Dynamic insights: prenatal ultrasound diagnosis and evolutionary patterns of bile duct hamartoma

Introduction

Bile duct hamartoma (BDH), also known as von Meyenburg complex (VMC), has a rare pathology characterized by benign biliary malformations originating from small intrahepatic bile ducts. Due to their asymptomatic clinical course, which often goes unnoticed during radiological or surgical procedures, these lesions are typically discovered incidentally during autopsy or laparotomy (1). BDH is primarily documented in adults, and to date, there appears to have been no prenatal reports on this condition. This study sought to address this gap in the literature by presenting the first exploration of dynamic changes in BDH findings through ultrasound (US) imaging, spanning from the fetal stage to birth. This novel investigation provides valuable insights into the prenatal manifestation and evolution of BDH, contributing to a comprehensive understanding of its developmental trajectory.

Case presentation

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s next of kin for publication of the details of their medical case and any accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

A 30-year-old female was referred to our institution at 22 weeks of gestation following the identification of multiple calcifications in the fetal abdominal region. Numerous hyperechoic dot-like formations were observed to be distributed uniformly throughout the liver with comet-tail echoes, creating a distinctive “starry sky” configuration (Video 1), and along the vascular structure as shown by color Doppler imaging (Video 2). Notably, there were no indications of biliary dilatations or focal liver lesions. Subsequent US examinations at 25 weeks of gestation revealed the presence of multiple hyperechoic dot-like formations with branching patterns (Figure 1A). Weekly US monitoring conducted in the three weeks preceding delivery revealed a gradual reduction in the number of hyperechoic spots, which became scattered and smaller in size (Figure 1B-1D). Nuchal translucency thickness was normal at 12 weeks of gestation. Fetal karyotyping and chromosomal microarray analysis (Affymetrix 750K; Thermo Fisher Scientific, Santa Clara, CA, USA) were performed and yielded normal results at 18 weeks of gestation. The toxoplasma gondii, rubella, cytomegalovirus, and herpes simplex virus results were negative at 18 weeks of gestation. Hemogram showed no infection and fetal biometry was in line with the gestational age based on the prenatal detection.

Figure 1 Antenatal transverse sonogram of the liver. (A) A “starry sky” configuration was observed at 25 weeks of gestation. Weekly ultrasound monitoring revealed that the hyperechoic spots became scattered and smaller in size at (B) 37, (C) 38, and (D) 39 weeks of gestation.

A female neonate, weighing 3,280 g, was delivered vaginally at 39+5 weeks of gestation. Postpartum US assessments were conducted in the first week (Figure 2A,2B), and hyperechoic dot-signs persisted in a diffuse distribution, additionally, uneven liver echo textures in the subcapsular area of both liver lobes, and multiple small cysts (less than 10 mm) unrelated to the biliary tract were observed in the liver parenchyma (as indicated by the red arrows). A subsequent magnetic resonance imaging (MRI) examination exhibited no evident abnormal signs in the liver (Figure 2C). Liver function assessments were repeated at six months of age, revealing no abnormalities. A final histological examination of a liver biopsy at one year of age confirmed the diagnosis of BDH (Figure 2D). At the current age of 15 months, the child is thriving appropriately with no discernible concerns.

Figure 2 Postnatal high-resolution sonogram, MRI, and photomicrograph. Scattered hyperechoic dot-like, uneven liver echo textures were observed at (A) 3 days, and multiple small cysts were observed at (A) 3 and (B) 7 days (as indicated by the arrows). (C) The T2-weighted MRI examination revealed no evident abnormal signs in the liver. (D) Photomicrograph of tissue sample showing different degrees of bile duct expansion into irregular cystic structure that was unrelated to the biliary tract (hematoxylin and eosin stain, ×4). MRI, magnetic resonance imaging.

