Follicular Lymphoma in Staging Bone Marrow Specimens: Correlation of Histologic Findings With the Results of Flow Cytometry Immunophenotypic Analysis

Abstract Context.—Bone marrow (BM) examination is part of the staging workup of lymphoma patients. Few studies have compared BM histologic findings with results of flow cytometric immunophenotyping analysis in follicular lymphoma (FL) patients. Objective.—To correlate histologic findings with immunophenotypic data in staging BM biopsy and aspiration specimens of FL patients. Design.—Bone marrow biopsy specimens of untreated FL patients were reviewed. Histologic findings were correlated with 3-color flow cytometric immunophenotyping results on corresponding BM aspirates. Results.—Bone marrow biopsy specimens (with or without aspirates) of 114 patients with histologic evidence of FL in BM were reviewed. There were 76 bilateral and 38 unilateral biopsies performed, resulting in 190 specimens: 187 involved by FL and 3 negative (in patients with a positive contralateral specimen). The extent of BM involvement was <5% in 32 (17.1%), ≥5% and ≤25% in 102 (54.6%), >25% and ≤50% in 27 (14.4%), and >50% in 26 (13.9%) specimens. The pattern of involvement was purely paratrabecular in 81 (43.3%), mixed in 80 (42.8%), and purely nonparatrabecular in 26 (13.9%). Immunophenotyping was only performed unilaterally, on BM aspirates of 92 patients, and was positive for a monoclonal B-cell population in 53 (57.6%) patients. Immunophenotyping was more often negative when biopsy specimens showed FL with a purely paratrabecular pattern. For comparison, we assessed 163 FL patients without histologic evidence of FL in BM also analyzed by flow cytometric immunophenotyping. A monoclonal B-cell population was identified in 5 patients (3%). Conclusions.—Our data suggest that 3-color flow cytometric immunophenotyping adds little information to the evaluation of staging BM specimens of FL patients.

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Characterization of Tissue Findings in Bone Marrow Biopsy Specimens With Small Monoclonal B-Cell Populations

American Journal of Clinical Pathology ◽

10.1309/ajcpd5tobdju4gko ◽

2014 ◽

Vol 141 (5) ◽

pp. 687-696 ◽

Cited By ~ 9

Author(s):

Beverly P. Nelson ◽

Anmaar Abdul-Nabi ◽

Charles Goolsby ◽

Jane Winter ◽

LoAnn Peterson

Keyword(s):

Bone Marrow ◽

B Cell ◽

Bone Marrow Biopsy ◽

Cell Populations ◽

Biopsy Specimens

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The Usefulness of Immunohistochemistry in the Diagnosis of Follicular Lymphoma in Bone Marrow Biopsy Specimens

American Journal of Clinical Pathology ◽

10.1309/w3qx-wj1c-wg2k-225v ◽

2002 ◽

Vol 117 (4) ◽

pp. 636-643 ◽

Cited By ~ 20

Author(s):

Robert B. West ◽

Roger A. Warnke ◽

Yasodha Natkunam

Keyword(s):

Bone Marrow ◽

Follicular Lymphoma ◽

Bone Marrow Biopsy ◽

Biopsy Specimens

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Immunophenotypic Analysis of Peripheral Blood and Bone Marrow in the Staging of B-Cell Malignant Lymphoma

Blood ◽

10.1182/blood.v94.11.3889 ◽

1999 ◽

Vol 94 (11) ◽

pp. 3889-3896 ◽

Cited By ~ 56

Author(s):

Curtis A. Hanson ◽

Paul J. Kurtin ◽

Jerry A. Katzmann ◽

James D. Hoyer ◽

Chin-Yang Li ◽

...

Keyword(s):

