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Methotrexate-related multifocal axonopathy. Report of an autopsy case
1Department of Pathology, Tokyo Medical and Dental University, Japan.
Abstract:
A case of multifocal axonopathy associated with intrathecal methotrexate (IT MTX) and radiation therapy is presented. A 33-year-old woman suffering from meningeal carcinomatosis of breast cancer origin had developed prominent multifocal axonal degeneration in the cerebral white matter after treatment with IT MTX therapy and cranial irradiation. The principal features of this axonal degeneration were segmental hydropic swellings, macrophage infiltration of swollen axons, and scattered spheroid formation associated with reactive astrocytosis. These features were similar to those observed in our previous experimental study using cats treated with IT MTX alone. This "multifocal axonopathy" without necrotizing lesions seems to be different from disseminated necrotizing leukoencephalopathy, and, therefore, may be another form of MTX-related leukoencephalopathy. IT MTX and cranial irradiation seem to have exerted synergistic effects in producing the "multifocal axonopathy" in this case.
Insights
A patient developed multifocal axonopathy, a brain white matter condition, after intrathecal methotrexate (IT MTX) and radiation therapy for breast cancer. This suggests a distinct MTX-related leukoencephalopathy possibly due to synergistic treatment effects.
Area of Science:
- Neuro-oncology
- Neuropathology
- Toxicology
Background:
- Meningeal carcinomatosis, a complication of breast cancer, is often treated with intrathecal methotrexate (IT MTX) and cranial irradiation.
- The neurotoxicity of these treatments, particularly IT MTX, can manifest in various ways, including leukoencephalopathy.
Observation:
- A case study of a 33-year-old woman with breast cancer-related meningeal carcinomatosis is presented.
- The patient developed significant multifocal axonal degeneration in the cerebral white matter following treatment with IT MTX and cranial irradiation.
Findings:
- The observed axonal degeneration featured segmental hydropic swellings, macrophage infiltration, and spheroid formation with reactive astrocytosis.
- These pathological findings resemble those seen in experimental studies with IT MTX alone, suggesting a specific pattern of injury.
- The condition, termed "multifocal axonopathy," appears distinct from disseminated necrotizing leukoencephalopathy and may represent a novel form of MTX-induced neurotoxicity.
Implications:
- The findings suggest that combined IT MTX and cranial irradiation may have synergistic effects, leading to this specific type of "multifocal axonopathy."
- This distinct pattern of leukoencephalopathy should be considered in patients receiving similar treatment regimens.
- Further research is warranted to elucidate the precise mechanisms and long-term consequences of this neurotoxic effect.