Hepatic biliary adenofibroma (BAF) is a rare benign bile duct neoplasm that has recently attracted attention due to its possible link to intrahepatic cholangiocarcinoma (iCCA). Despite its benign classification, emerging evidence suggests that BAF may undergo malignant changes. This article delves into the current understanding of BAF's characteristics, diagnostic challenges, and potential for transformation into iCCA. The rarity of this condition and limited molecular studies have led to uncertainties in diagnosis and treatment. The review aims to consolidate existing knowledge and outline future research directions to better understand this enigmatic entity.

Understanding the Clinicopathologic Features of BAF

Since its first documentation in 1993, fewer than 25 cases of BAF have been reported. This rare condition typically manifests as a well-defined mass within the liver, ranging from 1.7 cm to 16 cm in size. Histologically, BAF exhibits unique features such as biliary tubules, acini, and microcysts, which resemble von Meyenburg complexes but are larger and occasionally show nuclear atypia. Immunohistochemical staining reveals markers like CK7, CK19, and EMA, indicating a biliary epithelial phenotype. While most cases follow a benign course post-surgery, some reports suggest a possible transition to iCCA, raising concerns about its malignant potential.

The clinicopathologic characteristics of BAF highlight its distinct composition, comprising low-grade tubuloglandular and microcystic structures embedded in dense fibrous stroma. These features set it apart from other biliary lesions. Although most patients experience an indolent clinical course after surgical excision, the potential for malignant transformation remains a significant concern. Histological findings and immunohistochemical markers play crucial roles in diagnosing BAF, yet the rarity of cases complicates the establishment of definitive diagnostic criteria. Further studies are needed to clarify the exact nature of BAF and its relationship with iCCA.

Diagnostic Challenges and Future Directions

Diagnosing BAF presents several challenges due to its histological overlap with other biliary tumors. Distinguishing BAF from entities like von Meyenburg complexes, bile duct adenomas, and iCCA is essential for accurate diagnosis. Von Meyenburg complexes are smaller developmental anomalies, while bile duct adenomas are well-circumscribed lesions without cystic dilation. The "tubulocystic carcinoma" subtype of iCCA shares morphologic similarities with BAF, complicating differentiation. Molecular studies on BAF remain limited, but available data suggest distinct genetic alterations compared to iCCA, warranting further investigation.

Molecular pathogenesis studies indicate that BAF typically shows wild-type p53 expression, unlike iCCA, which frequently exhibits TP53 mutations. Some cases of BAF with malignant transformation demonstrate amplifications of CCND1 and ERBB2, along with NRAS mutations, hinting at oncogenic progression. Future research should focus on identifying reliable biomarkers for distinguishing BAF from iCCA and determining whether regular surveillance is necessary for diagnosed patients. Large-scale studies are also needed to assess the true incidence and clinical significance of BAF. Until more comprehensive data is available, thorough histological examination and complete surgical excision remain the best approaches for managing this intriguing condition.