Leukoencephalopathy in Waldenstromʼs Macroglobulinemia

The clinical and pathologic features of a case of Waldenströmʼs macroglobulinemia with leukoencephalopathy are reported. Multiple cerebral foci of de-myelination, accompanied to a lesser extent by axonal degeneration, were associated with perivascular infiltrates of plasmacytoid lymphocytes and with permeation of the white matter by macroglobulins. Immunohistochemical studies demonstrated a predominance of IgM kappa within the blood plasma, in cerebral blood vessel walls, in the foci of demyelination, and within perivascular histiocytes. Electron microscopy disclosed the presence, in macrophages and pericytes, of membrane-bound cytoplasmic inclusions consisting of tubular arrays, suggestive of cryoglobulin deposits. We hypothesize that the high serum levels of macroglobulins accompanied by lym-phoplasmocytic infiltrates may, either by way of viscosity-related ischemia, or by a direct toxic effect, have caused abnormal vascular permeability, infiltration of the cerebral parenchyma by paraproteins, and, ultimately, focal degeneration of the white matter.