Biliary adenofibroma (BAF) is a rare biliary neoplasm first recognized by Tsui et al. in 1993, with only a limited number of cases reported to date [1, 2]. It is classified as a benign biliary tumor in the 5th edition of the World Health Organization (WHO) Classification of Tumors. However, some reports have described malignant transformation, suggesting the need for periodic follow-up or aggressive treatment, such as surgical resection [3-6].

BAF shares histological similarities with the von Meyenburg complex (VMC) but typically presents as a larger tumor. BAF’s histologic resemblance to intrahepatic cholangiocarcinoma, and the occasional malignant transformation suggest that it may be a precursor lesion to cholangiocarcinoma, although this requires further clarification [7]. Furthermore, some genetic alterations and an increased Ki-67 proliferation index are known to be associated with malignant transformation [6].

As BAF is primarily documented in case reports and small case series, its imaging characteristics have not yet been definitively established. Various imaging findings have been reported, including multilocular, solid-cystic, or solid appearances, with or without necrosis [1, 3, 5, 8, 9]. Only a few case reports have described detailed enhancement patterns of BAF using computed tomography (CT) or magnetic resonance imaging (MRI) [5, 6, 8, 9].

Given that BAF is a rare tumor that often presents as a cystic or solid cystic mass, radiologists should include this entity in the differential diagnosis when evaluating liver lesions to ensure an accurate diagnosis. Here, we describe a rare case of biliary adenofibroma with mild cellular atypia.

A 43-year-old female was referred to our hospital with elevated serum alpha-fetoprotein (AFP) levels identified during a health checkup. Her AFP level was initially borderline at 9.3 ng/mL, and at follow-up 3 months later, it had risen to 11.6 ng/mL. Other laboratory findings, including serum carbohydrate antigen (CA) 19-9 and protein induced by vitamin K absence or antagonist-II levels, were unremarkable. She had no history of chronic viral hepatitis but reported a 20-year history of excessive alcohol intake (approximately 210 g of alcohol per week). Her medical history included hypothyroidism and the use of oral contraceptives.

The patient underwent liver dynamic CT, which revealed an approximately 2.2 cm hepatic mass in segments 5/6 (Fig. 1). The tumor exhibited hypoattenuation on the precontrast image, non-rim arterial-phase hyperenhancement, and washout on the portal- and delayed-phase images. The initial differential diagnoses included hepatic adenoma and hepatocellular carcinoma, considering the patient’s history of oral contraceptive use and mildly elevated serum AFP levels despite the absence of chronic viral hepatitis.

The patient subsequently underwent gadoxetic acid-enhanced liver dynamic MRI for further evaluation. MRI demonstrated an approximately 2 cm lesion in segments 5/6 with hypointensity on the pre-contrast T1-weighted image, non-rim arterial phase hyperenhancement, washout on the portal phase, and hypointensity on the transitional and hepatobiliary phases (Fig. 2). Additionally, the lesion exhibited bright hyperintensity on T2-weighted images and the absence of diffusion restriction, suggesting a solid and cystic nature. No fat components were observed in the in-phase and opposed-phase images. The radiological impression favored hepatocellular carcinoma, given the non-rim arterial phase hyperenhancement and washout of the tumor. Inflammatory-type hepatocellular adenoma was considered because of her history of oral contraceptive use and bright hyperintensity on T2-weighted imaging.

Consequently, she underwent wedge resection of hepatic segments 5/6. Gross examination of the resected specimen showed an approximately 2.0 × 1.7 × 1.2 cm, whitish, well-demarcated mass. Pathological examination revealed that the mass was composed of solid and sponge-like microcystic areas (Fig. 3). These microcystic areas showed glandular structures lined with non-mucin-secreting biliary-type epithelium embedded in abundant fibrotic stroma. These findings were suggestive of a biliary adenofibroma. Foci of mild epithelial atypia were observed (Figure 3B), and the Ki-67 proliferation index was 9.2%, which was considered mildly elevated. The background liver showed mild, nonspecific, and reactive hepatitis.

The patient's postoperative course was unremarkable, and she has remained recurrence-free for more than one year. The AFP level remained mildly elevated (6.5-7.9 ng/mL) even after wedge resection of the mass and was thus considered unrelated to the biliary adenofibroma.

The BAF is an extremely rare tumor, with fewer than 30 cases reported as of 2022 [1]. Patients are usually asymptomatic or may present with discomfort in the upper right quadrant. No specific laboratory findings are definitively associated with BAF, although elevated CA 19-9 levels have been reported in one patient [1]. According to the WHO tumor classification, BAF is a benign biliary neoplasm; however, malignant transformation, including multiple lung metastases, has been reported in seven cases [3, 4]. Therefore, periodic follow-ups or surgical resection may be required in patients with BAF.

