Liver and intrahepatic bile ducts - tumor
Benign tumors / conditions
Hepatocellular adenoma

Author: Deepali Jain, M.D. (see Authors page)

Revised: 17 November 2017, last major update February 2012

Copyright: (c) 2002-2017,, Inc.

PubMed Search: Hepatocellular adenoma[TI] free full text[sb]

See also: Atypical hepatocellular adenomaPigmented liver cell adenoma
Cite this page: Jain, D. Hepatocellular adenoma. website. Accessed September 26th, 2018.
Definition / general
  • Also called liver cell adenoma
  • Arises in normal or nearly normal liver in patients with abnormal hormonal or metabolic condition
  • 95% women, usually child bearing age (very rare in children), history of 5+ years of oral contraceptives in 85% (occasionally regress after discontinuation)
  • Also associated with anabolic steroids (in men), antiestrogens, Klinefelter syndrome or other abnormal secretion of sex steroids
  • Also associated with glycogen storage disease types Ia and III, Fanconi anemia, thalassemia, familial adenomatous polyposis, familial diabetes mellitus, Hurler disease, galactosemia or tyrosinemia; also spontaneous
  • 2 - 4% of hepatic tumors in children
  • Subcapsular tumors may rupture, particularly during pregnancy
  • Benign but may contain hepatocellular carcinoma or cause severe hemorrhage
  • 10% or lower risk of hepatocellular carcinoma if not resected; definite risk in young men with glycogen storage disease type Ia
  • Must sample generously to rule out coexisting hepatocellular carcinoma
  • Risk of malignancy is not related to number of adenomas but to size and pathological subtype (lower risk for steatotic subtype)
  • May contain hepatic progenitor cells (Am J Surg Pathol 2001;25:1388)
  • Normal liver function tests, may have elevated alpha fetoprotein
  • Hepatocellular adenomatosis: 10+ tumors, both in man and woman, genetic mutation of HNF1α no association with oral contraceptives
Case reports
  • Excision
Gross description
  • Solitary (70%, anabolic steroid related more often multiple), pale, yellow tan (different from surrounding liver), frequently bile stained nodules, often subcapsular, 10 - 30 cm, sharply demarcated or encapsulated
  • Usually right lobe, may be pedunculated (10%)
  • May have hemorrhagic, necrotic or infarcted foci
  • Usually no fibrous septa or central scar; adjacent liver is noncirrhotic
Microscopic (histologic) description
  • Sheets and cords 1 - 3 cells thick of normal appearing hepatocytes with variable glycogen
  • Prominent "free floating" arterial vessels and draining veins are present throughout tumor; intact reticulin framework
  • Pseudoglands may be present
  • May have cytoplasmic globules (PAS+, diastase resistant, alpha-1-antitrypsin+, AFP-), 10% have multinucleation
  • Degenerative changes include dilated sinusoids, blood filled (pelioid) spaces, myxoid stroma, focal necrosis, infarction, hematoma
  • Rarely contains abundant fat, oncocytic changes, Mallory hyaline, granulomatous inflammation
  • No atypia, no prominent nucleoli, no intranuclear vacuoles
  • No angiolymphatic invasion, no / rare extramedullary hematopoiesis, no epithelioid granulomas, no decreased reticulin framework
  • No / rare mitotic figures; no portal tracts; no central veins or connection with biliary system

  • Three major subtypes: (a) inflammatory / telangiectatic; (b) steatotic; with HNF1α gene mutation; (c) with β catenin activation; (d) also an additional unclassified / miscellaneous subgroup (Hepatology 2009;50:481)
    1. Inflammatory: previously misclassified as telangiectatic focal nodular hyperplasia; 40 - 55% of hepatocellular adenomas; increased risk of bleeding but small risk of malignant transformation
      • Due to mutations involving interleukin 6
      • Strong expression of serum amyloid associated protein A2 (SAA2) and CRP on IHC
      • Inflammation and peliosis at histology
    2. Steatotic: 35 - 50% of hepatocellular adenomas; no risk of malignant transformation
      • Develop familial adenomatosis and MODY3 diabetes mellitus
      • Lack of expression of liver fatty acid binding protein (LFABP) on immunohistochemistry
    3. With β catenin activation: 10 - 18% of hepatocellular adenomas
      • Affects men and women; increased risk of malignancy; associated with androgen therapy and glycogen storage disease
      • Strong diffuse overexpression of glutamine synthetase and nuclear β catenin staining (Hum Pathol 2002;33:852)
Microscopic (histologic) images

Images hosted on other servers:

14 year old with
subsequent fibrolamellar
carcinoma (figs A - D)

Positive stains
Negative stains
Differential diagnosis
  • Focal nodular hyperplasia: central stellate scar and radiating fibrous septa
  • Hepatocellular carcinoma: mitotic activity, atypia, trabecular growth, cell plates > 2 cells thick, vascular invasion, infiltrative, often different clinical features