Inadvertent Intrathecal Vincristine Administration with Widespread Axonal Injury Demonstrated by Amyloid Precursor Protein Immunohistochemistry

Abstract

Vincristine is a Vinca alkaloid chemotherapeutic agent used to treat hematologic and some solid organ neoplasms. As a microtubule inhibitor, an unfortunate side effect of this drug is disruption of axonal transport. Thus, the drug is intended for intravenous use only. We report a 59-year-old man with diffuse large B-cell lymphoma who inadvertently received intrathecal vincristine. The patient experienced progressive neurologic decline despite attempts at cerebrospinal fluid lavage with fresh frozen plasma and died five days after the incident. Grossly, there was evidence of prior shunt placement, the brain was mildly swollen, and the white matter appeared congested. Histological study revealed pallor of the centrum semiovale, focal perivascular hemorrhages, and widespread axonal spheroids that were demonstrated by immunohistochemical study for amyloid precursor protein (APP). There was subependymal spongiosis and focal hydropic-like change of the ependyma. Proximal axon segments of anterior horn neurons showed many APP-reactive spheroids as they exited the spinal cord. Anterior spinal nerve roots also contained APP-positive swellings. No significant pathologic changes were identified in the gray matter. In particular, there was no Purkinje cell loss. No evidence of residual lymphoma was identified. This case illustrates diffuse axonal injury that was caused by toxic disruption of axonal transport and was clearly demonstrated by immunohistochemistry for APP. This case emphasizes the need for continued awareness of this preventable medical error.