Flow cytometry shows added value in diagnosing lymphoma in brain biopsies

Meulen, Matthijs van der; Bromberg, Jacoline E C; Lam, King H.; Dammers, Rúben; Langerak, Anton W.; Doorduijn, Jeanette K.; Kros, Johan M.; Bent, Martin J. van den; Velden, Vincent H.J. van der

doi:10.1002/cyto.b.21641

Cited by 9 publications

(7 citation statements)

References 33 publications

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“…DLBCL-type PCNSL was confirmed by histopathology, IgH clonality analysis, and exclusion of extracerebral lymphoma manifestation by bone marrow aspirates in all cases (Additional file 1 : Table S1). Our study confirms previous reports investigating brain biopsies after mechanical disaggregation of tissue samples or pure analysis of the rinse fluid with increased proportion of malignant B cells (60–96% of CD45 + cells), Ig Kappa, or Lambda light chain restriction (69 - 83%) and high concordance rates of PCNSL diagnosis between flow cytometry and immunohistochemistry (>90%) [ 56 – 58 ]. Due to differences in the study protocols and tissue preparation, direct comparisons with previous approaches are difficult.…”

Section: Discussionsupporting

confidence: 91%

Intratumor heterogeneity and T cell exhaustion in primary CNS lymphoma

et al. 2022

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Background Primary central nervous system lymphoma (PCNSL) is a rare lymphoma of the central nervous system, usually of diffuse large B cell phenotype. Stereotactic biopsy followed by histopathology is the diagnostic standard. However, limited material is available from CNS biopsies, thus impeding an in-depth characterization of PCNSL. Methods We performed flow cytometry, single-cell RNA sequencing, and B cell receptor sequencing of PCNSL cells released from biopsy material, blood, and cerebrospinal fluid (CSF), and spatial transcriptomics of biopsy samples. Results PCNSL-released cells were predominantly activated CD19+CD20+CD38+CD27+ B cells. In single-cell RNA sequencing, PCNSL cells were transcriptionally heterogeneous, forming multiple malignant B cell clusters. Hyperexpanded B cell clones were shared between biopsy- and CSF- but not blood-derived cells. T cells in the tumor microenvironment upregulated immune checkpoint molecules, thereby recognizing immune evasion signals from PCNSL cells. Spatial transcriptomics revealed heterogeneous spatial organization of malignant B cell clusters, mirroring their transcriptional heterogeneity across patients, and pronounced expression of T cell exhaustion markers, co-localizing with a highly malignant B cell cluster. Conclusions Malignant B cells in PCNSL show transcriptional and spatial intratumor heterogeneity. T cell exhaustion is frequent in the PCNSL microenvironment, co-localizes with malignant cells, and highlights the potential of personalized treatments.

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Section: Discussionsupporting

confidence: 91%

Intratumor heterogeneity and T cell exhaustion in primary CNS lymphoma

et al. 2022

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“…Likewise, a sub-population of T cells has been identified in CSF samples positive for B non-Hodgkin lymphoma infiltration (7,19). Moreover, an active mechanism of reactive CD8 T-lymphocyte migration through the blood-brain barrier has been consistently shown in PCNSL (20,21). In this study, the ratio between CD4/CD8-positive T cells was shifted significantly in favor of CD4-positive T cells in CSF compared to corresponding peripheral blood (ratio = 2 versus ratio=1.4 respectively; p < 0.0001).…”

Section: Discussionsupporting

confidence: 56%

“…However, cancer cells represent only a proportion, often a minority, of the CSF population in neoplastic meningitis. A significant presence of lymphocytes has been documented, together with floating malignant cells, in CSF samples from patients with non-Hodgkin lymphomas and breast cancer leptomeningeal metastasis ( 18 , 19 ); an active mechanism of reactive CD8 T-lymphocyte migration has been observed in primary central nervous system lymphomas (PCNSL) of B-cell type ( 20 , 21 ). These findings suggest an active role of the central nervous system (CNS) lymphatic system in both lymphoid and tumor cells migration into and out of the meninges.…”

