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biliary adenofibroma

Tuesday 3 May 2011

The “biliary adenofibroma” (BAF) has been described by Tsui et al. in 1993.

BAF is a rare tumour of bile duct origin. In 2010, only six cases of BAF of the liver have been reported in the literature. Two of us reported a morphologically similar tumour in equine.

BAF is equally reported both in women and men ranging in age from 21 to 79 years. Most patients complain of abdominal pain in the right hypochondrium.

Grossly, BAF presents as an unencapsulated, well-circumscribed, solid-cystic nodule. Histologically, it is composed of a tubulocystic proliferation of variable-sized bile ducts with an immunohistochemical profile (CK7+ , CK19+) suggesting a bile duct origin. The lumens of the tubules contain eosinophilic material and/or red blood cells but bile was absent. The epithelial component is embedded in a moderately cellular fibrous stroma, predominantly containing myofibroblasts as documented by a diffuse and strong immunoreactivity for α-smooth muscle actin.

Notably, the cellular stromal component of liver BAF has been reported to be fibroblastic rather than myofibroblastic in nature, because only scattered α-smooth muscle actin+ cells have been identified.


Imaging studies, including ultrasonography, computerized tomography and magnetic resonance imaging, usually reveal a well-circumscribed solid-cystic mass, variable in size from 5.5 to 20 cm. Unfortunately, radiologic images, including those of our case, are nonspecific, and the diagnosis of BAF of the liver is based on histological examination.

Etiology of BAF is still unknown, even if its immunophenotypic profile (cytokeratins 7+, 8+, 18+, 19+, D10+, 1F6−) suggests a large bile and/or interlobular duct origin.

Although BAF is a benign tumour with a clinical indolent behavior, malignant transformation of the epithelial component with associated distant metastases has been documented.


- nodular mass
- cut surface: unencapsulated, well-circumscribed, and firm lesion with a solid and microcystic appearance.
- Cysts range in size from 0.1 to 0.5 cm.


BAF is characterized by a proliferation of tubulocystic structures variably embedded in a fibrous stroma.

- Multiple nonmucin-secreting, tubulocystic structures, embedded in a moderately cellular fibrous stroma (Figure 1).
- Both tubules and cysts are lined by a single layer of cuboidal to flat, bile duct-type epithelium.
- Lumens of the tubulocystic structures contain eosinophilic material and/or red blood cells, while bile was absent.
- Nuclei are round to oval in shape and centrally located.
- No goblet cells are observed.
- In some areas, the epithelium forms papillary projections into the lumens.
- Necrosis, mitoses, and nuclear pleomorphism are absent.
- Stromal component contained spindle-shaped fibroblast-like cells and scattered lymphocytes.
- Islands of hepatic parenchyma were seen scattered throughout the tumour.


- The epithelial component is stained with cytokeratins 7, 8, 18, and 19 (Figure 4) and epithelial membrane antigen (EMA).
- Carcinoembryonic antigen (CEA), cytokeratins 5/6, p53, calretinin, HBME-1, and beta-catenin are negative.
- Ki-67/index proliferation is low (1%).
- The stromal cells are strongly and diffusely stained with vimentin and α-smooth muscle actin, while no immunoreactivity is detected for desmin. Based on their morphological and immunohistochemical profile, these cells are regarded to be myofibroblastic in nature.


Monosomy 22, a cytogenetic alteration found in some benign mesenchymal neoplasms, has been documented in one case of BAF.

Differential diagnosis

> hepatic cystic biliary lesions

- von Meyenburg complex

  • BAF generally presents as a large-sized nodule with a solid microcystic appearance, whereas von Meyenburg complex can be incidentally found either as single or multiple subcapsular nodules of small size, usually less than 5 mm in diameter. This complex may represent part of the spectrum of ductal plate malformation and may be related to adult type polycystic disease. Histologically, von Meyenburg complex is located within or adjacently to portal tracts and it is composed of multiple-branched bile ducts, sometimes with an angulated appearance, set in a collagenous stroma. These tubular structures contain bile and/or eosinophilic material.
    - bile duct adenoma
  • Bile duct adenoma is generally a well-demarcated, small-sized lesion with a diameter ≤1 cm, usually located directly underneath the liver capsule. Occasionally, this lesion may present as two or more nodules with a maximal diameter of 2 cm. Histologically, it is characterized by closely packed tubules with narrow lumens, lined by cuboidal bile-type epithelium, set in an edematous to dense fibrous stroma which may contain a variable amount of inflammatory cells. Unlike BAF, these tubules show more irregular outlines and less cystic configuration while stromal component is less prominent. Bile duct adenoma is not a true neoplasm but it is currently regarded as a peribiliary gland hamartoma or a localized reactive ductular proliferation as result of a previous unknown injury.
    - biliary cystadenoma
  • Unlike BAF, biliary (peribiliary) cystadenoma is a large-sized cystic tumour with multilocular appearance, in which cysts may be up to 15 cm of diameter. Two histological variants were recognized: serous and mucinous types. The former consists of small cysts lined by a single layer of low cuboidal or flat epithelium with a clear cytoplasm; the latter contains cysts lined by columnar, cuboidal or flattened mucous-secreting epithelial cells with occasionally papillary projections and an ovarian-like stroma appearance, especially if the lesion occurs in women, with a characteristic immunoreactivity for oestrogen and progesterone receptors.
    - congenital biliary cysts (simple biliary cysts)
  • The congenital biliary cysts (simple cysts) are lined by bile duct-type epithelium, and they may be solitary or multiple; the multiple form may be part of the polycystic disease.
    - benign cystic mesothelioma
  • Benign cystic mesothelioma can also be included, a rare neoplasm which may occur in the liver. It is a large, partially cystic, well-encapsulated lesion, characterized by anastomosing cords of tumour cells, separated by large thick-walled vessels, closely reminiscent of a vascular neoplasm.
  • This morphological pattern is quite different from that exhibited by the tumour herein presented. In addition, neoplastic cells of benign cystic mesothelioma are positive to calretinin, HBME-1, and cytokeratins 5/6.

Nota bene: Benign biliary tumours are uncommon, including bile duct adenoma (also known as "peribiliary gland hamartoma"), biliary hamartoma (von Meyenburg complex), biliary cystadenoma, and the solitary bile cysts.


It is noteworthy that histological features similar to BAF and von Meyenburg complex have been obtained in animal-model of aflatoxin-induced cholangiocarcinoma.

These experimental findings, along with the large size, the p53 expression, and the tetraploidy status with a low S-phase being occasionally reported, strongly suggest that BAF could represent a premalignant lesion. This hypothesis seems to be supported by the evidence that two cases of liver BAF underwent epithelial malignant transformation.

Open references

- Biliary adenofibroma of the liver: report of a case and review of the literature. Gurrera A, Alaggio R, Leone G, Aprile G, Magro G. Patholog Res Int. 2010 Oct 28;2010:504584. PMID: 21151526 (Free)