Background Systemic malignancy and its treatment can produce a variety of cerebral abnormalities. Malignancy itself can lead to metastatic disease and paraneoplastic encephalomyelitis Patients on chemotherapy can develop the Posterior Reversible Encephalopathy Syndrome (PRES) and Progressive Multifocal Leucoencephalopathy (PML). Certain chemotherapy agents such as methotrexate can induce toxic leucoencephalopathy (TLE), which can be difficult to distinguish from the above. We present 2 cases of progressive leucoencephalopathy in patients with cancer, with serial imaging and histology to highlight the distinguishing features of PML and TLE secondary to methotrexate.

Patients Case 1 was a 36 year old lady who had chondrosarcoma of the left knee treated with above knee amputation and chemotherapy with high dose methotrexate, cisplatin and doxorubicin. She developed weakness of the left arm, and on MRI scanning was shown to have an area of T2 high signal in the right centrum semiovale. The weakness resolved over a few days, but repeat MRI scan showed increasing size of the white matter abnormality, raising suspicion of PML. PCR on CSF was negative for JC and BK viruses. Serial imaging showed continued increase in the size of the lesion, even after chemotherapy had been discontinued. She developed metastatic cancer and died 15 months later. At post mortem, analysis of the brain revealed patchy low grade demyelinating process with myelin pallor and vacuolation, and axonal sparing. There were no areas of necrosis. PCR was negative for JC and BK virus DNA. The pathological changes were characteristic of methotrexate induced TLE.

Case 2 is a 66 year old man who was receiving chemotherapy with fludarabine for chronic lymphocytic leukaemia. He developed an elementary visual aura followed by a generalised seizure. MRI scan showed high signal abnormality in the occipital regions, raising the possibility of PRES. Serial imaging showed progressive increase in the size of the lesion over 9 months, followed by a degree of involution. He suffered a further episode of probable complex partial seizure and was started on lamotrigine. CSF analysis showed no evidence of JC or BK virus DNA. A brain biopsy was performed which showed astrocytes with copious eosinophilic cytoplasm, and irregular bizarrely shaped enlarged nuclei with nucleolar prominence. JC virus DNA was detected by PCR, confirming the diagnosis of PML

Conclusion We present serial MRI scanning changes at 3 monthly intervals over 15 months in 2 patients developing progressive leucoencephalopathy in the setting of malignancy. CSF analysis was normal in both patients, but histology showed features of PML in one case and toxic leucoencephalopathy in another. The clinical imaging and pathological characteristics of TLE, PML and PRES are summarised.