An Intrahepatic Cholangiocarcinoma with Focal Rhabdoid Features and SMARCA4-Deficiency.

Area of Science:

• Oncology
• Gastroenterology
• Genetics

Background:

• Intrahepatic cholangiocarcinoma (ICC) is a primary liver cancer with limited treatment options.
• Rhabdoid morphology in ICC is exceptionally rare, with minimal understanding of its underlying genetic alterations.
• Previous reports on ICC with rhabdoid features have not investigated genetic changes in the rhabdoid component.

Observation:

• A rare case of intrahepatic cholangiocarcinoma with focal rhabdoid features was identified in a Japanese male patient.
• The tumor exhibited heterogeneous morphology, including moderately differentiated adenocarcinoma, focal poorly differentiated adenocarcinoma, and an undifferentiated rhabdoid component.
• Immunohistochemistry revealed distinct staining patterns for keratin AE1/AE3 and vimentin in the rhabdoid cells.

Findings:

• SMARCA4-deficiency was detected in the poorly and undifferentiated components of the intrahepatic cholangiocarcinoma.
• BRG1/SMARCA4 was present in the differentiated tumor component but absent in the rhabdoid areas.
• Immunohistochemistry demonstrated an inclusion-like staining pattern for keratin and vimentin within the rhabdoid component.

Implications:

• This case highlights the morphological and genetic heterogeneity of intrahepatic cholangiocarcinoma.
• The identification of SMARCA4-deficiency in the rhabdoid component offers new insights into ICC pathogenesis.
• Findings may guide the development of targeted therapies for intrahepatic cholangiocarcinoma, particularly those targeting the SWItch/Sucrose NonFermentable (SWI/SNF) complex.