Liver & intrahepatic bile ducts


High grade dysplastic nodule

Topic Completed: 27 January 2021

Minor changes: 28 January 2021

Copyright: 2002-2021,, Inc.

PubMed search: High grade "dysplastic nodule" liver

Naziheh Assarzadegan, M.D.
Raul S. Gonzalez, M.D.
Page views in 2020: 2,773
Page views in 2021 to date: 3,268
Cite this page: Assarzadegan N, Gonzalez RS. High grade dysplastic nodule. website. Accessed November 27th, 2021.
Definition / general
  • Discrete nodules in cirrhotic livers, containing high grade architectural and cytologic changes insufficient for a diagnosis of carcinoma (Hepatology 2009;49:658)
Essential features
  • Dysplastic nodules (both low grade and high grade) are associated with higher risk of development of hepatocellular carcinoma
  • High grade dysplastic nodules have a higher risk of transformation into hepatocellular carcinoma than low grade nodules and themselves show molecular changes similar to carcinoma (J Hepatol 2003;39:208)
  • Also called borderline nodule, macroregenerative nodule type II, atypical macroregenerative nodule, atypical adenomatous hyperplasia
Clinical features
  • Considered a precursor to hepatocellular carcinoma
  • Usually increase in size over time and do not regress
Radiology description
  • Reduced portal blood flow in the nodule on computed tomography is an important predictor for development of hepatocellular carcinoma (Cancer 2006;106:636)
  • Usually isovascular or hypovascular compared to surrounding parenchyma, whereas hepatocellular carcinoma appears hypervascular
  • Ablation or resection should be strongly considered
Gross description
  • Often vaguely nodular; can be a distinct nodule often in the background of cirrhosis
  • Lack a true capsule
  • Typically about 1 cm; can be single or multiple
Microscopic (histologic) description
  • Increased cellularity (more than 2 times higher than the adjacent nontumoral liver), often with an irregular trabecular pattern
  • Cytologic atypia is usually small cell change; large cell change may or may not be seen (Arch Pathol Lab Med 2011;135:704)
  • Portal tracts can be present within the nodules
  • Unpaired arteries can be present but not in great numbers (Dig Liver Dis 2011;43:S361)
  • "Nodule in nodule" appearance may be seen, where the larger nodule is a high grade dysplastic nodule and the inside subnodule is usually a well differentiated hepatocellular carcinoma
Microscopic (histologic) images

Contributed by Raul S. Gonzalez, M.D.

High grade dysplastic nodule

Images hosted on other servers:

Increased cellularity and unpaired arteries (B)

Molecular / cytogenetics description
  • Telomere shortening, increased telomerase activity and strong expression of hTERT mRNA at levels similar to hepatocellular carcinoma (Hepatology 2014;60:1983)
  • Inactivation of p21 in contrast to cirrhotic nodules, which show activation (Mod Pathol 2009;22:1121)
Sample pathology report
  • Liver, native, orthotopic transplantation:
    • Cirrhosis with mild chronic inflammation and two high grade dysplastic nodules (see comment)
    • Negative for malignancy.
    • Margins of resection unremarkable.
    • Comment: The findings are consistent with the patient’s reported history of chronic hepatitis B infection. A trichrome stain confirms cirrhosis. An iron stain is unremarkable.
Differential diagnosis
Board review style question #1

Which of the following is true about high grade dysplastic nodules of the liver?

  1. They arise in noncirrhotic livers
  2. They may contain unpaired arteries
  3. Their molecular profile is the same as that of normal hepatocytes
  4. They usually measure several centimeters
Board review style answer #1
B. They may contain unpaired arteries

Comment Here

Reference: High grade dysplastic nodule
Back to top
Image 01 Image 02