Liver & intrahepatic bile ducts

Benign / nonneoplastic

Biliary adenofibroma


Editorial Board Member: Monika Vyas, M.D.
Deputy Editor-in-Chief: Aaron R. Huber, D.O.
Hunter Monroe, B.S.
Reima El Naili, M.D.

Last author update: 29 June 2023
Last staff update: 29 June 2023

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PubMed Search: Biliary adenofibroma

Hunter Monroe, B.S.
Reima El Naili, M.D.
Page views in 2023: 2,363
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Cite this page: Monroe H, El Naili R. Biliary adenofibroma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/livertumorbiliaryadenofibroma.html. Accessed May 19th, 2024.
Definition / general
  • Premalignant hepatic neoplasm of bile duct origin with epithelial and myofibroblastic stromal components
Essential features
Terminology
ICD coding
  • ICD-O: 9013/0 - adenofibroma, NOS
  • ICD-11: 2E92.7 & XH91Y8 - benign neoplasm of liver or intrahepatic bile ducts & adenofibroma, NOS
Epidemiology
Sites
  • Liver; slight predilection for right lobe
Pathophysiology
Etiology
  • Precise etiology unknown at this time
Clinical features
Diagnosis
  • Ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) used to screen for lesion
  • Histology is gold standard
    • WHO essential criteria
      • Solid microcystic epithelial neoplasm
      • Microcystic and tubuloacinar glandular structures lined by nonmucinous biliary epithelium
      • Supporting fibroblastic / myofibroblastic stroma
Laboratory
Radiology description
  • Ultrasound
  • CT
    • Solitary, hypodense lobulated solid cystic mass with well defined margins, internal septation and capsular retraction (BMC Med Imaging 2022;22:47)
  • MRI (BMC Med Imaging 2022;22:47, Korean J Gastroenterol 2019;74:356)
    • Generally considered most reliable screening method
    • Solitary, subcapsular, multilocular, solid cystic mass
      • T1 weighted: low intensity
      • T2 weighted: high intensity; well circumscribed, lobular mass with no intrahepatic bile duct communication
      • Contrast enhanced: delayed enhancement
    • Features favoring malignancy (BMC Med Imaging 2022;22:47)
      • Multiple lesions
      • Poorly defined margins
      • Unilocular
      • Marked enhancement in arterial phase and washout in venous phase
      • Peripheral edematous halo
      • Diffusion weighted imaging (DWI): restricted diffusion
  • Portal venography (BJR Case Rep 2015;1:20150100)
    • Portal vein branches moderately displaced with faintly enhancing mass in background
Radiology images

Images hosted on other servers:
Multiple cysts

Abdominal CT scan

Multiple cysts

Ultrasound and MRI findings

Multiple cysts

MRI

Multiple cysts

Portal venography

Prognostic factors
  • Benign form is associated with favorable prognosis and no risk of recurrence
  • Malignant form has risk of local recurrence and distant metastasis
Case reports
Treatment
Gross description
Gross images

Images hosted on other servers:
Multiple cysts

Mixed solid cystic mass

Multiple cysts

Tumor and liver parenchyma

Microscopic (histologic) description
  • Benign (Patholog Res Int 2010;2010:504584)
    • Complex nonmucinous, tubuloacinar glandular structures
      • Lining cells are cuboidal to flattened with central round to ovoid nuclei, amphophilic cytoplasm and no significant atypia
      • Red blood cells or eosinophilic material may be present in lumina
      • Rare papillary projections into lumina
    • Cystically dilated glands lined by a single layer of flat epithelial cells
    • Moderately cellular fibrous stroma containing bland, myofibroblastic spindle cells
    • Mild chronic inflammation characterized by scattered lymphocytes may be present
  • Malignant
Microscopic (histologic) images

Contributed by Reima El Naili, M.D.

