Liver & intrahepatic bile ducts


Macroregenerative nodule

Last author update: 27 January 2021
Last staff update: 28 January 2021

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PubMed Search: Macroregenerative nodule[TIAB]

Naziheh Assarzadegan, M.D.
Raul S. Gonzalez, M.D.
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Cite this page: Assarzadegan N, Gonzalez RS. Macroregenerative nodule. website. Accessed January 28th, 2023.
Definition / general
  • Discrete regenerative hepatocellular nodule that often arises in the background of cirrhosis
Essential features
  • May represent a precursor of hepatocellular carcinoma (Hepatology 1992;16:949)
  • Classified into type I and type II, based on cytological and architectural atypia (Cancer 1998;61:99)
    • Macroregenerative nodule (MRN) II shows atypical cytologic or architectural features that are insufficient for a diagnosis of malignancy
  • Also called hepatocellular pseudotumor, adenomatous hyperplasia, adenomatous hyperplastic nodule or adenomatous regeneration
Clinical features
  • Most MRNs are seen in cirrhotic livers
  • Occurs in about 10% of cirrhotic livers at autopsy or at time of transplantation
  • Role of MRN in hepatocarcinogenesis varies in different studies and the true biologic nature of these nodules is uncertain (Int J Hepatol 2016;2016:4390434)
Radiology description
  • Well defined isointense nodules relative to the background liver
Gross description
  • Usually multiple, large, discrete, tumor-like hepatocellular masses > 1 cm in diameter (rarely > 5 cm)
  • Often differ from surrounding nodular parenchyma in color, texture or degree to which they bulge beyond the cut liver surface
Gross images

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Macroregenerative nodules in explanted liver

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Macroregenerative nodule with atypical features

Microscopic (histologic) description
  • Liver cell plates 1 - 2 cells thick, reduced and scattered portal tracts with variable structural distortion (prominent bile ductules, absent interlobular bile ducts)
  • Hepatocytes resemble those in adjacent liver and may reflect any disease process there
  • MRN type II may have architectural and cytologic atypia
Microscopic (histologic) images

Contributed by Raul S. Gonzalez, M.D.

Macroregenerative nodule

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Macroregenerative nodule with thickened hepatic plates

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Atypical macroregenerative nodule

Sample pathology report
  • Liver, native, orthotopic transplantation:
    • Cirrhosis with mild to moderate chronic inflammation and occasional macroregenerative nodules (see comment)
    • Negative for dysplasia or malignancy.
    • Margins of resection unremarkable.
    • Comment: The findings are consistent with the patient’s reported history of autoimmune hepatitis. A trichrome stain confirms cirrhosis. An iron stain is unremarkable.
Differential diagnosis
Board review style question #1
    Which of these liver lesions is the least likely to arise in the background of cirrhosis?

  1. High grade dysplastic nodule
  2. Large regenerative nodule
  3. Low grade dysplastic nodule
  4. Macroregenerative nodule
Board review style answer #1
B. Large regenerative nodule

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Reference: Macroregenerative nodule
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