Novel immunophenotypic features of marrow lymphoplasmacytic lymphoma and correlation with Waldenström's macroglobulinemia

Abstract

Lymphoplasmacytic lymphoma involving the bone marrow can be difficult to diagnose, and pathological features that predict the presence of associated Waldenströ m's macroglobulinemia have yet to be identified. To address these issues, marrow histology, immunohistochemistry, and flow cytometry were studied from 35 lymphoplasmacytic lymphoma cases that had comprehensive clinical assessment for Waldenströ m's macroglobulinemia. In all cases, the plasma cells were analyzed by a novel 6-color flow method. Both immunohistochemistry and flow cytometry were useful in identifying the lymphoid and plasmacytic disease components. In 19 cases, immunohistochemistry revealed an earlier unrecognized pattern of plasma cell infiltration in which they were physically separate from the lymphoid infiltrates. B-cell flow cytometry revealed monotypic cells in 96% of the cases. Approximately half of these were CD5 and/or CD23 positive, although none had features of chronic lymphocytic leukemia, and none of the B cells had flow cytometric features suggesting plasmacytic differentiation. In contrast, highly sensitive 6-color plasma cell flow cytometry revealed monotypic cells in 32 of the 35 cases; in 20 cases, the pattern of CD38 and CD138 coexpression detected was identical to that seen in plasma cell malignancies such as multiple myeloma. In 18 of these 20 lymphoplasmacytic lymphoma cases, these plasma cells were CD19 positive, distinguishing them from those of true plasma cell neoplasms, which are CD19 negative. It is interesting that the two lymphoplasmacytic lymphoma cases with CD19-negative plasma cells had an IgG isotype serum paraprotein. Apart from this, no other pathological correlates of the clinical or laboratory features of symptomatic Waldenströ m's macroglobulinemia were identified.

Six color flow cytometry detects plasma cells expressing aberrant immunophenotype in bone marrow of healthy donors

“…CD19þ PC immunophenotype although rare in MM is not exclusive of malignancy. Not yet terminally differentiated ''normal'' CD19þ PCs may have a malignant CD138þ/CD38þ/CD19þ clonal counterpart as recently demonstrated by Morice et al (19) in Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma patients. Thus CD19þ/CD56À PCs could be classified as early rather than ''normal'' PCs.…”

Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell‐related disorders

“…Accordingly, we showed in a large series of uniformly treated MM cases (n ¼ 765), that quantification of BMPC at diagnosis based on MFC provides prognostic information of higher value than that obtained with morphological counts (34). In fact, although MFC yielded (24,56,57).…”

“…2) and other clonal B-cell chronic lymphoproliferative disorders (24,56,57); in contrast, no clear phenotypic differences have been reported so far between aberrant PC from MGUS, MM, and PCL cases except for molecules involved in the interaction between PC and their BM microenvironment. Among others, these include greater expression of CD38, HLA-I, b2microglo-bulin, and CD40 in MGUS versus MM and PCL and higher soluble levels of CD95 in the latter group (21).…”

“…Of note, the same markers have also proven to be helpful in the differential diagnosis between WM and MGUS, MM or PCL, since PC from WM display an aberrant, but clearly different antigenic profile: CD19 þ , CD45 þ , CD56 À (Fig. 2), associated with (surface) j light chain restriction in around 80% of all patients with WM (24,56). In line with this, Seegmiller et al (57) have also confirmed in a series of 41 B-lineage non-Hodgkin lymphoma (B-NHL) cases that CD19, CD45, and CD56 are also reliable markers to distinguish clonal PC from B-NHL cases and myeloma.…”

Waldenstrom’s Macroglobulinemia - a coincidental finding in a case of carcinoma of buccal mucosa

“…14 The cells express pan B-cell markers (e.g., CD19 and CD20) and typically test negative for CD3 and CD103. 15 In the described case, IHC analysis of bone marrow biopsy showed infiltration of lymphoplasmacytoid CD20 positive cells.…”