Novel isolated cerebral ALlambda amyloid angiopathy with widespread subcortical distribution and leukoencephalopathy due to atypical monoclonal plasma cell proliferation, and terminal systemic gammopathy.
Neuropathologic and biochemical findings in a 34-year-old man whose disease began 2 years before death appearing as chronic progressive encephalitis and culminated in mutism are reported. Cerebrospinal fluid and serum of the patient showed a brain-restricted monoclonal lambda-light chain apparently produced by a small monoclonal immunoglobulin Glambda plasma cell population. In the preterminal stage, there was a systemic monoclonal gammopathy, the source of which could not be identified. At autopsy, there was extensive amyloid deposition in most vessels throughout the cerebral and cerebellar white matter, basal ganglia, and thalamus and diffuse leukoencephalopathy; cerebral and cerebellar cortices, other portions of the CNS, and non-CNS tissues were spared. Partial amino acid sequence analysis demonstrated that the amyloidogenic protein originated from immunoglobulin lambda-light chains which were produced by monoclonal plasma cells. There are 2 similar cases reported in the literature. The distribution of ALlambda deposits in these 3 cases indicates that widespread subcortical vascular amyloidosis with leukoencephalopathy is a novel clinicopathologic entity distinguished from other cerebral diseases with local amyloid light chain deposition, including amyloidoma, leptomeningeal vascular amyloidosis, solitary intracerebral plasmacytoma, primary intracerebral lymphoma with plasmacytic differentiation, and multiple sclerosis with demyelination-associated amyloid deposition.
Schröder
Roland
R
Department of Neuropathology, University Hospital of Cologne, Cologne, Germany. neuropatho@uni-koeln.de
Deckert
Martina
M
Linke
Reinhold P
RP
D000328:Adult; D000595:Amino Acid Sequence; D000682:Amyloid / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D016657:Cerebral Amyloid Angiopathy / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015140:Dementia, Vascular / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D017809:Fatal Outcome; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000032:analysis; D007150:Immunohistochemistry; D007525:Isoelectric Focusing; D008297:Male; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D010265:Paraproteinemias / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
D000682:Amyloid; D007146:Immunoglobulin lambda-Chains; C035222:amyloid protein AL