Enhanced Detection of Malignant Lymphoma in Cerebrospinal Fluid by Multiparameter Flow Cytometry

Finn, William G.; Peterson, Lo Ann C.; James, Catherine; Goolsby, Charles L.

doi:10.1093/ajcp/110.3.341

Cited by 68 publications

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“…In this sense, 'double negative' flow cytometry and cytological findings suggest that other nonmalignant conditions are responsible for the patient's CNS symptoms. We and others have previously obtained similar findings in patients with acute leukaemia [9,13] and NHL [10,11] but, to the best of our knowledge, this is the first report of a study involving a large number of HIV-positive patients. Parenchymal cerebral masses with deep locations do not seed malignant cells into the subarachnoid space, and this might explain the negative results of the cytological and flow cytometry analyses in some cases [15,16].…”

Section: Discussionsupporting

confidence: 77%

Advantages of flow cytometry immunophenotyping for the diagnosis of central nervous system non‐Hodgkin's lymphoma in AIDS patients

et al. 2005

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BackgroundNeurological disorders are common in HIV-infected patients. Central nervous system (CNS) lymphoma should always be considered because it is an important cause of morbidity and mortality. ObjectivesTo investigate the clinical utility of flow cytometry immunophenotyping (FCI) in diagnosing or discarding leptomeningeal involvement in HIV-infected patients and to compare its sensitivity with that of conventional cytological methods. MethodsFifty-six cerebrospinal fluid (CSF) samples from 29 HIV-infected patients were independently evaluated by flow cytometry and cytology. The description of an aberrant immunophenotype was the criterion used to define the malignant nature of any CSF cell population. ResultsFCI and cytology gave concordant results for 48 of the 56 CSF samples studied: 37 were negative for malignancy and 11 had evidence of CNS lymphoma. Discordant results were obtained for eight CSF samples, and the accuracy of the FCI findings could be demonstrated for four CSF samples described as positive for malignancy according to the FCI criteria. ConclusionsA high level of agreement was found between the results obtained using the two methods, but FCI gave at least 25% higher sensitivity than conventional cytomorphological methods for the detection of malignant cells. This advantage suggests that, in case of negative flow cytometry results, disorders other than non-Hodgkin's lymphoma should be strongly considered.Keywords: AIDS lymphoma, central nervous system, cerebrospinal fluid, flow cytometry IntroductionDespite the great advances that have been achieved with highly active antiretroviral therapy (HAART) in improving the management of AIDS patients and their outcome [1], non-Hodgkin's lymphoma (NHL) remains an important cause of morbidity and mortality in these patients [2,3]. Invasion of the central nervous system (CNS) in this type of lymphoma is particularly common in the HIV-infected population; in necropsy studies, it has been estimated that it occurs in more than two-thirds of these cases [4]. Forty percent of AIDS patients with NHL and bone marrow invasion at the time of diagnosis show CNS involvement [5]. Therefore, cytological investigation of the cerebrospinal fluid (CSF) is mandatory for the initial staging evaluation of a recently diagnosed NHL, and also in patients with neurological signs or symptoms suggestive of meningeal involvement. Conventional cytological investigation of the CSF has limited sensitivity, and malignant cells will only be detected in 15-25% of patients [4]. An improved diagnostic test would therefore be of great value.Flow cytometry immunophenotyping (FCI) is an indispensable tool for the diagnosis and ulterior evaluation of many haematological malignancies in routine clinical At the time of the study, 17 patients were diagnosed with systemic haematological malignancies (15 with systemic NHL, one with Hodgkin's disease and one with multiple myeloma), one patient was suspicious for primary CNS lymphoma and 11 patients had no previous evidence of haematological disea...

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Section: Discussionsupporting

confidence: 77%

Advantages of flow cytometry immunophenotyping for the diagnosis of central nervous system non‐Hodgkin's lymphoma in AIDS patients

et al. 2005

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“…2 Diagnosis of CNSi in CLL may be difficult because of the low burden of CLL cells in CSF, raising the issue of false positivity. However, the diagnosis of CNSi with a low percentage of malignant cells in CSF examination has previously been reported [12][13][14] and our patients were all symptomatic. Infectious investigation was negative.…”

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confidence: 57%

“…Both patients with brain mass had near normalization of neuroimaging. Since ibrutinib initiation, 1 patient has died in neurologic CR at 9 months and 3 are alive in CR after a median of 9 months (range, [8][9][10][11][12][13][14]. None of them needed additional treatment, for neither hematologic nor neurologic disease.…”