Mixed epithelial stromal lesion

Tubuloacinar glands

Bland epithelial cells

Cystically dilated gland

Fibrous stroma

Intraluminal material


Demarcation

CK7

CK20

Vimentin

SMA

Desmin

Cytology description
  • Cytologic features have not been described for this entity
  • FNA may be avoided due to possible risk of seeding in setting of malignancy (BJR Case Rep 2015;1:20150100)
Positive stains
Electron microscopy description
  • Electron microscopy findings have not been reported for this entity
Molecular / cytogenetics description
Sample pathology report
  • Liver, left lateral segment, segmentectomy:
    • Biliary adenofibroma (see comment)
    • Comment: Histologic evaluation reveals benign appearing bile ducts without significant cytologic or architecture atypia. Immunohistochemical stains with adequate controls show the lesional cells to be positive for CK7 with low Ki67 and wild type staining pattern with p53. The lesional cells are negative for PAX8, TTF1, CK20, NKX3, HepPar1, arginase and glypican 3. BAP1 immunostain is retained. Overall, based on morphology, low Ki67 and BAP1 retention, a benign biliary lesion is favored. Due to the presence of extensive fibroblastic stroma, this entity may be further classified as biliary adenofibroma.
Differential diagnosis
  • Von Meyenburg complex (Patholog Res Int 2010;2010:504584):
    • Usually presents as multiple, small (< 0.5 cm) cysts
    • Irregular curvilinear ducts lined by cuboidal or flattened cells
    • May exhibit dense fibrous stroma similar to adenofibroma
  • Bile duct adenoma:
    • Small (usually < 1 cm)
    • Closely packed tubules with cuboidal lining and narrow lumina
    • Cystic dilation is rarely present
    • Fibrous stroma is less prominent
  • Congenital biliary cyst / simple cyst:
    • Usually multiple
    • Strong association with autosomal dominant polycystic disease due to PKD1 or PKD2 mutations
  • Serous cystadenoma:
    • Often large (up to 15 cm)
    • Small cysts lined by cuboidal or flattened cells with clear cytoplasm
  • Mucinous cystic neoplasm (ACG Case Rep J 2018;5:e72):
    • Often large (up to 15 cm)
    • Prominent ovarian stroma
    • On MRI, presents as fluid filled multilocular mass with low T1 weighted signal and high T2 weighted signal
    • Capable of malignant transformation
  • Cholangiocarcinoma:
    • Infiltrating glands in fibrous stroma
    • Neoplastic cells exhibit at least mild atypia
    • May arise in background of chronic schistosomiasis or primary sclerosing cholangitis
    • CA 19-9 and CA125 exhibit greater elevation
    • Large, homogenous mass with irregular margins by imaging
    • Albumin in situ hybridization (ISH) + (80%)
  • Benign cystic mesothelioma / peritoneal inclusion cyst (Patholog Res Int 2010;2010:504584):
    • Cysts lined by bland cuboidal or flattened mesothelial cells
    • Prominent chronic inflammatory infiltrate usually present
    • Presents as papillae protruding into cystic lumina
    • Calretinin, HBME1, CK5/6, WT1+
  • Hepatic endometrial cyst (Eur J Med Res 2015;20:48):
    • Exclusively present in women
    • Well circumscribed cystic lesion, often with thick overlying fibrous capsule
    • Histology is characterized by at least 2 of the following
      • Endometrial glands lined by Mullerian epithelium
      • Endometrial type stroma
      • Hemosiderin laden macrophages
    • Epithelial and stroma cells positive for ER, PR and PAX2
    • Stromal cells positive for CD10
  • Intraductal papillary neoplasm of bile ducts (Proc (Bayl Univ Med Cent) 2019;32:124):
    • Histologically characterized by intraductal papillary growth pattern with fibrovascular cores
    • May present with pancreatobiliary, intestinal, gastric or oncocytic phenotypes
    • Typically multifocal
    • Frequently presents with high grade cytologic features
    • May undergo malignant transformation into cholangiocarcinoma
  • Hepatic foregut cyst (Diagn Pathol 2015;10:81):
    • Small (< 4 cm) unilocular cysts
    • Typically benign and asymptomatic
    • Primarily found in segment 4 of the left lobe
    • From deep to superficial, histologically characterized by inner ciliated pseudostratified columnar epithelium, loose lamina propria, smooth muscle band and outer fibrous capsule
    • Epithelium may contain goblet cells or gastric metaplasia
Board review style question #1

The image above was taken from the right hepatic lobe of a 54 year old woman who presented with dull right upper quadrant (RUQ) pain that began 2 weeks ago. Liver function tests were unremarkable. Per MRI, a large solid cystic mass was identified. Left lateral segmentectomy was pertinent for a single 15.3 cm solid cystic mass with white-purple, spongy cut surface. By immunostaining, a subset of cells were positive for CK7 and CK19 while negative for CK20, CDX2, calretinin and HBME1. The surrounding cells were positive for SMA and vimentin and negative for desmin, ER and PR. The Ki67 index was < 3% while p53 exhibited wild type staining in lesional cells. What is the patient's diagnosis?

  1. Bile duct adenoma
  2. Biliary adenofibroma
  3. Biliary cystadenoma
  4. Peritoneal inclusion cyst
  5. Von Meyenburg complex
Board review style answer #1
B. Biliary adenofibroma. The presence of neoplastic glands with biliary type epithelium in an abundantly fibrous stroma (per morphology and immunohistochemistry) in addition to the large size and solid cystic nature of the lesion favors biliary adenofibroma. The large size of this lesion is virtually unheard of among other biliary lesions such as bile duct adenomas and von Meyenburg complexes. Moreover, bile duct adenomas generally lack the overt fibrous stroma of this lesion while von Meyenburg complexes usually present as multiple lesions with irregular curvilinear glands by histology. Though biliary cystadenomas may also present as large cystic masses, the lesion in question does not harbor the clear cytoplasm of serous cystadenoma and lacks the mucin and ER / PR+ ovarian stroma of the mucinous type. Finally, the lesion lacks the papillary luminal infoldings and mesothelial immunohistochemical profile of peritoneal inclusion cysts.

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Reference: Biliary adenofibroma
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