LOBAR PILOCYTIC ASTROCYTOMAS OF THE CEREBRAL HEMISPHERES .2. PATHOBIOLOGY - MORPHOGENESIS OF THE EOSINOPHILIC GRANULAR BODIES

This study provides new immunocytochemical observations on the so-call ed eosinophilic granular bodies (EGBs), seen predominantly (but not ex clusively) in pilocytic astrocytomas. Using combined immunohistochemic al and immunoelectron microscopic approaches on formalin-fixed, paraff in-embedded tissues, we have demonstrated that (1) EGBs exhibit pronou nced 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 floc cular densities, or larger conglomerates of amorphous, globular materi al; (2) an antiserum to ubiquitin-protein conjugates, codistributes in the EGBs at the light microscopic level, while ultrastructurally is e ither localized in diffuse, finely granular deposits, and/or fragmente d filamentous particles; and (3) that a monoclonal antibody to beta-am yloid 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 proteas es. We postulate that EGBs contain complexes of serpins and hitherto u nknown protease(s), which are in turn probably degraded via ubiquitin mediated mechanism(s). Although EGBs typify pilocytic astrocytomas, th ey may be exceptionally present in malignant astrocytomas, calling for cautious interpretation of their biologic as well as prognostic impor t.