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Liver and intrahepatic bile ducts - Tumor

Benign tumors

Nodular regenerative hyperplasia

Reviewers: Deepali Jain, M.D. (see Reviewers page)
Revised: 9 January 2013, last major update February 2012
Copyright: (c) 2004-2013, PathologyOutlines.com, Inc.


● Nodular hyperplasia diffusely affecting entire liver, but with no/minimal fibrous septa

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
Laboratory findings: 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

Micro description

(a) Diffuse nodules of hyperplastic hepatocytes with central, single portal tract but with different orientation at low power
(b) 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
(c) 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

Micro images

H&E and reticulin stain

Positive stains

● Reticulin highlights nodular architecture and hepatocyte atrophy, trichrome highlights compressed central veins

Differential diagnosis

● Cirrhosis, primary biliary cirrhosis, focal nodular hyperplasia (central scar), other noncirrhotic portal hypertension, incidental focus of nodular hyperplasia, hepatocellular adenoma

Partial nodular transformation


● Very rare, focal form of nodular regenerative hyperplasia, usually perihilar region
● Portal hypertension usually prominent due to portal venous thrombosis

Micro description

● 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

End of Liver and intrahepatic bile ducts - Tumor > Benign tumors > Nodular regenerative hyperplasia

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