Differential diagnosis of WM from other diseases that may share a similar phenotype
| . | BM biopsy . | Cytogenetics . | MYD88L265P . | Immunophenotype (by IHC or flow cytometry in BM) . | Clinical presentation . |
|---|---|---|---|---|---|
| WM | Morphology: lymphoplasmacytes or cells with lymphoplasmacytic differentiation, together with a small population of clonal plasma cells ≥10% LPL* | Del6q (30%-50%) | 70%-90% | B-cell population: CD20+, sIgM+, CD22 + (weak), CD79+, CD25+, CD27+, FMC7+, BCL-2+, CD52+, CD5+/−, CD10+/−, CD23+/−, CD103−; plasma cell population: CD138+ CD38++, CD19+, CD45+, CD56− | Hyperviscosity, lymphadenopathy, splenomegaly, neuropathy |
| IgM MGUS | <10% LPL in the BM and <3 g/dL IgM* | ? | 30%-60% | Usually few cells found | No symptoms or only IgM-related |
| Myeloma | Plasma cells | t(11;14) or other IgH translocations | 0 | CD138+, CD38+, CD19− | Lytic bone disease Cyclin D1 staining positive in 75% [usually associated with t(11;14)] |
| SMZL | Intrasinusoidal infiltration by CD20+ cells | Del7q (19%), +3q(19%), +5q(10%) | 10% | CD19+, CD20+, CD22+, CD79a+, CD79b+, FMC7+ IgM+ CD5− (weakly + in 10%-25%), CD10−, CD43−, BCL6−, cyclin D1−CD103−, but occasionally + CD11c−/+ CD25−/+CD11c+ | Splenomegaly more common; circulating cells of characteristic morphology may be found |
| Follicular lymphoma | Small cleaved lymphocytes, paratrabecular localization in the BM | Translocations involving BCL-2 (70-90%) | 0 | CD5−, CD10+/−, CD11c−/+, CD103−, CD25−, CD138−, CD38+, CD45+, bcl2+, bcl6+ | Lymphadenopathy predominates |
| Mantle cell lymphoma | Monotypic, medium-small-sized lymphocytes with abnormal nucleus | t(11;14)(q13;q32) | 0 | CD5+, CD10−, CD23−, CD25−, CD45+, CD103−, CD138− | Lymphadenopathy and extranodal involvement common |
| . | BM biopsy . | Cytogenetics . | MYD88L265P . | Immunophenotype (by IHC or flow cytometry in BM) . | Clinical presentation . |
|---|---|---|---|---|---|
| WM | Morphology: lymphoplasmacytes or cells with lymphoplasmacytic differentiation, together with a small population of clonal plasma cells ≥10% LPL* | Del6q (30%-50%) | 70%-90% | B-cell population: CD20+, sIgM+, CD22 + (weak), CD79+, CD25+, CD27+, FMC7+, BCL-2+, CD52+, CD5+/−, CD10+/−, CD23+/−, CD103−; plasma cell population: CD138+ CD38++, CD19+, CD45+, CD56− | Hyperviscosity, lymphadenopathy, splenomegaly, neuropathy |
| IgM MGUS | <10% LPL in the BM and <3 g/dL IgM* | ? | 30%-60% | Usually few cells found | No symptoms or only IgM-related |
| Myeloma | Plasma cells | t(11;14) or other IgH translocations | 0 | CD138+, CD38+, CD19− | Lytic bone disease Cyclin D1 staining positive in 75% [usually associated with t(11;14)] |
| SMZL | Intrasinusoidal infiltration by CD20+ cells | Del7q (19%), +3q(19%), +5q(10%) | 10% | CD19+, CD20+, CD22+, CD79a+, CD79b+, FMC7+ IgM+ CD5− (weakly + in 10%-25%), CD10−, CD43−, BCL6−, cyclin D1−CD103−, but occasionally + CD11c−/+ CD25−/+CD11c+ | Splenomegaly more common; circulating cells of characteristic morphology may be found |
| Follicular lymphoma | Small cleaved lymphocytes, paratrabecular localization in the BM | Translocations involving BCL-2 (70-90%) | 0 | CD5−, CD10+/−, CD11c−/+, CD103−, CD25−, CD138−, CD38+, CD45+, bcl2+, bcl6+ | Lymphadenopathy predominates |
| Mantle cell lymphoma | Monotypic, medium-small-sized lymphocytes with abnormal nucleus | t(11;14)(q13;q32) | 0 | CD5+, CD10−, CD23−, CD25−, CD45+, CD103−, CD138− | Lymphadenopathy and extranodal involvement common |
SMZL, splenic marginal zone lymphoma.
This classification follows the proposal of Kyle et al.8 Per Consensus criteria5 and World Health Organization definitions,6 there is no threshold for the BM infiltration by clonal cells to define WM.5 Individuals with less than 10% clonal cells have an indolent course7 similar to that of MGUS compared with those with at least 10% LPL infiltration who have a higher risk for progression to symptomatic WM.8 However, patients not fulfilling WM criteria may still need treatment of the management of IgM-related complications.