Sandbox:MGS

Pathogenesis

Waldenström Macroglobulinemia arises from B lymphocytes, which are normally involved in humoral immunity. The malignant cells in Waldenström Macroglobulinemia are the peripheral B lymphocyte stimulated to undergo somatic hypermutation of the immunoglobulin heavy chain gene, without class switching.

Genetics=

• Development of Waldenström Macroglobulinemia is the result of multiple gene mutations.
• Genes involved in pathogenesis of Waldenström Macroglobulinemia are:

• MYD88
• CXCR4
• ARID1A.

• MYD88: has a role in toll-like receptor and interleukin-1 receptor signaling causing activation of transcription factors of the NF-kB family. Thus, activating point mutation of MYD88 augments growth and survival of both normal and neoplastic B cells. MYD88 also has role in BTK signaling which also helps in B cell growth and survival.

• Patients with Waldenström Macroglobulinemia with co-existing mutation of MYD88 & CXCR4 are more likely to have hyperviscosity syndrome and bone marrow involvement.

Pathology

Immunohistochemistry

Malignant cells in Waldenström Macroglobulinemia express igM type of surface immunoglobulin.

LPL cells express high levels of surface immunoglobulin (sIg), usually of IgM type; surface IgD is usually lacking. Cases in which IgG and IgA are expressed have been described.

The lymphocytic component of these tumors expresses pan B cell antigens (CD19, CD20, CD22, CD79a), while the plasma cell component usually downregulates CD20 and upregulates expression of CD138. The majority express lymphocyte function associated antigen 1 (LFA-1). Adhesion molecules expressed on approximately half of these tumors include L-selectin, ICAM-1, CD44 and CD11c. The cells are variable in their expression of CD43; CD25 or CD11c may be faintly positive in some cases [33-36]. A minority of cases expresses CD5 [37]. CD10, CD103, and CD23 are usually not expressed.