Rethinking fibrinogen storage disease of the liver: ground glass and globular inclusions do not represent a congenital metabolic disorder but acquired collective retention of proteins.

Abstract

Three types of intracytoplasmic inclusions immunoreactive to fibrinogen are collectively diagnosed as hepatic fibrinogen storage disease. This study aimed to better characterize ground glass (type II) and globular (type III) fibrinogen inclusions by the pathological examination of 3 cases and a literature review. Three adults (age: 32-64 years; male/female = 2:1) were unexpectedly found to have fibrinogen-positive ground glass changes (type II inclusions) by liver needle biopsy, against a background of acute hepatitis E, resolving acute cholangitis, or severe lobular hepatitis of unknown etiology. One patient also had fibrinogen-positive intracytoplasmic globules (type III inclusions) in the first biopsy, but they were not present in a second biopsy. None had coagulation abnormalities or hypofibrinogenemia. On immunostaining, both inclusions were strongly positive for not only fibrinogen but also C-reactive protein and C4d. Ultrastructurally, ground glass changes corresponded to membrane-bound cytoplasmic inclusions containing amorphous, granular material. The pathological features of type II fibrinogen inclusions were identical to those of pale bodies in hepatocellular carcinoma. The literature review suggested that type I fibrinogen inclusions characterized by a polygonal appearance are strongly associated with mutations in fibrinogen genes, coagulopathy, and family history, whereas type II/III inclusions are immunoreactive to multiple proteins and typically develop in cases of other unrelated liver diseases. In conclusion, type II and III fibrinogen inclusions do not represent a true hereditary storage disease but instead the collective retention of multiple proteins. Given the lack of clinical significance, a less specific name (e.g., pale body) may be more appropriate for those inclusions.

• Authors: Yoh Zen, Takashi Nishigami
• Journal: Human pathology (Hum Pathol) Vol. 100 Pg. 1-9 (06 2020) ISSN: 1532-8392 [Electronic] United States
• PMID: 32330484 (Publication Type: Case Reports, Journal Article, Review)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Peptide Fragments
• Complement C4b
• complement C4d
• Fibrinogen
• C-Reactive Protein

Topics

• Adult
• Biomarkers (analysis)
• Biopsy
• C-Reactive Protein (analysis)
• Complement C4b (analysis)
• Female
• Fibrinogen (analysis, genetics)
• Humans
• Immunohistochemistry
• Inclusion Bodies (chemistry, genetics, ultrastructure)
• Liver (chemistry, ultrastructure)
• Liver Diseases (classification, genetics, metabolism, pathology)
• Male
• Metabolism, Inborn Errors (classification, genetics, metabolism, pathology)
• Middle Aged
• Peptide Fragments (analysis)
• Terminology as Topic