Histopathologically, BAF is composed of non-mucin-producing cuboidal to low-columnar biliary epithelium embedded in an abundant fibrous stroma [2]. The epithelium stains positive for D10 and negative for 1F6, suggesting that the tumor originates from the interlobular or larger bile ducts [10]. The tumor shares histological features with VMC, which is characterized by abnormal bile ducts embedded in fibrous tissue stroma. However, the BAF is larger than the VMC, and whether it originates from the VMC remains controversial [2, 4].

The malignant transformation occasionally observed in BAF raises the possibility that it is a precursor to intrahepatic cholangiocarcinoma. The tubulocystic variant of intrahepatic cholangiocarcinoma shares histological features with BAF, including low-grade atypia and low desmoplastic reaction [7]. The pathological features of malignant BAF are not yet well established; however, the presence of epithelial components with architectural complexity, such as atypical papillary or tubulopapillary growth patterns and back-to-back or cribriform glands, may suggest malignant transformation [5]. A recent report suggested that more convincing histopathological findings include an abrupt transition from BAF to an adjacent cholangiocarcinoma or the presence of high-grade dysplasia within the lesion [11]. Additionally, the Ki-67 proliferation index reportedly differs between the benign (<10%) and malignant (20-30%) portions of the BAF. Mutations in CDKN2A, CCND1, ERBB2, TP53, and KIT may contribute to the malignant transformation of BAF [6, 12].

Due to their rarity and varying appearance, no specific imaging features of BAF have been established. Various imaging features have been reported, including multilocular cystic masses, solid cystic masses, and hypervascular solid masses with or without central necrosis; however, most tumors are multilocular or solid cystic [1, 3, 5, 8, 9]. Our patient demonstrated bright T2 hyperintensity, suggesting the presence of a cystic component, and the lesion comprised microcystic portions.

Moreover, it is difficult to differentiate benign and malignant BAF based solely on imaging findings. In one case series, benign BAF exhibited delayed enhancement due to abundant fibrous stroma, whereas their malignant counterparts typically showed arterial-phase hyperenhancement and washout. Other reported features suggestive of malignancy include a multiplicity of lesions, unilocular solid cystic masses, restricted diffusion, a peripheral edematous halo, and a pseudocapsule [6]. Our patient demonstrated arterial-phase hyperenhancement with washout; however, no other malignant imaging features were observed. Our case, which showed mild atypia and a borderline Ki-67 proliferation index, might represent an intermediate imaging presentation between previously described benign and malignant BAF. As the number of reported BAF cases is small, the diagnostic accuracy of these imaging findings is unknown, and further research is needed.

As BAF is a rare tumor that usually presents as a cystic or solid cystic mass, several other liver lesions with similar features should be included in the differential diagnosis, such as intraductal papillary neoplasm of the bile duct (IPNB), mucinous cystic neoplasm (MCN), cystic metastases, and hepatocellular carcinoma with extensive necrosis. In all BAF cases reported to date, neither imaging (CT, MRI) nor pathological evaluation has demonstrated evident communication between the BAF and the adjacent intrahepatic bile duct; therefore, this feature can be used to differentiate BAF from IPNB. However, a recent report described a case of BAF with subtle hepatobiliary uptake and the presence of bile pigment on histology, suggesting possible bile duct communication [8]. Nevertheless, even in this case, a clear connection between the BAF and the bile duct was not evident on MRI or histology [8]. Despite the aforementioned controversy regarding bile duct communication, the current understanding is that visible communication on imaging favors the diagnosis of IPNB over BAF. An MCN is typically a cystic lesion found in middle-aged females, characterized by a smooth outer wall and septa arising from the cyst wall without bile duct communication. Although MCN may be accompanied by calcifications and mural nodules, BAF more commonly presents as a solid-cystic mass with an internal solid portion, and calcification is rare, which can be a clue for differentiation [9, 13]. Cystic metastases present as multiple round, unilocular cystic lesions in patients with known primary malignancies. Hepatocellular carcinoma with necrosis or degeneration usually develops in a cirrhotic liver and has an irregular wall or a remaining enhancing portion. Elevated AFP levels are suggestive of hepatocellular carcinoma [6, 9].

In conclusion, BAF is a rare, benign biliary neoplasm with malignant potential. We report a rare case of BAF that presented as a solid-cystic mass showing arterial-phase hyperenhancement and washout on gadoxetic acid-enhanced MRI. BAF is known to exhibit various imaging features, including multilocular cystic, solid-cystic, and solid appearances. This case may represent an intermediate presentation, as it showed arterial phase hyperenhancement and washout without other imaging features of malignancy, and was pathologically benign but accompanied by mild atypia and a mildly elevated Ki-67 index.