Rod-shaped filamentous inclusions and other ultrastructural features in a cerebellar astrocytoma

Abstract

A biopsy specimen of a cerebellar astrocytoma from a 14-year-old girl was studied by light and electron microscopy. Histologically the tumor showed a mixture of loose and compact areas with numerous Rosenthal fibers. By electron microscopy most tumor cells contained, besides the usual organelles, large amounts of 70 to 100 A thick filaments. Classical Rosenthal fibers were also identified. In addition many cell bodies and processes were sprinkled with fragments of Rosenthal fiber material. Ordered filamentous arrays (so-called Hirano bodies) were seen in a number of tumor astrocytes. They are considered to be a nonspecific arrangement of filament units largely devoid of cytopathologic significance. Other ultrastructural features of some tumor cells were inchoate forms of the granulated bodies of conventional histology, paired cisternal elements of rough endoplasmic reticulum, and honeycomb-like profiles of transversely cut cylindrical units of smooth endoplasmic reticulum. Microtubular bodies were numerous in the endothelial cells of the tumor vessels.

Formation of Hirano Bodies Induced by Expression of an Actin Cross-Linking Protein with a Gain-of-Function Mutation

“…More generally, the formation of Hirano bodies is a general response of eucaryotic cells to or a consequence of aberrant function of the actin cytoskeleton. Hirano bodies cannot be regarded as "non-specific manifestations of neuronal degeneration" (62) or a "non-specific finding largely devoid of cytopathologic significance" (20). The formation of Hirano bodies may sequester actin, actin-associated proteins, and other components that contribute to morphogenesis and to the plasticity of synaptic connections essential to neuronal function (38).…”

“…During the past three decades, Hirano bodies have been reported to be associated with a broad array of conditions, including Alzheimer's disease (21,44,45,60), Parkinson's disease (25), Pick's disease (61), amyotrophic lateral sclerosis (25), ataxic Creutzfeldt-Jakob disease (3), kuru (9), scrapie (10), leukoencephalopathy (23), chronic alcoholism (32), diabetes (64), cancer (12,20), muscle degeneration (11), and neuronal degeneration associated with abnormal copper homeostasis (1,46,53,71). Hirano bodies are paracrystalline cytoplasmic inclusions that contain actin filaments and actinassociated proteins (19,22,39).…”

Systemic lupus erythematosus clinically resembling multiple sclerosis and with unusual pathological and ultrastructural features.

“…In these situations their fine structure was indistinguishable from that of the classic Hirano bodies initially described in Sommer's sector of the hippocampus in Guamian amyotrophic lateral sclerosis-Parkinsonism-dementia complex (Hirano et al, 1968). Similar though often smaller inclusions have also been seen in other circumstances-for example, in cerebellar tumours (Gessaga and Anzil, 1975), in normal and kuruinfected cerebellum (Field and Raine, 1968), in muscle disease (Neville, 1973), and within neuronal nuclei in both normal and pathological CNS (Feldman and Peters, 1972;Cragg, 1976).…”

Screening for GFAP rearrangements in a cohort of Alexander disease and undetermined leukoencephalopathy patients

“…Moreover, gene expression analysis by micro-array reveals a similar expression profile of stress-and immune-related genes between transgenic mice overexpressing human wild-type GFAP and AxD patients, confirming the reliability of this model [Hagemann, et al, 2005]. Finally some M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 7 human diseases such as pilocytic astrocytoma [Gessaga and Anzil, 1975] or multiple sclerosis [Herndon, et al, 1970] display prolonged GFAP overexpression, resulting in RF formation despite the absence of a mutation. Together, these data confirm that GFAP overexpression in astrocytes could promote aggregation into RFs independently of a mutant protein, and so be involved in AxD pathogenesis.…”