A case of primary biliary cirrhosis accompanied with fibrinogen storage disease.
We report the first case of primary biliary cirrhosis (PBC) accompanied by fibrinogen storage disease (FSD). A 50-year-old Japanese woman had been treated for numbness of her right-side extremities for 5 years. Mildly elevated serum levels of alkaline phosphatase and gamma-glutamyl transferase were detected. The titers of both anti-mitochondrial (x 320) and anti-mitochondrial M2 (x 84) antibodies were elevated. The biopsied liver specimen showed mononuclear cell infiltrate densely encircling the bile ducts, poorly developed epithelioid cell granuloma, and loss of integrity of bile duct organization, which permitted a diagnosis of stage I PBC according to Scheuer's histologic classification. In addition, round to oval, eosinophilic, homogenous intracytoplasmic inclusions, several microm in average size, with a surrounding halo were found in the vast majority of hepatocytes. These inclusions were negative for the periodic acid-Schiff reaction. In immunohistochemistry, the inclusions were positive for fibrinogen and complement C3c, but not for HBs antigen and alpha1-antitrypsin. These findings were identical to FSD. To investigate the mechanism(s) of abnormal fibrinogen storage, immunostaining for heat shock protein 70 and ubiquitin was performed. The former was detected in all intracytoplasmic inclusions, whereas the latter was detected in only some inclusions, suggesting a partial loss of ubiquitin expression.
Mitsui
Hiroko
H
Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
Miyauchi
Eisaku
E
Miyahara
Jun
J
Wada
Kiriko
K
Yamakawa
Mitsunori
M
Kawata
Sumio
S
D000469:Alkaline Phosphatase / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008661:Metabolism, Inborn Errors / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D008928:Mitochondria / Q000276:immunology; D025801:Ubiquitin / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
D001323:Autoantibodies; D015415:Biomarkers; D018840:HSP70 Heat-Shock Proteins; D025801:Ubiquitin; D005340:Fibrinogen; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase