Utility of Flow Cytometry of Cerebrospinal Fluid as a Screening Tool in the Diagnosis of Central Nervous System Lymphoma

Abstract

Context.-Experiences at our institution show that flow cytometry analysis (FCA) has become routine clinical practice in the workup of patients with altered mental status, even if risk factors are low.Objective.-To assess diagnostic accuracy of combined FCA and cytology in the diagnosis of central nervous system lymphoma in an unselected patient population with neurologic symptoms, including patients with no history of lymphoma or suspicious radiology.Design.-Between 2001 and 2011, cerebrospinal fluid was submitted from 373 patients for lymphoma screening by FCA. The medical records were reviewed for patient symptomatology, history of malignancy, brain imaging, FCA results, cytology results, brain biopsy, and clinical follow-up.Results.-A lymphoid malignancy was detected by FCA in 4% of cases. A positive diagnosis was more likely in patients with either a history of hematologic malignancy and/or a suspicious radiology result (P ¼ .009). All patients with no history of lymphoma and no suspicious radiology (n ¼ 102) had negative cytology, and none had a correspondingly positive FCA result. The positive and negative predictive values of combined cytology and FCA in the patients with history of lymphoma and/or abnormal imaging results were 92% and 89%, respectively, when compared with open brain tissue biopsy, and 89% and 86%, respectively, when compared with clinical followup. When low-risk patients were included, the positive predictive value remained at 92%, but the negative predictive value dropped to 52% with the open brain biopsy as the reference, and values did not change significantly for the group with clinical follow-up.Conclusions.-Concurrent FCA and cytology are most useful in the appropriate clinical setting, and we propose a triage algorithm for how FCA on cerebrospinal fluid is best used.

Clinical Presentation, Diagnosis, and Radiological Findings of Neoplastic Meningitis

“…1,[63][64][65]97 Several studies have demonstrated that the sensitivity of flow cytometry is several-fold higher than that of cytology for detecting CSF leukemia or lym-phoma. 98,99 Flow cytometry allows for the early detection of neoplastic meningitis before the onset of clinical symptoms and CSF pleocytosis; therefore, its use may enable more effective treatment. Patients with negative findings on cytology but positive findings on flow cytometry are often asymptomatic and have lower CSF cell counts and fewer neoplastic B cells when compared with patients whose cytology findings are positive.…”

The current role of clinical flow cytometry in the evaluation of mature B‐cell neoplasms

“…Therefore, FC has become a well-established tool in the diagnostic work-up of these diseases and has demonstrated utility in the evaluation of peripheral blood, bone marrow, body fluids, and disaggregated tissue biopsies (1). They are derived from the B-cell lineage, are clonal, and have morphologic, immunophenotypic, and genetic characteristics of mature (as opposed to precursor) B-cells.…”

“…All of these common features can be assessed, to some degree, by flow cytometry (FC), a rapid and sensitive technique for assessing protein expression on individual cells in a mixed cell suspension. Therefore, FC has become a well-established tool in the diagnostic work-up of these diseases and has demonstrated utility in the evaluation of peripheral blood, bone marrow, body fluids, and disaggregated tissue biopsies (1). However, as other modalities such as molecular testing are incorporated into the diagnostic workup of lymphoid neoplasms and new therapeutic options emerge, the role of FC has changed.…”

Accuracy of flow cytometry and cytomorphology for the diagnosis of meningeal involvement in lymphoid neoplasms: A systematic review

“…A total of 41 studies comparing flow cytometry and cytology in CSF samples from patients with lymphoid neoplasia were identified . Additionally, three more articles were excluded given they contained significant numbers of myeloid malignancies which could not be excluded during data extraction (47 in Bromberg et al, 22 samples in Cesana et al, 8 cases in Kovach et al): their applicability to our research question was therefore considered too low to be included in this review.…”