DIAGNOSIS - Cerebral T-cell lymphoma.
Primary CNS lymphomas constitute about 6% of all primary brain tumours. The great majority of these tumours are of B-cell phenotype, and in Western countries only 2-5% of CNS lymphomas are derived from T-cells (3).
Primary CNS lymphomas of T-cell type (T-PCNSL) may appear at any age, with a median age of about 60 years at diagnosis and with a slight male predominance (10). Most affected patients are immunocompetent, but T-PCNSL has been reported in patients with human immunodeficiency virus (HIV) or human T-lymphotropic virus 1 (HTLV-1) infections (9, 10). Epstein-Barr virus (EBV) plays a roll in B-cell lymphomas, especially in immunocompromised patients (3), but the virus has not been linked to T-PCNSL (5, 8). In the present case, a serologic test for HIV was negative, but HTLV-1 status was not determined. In situ hybridisation for EBV on autopsy material was negative.
Patients with T-PCNSL are usually treated with chemotherapy followed by irradiation, with or without initial corticosteroid treatment. The prognosis is poor, with a 5-year disease-specific survival of 17% and a median progression-free survival of 22 months, as reported in a study of 45 patients (10). Several factors have been linked to a worse prognosis, such as advanced age, tumour in deep brain structures (cerebellum, brainstem, corpus callosum, and basal ganglia), elevated serum lactate dehydrogenase, and elevated CSF protein levels (1, 6). In the present case, the approximate duration of the illness was 14-15 months.
It may prove difficult to clinically diagnose a T-cell lymphoma of the CNS, as illustrated in the present case with negative CSF cytology, positive octreotide scintigraphy and meningeal enhancement on MRI (probably due to repeated lumbar punctures). As in this case, MRI often shows a non-specific solitary mass located in one of the cerebral hemispheres (7, 8, 10), and brain biopsy is required for diagnosis. However, in the CNS, T-cell lymphomas often present as infiltrating cells with small nuclei and bland morphology, although pleomorphic or large cell phenotypes are not infrequent (10), which explains why T-PCNSL may be mistaken for non-neoplastic lymphoid infiltrates. In addition, previously administered corticosteroid treatment may further complicate the histopatholoigcal diagnosis.
Genotypic analysis for TCR gamma (5) and other (4) TCR gene rearrangements, in order to detect monoclonality, may be necessary to establish the diagnosis, as no immunohistochemical marker to detect T-cell monoclonality exists. In the present case, in which a tumour diagnosis was not anticipated, the whole brain was routinely fixed for several days in formaldehyde solution before sectioning and staining, and genotypic analysis was therefore not possible. However, the autopsy could provide a more solid base for diagnosis than a brain biopsy would have done in this case, especially in the light of the rather loosely scattered tumour cells and their non-neoplastic appearance.
The immunophenotype of T-PCNSL varies among cases reported in the literature. Staining may be positive for either or both CD4 and CD8 or as in the present case both may be negative (2, 5, 8). Also, lymphoma cells may lose their expression of CD5 and CD7 (5), as seen in many cells in the present case.
Although alternative conditions (such as infection, granulomatous diseases and other inflammation) may be considered, the presentation of unusually fluctuating symptoms in a patient with progressive deterioration and contrast-enhancing lesions on MRI should be considered to represent a brain tumour until proven otherwise.
Contributed by Hans Brunnström, Michael Dictor, Christer Nilsson, Dag Gülich, Elisabet Englund