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Central nervous system (CNS) involvement in acute leukemia and lymphoma: indications for CNS assessment and advice for diagnostic strategy1)

Abstract Involvement of the central nervous system (CNS) must be considered in leukemia and lymphoma to develop a promising treatment strategy. In particular, a relapse within the CNS compartment is associated with a dismal prognosis. Therefore, CNS involvement should be detected as early as possible during the disease course. The risk for CNS disease varies considerably between the diseases. For diseases with a proven high-risk for CNS involvement, such as acute lymphoblastic leukemia (ALL) or Burkitt’s lymphoma, prophylactic strategies are used. Although not in every entity, evidence-based therapeutic standards do exist, the detection of tumor cells in the cerebrospinal fluid (CSF) will have an impact on the therapeutic concept. This holds true for the preemptive situation with low tumor burden as well as for the therapeutic situation with a symptomatic patient. Whereas parenchymatous lesions are detected by magnetic resonance imaging, CSF analysis is the method of choice for the diagnosis of neoplastic meningitis. Cytomorphology of CSF cells, if used by an experienced cytopathologist, is of sufficient specificity but limited sensitivity for the diagnosis of leukemia. In lymphoma, cytomorphology has only modest specificity, because rather seldom conclusions can be drawn about the lineage commitment of the lymphoma cells and there is no possibility to prove clonal disease. Furthermore, it is often very difficult to discriminate between neoplastic meningitis and reactive pleocytosis. By combining cytomorphology with flow cytometry, sensitivity as well as specificity can be improved. Careful acquisition of the CSF sample by lumbar puncture is important. Only the last of several CSF fractions should be assessed by cytomorphology and flow cytometry to avoid contamination with peripheral blood. It is further mandatory that essential clinical information is provided by the clinician to the laboratory, so that a well-suited antibody panel can be chosen. This will save material and laboratory time and will further accelerate analysis. Owing to the limited number of cells within the CSF, analysis should always start with a basic antibody panel, which can then be extended on demand.