Section: Introductionmentioning

confidence: 99%

Major Differences in Lymphocyte Subpopulations Between Cerebrospinal Fluid and Peripheral Blood in Non-Hodgkin Lymphoma Without Leptomeningeal Involvement: Flow Cytometry Evidence of a Cerebral Lymphatic System

et al. 2021

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Cerebrospinal fluid (CSF) flow cytometry has a crucial role in the diagnosis of leptomeningeal disease in onco-hematology. This report describes the flow cytometry characterization of 138 CSF samples from patients affected by non-Hodgkin lymphoma, negative for disease infiltration. The aim was to focus on the CSF non-neoplastic population, to compare the cellular composition of the CSF with paired peripheral blood samples and to document the feasibility of flow cytometry in hypocellular samples. Despite the extremely low cell count (1 cell/µl, range 1.0–35) the study was successfully conducted in 95% of the samples. T lymphocytes were the most abundant subset in CSF (77%; range 20–100%) with a predominance of CD4-positive over CD8-positive T cells (CD4/CD8 ratio = 2) together with a minority of monocytes (15%; range 0–70%). No B cells were identified in 90% of samples. Of relevance, a normal, non-clonal B-cell population was documented in 5/7 (71%) patients with primary central nervous system lymphoma at diagnosis (p<0.0001), suggesting a possible involvement of blood-brain barrier cell permeability in the pathogenesis of cerebral B-cell lymphomas. The highly significant differences between CSF and paired peripheral blood lymphoid phenotype (p<0.0001) confirms the existence of an active mechanism of lymphoid migration through the meninges.

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“…It is recommended that, in addition to routine histopathology and IHC, an FCM test be performed in bone marrow or extramedullary tissue as much as possible to accurately locate and analyze cell differentiation. For some special or small specimen, as for instance, FCM on brain biopsy rinse fluid is a potentially useful strategy for multidisciplinary diagnosis of central nervous system (CNS) lymphoma ( 18 , 19 ).…”

Section: Discussionmentioning

confidence: 99%

Misdiagnosis analysis of 2291 cases of haematolymphoid neoplasms

et al. 2023

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ObjectiveTo retrospectively analyze the reasons for misdiagnosis of haematolymphoid neoplasms and provide experience for improving the diagnostic level in China.MethodsA retrospective analysis was performed on 2291 cases of haematolymphoid diseases evaluated by the Department of Pathology of our hospital from 1 July 2019 to 30 June 2021. All 2291 cases were reviewed by two hematopathologist experts and classified according to the 2017 revised WHO classification criteria, supplemented immunohistochemistry (IHC), molecular biology and genetic information as needed. The diagnostic discordance between primary and expert review was evaluated. The possible causes of the diagnostic discrepancies were analyzed for each step involved in the procedure of diagnosis.ResultsIn total, 912 cases did not conform to the expert diagnoses among all the 2291 cases, with a total misdiagnosis rate of 39.8%. Among them, misdiagnosis between benign and malignant lesions accounted for 24.3% (222/912), misdiagnosis between haematolymphoid neoplasms and non-haematolymphoid neoplasms accounted for 3.3% (30/912), misdiagnosis among lineages accounted for 9.3% (85/912), misclassification in lymphoma subtypes accounted for 60.8% (554/912), and other misdiagnoses among benign lesions accounted for 2.3% (21/912) of cases, among which misclassification of lymphoma subtypes was the most common.ConclusionThe accurate diagnosis of haematolymphoid neoplasms is challenging, involving various types of misdiagnosis and complicated causes, however, it is important for precise treatment. Through this analysis, we aimed to highlight the importance of accurate diagnosis, avoid diagnostic pitfalls and to improve the diagnostic level in our country.

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Flow cytometry shows added value in diagnosing lymphoma in brain biopsies

Cited by 9 publications

References 33 publications

Intratumor heterogeneity and T cell exhaustion in primary CNS lymphoma

Intratumor heterogeneity and T cell exhaustion in primary CNS lymphoma

Major Differences in Lymphocyte Subpopulations Between Cerebrospinal Fluid and Peripheral Blood in Non-Hodgkin Lymphoma Without Leptomeningeal Involvement: Flow Cytometry Evidence of a Cerebral Lymphatic System

Misdiagnosis analysis of 2291 cases of haematolymphoid neoplasms

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