Immunohistochemical and Ultrastructural Features of Hepatocellular Cytoplasmic Globules in Venous Outflow Impairment

Objectives: To examine the immunohistochemical and ultrastructural features of hepatocellular cytoplasmic globules in venous outflow impairment (VOI). Methods: Sixty-four liver core biopsies were screened. Patients with α-1 antitrypsin (AAT) deficiency were excluded. All biopsies were stained with H&E, Masson trichrome, periodic acid-Schiff with diastase digestion (PAS-D), phosphotungstic acid hematoxylin (PTAH), complement protein 4d (C4d) immunostain, and AAT immunostain. Electron microscopy was also performed. Results: Hepatocellular globules were identified in 8% of in-house cases. Causes of VOI included heart failure and Budd-Chiari syndrome. The hepatocellular cytoplasmic globules showed size variability, random distribution, and positivity for PAS-D, PTAH, and AAT. C4d was inconsistently positive. Electron microscopy showed that the globules were lysosome-bound inclusions containing microfibrillar material and fibrinogen. Conclusions: PAS-D-positive hepatocellular globules occur in VOI. They cross-react with AAT but have different appearance, localization, and ultrastructural composition from globules in AAT deficiency.