A man aged 50 years is brought to Accident and Emergency having apparently experienced a fit while shopping. He gives a history of occasional headaches over the past few weeks and some intermittent double vision in the last week. On examination, he has a right sixth nerve palsy but is fully orientated. His family, however, report some changes in his behaviour in the last month and were becoming concerned. He had made an appointment with his General Practitioner for the following day. A computed tomography (CT) scan of his head shows a single 3 cm lesion in the left frontal lobe with some mass effect. Neurosurgical biopsy gives a histological diagnosis of diffuse large B-cell lymphoma. There is no evidence of lymphoma in any other anatomical site.
How does one arrive at the diagnosis of primary central nervous system lymphoma (PCNSL)?
What biological and patient factors may influence the prognosis and management plan?
What are the issues in deciding on the optimum treatment for this patient?
Primary central nervous system (CNS) lymphoma is a distinctive form of the commonest high-grade type of non-Hodgkin lymphoma (NHL) – diffuse large B-cell lymphoma. It is unusual in being entirely localized to the CNS, in contrast to systemic high-grade NHL, which is often disseminated at diagnosis. There is thus a paradox: NHL presenting outside the CNS may spread to it but PCNSL does not become systemic. There is no clear biological explanation for this.
Primary CNS lymphoma is rare but on the increase. Recent UK figures report an incidence of 2.8 per million. It may account for up to 5% of primary brain tumours. The increasing incidence appears real and is not explained by improved diagnostics or by the human immunodeficiency virus (HIV) epidemic.
It presents as a space-occupying lesion in the CNS, with or without features of meningeal involvement (e.g. cranial nerve palsies). The clinical history is short. Personality changes and cognitive impairment are common. Focal neurological impairment such as hemiparesis and aphasia is also frequently seen. Seizures occur in approximately 10%–20% of patients. Headache is rarely a prominent complaint. Radiology reveals a mass lesion which is multifocal in over a third of cases.1 A diffuse brain abnormality with no mass lesion is also recognized and histologically there is often evidence of disease in brain tissue distant from the principal site. Primary CNS lymphoma is frequently not suspected on the basis of its radiological appearance, which may closely mimic the appearance of other CNS tumours.
Diagnosis usually requires a brain biopsy but this may be avoided if there is clear evidence on an examination of cerebrospinal fluid (CSF). Lumbar puncture is therefore essential (unless contraindicated) and is positive in 20% of cases,1 although autopsy studies suggest that unrecognized meningeal involvement is more common.2 Involvement of the ocular structures is detected by slit-lamp examination in ...