Bone marrow infiltration by flow cytometry at diffuse large B‐cell lymphoma NOS diagnosis implies worse prognosis without considering bone marrow histology

Abstract

Background: The significance of discrepant findings between histology (BMB) and flow cytometry (FC) in bone marrow (BM) examination at diffuse large B-cell lymphoma (DLBCL) diagnosis is uncertain. Methods: We performed a 5-year retrospective single-center study of patients diagnosed by DLBCL not otherwise specified (n = 82), divided into three groups according to BM infiltration at diagnosis: BMB−/FC− (75.6%), BMB+/FC+ (13.4%), and BMB−/FC+ (11%). Results: Median infiltration by FC analysis of the BMB−/FC+ group was 0.8% and if we considered BM infiltration as positive in all cases, 4/9 would be upstaged. Median follow was 33 months. Event-free survival (EFS) after 18 months was 82, 23, and 27% for BMB −/FC−, BMB−/FC+, and BMB+/FC+, respectively (p < .001). After 18 months of observation, OS was 87, 46, and 55% for BMB−/FC−, BMB−/FC+, and BMB+/FC+, respectively (p = .001). In multivariate analysis (BM infiltration vs. cell-of-origin according to Hans algorithm and standard IPI), BM infiltration was independently associated with EFS

Combination of Bone Marrow Biopsy and Flow Cytometric Analysis: The Prognostically Relevant Central Approach for Detecting Bone Marrow Invasion in Diffuse Large B-Cell Lymphoma

“…Based on this finding, we speculate the complementary role between the two modalities. Although the prognostic association between BM involvement detection by biopsy and FCM has been controversial [ 18 , 19 , 20 , 27 ], our result indicated the combination of BM biopsy and FCM as the central component in BM analysis. BM smear and clot examinations are also useful modalities, as they may provide additional information and play the alternative role in some clinical situations.…”

“…Antigens examined included CD2, CD3, CD4, CD7, CD8, CD10, CD11c, CD16, CD19, CD20, CD23, CD25, CD34, CD45, CD56, kappa light chain, and lambda light chain. The presence of light chain restriction in B lymphoid cells was regarded as positive BM invasion [ 15 , 16 , 17 , 18 , 19 , 20 ]. BM aspirate smear specimen was subjected to Wright–Giemsa staining and 500 BM nucleated cells were cytologically evaluated to detect abnormal lymphoid cells under an optical microscope.…”

Comparative Review of the Current and Future Strategies to Evaluate Bone Marrow Infiltration at Diffuse Large B-Cell Lymphoma Diagnosis

“…As described in the BMB/PET analysis, in one study [ 37 ], the agreement among FCM and PET rose from moderate (Cohen’s kappa index 0.54) to substantial (Cohen’s kappa index 0.74) after performing a second BM punction in patients with BMB−/PET+. The other study [ 43 ] reported a fair agreement between techniques (Cohen’s kappa index 0.3). Both articles agree in describing that approximately 70% of cases are both FCM/PET negative, while 8–14% are FCM+/PET+.…”

Assessment of Bone Marrow Involvement in B‐Cell non‐Hodgkin Lymphoma Using Immunoglobulin Gene Rearrangement Analysis with Next‐Generation Sequencing

“…BMI is typically assessed by histologic and immunohistochemical (IHC) analysis of bone marrow biopsies and aspirations [ 5 ]; however, histopathological detection of BMI has limitations, notably the possibility of false‐negative results in cases with nontypical histomorphologic features, minimal BMI, or inadequate specimens. Immunophenotyping with flow cytometry and molecular studies using immunoglobulin (Ig) gene rearrangement can aid in determining the clonality of lymphoproliferative tissues [ 1 , 6 , 7 , 8 , 9 , 10 , 11 ]. Recent studies demonstrate that positron emission tomography (PET)/computed tomography (CT) may possess adequate sensitivity for BMI assessment in some diffuse large B‐cell lymphoma (DLBCL) cases [ 12 , 13 ].…”