Bone Marrow ◽

Blood Flow ◽

B Cell ◽

Malignant Lymphoma ◽

Peripheral Blood ◽

Large Cell ◽

Low Grade ◽

Bone Marrow Biopsies ◽

Flow Cytometric Immunophenotyping ◽

Flow Cytometric

Abstract This study evaluated the contributing roles of flow cytometric immunophenotyping of blood and bone marrow and immunohistochemical paraffin section staining of bone marrow biopsies in the staging of B-cell malignant lymphoma. Flow immunophenotyping was performed on a marrow specimen in 175 cases; a corresponding blood specimen was also immunophenotyped in 135 of these cases. Morphologic marrow involvement by lymphoma was found in 59 cases; flow immunophenotyping identified 54 cases with a monoclonal B-cell process: morphology-positive/flow-positive (n = 49), morphology-positive/flow-negative (n = 10), morphology-negative/flow-positive (n = 5), and morphology-negative/flow-negative (n = 111). The 10 morphology-positive/flow-negative cases included 5 follicular and 5 large-cell lymphomas with minimal marrow involvement. All 5 morphology-negative/flow-positive cases were from patients with large-cell lymphomas and bulky clinical disease. Because the blood contained the same B-cell clone in 2 of 2 morphology-negative/flow-positive cases studied, blood contamination of marrow may account for these findings. Blood flow cytometric immunophenotyping studies were positive in 32 cases; 30 had marrow involvement by morphology and were from patients with follicular, mantle cell, lymphoplasmacytic, small lymphocytic, or marginal zone lymphomas. From our results, we conclude that (1) bone marrow flow cytometric immunophenotyping is not a cost-effective replacement for good morphologic evaluation in lymphoma staging and that (2) a positive peripheral blood flow cytometric immunophenotyping study when performed in low-grade lymphomas correlates with marrow involvement.

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Flow Cytometric Immunophenotyping of Bone Marrow Core Biopsies

Archives of Pathology & Laboratory Medicine ◽

10.5858/1999-123-0206-fciobm ◽

1999 ◽

Vol 123 (3) ◽

pp. 206-212 ◽

Cited By ~ 2

Author(s):

Cherie H. Dunphy ◽

Frank R. Dunphy ◽

John L. Visconti

Keyword(s):

Bone Marrow ◽

Core Biopsy ◽

Hematologic Malignancy ◽

Data Extraction ◽

Final Diagnosis ◽

Hematologic Malignancies ◽

Cell Of Origin ◽

Flow Cytometric Immunophenotyping ◽

Flow Cytometric ◽

Biopsy Specimens

Abstract Objective.—To report a method for flow cytometric immunophenotyping (FCI) bone marrow (BM) core biopsies in patients with hematologic malignancies of the BM who present with a failed BM aspiration (“dry tap”). Design and Setting.—Core biopsy specimens of BM were obtained from 8 patients who presented with previously undiagnosed hematologic malignancies arising in (7 cases) or secondarily involving (1 case) the BM and a dry tap. Suspensions of the BM core biopsy specimens were prepared and analyzed by FCI methods. Data Extraction and Data Synthesis.—The FCI data were analyzed in conjunction with cytomorphologic, histologic, immunohistochemical, and cytogenetic findings in all cases to determine a final diagnosis. Conclusions.—The prepared BM core suspensions were viable and allowed for a complete immunophenotype profile by FCI in all cases, resulting in a clear definition of the cell of origin of the hematologic malignancy. Because of lack of preservation of architectural features and the potential for artifactual alterations of the relative frequency of abnormal cells, the FCI data must always be correlated with histologic sections of the BM biopsy.

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The Percentage of Tumor-Infiltrating T Cells Is Not Correlated with Overall Survival in Follicular B-Cell Lymphomas.

Blood ◽

10.1182/blood.v104.11.3262.3262 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3262-3262

Author(s):

Wei Yun Ai ◽

Debra K. Czerwinski ◽

Rob Tibshirani ◽

Sandra J. Horning ◽

Ronald Levy

Keyword(s):

