Liver & intrahepatic bile ducts
Benign / nonneoplastic
Nodular regenerative hyperplasia
Author: Deepali Jain, M.D.
Last author update: 1 February 2012
Last staff update: 27 April 2023 (update in progress)
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed Search: Nodular regenerative hyperplasia liver
Table of Contents
Definition / general | Clinical features | Laboratory | Gross description | Microscopic (histologic) description | Positive stains | Differential diagnosisCite this page: Jain D. Nodular regenerative hyperplasia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/livertumornodularregenhyper.html. Accessed September 30th, 2023.
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 ≥ 40 years old
- 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
Laboratory
- 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
- Diffuse nodules of hyperplastic hepatocytes with central, single portal tract but with different orientation at low power
- 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
- 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
Differential diagnosis
- Cirrhosis
- Focal nodular hyperplasia:
- Central scar
- Hepatocellular adenoma
- Incidental focus of nodular hyperplasia
- Other noncirrhotic portal hypertension
- Primary biliary cirrhosis
