Cerebrospinal fluid abnormalities in meningeosis neoplastica: a retrospective 12-year analysis.

BACKGROUND: Meningeosis neoplastica is a diffuse metastatic spread of tumor cells in the subarachnoid space. Although first recognized in 1870, systematic investigations regarding cerebrospinal fluid (CSF) constituents in this condition are scarce. METHODS: Routine CSF samples analyzed from 2001 to 2012 at the Laboratory of Clinical Neurochemistry, University of Göttingen, were re-evaluated. Patients, whose CSF contained malignant cells were included in this study. RESULTS: Patients (n = 132, age 59.1 ± 29.1, 58% women) were identified, whose CSF contained malignant cells. The most frequent primary tumor was breast cancer (32.6%), followed by lung cancer (25.0%) and hematologic malignancies (21.2%). The most frequent clinical symptoms were affections of cranial nerves (41.7%), psychiatric abmormalities (32.6%) and radicular lesions of the lower extremities (20.5%). CSF cell counts ranged from 0 to 4692 cells/µl (median 4 cells/µl) and were elevated in 50%. The CSF-to-serum albumin ratio was abnormal in 69.4%. It ranged from 1.8 to 330 x 10-3 (median 17.5 x 10-3). Total CSF protein ranged from 166 to 15,840 mg/l (median 1012 mg/l). CSF lactate was elevated (>2.4 mmol/l) in 65.2% [3.6 mmol/l (1.3/15.6 mmol/l); median (minimum/maximum)]. In 50% of all patients CSF lactate was ≥3.5 mmol/l. The CSF cell counts correlated significantly with the CSF lactate levels and the CSF protein contents. In 56 of 118 CSF samples (47.5%) ferritin was elevated, and in 25 of 65 carcinoma patients (38.5%) an intrathecal production of carcinoembryonic antigen (CEA) was detected. Granulocytes were found in 52.7% of the CSF samples. The percentages of granulocytes and lymphocytes were higher in samples with an elevated cell count. CONCLUSION: In approximately 50% of CSF samples with meningeosis neoplastica the CSF cell count is not elevated. Diagnosis may be missed when only CSF samples with elevated cell counts are subjected to cytological analysis. CSF lactate and protein and the CSF-to-serum albumin ratio are frequently increased in meningeosis neoplastica. The differential diagnosis between meningeosis neoplastica and central nervous infections, in particular tuberculous or fungal meningitis, can be difficult.

CSF cytology--the ongoing dilemma to distinguish neoplastic and inflammatory lymphocytes.

To evaluate different morphological criteria for the distinction between inflammatory and neoplastic lymphocytes in the cerebrospinal fluid (CSF). Forty-two cytospin preparations of CSF from patients with confirmed CSF involvement by aggressive B-cell lymphoma or acute leukemia were compared with 26 samples of inflammatory diseases. CSF cytology was analyzed morphologically for preselected parameters of cell, cytoplasm and nucleic appearance, and the presence of mitoses or apoptoses. None of the evaluated parameters sharply discerns neoplastic and inflammatory changes. However, neoplastic cells were significantly larger. Moreover, irregular shape and pointed borders of the cytoplasm, and deep notches in the nucleus were significantly more frequent in neoplastic than in inflammatory lymphocytes. No single parameter is sufficient to detect neoplastic lymphocytes. Considering a combination of cell size and irregular shape of cell and nucleus, however, may improve the diagnostic accuracy of CSF dissemination by aggressive hematological malignancies.

Automated cerebrospinal fluid cytology.

OBJECTIVE: To evaluate the Abbott CELL-DYN Sapphire cytometer for cerebrospinal fluid (CSF) cell count and differentiation. METHODS: One hundred three analyses of CSF cells by the CELL-DYN Sapphire were compared with routine cell count and microscopic differentiation and correlation coefficients calculated. RESULTS: The total cell count of both methods correlated well. The detection of erythrocytes was good (0.898), and a higher content of erythrocytes >100/microL had little effect on total leukocyte count. The correlation between both methods was best with higher leukocyte counts >25/microL (r=0.987), whereas at cell counts <25/microL, the correlation was considerably less precise (r=0.613). For the differentiation of cells, lymphocytes and neutrophils showed moderate correlation. The results for monocytes and eosinophils did not correlate. CONCLUSION: The results for the total cell count in this study are comparable with those achieved with the Bayer Advia 120. While the Abbott CELL-DYN Sapphire yielded slightly better results for erythrocytes and total cell count with a higher erythrocyte content, the Advia 120 achieved slightly better results of lymphocyte and neutrophil count in a previous study.

Automated cerebrospinal fluid cytology: limitations and reasonable applications.

OBJECTIVE: To evaluate the precision and clinical applicability of the Bayer ADVIA 120 cytometer (Bayer Healthcare, Fernwald, Germany) for cerebrospinal fluid (CSF) cell count and differentiation. STUDY DESIGN: One hundred six analyses of CSF from 98 patients by the ADVIA 120 were compared with routine cell count and microscopic differentiation. Correlation coefficients were calculated. RESULTS: In general, the total cell counts of both methods correlated well. The best correlations were seen at higher cell counts, > or = 100 cells per microliter with < 100 erythrocytes per microliter. The best correlations of cell differentiation were seen for lymphocytes and neutrophils, while the results for monocytes and eosinophils were less precise. In some cases, considerable differences between automated and microscopic cell counts and differentiation were seen that were relevant to clinical decision making. The detection of pathologic cell types, such as hemosiderophages, mitoses and neoplastic cells, was not provided by automated cytometry. CONCLUSION: When experienced personnel are not available, a preliminary cell count and differentiation between neutrophilic and lymphocytic reactions by automated cytometry may be valuable in allowing initial therapeutic decision making. Since the detection of pathologic cell types is not provided and the precision at low cell counts is only moderate, a personal microscopic evaluation of each sample is still indispensable to avoid misdiagnoses.