Overall Survival ◽

T Cells ◽

Follicular Lymphoma ◽

B Cell ◽

Cell Population ◽

Cell Lymphoma ◽

Cell Populations ◽

Activated T Cells ◽

Biopsy Specimens ◽

Hla Dr

Abstract Introduction: The function of tumor-infiltrating T cells in lymphoma is unknown. Previous studies have shown that an increased percentage of tumor-infiltrating CD4+ T cells was associated with a better overall survival in diffuse large B-cell lymphoma (Ansell S. et al. JCO 2001; Xu et al., British Journal of Haematology 2001). Furthermore, the CD4+ T cells observed in one study was associated with a CD3+/HLA-DR + phenotype, suggesting that they were activated T helper cells. Recently, a molecular predictor model for follicular lymphoma was reported based on microarray analysis of gene expression within the cell populations of biopsy specimens. Three groups of “predictor genes” were identified: one representing B-cell differentiation and two groups representing genes expressed by T cells and macrophages, respectively (ASH abstract, 2003). This raised the question of whether it was simply the presence of tumor-infiltrating T cells that correlated with clinical outcome as opposed to specific activation pathways within those cells. Purpose: The purpose of this study was to examine whether the percentage of tumor-infiltrating T cells is correlated with prognosis of follicular lymphoma. Patients and Methods: We identified 293 follicular lymphoma patients with clinical outcomes available within the Stanford lymphoma database, who had undergone an excisional biopsy, and whose tumor biopsy specimens had been analyzed by flow cytometry. These patients were diagnosed between 1977 and 2003. Among these patients, 167 (57%) had follicular small cleaved lymphoma, 112 (38%) had follicular mixed lymphoma, and 14 (5%) had follicular large cell lymphoma. A total of 66 deaths were documented. The overall survival was estimated from the time of diagnosis to the time of death or last follow-up. Biopsies had been analyzed for cell surface marker expression by single parameter flow cytometry. The percentage of CD3+, CD4+, CD8+, CD20+, and HLA−DR+ cells was determined directly. We also estimated activated T cells, defined by HLA−DR+ T cells, by subtracting the value for total B cells from the value for HLA + cells. Cell population percentages were treated as continuous variables and related to overall survival, each in a univariate analysis. Results: We found no statistically significant correlation between the percentage of any cell population and overall survival. For each group (CD3+, CD4+, CD8+, and estimated HLA−DR+ T cells), we used the percentage of the cell population to divide patients into 3 subgroups of equal number of patients: low-, medium-, and high-percentage. We then compared Kaplan-Meier curves of the 3 subgroups for each cell population. We found no significant differences in survival among the 3 subgroups for each of the cell populations, CD3+, CD4+, CD8+, and the estimated activated T cells, after correcting for multiple hypotheses testing. Conclusion: The percentage of tumor-infiltrating T cells or T cell subsets was not correlated with survival outcome in patients with follicular lymphoma. This finding provides the basis for building molecular predictive models based on gene expression analysis, which represents not only the presence of certain cells but their physiologic state as well.

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Immunophenotypic Analysis of Peripheral Blood and Bone Marrow in the Staging of B-Cell Malignant Lymphoma

Blood ◽

10.1182/blood.v94.11.3889.423k13_3889_3896 ◽

1999 ◽

Vol 94 (11) ◽

pp. 3889-3896

Author(s):

Curtis A. Hanson ◽

Paul J. Kurtin ◽

Jerry A. Katzmann ◽

James D. Hoyer ◽

Chin-Yang Li ◽

...

Keyword(s):

Bone Marrow ◽

Blood Flow ◽

B Cell ◽

Malignant Lymphoma ◽

Peripheral Blood ◽

Large Cell ◽

Low Grade ◽

Bone Marrow Biopsies ◽

Flow Cytometric Immunophenotyping ◽

Flow Cytometric

This study evaluated the contributing roles of flow cytometric immunophenotyping of blood and bone marrow and immunohistochemical paraffin section staining of bone marrow biopsies in the staging of B-cell malignant lymphoma. Flow immunophenotyping was performed on a marrow specimen in 175 cases; a corresponding blood specimen was also immunophenotyped in 135 of these cases. Morphologic marrow involvement by lymphoma was found in 59 cases; flow immunophenotyping identified 54 cases with a monoclonal B-cell process: morphology-positive/flow-positive (n = 49), morphology-positive/flow-negative (n = 10), morphology-negative/flow-positive (n = 5), and morphology-negative/flow-negative (n = 111). The 10 morphology-positive/flow-negative cases included 5 follicular and 5 large-cell lymphomas with minimal marrow involvement. All 5 morphology-negative/flow-positive cases were from patients with large-cell lymphomas and bulky clinical disease. Because the blood contained the same B-cell clone in 2 of 2 morphology-negative/flow-positive cases studied, blood contamination of marrow may account for these findings. Blood flow cytometric immunophenotyping studies were positive in 32 cases; 30 had marrow involvement by morphology and were from patients with follicular, mantle cell, lymphoplasmacytic, small lymphocytic, or marginal zone lymphomas. From our results, we conclude that (1) bone marrow flow cytometric immunophenotyping is not a cost-effective replacement for good morphologic evaluation in lymphoma staging and that (2) a positive peripheral blood flow cytometric immunophenotyping study when performed in low-grade lymphomas correlates with marrow involvement.

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