Waldenström Macroglobulinemia

Abstract

The definition of Waldenström macroglobulinemia (WM), originally described in 1944, has been refined substantially over time. The current fourth edition of the World Health Organization of lymphoid neoplasms, in large part, adopted criteria proposed for WM at a consensus conference in 2002. WM is defined as lymphoplasmacytic lymphoma involving the bone marrow associated with a serum immunoglobulin (Ig) M paraprotein of any concentration. Morphologically, WM is composed of a variable mixture of lymphocytes, plasmacytoid lymphocytes, and plasma cells. Immunophenotypically, the neoplastic cells express monotypic IgM and light chain: B lymphocytes express pan-B-cell antigens and surface Ig are usually negative for CD5 and CD10; and plasma cells are typically positive for CD138, CD38, CD45, cytoplasmic Ig, and CD19 (in a substantial subset of cases). The putative cell of origin of WM is a postantigen selected memory B-cell that has undergone somatic hypermutation. The most common cytogenetic abnormality in WM is del(6q), usually in the region 6q23-24.3, present in 40% to 50% of cases. IGH gene translocations are rare and recurrent chromosomal translocations or gene aberrations have not been identified in WM. Here, we provide a historical perspective of WM, review clinical and pathologic aspects of the disease as it is currently defined, and discuss some practical issues in the differential diagnosis of WM that pathologists encounter in the signout of cases.

Waldenström's macroglobulinemia with necrotic extremities: A case with challenging diagnosis

“…Some cases of lymphoplasmacytic lymphoma (LPL) infiltrate the bone marrow with small lymphocytes, plasma cells, and plasmacytoid cells but secrete IgA or IgG instead of IgM. 7 Conversely, there are cases of LPL that share a strong morphological resemblance with WM but are not associated with elevated serum paraproteins. Bruton's tyrosine kinase (BTK) inhibitors have recently appeared to be secure and profoundly active as monotherapy in WM.…”

“…It is also important to note that some permutations of the disease do not elevate serum immunoglobulin levels or infiltrate the bone marrow. Some cases of lymphoplasmacytic lymphoma (LPL) infiltrate the bone marrow with small lymphocytes, plasma cells, and plasmacytoid cells but secrete IgA or IgG instead of IgM 7 …”

“…Other disease manifestations are due to a rise in immunoglobulins. Since these large proteins contain a high volume of carbohydrates, an aggregated form of these paraproteins can bind to water and increase osmotic pressure and blood flow resistance 7 . It can also interact with red blood cells by increasing their viscosity and reducing their ability of it to deform.…”

“…It can also interact with red blood cells by increasing their viscosity and reducing their ability of it to deform. Blood viscosity over eight is associated with hyperviscosity‐related symptoms (normal value <1.8 centipose) 7 . Lastly, monoclonal IgMs can bind to coagulation factors and platelets, resulting in impaired clotting.…”

“…In this clinicopathologic entity, infiltration of small lymphocytes, plasmacytoid lymphocytes, and plasma cells causes a rise in monoclonal immunoglobulins. In 26% of patients, mast cells increase as well 6,7 . WM patients may be asymptomatic or have symptoms attributed to the tumor infiltration; or hyperproduction of IgM 8,9 .…”