Role of macrophages in onion-bulb formation in localized hypertrophic mononeuritis (LHM)

A unique pathogenetic process for onion-bulb (Ob) formation is disclosed with disclosed with immunohistochemistry and electron microscopy. Biopsy of a swollen segment of tibial nerve from a 42 year-old white female histologically demonstrated diffuse and angiocentric lymphocytic infiltrate in both endo- and perineurium with occasional lymphofollicular formation. Extensive Ob formation of nerve fibers was most striking with or without associated lymphocytes. Axis-cylinders were intact in the majority of Ob. Immunocytochemically, Ob are composed of alternately laminated leaflets of Schwann cells (S100+) and mononuclear macrophage (HAM56+/LeuMl+/Muramidase+) processes but no perineurial (EMA+) cells. Immunohistochemical evidence of antigen presentation (HLA-DR/LN3+/Ia+) was confined to macrophages. Electron microscopy insinuates that intricate interactions between macrophages and Schwann cells exists. Putative inhibition of remyelination along with proliferation of Schwann cells most probably is secondary to the effects of macrophages secretory products. No direct participation of B or T lymphocytes was detected in Ob. Thus, modified macrophages may emit a factor for concomitantly promoting proliferation of Schwann cells and an enzyme for myelin breakdown. In addition, only a few macrophages could be detected in some Ob and could be easily overlooked or misinterpreted as "vacuolated fibroblasts", if no immunohistochemical correlation is made, as modified macrophages making the external leaflets of Ob are more vacuolated.