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

Hereditary Hypofibrinogenemia with Hepatic Storage

“…More recently, a re-evaluation of HHHS inclusions was proposed by Zen and Nishigami [ 27 ] through the study of three peculiar cases of liver disease and, above all, by an in-depth review of the literature. At biopsy, the three patients all showed fibrinogen-positive ground glass changes (type II inclusions), with one also having fibrinogen-positive intracytoplasmic globules (type III inclusions), but none of them suffered from hypofibrinogenemia.…”

“…By reviewing the literature, it became evident that: (i) Type I fibrinogen deposits are strongly associated with fibrinogen mutations, hypofibrinogenemia, and familiarity for the coagulopathy (i.e., though the relevant mutation has not been disclosed, it is possible that the condition is genetically determined); whereas (ii) type II and III inclusions are immunoreactive to many different proteins and are usually associated with liver diseases not related to fibrinogen deficiency. Given the lack of association with hypofibrinogenemia, a less specific name (e.g., pale body) was proposed as more suitable for these deposits [ 27 ].…”

Hepatocellular type II fibrinogen inclusions in a patient with severe COVID-19 and hepatitis

“…7 Of note, fibrinogen storage disease without hypofibrinogenemia, which corresponds to the clinical picture presented by our patient, has rarely been associated with acute infections in patients without any hereditary defect of fibrinogen. 8,9 Our patient presented very high plasma fibrinogen levels, making the presence of a known FGG mutation very unlikely, as confirmed by genetic testing. Increased fibrinogen production likely played a key role in the hypercoagulable state and pulmonary embolism.…”

Rare Case of Advanced Gastric Cancer Complicated with Fibrinogen Storage Disease Treated with Chemotherapy plus Immune Checkpoint Inhibitor: A Case Report

“…FSD is classified into three groups (type I, type II, and type III) based on differences in the form of fibrinogen that abnormally accumulates. Type I is inherited in an autosomal dominant manner with mutations in the fibrinogen gamma chain [10], whereas type II and type III are nonhereditary and are caused by acquired intracellular secretory dysfunction due to infection or other agents [6]. Pathologically, type I inclusions are characterized by irregularly contoured Case Reports in Oncology circular to polygonal inclusions; type II, by large, single, frosted, glass-like inclusions; and type III, by circular inclusions with halos [10,11].…”