Purpose: Univentricular heart is corrected with the Fontan procedure (FP). In the long term, so-called Fontan-associated liver diseases (FALDs) can develop. The aim of this study is to analyze the molecular profile of FALDs. Methods: FALDs between January 1990 and December 2022 were reviewed for histology and immunohistochemistry, laboratory data, and images. Targeted next generation sequencing (NGS), performed on the DNA and RNA of both neoplastic and non-lesional liver tissue, was applied. Results: A total of 31/208 nodules > 1 cm in diameter were identified on imaging, but a liver biopsy was available for five patient demonstrating the following: one hepatocellular adenoma (HA), two hepatocellular carcinomas (HCCs), one fibrolamellar carcinoma (FLC), and one intrahepatic cholangiocarcinoma (ICC). Molecular analysis showed a copy number alteration involvingFGFR3in three cases (two HCCs and one ICC) as well as one HCC with a hotspot mutation on theCTNNB1andNRASgenes. Tumor mutational burden ranged from low to intermediate. A variant of uncertain significance inGNASwas present in two HCCs and in one ICC. The same molecular profile was observed in a non-lesional liver. ADNAJB1-PRKACAfusion was detected only in one FLC. Conclusions: Neoplastic FALDs show some unusual molecular profiles compared with non-Fontan ones. The presence of the same alterations in non-lesional cardiac cirrhosis could contribute to the development of FALD.
目的：单心室心脏病通过Fontan手术（FP）进行矫正。长期来看，可能发展为所谓的Fontan相关性肝病（FALDs）。本研究旨在分析FALDs的分子特征。方法：回顾分析了1990年1月至2022年12月期间FALDs的组织学、免疫组化、实验室数据和影像学资料。对肿瘤性和非病变肝组织的DNA和RNA进行了靶向下一代测序（NGS）。结果：影像学检查共发现31/208个直径大于1厘米的结节，但仅对五名患者进行了肝活检，结果显示：一例肝细胞腺瘤（HA）、两例肝细胞癌（HCCs）、一例纤维板层癌（FLC）和一例肝内胆管癌（ICC）。分子分析显示，三例（两例HCC和一例ICC）存在涉及FGFR3的拷贝数变异，另有一例HCC在CTNNB1和NRAS基因上存在热点突变。肿瘤突变负荷从低到中等不等。两例HCC和一例ICC中存在GNAS意义未明变异。在非病变肝脏中也观察到了相同的分子特征。仅在FLC中检测到DNAJB1-PRKACA融合。结论：与非Fontan相关肝病相比，肿瘤性FALDs显示出一些不寻常的分子特征。非病变性心源性肝硬化中存在相同变异可能促进了FALD的发生发展。
肿瘤(癌症)患者之家