Discussion

BDH was first described by von Meyenburg in 1918 and was referred to as VMC (2). BDH has reported incidence rates of 5.6% in adults and 0.9% in children (1). It is often found unexpectedly by laparotomy or autopsy. The prevalence of BDH at autopsy has been reported to be 0.69–2.8% (3). Due to the lack of any adequate understanding of the ultrasonic manifestations of BDH, it is easily misdiagnosed. The US misdiagnosis rate of this disease is high at ~80% (4). Embryologically, BDH originates from embryonic bile ducts that fail to involute, resulting in blocked bile ducts, and the subsequent accumulation of epithelial secretion cells and fluid, culminating in the formation of cystic lesions. The precise etiology of BDH remains unknown; however, its incidence has been noted to increase in the presence of liver diseases, and has been attributed to inflammation or ischemia, which suggests it may be acquired (5). In the present case, BDH was detected during the prenatal period, indicating a congenital origin. Pathologically, BDH manifests as multiple small greyish-white nodules scattered beneath the liver capsule and around the portal vein (4,6,7). From a pathological standpoint, the US presentation of our case aligns with the characteristic features of BDH.

BDH has diverse US imaging features that are intricately linked to the size of the dilated bile ducts. Previous studies have predominantly focused on US findings in adults (1,5). When a dilated bile duct is observable, it manifests as a cystic echo pattern. In instances in which the dilated bile duct lumens contain a high concentration of cholestasis, there is no enhancement effect behind the cystic lesions, which often present as hyperechoic (4). In cases in which the dilated bile duct is diminutive, difficulties in delineating the internal anechoic components can be encountered in US imaging, and only the thick capsule wall interface may be discernible, resulting in comet-tail signs generated by multiple reflections off the dilated bile duct. The detection of tiny hamartomas may prove challenging, but they may be depicted as diffuse and uneven liver echo textures. On occasion, BDH also manifests as a large solitary lesion in imaging. In 1998, Luo et al. stated that multiple comet-tail echoes in the liver should be considered a characteristic US feature of BDH (8).

In the present case, the primary US images during the prenatal period featured dot-hyperechoic signs distributed along the vasculature with comet tails. This observation may be attributed to the small, dilated bile duct lumens in the fetal stage. Notably, as the pregnancy progressed, we observed a reduction in the number of intrahepatic dot-hyperechoic signs with comet-tail signs. Postnatally, high-resolution sonography revealed multiple small cysts in the liver lesion, prompting speculation that this could be associated with the gradual widening of intrahepatic bile ducts during development. Despite the acknowledged superiority of MRI in identifying bile duct disorders and producing a “starry sky” configuration (3), it failed to detect lesions in this case. This might have been due to their small size and limited coordination during infancy.

Possible causes for fetal US hyperechogenicities in the area of the liver include infections, ischemic causes, portal and hepatic vein thrombosis, tumors, chromosomal abnormalities, cystic fibrosis, and gallbladder sludge and lithiasis (9). In the present case, a thorough and meticulous investigation was undertaken, revealing the absence of any other structural abnormalities. Chromosomal abnormalities and intrauterine infection were systematically ruled out. Despite being identified as a benign hepatic cystic lesion, it is crucial to note that such lesions have the potential for cystic enlargement and may undergo transformation into cholangiocarcinoma or hepatocellular carcinoma (4,10,11). Consequently, a prudent approach involves regular observation. Given the absence of additional fetal abnormalities, we opted for long-term and close follow-up. We acknowledge the limitations inherent in this small case study and noted that a more extensive series could provide further insights into BDH, particularly in relation to the prenatal onset of the disease. Such expanded studies could provide valuable guidance for the effective management of similar cases.

In conclusion, we reported a case in which the initial prenatal diagnosis of BDH was made by US. In this case, the BDH spanned from fetal development to birth, and exhibited distinctive characteristics. We observed a decline in intrahepatic dot-hyperechoic signs as the pregnancy advanced, accompanied by the emergence of multiple small cysts in the fetal. The significance of prenatal diagnosis using US lies in its ability to provide dynamic monitoring, facilitating differential diagnosis and potentially averting unnecessary induced labor. In cases in which a diagnosis of BDH is under consideration, we recommend regular and periodic follow-up to ensure comprehensive management.

Acknowledgments

Funding: This study was supported by the Science and Technology Program of Gansu Province Grant (No. 22JR5RA922) and the Lanzhou University First Hospital Grant (No. ldyyyn2019-64) awarded to F.F.

Footnote

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1788/coif). F.F. received grants from the Science and Technology Program of Gansu Province Grant (No. 22JR5RA922) and the Lanzhou University First Hospital Grant (No. ldyyyn2019-64). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s next of kin for publication of the details of their medical case and any accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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