Liver mass pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]


The exact pathogenesis of a liver mass depends upon the underlying disease. Increased estrogen in hepatic adenoma stimulates hepatocytes via steroid receptors and results vascular ectasia. While in FNH excessive release of growth factors promote growth of small arteries. Some conditions such as hemangioma, hepatic cysts are believed to be as result of genetic abnormality. Precancerous lesions are responsible for HCC, cholangiosarcoma. Hepatic abscess and echinoccosiosis are due to infectious agents.


The exact pathogenesis of a liver mass depends upon the underlying disease. The following table summarizes the various causes of liver masses:

Disease Pathogenesis Genetics Associated Conditions Gross Pathology Microscopic Pathology
Hepatocellular adenoma
  • Estrogens cause the transformation of hepatocytes via steroid receptors
  • Results in generalized vascular ectasia
  • Transcription factor 1 gene (TCF1)
  • Interleukin 6 signal transducer gene (IL6ST)
  • β catenin-1 gene (CTNNB1)
  • Well circumscribed
  • Non-lobulated
  • Smooth and soft
  • White to yellow to brown lesions
Focal nodular hyperplasia
  • β-catenin gene (CTNNB1)
  • TP53
  • APC or HNF1α
  • Klippel-Trénaunay-Weber syndrome
  • Well-circumscribed
  • Non-encapsulated
  • Central fibrous scar
  • Hepatic parenchyma arranged in incomplete nodules
  • Fibrous tissue with thick-walled vessels
  • Bile ductular proliferation
  • Cells of chronic inflammation
  • Congenital disorder
  • Vascular malformations that enlarge by ectasia 
  • Estrogen and progesterone influence over tumor growth
  • More common in females
  • Von Hippel Lindau disease
  • Well-circumscribed
  • Appear red-brown
  • Solitary nodules
  • Less than 5cms
  • Large cystically dilated vessels
  • Thin walls
  • Intravascular thrombosis
  • Calcifications
Hepatic Cyst
  • Von Meyenburg complexes separate from biliary tree and dilate to form cyst
  • Single, unilocular cyst
  • Variable amounts of clear amber fluid (may contain blood, bile, mucus, pus)
  • Lined by flat / cuboidal epithelium
  • Epithelium rests on thin collagenous wall without spindle cell stroma
  • Degenerative changes include epithelial desquamation, multiloculation, calcification
  • Lymphangioma is caused by either sequestration of
    • Lymph tissue
    • Abnormal budding of lymph vessels
    • Lack of fusion with the venous system,
    • Obstruction of lymph vessels.
  • Grey-white mass
  • Well circumscribed
  • Edematous appearance
  • Variable size (may be massive)
  • Filled with serous fluid
  • Smooth inner lining
  • Well circumscribed
  • Uniform yellow mass
Hepatocellular carcinoma
  • Arises from precancerous lesions.[1]:


    • Genomic alterations
    • Epigenetic modifications
    • Growth factor pathway alterations
  • Nodular or diffusely infiltrative
  • Pale in relation to surrounding liver or green
  • Large polygonal tumours cells
  • Graunular eosinophilic cytoplasm
  • Layered dense collagen bundles
  • The epithelial cell lining the bile ducts are called cholangiocytes.
  • The malignant transformsation of cholangiocytes leads to cholangiocarcinoma.[8]
  • Malignant transformation of cholangiocytes into cholangiocarcinoma include following stages:[9]
  • Hyperplasia
  • Metaplasia
  • Dysplasia
  • Frank carcinoma
  • Progression of malignancy is believed to be due to:[9][10][11]
    • Inflammation
    • Obstruction of bile ducts
    • Biliary intraepithelia neoplasia.
  • ARID1A
  • BAP1
  • BRAF
  • FGFR2
  • IDH1
  • IDH2
  • KMT2C
  • KRAS
  • PBRM1
  • PEG3
  • PTPN3
  • RNF43
  • ROBO2
  • SMAD4
  • TERT
  • TP53
  • Mass-forming
    • Nodular lesion or mass in the hepatic parenchyma
    • Gray to gray-white, firm and solid carcinoma
  • Periductal infiltrating
    • Spreading of the carcinoma along the portal tracts with stricture of the affected bile ducts
    • Dilatation of the peripheral bile ducts
  • Intraductal growth types
    • Polypoid or papillary tumor within the variably dilated bile duct lumen
    • Malignant progression of an intraductal papillary neoplasm of the bile duct
  • Cuboidal or columnar mucin producing cells
  • Dense fibrous(desmoplastic) stroma.
Hepatic abscess
Parasitic cysts:[18][19][20](Echinococcous)
  • Cysts tend to be:
    • Filled with clear fluid
    • White appearance
    • Solitary
    • Unilocular
  • Cyst wall composed of an acellular laminated external layer and a thin, germinal (nucleated) inner layer
  • Brood capsule with protoscoleces inside


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