients were alive without recurrence during an average follow-up period of 57 months. Sequencing data revealed 64 mutated genes in the five cases, among which FGFR and PTPRT were most frequently mutated (three cases each) including an FGFR-TNC fusion in one case. Mutations in ARID1A and CDKN2A were found in two cases, and mutations in TP53, BAP1, ATM, NF1, and STK11 were observed in one case each. No IDH1, KRAS, or PBRM1 mutations were found.
Conclusions: iCCAs with DPM pattern have different clinico-radio-pathologic and genetic characteristics compared to conventional iCCAs. Moreover, FGFR and ARID1A variants were identified. Altogether, these findings further suggest that iCCA with DPM pattern represents a specific subtype of small duct type iCCA.
Keywords: Cholangiocarcinoma; High-throughput nucleotide sequencing; Immunohistochemistry; Magnetic resonance imaging.
Conflict of interest statement
CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.
Figures
Fig. 1
Representative gadoxetic acid-enhanced magnetic resonance imaging (MRI) findings of two cases of intrahepatic cholangiocarcinoma with ductal plate malformation pattern. (A-F) Case no. 3, a 77-year-old female with hepatitis B virus-related chronic hepatitis showing imaging findings similar to hepatocellular carcinoma. A small hepatic lesion in liver segment 3 exhibited low-signal intensity in precontrast T1-weighted imaging (A), non-rim hyperenhancement in the arterial phase (B), and iso-signal intensity in the portal phase (C) and transitional phase (D) of gadoxetic acid-enhanced MRI. Peritumoral shunt was observed in the arterial phase and portal phase images (arrow). The lesion also showed hypo-signal intensity in the hepatobiliary phase (E) and hypersignal intensity in the T2 weighted image (F). Based on the imaging findings, the lesion could be categorized as LR-4 (probable hepatocellular carcinoma). (G-L) Case no. 5, a 60-year-old female with hepatitis B virus-related chronic hepatitis showing rim-like enhancement. A mass lesion of approximately 3 cm in liver segment 3 exhibited low-signal intensity in the precontrast T1-weighted imaging (G), rim-like hyperenhancement in the arterial phase (H), and hypo-signal intensity in the portal phase (I) and transitional phase (J) of gadoxetic acid-enhanced MRI. Peritumoral shunt was observed in the arterial phase image (arrows). The lesion also showed hypo-signal intensity in the hepatobiliary phase (K) and hypersignal intensity in the T2 weighted image (L). Due to rim-like arterial phase enhancement, the lesion was categorized as LR-M.
Fig. 2
Representative pathological features of intrahepatic cholangiocarcinoma (iCCA) with ductal plate malformation (DPM) pattern. (A) Representative gross image of an iCCA with predominant DPM pattern (case no. 1). The tumor mass had a yellow-tan solid appearance and was, relatively well-circumscribed without capsulation. (B,C) Microscopic images of iCCA with predominant DPM pattern (H&E; B, ×40 and C, ×100). (D-F) The tumor epithelial component was positive for N-cadherin (D), focally positive for neural cell adhesion molecule (E), and negative for S100 calcium-binding protein P (F) by immunohistochemical staining (×100). (G) Alcian blue staining showed absence of intra/extracellular mucin (×100). (H-K) Representative immunohistochemical staining images of CD4 (H), CD8 (I), FOXP3 (J), and CD163 (K) (H and I, ×40 and J and K, ×100). Right-upper side of the dotted lines of (H) and (I) indicate the tumor area.
Fig. 3
Somatic mutation profiles of five patients with intrahepatic cholangiocarcinoma (iCCA) with ductal plate malformation pattern. Distribution of the identified somatic mutations in 64 genes across the five iCCA cases. The list of genes is ordered by the frequency of the mutations according to cBioPortal (
) data regarding cholangiocarcinoma.
References
- WHO Classification of Tumours Editorial Board, author. Digestive system tumours. 5th ed. International Agency for Research on Cancer; Lyon: 2019. - DOI
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