Meningeal Dissemination (MD) in Primary CNS Lymphoma (PCNSL): Multimodal Diagnosis, Presentation and Outcome in a Large Monocenter Patient Cohort

Introduction: The frequency of meningeal dissemination (MD) in primary central nervous system lymphoma (PCNSL) reported in the literature differs. The optimal management and the prognostic impact of MD have not been defined.

Methods: Data on MD from all 92 immunocompetent patients primarily diagnosed with PCNSL at our institution between January 1994 and February 2007 were retrospectively analysed for MD evaluation. All patients received cranial MRI or CT, and in 71 patients CSF was obtained by lumbar puncture. High-dose methotrexate was the intended treatment in all patients.

Results: Cerebrospinal fluid (CSF) was obtained by lumbar puncture in 71 patients (median age 62 years) of a total of 92 patients with PCNSL. Cytomorphologic CSF examination was performed in 63, immunophenotyping in 32 and PCR of the CDR3 region in 37 patients. Eight of 63 patients (13%) had positive cytomorphology, one of 32 (3%) positive immunocytology and 6 of 37 (16%) had monoclonal B-cells on PCR analysis. Evidence of MD on MRI or CT was found in three of the 71 patients (4%). Altogether, 11 (16%) patients had evidence of MD diagnosed by either of the methods used. Median CSF cell count was 5/μl (range, 0–237; n=66), and median protein concentration 76 mg/dl (range, 93–4117; n=55). An elevated cell count (>5/μl) was found in 27 (41%) patients, an elevated protein (>45 mg/dl) in 44 (80%). No significant correlation was found between proof of MD and CSF pleocytosis or elevated protein. Patients with MD did not differ from other patients with respect to age, gender, clinical presentation, performance status, CSF cell count and protein concentration, number of intracerebral lesions, lesion location or histology. After a median follow-up of 56 months, median EFS was 26 (95% CI, 4.3 to 47.7) months for MD patients and 34.1 (95% CI, 26.2 to 42) months for those without MD, p=0.26 (log-rank). Of 21 patients with relapse after initial treatment response, 16 had isolated cerebral relapse, one isolated meningeal relapse, two systemic relapse (one with cutaneous, and one with testicular manifestation), and one concomitant systemic (lung/thoracic wall) and cerebral relapse. Of the four MD patients with relapse after initial response, three had cerebral relapse, and one had systemic (cutaneous) relapse. The median overall survival (OAS) of patients with MD was 45.5 months (95% CI, 16.6 to 74.4), of those without MD 42.5 months (95% CI, 35.8 to 49.2) (p=0.27).

Conclusions: The frequency of MD detected in our cohort was low despite the use of highly sensitive diagnostic methods. No impact on either EFS or OAS was seen for MD.