Diagnostic Images: Cirrhotic nodules

Femela M

Consultant – Pathology, Kauvery Hospital, Radial Road, Chennai

Diagnostic Images

Figure legend: Cirrhotic nodules of liver highlighted by Masson trichrome stain (MTS × 40) (fibrous septae stained blue and hepatocytes comprising the nodules stained red)

Definition

Cirrhosis is a chronic, progressive liver disease characterized by diffuse fibrosis, the formation of regenerative nodules, and architectural distortion of the hepatic parenchyma. It represents the final common pathway of many chronic liver diseases.

Etiologies of Cirrhosis

  • Chronic viral hepatitis (HBV, HCV)
  • Alcoholic liver disease
  • Non-alcoholic steatohepatitis (NASH)
  • Autoimmune hepatitis
  • Biliary cirrhosis (PBC, PSC)
  • Metabolic disorders (e.g., hemochromatosis, Wilson’s disease)
  • Drug-induced liver injury

Gross Pathology

  • The liver appears shrunken, firm, and nodular.
  • Nodules are surrounded by fibrous septa.
  • Depending on the nodule size, cirrhosis is classified as:
    • Micronodular (<3 mm)
    • Macronodular (>3 mm)
    • Mixed

Histopathological Features

1. Fibrosis

  • Irregular deposition of collagen in the portal tracts and between hepatocytes.
  • Formation of fibrous septa connecting portal tracts to each other or to central veins.
  • Leads to disruption of lobular architecture.

2. Nodular Regeneration

  • Hepatocytes proliferate in response to injury, forming nodules.
  • Surrounded by fibrous tissue; lacks central veins in many cases.
  • Nodules vary in size based on etiology and progression.

3. Architectural Distortion

  • Loss of the classic hepatic lobular and acinus architecture.
  • Abnormal vascular connections (e.g., arterio-venous shunts).
  • Sinusoidal capillarization: sinusoids lose fenestrations and develop a basement membrane.

4. Inflammation

  • Portal tracts show chronic inflammatory infiltrates, mainly lymphocytes.
  • Interface hepatitis (piecemeal necrosis) may be present in active disease.
  • Kupffer cell hyperplasia may also be seen.

5. Hepatocyte Changes

  • Ballooning degeneration
  • Fatty change (steatosis), especially in alcoholic and NASH-related cirrhosis
  • Mallory–Denk bodies in alcoholic and NASH
  • Apoptosis and necrosis in active disease

6. Bile Ductular Reaction

  • Proliferation of bile ductules at the interface of portal tracts and parenchyma.
  • Seen in cholestatic liver diseases and cirrhosis due to other causes.

Special Stains in Diagnosis

StainUses
Masson's TrichromeHighlights collagen (fibrosis)
Reticulin stainShows collapse or altered architecture
PAS/PAS-DGlycogen, α1-antitrypsin globules
Prussian BlueIron deposits (e.g., hemochromatosis)
Orcein stainHepatitis B surface antigen (HBsAg)
ImmunohistochemistryCD34 (capillarization), CK7/CK19 (ductular reaction), α-SMA (stellate cell activation)

Pathogenesis of Cirrhosis (Histologic Perspective)

  • Hepatocyte injury:  necrosis/apoptosis
  • Inflammation: cytokine release
  • Activation of hepatic stellate cells (HSCs): ECM deposition
  • Fibrous septa formation: bridging fibrosis
  • Nodule formation: via regeneration

Conclusion

Histopathological examination is essential for:

  • Confirming the diagnosis of cirrhosis
  • Determining etiology
  • Assessing severity and staging
  • Evaluating prognosis

A liver biopsy, while limited by sampling error, remains the gold standard for assessing the degree of fibrosis, the presence of inflammation, and nodular regeneration, all of which have significant clinical implications.

References

  • Schuppan D, Afdhal NH. Liver cirrhosis. 2008;371(9615):838–851.
  • Anthony PP et al. The morphology of cirrhosis. Bull WHO. 1977;55(4):521–540.
  • Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005;115(2):209–218.
  • Rastogi A, et al. Laennec staging and portal hypertension. 2013;62(5):696–706.
  • Friedman SL. Stellate cells in liver fibrosis. Physiol Rev 2008.
  • Schuppan D, Afdhal NH. Liver cirrhosis. 2008 Mar;371(9615):838–851. doi:10.1016/S0140-6736(08)60383-9
  • MacSween RNM, Burt AD. Muir’s Textbook of Pathology, 14th Ed. Arnold Publishers, 2008.
  • Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005;115(2):209–218. doi:10.1172/JCI24282
  • Anthony PP, Ishak KG, Nayak NC, et al. The morphology of cirrhosis: recommendation of a nomenclature system. Bull WHO. 1977;55(4):521–540.
  • Desmet VJ. The liver: an overview of basic morphology. In: Histopathology of the Liver. Springer; 1994.
  • Brunt EM, Tiniakos DG. Histopathology of nonalcoholic fatty liver disease. World J Gastroenterol. 2010;16(42):5286–5296.
  • Zatloukal K, Stumptner C, Fuchsbichler A, et al. Mallory bodies: lessons from keratin-containing inclusions in liver disease. Am J Pathol. 2002;160(3):763–778.
  • Libbrecht L, Cassiman D, Desmet V, Roskams T. The role of progenitor cells in the development of fibrous septa in human liver. 2002;36(3):704–713.
  • Rosai J. Rosai and Ackerman’s Surgical Pathology, 10th Ed. Elsevier; 2011.
  • Friedman SL. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev. 2008;88(1):125–172.

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