Hepatobiliary and Pancreatic: Hepatic mass discovered incidentally with telangiectasia.

Abstract

A 48-year-old woman with no history of alcohol use or medical history was referred to our hospital for abnormal endoscopic and liver sonography findings collected at another hospital. An gastric angiodysplasia (telangiectasia) on endoscopy and two suspicious liver echogenic masses in hepatic S4 and S6 were detected. Her laboratory tests, including liver function tests and tumor markers, were within the normal ranges and the viral markers were negative. Autoimmune antibodies related to autoimmune hepatitis were negative. As she had a severe allergic reaction to the computed tomography (CT) contrast agent, she underwent liver magnetic resonance imaging (MRI) for further evaluation. The liver MRI revealed dozens of hypervascular nodules of various sizes with a central scar and diffuse vascular abnormalities with peripheral vascular obliteration (Fig. 1a). She had experienced intermittent bleeding of the tongue and several telangiectasias were observed on her tongue (Fig. 1b). The differential diagnoses included hepatocellular adenoma and multiple focal nodular hyperplasia (FNH) syndrome with primary or secondary hepatic vascular abnormalities. Osler-Weber-Rendu disease (hereditary hemorrhagic telangiectasia [HHT]) was also possible considering the diffuse vascular abnormalities in the liver and the telangiectasia on the tongue. The pathology report based on the targeted liver biopsy described a hepatocellular nodular lesion composed of bland looking hepatocytes with sinusoidal dilatation and abnormal vessels, suggesting FNH or hepatocellular adenoma; however, immunohistochemical staining did not confirm either disease (Fig. 2). On the annual MRI follow up, innumerable hypervascular nodules, irregular heterogeneous enhancement of the liver (Fig. 3a), and diffuse vascular abnormalities with peripheral vascular obliteration (Fig. 3b) were the major findings, with no changes seen from the previous exam. Given that the pathology report did not definitively diagnose hepatocellular adenoma or multiple FNH syndrome, a hepatic vascular disorder such as HHT was considered in the differential diagnosis and genetic testing was performed. HHT is an autosomal dominant inherited disorder that affects the vasculature and is considered a rare disease, with a prevalence of 1 in 5000 or 1 in 10 000 births. The pathogenesis of HHT is a heterozygous mutation in the endoglin (ENG) gene or the activin receptor-like kinase type 1 gene, both of which are associated with the transforming growth factor-β superfamily signaling pathway, expressed mostly in the vascular endothelium. As 97% of patients with definite HHT carry a mutation in one of three genes, including ENG, a mutation in a locus mapped to chromosome 5, or an activin receptor-like kinase-1 (ACVRL1), we consulted the genetics department to evaluate the patient for HHT. HHT has traditionally been diagnosed based on clinical features (the Curacao criteria), but can now also be diagnosed by genetic testing. HHT is clinically suspected if two of the four Curacao criteria are met (family history of the disease, hemorrhage, telangiectasia, and visceral involvement) and definite if more than three of the criteria are met. The presence of intrahepatic shunts, disseminated intraparenchymal telangiectases, and other vascular lesions are the typical findings of hepatic involvement. In this patient, three (epistaxis, telangiectasia, and visceral involvement) of the four Curacao criteria were satisfied, leading to a definite diagnosis of HHT. Next-generation sequencing (NGS) panel performed also showed heterozygous mutation of the ACVRL1 (ALK1) gene, which is consistent with HHT type 2.