Prospective evaluation of meningeal involvement in primary CNS lymphoma (PCNSL)

Abstract

2029 Background: The prognostic impact of meningeal dissemination (MD) in PCNSL is still debated, and the reported incidence varies. Sensitive methods like polymerase chain reaction (PCR) might enhance the diagnostic accuracy to detect clonal cells in the cerebrospinal fluid (CSF). We prospectively evaluated the diagnostic value of PCR in comparison with CSF cytomorphology and cerebral magnetic resonance imaging (MRI) for diagnosing MD in PCNSL. Methods: A total of 282 patients from a multicenter therapy trial for PCNSL were evaluated for the presence of MD: 217 with cranial MRI, 205 with CSF cytomorphology and 171 with PCR of the rearranged immunoglobulin heavy-chain CDRIII region genes in CSF. A CSF protein ≥45mg/dl and a CSF cell count > 5/μl were denoted as abnormal. Results: MD was found in 33 of 205 patients (16%) by cytomorphologic examination, in 19 of 171 (11%) patients evaluated by PCR and in eight of 216 patients (4%) by MRI. Considering all methods, the incidence of MD was 17.4% (49 of 282 patients). PCR was monoclonal in six of 19 samples (32%) with positive, in one of 13 samples (7.7%) with suspicious, and in ten of 105 (9.5%) samples with negative cytology. In 11 samples with positive and 12 with suspicious cytology PCR was polyclonal. Of the eight MRI positive patients, CSF cytology was positive in five (two patients not evaluated), and a monoclonal PCR product was found in two (six patients not evaluated). MD was more probable in cases with CSF pleocytosis with an odds ratio of 2.48 (95% CI: 1.15 - 5.34, p=0.018), whereas CSF protein had no predictive value for MD detection. Pleocytosis correlated significantly with a positive cytology (23% vs. 5%, p=0.001) but not with MD detection by PCR. Conclusions: A low incidence of MD in PCNSL was found in this large prospective study, despite the use of PCR. The diagnostic accuracy was enhanced by PCR, however, discordant PCR and cytologic results were frequent. CSF pleocytosis had predictive value for MD detection. No significant financial relationships to disclose.