Liver & intrahepatic bile ducts

Benign / nonneoplastic

Nodular regenerative hyperplasia

Topic Completed: 1 February 2012

Minor changes: 23 September 2020

Copyright: 2002-2021,, Inc.

PubMed Search: Nodular regenerative hyperplasia[TI] liver[TI] full text[sb]

Deepali Jain, M.D.
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Cite this page: Jain D. Nodular regenerative hyperplasia. website. Accessed November 27th, 2021.
Definition / general
  • Nodular hyperplasia diffusely affecting entire liver but with no / minimal fibrous septa

Partial nodular transformation:
  • Very rare, focal form of nodular regenerative hyperplasia, usually perihilar region
  • Portal hypertension usually prominent due to portal venous thrombosis
Clinical features
  • Incidental finding at autopsy in 1 - 3%; present in 5% of elderly
  • Develops at all ages but usually symptomatic at age 40+
  • Associated with portal hypertension, connective tissue disease (rheumatoid arthritis, polyarteritis nodosa), myeloproliferative or lymphoproliferative disorders, vascular disorders, chemotherapy or immunosuppressive drugs (Arch Pathol Lab Med 2004;128:49), HIV, CHF, Felty syndrome
  • May be part of the early noncirrhotic stages of primary biliary cirrhosis
  • May be due to moderate to severe sclerosis of small portal veins, portal venous thrombosis or arteriosclerosis causing heterogeneous blood flow, variable ischemia and reactive hepatocyte hyperplasia
  • Mildly elevated alkaline phosphatase, gamma GT, normal alpha fetoprotein
Gross description
  • Heavy liver in patients with myeloproliferative disorders, otherwise normal
  • Finely granular capsule, parenchyma has multiple tan white nodules, 0.1 to 1 cm, separated by congested parenchyma
  • Large nodules may exhibit hemorrhage or necrosis
  • May resemble metastatic carcinoma or cirrhosis
Microscopic (histologic) description
  1. Diffuse nodules of hyperplastic hepatocytes with central, single portal tract but with different orientation at low power
  2. Regions of internodular hepatocyte atrophy, usually centrilobular, associated with areas of hepatocyte regeneration (plump hepatocytes with pale cytoplasm), sinusoidal congestion / dilation and compression of central veins making them difficult to identify
  3. No / minimal fibrosis
  • Hepatocyte plates are usually 2 - 3 cells thick compared to thin plates in atrophic areas
  • Hepatocytes may have clear / vacuolated cytoplasm, cholestasis associated with pseudoglandular spaces, variable large cell change
  • No lipofuscin in atrophic hepatocytes
  • No / rare extramedullary hematopoiesis, no / minimal inflammation
  • On biopsy, apparent lack of central veins and presence of curvilinear areas of congestion are suggestive

Partial nodular transformation:
  • Nonfibrotic nodules in liver near porta hepatis
  • Regenerating hepatocytes with thickened cell plates compressing adjacent single cell plates (highlighted with reticulin stain); normal portal tracts
  • Nodules are larger than nodular regenerative hyperplasia
Positive stains
  • Reticulin highlights nodular architecture and hepatocyte atrophy, trichrome highlights compressed central veins
Differential diagnosis
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