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confidence: 99%

Ibrutinib responsive central nervous system involvement in chronic lymphocytic leukemia

Wanquet

Birsen

Hunault

et al. 2016

Blood

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“…10,42,45,46 Early studies analyzing non-stabilized CSF samples by ≤4-color FCM already demonstrated increased sensitivity in between 3% and 20% of cases as compared with cytology (Table 2). 42,[47][48][49][50] More recent analyses of larger series of CSF-stabilized samples using 4-8 color FCM have confirmed the greater sensitivity of FCM vs. CC with a median proportion of occult CNSL (FCM+/CC-CSF) of 12% (range: 5%-13%) ( Table 1). 10,45,51 Patients with occult CNSL (i.e., CC-and FCM+ CSF) typically showed lower levels of CSF infiltration (<20% or <1 tumor B cell/μL) than FCM+/CC+ cases, 45 further supporting the greater sensitivity of FCM vs. CC.…”

Section: Multiparameter Flow Cytometry Analysis Of Csf Samplesmentioning

confidence: 88%

Guidelines for diagnosis, prevention and management of central nervous system involvement in diffuse large B-cell lymphoma patients by the Spanish Lymphoma Group (GELTAMO)

et al. 2016

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Several factors hinder the identification of risk factors for central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL), including the retrospective nature of most studies, the relatively low frequency of CNS relapse in DLBCL, and the heterogeneity of CNS prophylaxis methods used in these studies. Moreover, the impact of newly developed diagnostic tools (such as multiparameter flow cytometry [FCM]) and new treatments introduced in the last decade, in particular rituximab, has still not been fully clarified.Several studies 4,5,[7][8][9][10] and a recent meta-analysis 1 have described a decrease in rates D iffuse large B-cell lymphoma patients have a 5% overall risk of central nervous system events (relapse or progression), which account for high morbidity and frequently fatal outcomes, 1 and shortened overall survival of <6 months.2 Early diagnosis of central nervous system events is critical for successful treatment and improved prognosis. Identification of patients at risk of central nervous system disease is critical to accurately identify candidates for central nervous system prophylaxis vs. therapy. [3][4][5] This report by the Spanish Lymphoma Group (GELTAMO) aims to provide useful guidelines and recommendations for the prevention, diagnosis, and treatment of central nervous system diffuse large B-cell lymphoma patients with, or at risk of, leptomeningeal and/or brain parenchyma lymphoma relapse. A panel of lymphoma experts working on behalf of GELTAMO reviewed all data published on these topics available in PubMed up to May 2016. Recommendations were classified according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) approach. 6 A practical algorithm based on the proposed recommendations was then developed (Figure 1 have concluded that the incidence of CNS relapse decreased after the introduction of rituximab (Table 1). The identification of risk factors has been the major goal of many studies of CNS involvement. Several large retrospective studies conducted in the pre-rituximab era [12][13][14][15] reported higher rates of CNS relapse in patients with increased serum lactate dehydrogenase (LDH) levels and/or involvement of >1 extranodal site, although these factors failed to predict CNS relapse in more than half of all cases.12 In addition to the involvement of >1 extranodal site and increased LDH, International Prognostic Index (IPI) score was also identified as an independent predictor for CNS relapse in other studies.13,16 A post-rituximab era study of 399 DLBCL patients, randomized to R-CHOP or CHOP chemotherapy, 3 identified an age-adjusted IPI (aaIPI) >1 as the only risk factor for CNS involvement, although a high aaIPI score was recorded for more than 60% of the patients. When aaIPI was excluded from the analysis, elevated LDH and a poor performance status (PS >1) were identified as independent predictive factors for CNS relapse. Similarly, in the randomized RICOVER-60 trial, 4 the combination of increased LDH levels, the involvement of >1 ex...

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Enhanced Detection of Malignant Lymphoma in Cerebrospinal Fluid by Multiparameter Flow Cytometry

Abstract: A b s t r a c t

Cited by 68 publications

References 5 publications

Advantages of flow cytometry immunophenotyping for the diagnosis of central nervous system non‐Hodgkin's lymphoma in AIDS patients

Advantages of flow cytometry immunophenotyping for the diagnosis of central nervous system non‐Hodgkin's lymphoma in AIDS patients

Ibrutinib responsive central nervous system involvement in chronic lymphocytic leukemia

Guidelines for diagnosis, prevention and management of central nervous system involvement in diffuse large B-cell lymphoma patients by the Spanish Lymphoma Group (GELTAMO)

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