title: Methotrexate-related nonnecrotizing multifocal axonopathy detected by beta-amyloid precursor protein immunohistochemistry.
abstract: We describe a 64-year-old woman with biphenotypic leukemia involving the meninges who received 2 doses of intrathecal methotrexate. Soon after treatment, the patient developed postural rigidity and a marked decline in mental status. The patient died of respiratory failure 1 month after methotrexate treatment was initiated. At autopsy, the brain was grossly normal. Routine microscopy showed no evidence of leukemic infiltrates or necrotizing lesions. However, when stained with beta-amyloid precursor protein, multifocal axonal injury was evident in the brain, spinal cord, and nerve roots. Our findings show that immunohistochemical staining for beta-amyloid precursor protein can effectively demonstrate axonal injury associated with methotrexate neurotoxicity, even when conventional staining procedures are negative. This technique may therefore reveal a possible pathologic substrate for some of the neurological complications seen in patients with methotrexate neurotoxicity.
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA. MooreB01@ummhc.org
authors.forename: Brian E
authors.initials: BE
authors.lastname: Moore
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Somers
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Smith
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D001369:Axons; D002493:Central Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007278:Injections, Spinal; D007938:Leukemia / Q000188:drug therapy; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged
chemical_list: D016564:Amyloid beta-Protein Precursor; D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate