Lobar pilocytic astrocytomas of the cerebral hemispheres: II. Pathobiology--morphogenesis of the eosinophilic granular bodies.

This study provides new immunocytochemical observations on the so-called eosinophilic granular bodies (EGBs), seen predominantly (but not exclusively) in pilocytic astrocytomas. Using combined immunohistochemical and immunoelectron microscopic approaches on formalin-fixed, paraffin-embedded tissues, we have demonstrated that (1) EGBs exhibit pronounced reactivity with antibodies to serine protease inhibitors alpha-1-antichymotrypsin and alpha-1-antitrypsin; by immunoelectron microscopy, the reaction product is localized either in the form of diffuse floccular densities, or larger conglomerates of amorphous, globular material; (2) an antiserum to ubiquitin-protein conjugates, codistributes in the EGBs at the light microscopic level, while ultrastructurally is either localized in diffuse, finely granular deposits, and/or fragmented filamentous particles; and (3) that a monoclonal antibody to beta-amyloid precursor protein (beta-APP) stains smaller EGBs. The detection of serpin-like and beta-APP-like staining in EGBs may be a reflection of acute phase reactant activity in response to tumor-produced proteases. We postulate that EGBs contain complexes of serpins and hitherto unknown protease(s), which are in turn probably degraded via ubiquitin mediated mechanism(s). Although EGBs typify pilocytic astrocytomas, they may be exceptionally present in malignant astrocytomas, calling for cautious interpretation of their biologic as well as prognostic import.