If the monoclonal Ig is IgM

When the monoclonal Ig is an IgM, Waldenström’s macroglobulinaemia (WM) is the main suspected diagnosis. MW is defined by a monoclonal IgM and a polymorphous infiltrate in the bone marrow composed of lymphocytes, lymphoplasmacytic cells and plasma cells. This definition usually enables MW to be distinguished from chronic lymphocytic leukaemia (CLL) and various non-Hodgkin’s lymphomas (NHL) that can also be associated with monoclonal IgM. IgM-secreting myelomas occur but infrequently.

Representation of an immunoglobulin molecule of the IgM class

When monoclonal IgM is detected, its origin is generally investigated by looking for enlargement of lymph nodes and the spleen, through physical examination, chest radiography, and ultrasonography or a CT scan, rather than bone signs. The blood lymphocyte count may be elevated. Bone marrow aspiration and bone marrow biopsy are performed to look for lymphoplasmacytic infiltration.

As with the myeloma workup, three situations are identifiable:

1) Overt symptomatic WM, requiring treatment to minimize the complications of both the clone (bone marrow failure, compression) and the monoclonal IgM (e.g. hyperviscosity, see below).

2) Asymptomatic WM with low-level IgM, requiring monitored and treatment only if the level of monoclonal Ig and/or lymph node or spleen volume increases.

3) Monoclonal IgM with no detectable lymphoid proliferation, i.e. monoclonal gammopathy of undetermined significance.