Practical diagnostic approaches to composite plasma cell neoplasm and low grade B‐cell lymphoma/clonal infiltrates in the bone marrow

Abstract

Composite plasma cell neoplasm (PCN) and low grade B-cell lymphoma (B-NHL) in the bone marrow are uncommon and raise the differential diagnosis of B-NHL with plasmacytic differentiation and PCN with lymphoplasmacytic morphology. This can be a challenging differential diagnosis, and the distinctions are important because of differences in management. We report five cases of composite PCN with B-NHL or clonal B-cell infiltrates involving the bone marrow. By using multiple different diagnostic modalities, including immunophenotyping by flow cytometry and immunohistochemistry, cytogenetic analysis and IGH gene rearrangement studies by polymerase chain reaction, we were able to distinguish two distinct clonally unrelated neoplasms in all cases. We describe the utility and pitfalls of these different diagnostic modalities. Flow cytometric analysis with a panel of antibodies that includes CD19, CD56, CD138, CD45 and other aberrant markers commonly expressed by PCN will allow identification of clonally unrelated PCN and B-NHL in a composite neoplasm, and distinguish them from B-NHL with plasmacytic differentiation and PCN with lymphoplasmacytic morphology. Cytogenetic and molecular analyses can give false-negative or false-positive results. In summary, a multimodal approach utilizing these different tools, including clinical data, should be used to arrive at the correct diagnosis.

Issues in diagnosis of small B cell lymphoid neoplasms involving the bone marrow and peripheral blood. Report on the Bone Marrow Workshop of the XVIIth meeting of the European Association for Haematopathology and the Society for Hematopathology

“…Approximately 80 patients with plasma cell dyscrasia (myeloma or amyloidosis) and concomitant or consecutive B cell LPD have been described in the literature . By immunophenotype, most of the B cell lymphoproliferations were CLL/SLL.…”

“…In patients where both populations express the same light chain, molecular studies are necessary. Sequencing the IGH gene rearrangement of the components is required, as the presence of two separate peaks by PCR may be seen in cases with bi‐allelic rearrangements or ongoing Ig gene alterations . In‐depth molecular analysis showed the presence of separate clones identified by their specific IgHVDJ sequences distinct from those of dominant MM clones in 12% of 74 studied myeloma patients .…”

“…Approximately 80 patients with plasma cell dyscrasia (myeloma or amyloidosis) and concomitant or consecutive B cell LPD have been described in the literature. [122][123][124][125][126] By immunophenotype, most of the B cell lymphoproliferations were CLL/SLL. True incidence of composite plasma cell myeloma and lymphoma in the bone marrow is difficult to assess, as most of the literature is based on case reports.…”

Characteristics of Lymphoproliferative Disorders with More Than One Aberrant Cell Population as Detected by 10‐Color Flow Cytometry

“…B-LPD are most often diagnosed by flow cytometric (FC) immunophenotyping that identifies a clonal light-chain (kappa or lambda) restricted population expressing B-cell markers in the blood or BM (1) or rarely lack surface Ig (sIg) light chain expression (2). Although most B-LPDs are derived from a single clone, the emergence of more than one clone has already been reported in the literature (3)(4)(5)(6)(7)(8)(9). Although most B-LPDs are derived from a single clone, the emergence of more than one clone has already been reported in the literature (3)(4)(5)(6)(7)(8)(9).…”

“…However, monotypic expression of Ig light chain is not always equal to neoplasia because it has been reported in some reactive conditions (2). Although most B-LPDs are derived from a single clone, the emergence of more than one clone has already been reported in the literature (3)(4)(5)(6)(7)(8)(9). The detection of two different B-cell clones, at diagnosis or during follow up, may be interpreted as the emergence of two clonal populations arising from a single primary tumor or coexistence of two distinct lymphoid tumors (5,6).…”