Waldenström macroglobulinemia: Imaging Checklist

Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma that is associated with an immunoglobulin M (IgM) monoclonal protein (M-protein). To establish the diagnosis of WM, it is necessary to demonstrate IgM monoclonal protein in the serum, along with histologic evidence of lymphoplasmacytic cells in the bone marrow. There is a similar spectrum of disease to that seen multiple myeloma (MGUS, smoldering myeloma, and frank myltiple myeloma) in WM: IgM monoclonal gammopathy of undetermined significance, smoldering macroglobulinemia, and WM.

WM is more common in men and in whites. The most common presenting symptom is fatigue related to a normochromic or normocytic anemia. Patients can also have peripheral neuropathy. Hyperviscosity syndrome, which includes epistaxis, gingival bleeding, and retinal hemorrhage is related to high plasma IgM concentrations and is becoming less common due to earlier diagnosis. It is rarely seen in patients with IgM concentration of <4,000 mg/dL.

The checklist for reviewing images in these patients includes clinical features, complications of the disease, and potential mimickers. These include:

• Lymph nodes: The majority of patients have adenopathy on FDG-PET and CT.
• Bone marrow: Almost half of patients show diffuse increased uptake on PET, and about 90% will show marrow signal changes on MRI (diffuse in more than half). This can be due to marrow infiltration or hyperplasia due to anemia.
• Spleen size: Between 10-20% of patients will have splenomegaly on imaging
• Liver size: Hepatomegaly can be seen in patients, but the prevalence on imaging has not been reported.
• Viscera: Between 10-20% of patients will have visceral or extra-nodal sites of involvement on imaging.
• Venous patency: To assess for thrombosis due to hyperviscosity from high IgM protein
• Vessel walls: To assess for immune complex vasculitis due to IgM protein
• Presence of hemorrhage: Due to low levels of von Willebrand factor
• Central nervous system: To assess for presence of Bing-Neel syndrome, which is perivascular infiltration of small lymphocytes, lymphoplasmacytoid cells, and plasma cells in the brain parenchyma and/or spine.
• Amyloidosis: Imaging features of amyloidosis should be sought, since it can also present with an IgM monoclonal protein and neuropathy (particularly if the light-chain isotype is lambda).

WM can be difficult to differentiate from marginal zone lymphoma. MYD88 mutation L265P is more commonly seen in WM (67% of cases), and less commonly in splenic marginal zone lymphoma (4%) and mucosa-associated lymphatic tissue lymphoma (7%).

Because the M-protein of patients with WM is almost always IgM, a broad differential should be considered for lucent bone lesions (the M-protein of multiple myeloma is usually IgG, followed by IgA and IgD, with IgM myeloma making up about 1% of cases). The same can be said for sclerotic bone lesions with or without peripheral neuropathy (the M-protein of POEMS is usually IgG and IgA, with IgM POEMS being very rare). However, this information is not always available when interpreting initial staging studies for patients with newly diagnosed plasma cell dyscrasia.

References

• Banwait R, O'Regan K, Campigotto F, Harris B, Yarar D, Bagshaw M, Leleu X, Leduc R, Ramaiya N, Weller E, Ghobrial IM. The role of 18F-FDG PET/CT imaging in Waldenstrom macroglobulinemia. Am J Hematol. 2011 Jul;86(7):567-72.
• Gertz MA. Waldenström macroglobulinemia: 2013 update on diagnosis, risk stratification, and management. Am J Hematol. 2013 Aug;88(8):703-11.
• Moulopoulos LA, Dimopoulos MA, Varma DG, Manning JT, Johnston DA, Leeds NE, Libshitz HI. Waldenström macroglobulinemia: MR imaging of the spine and CT of the abdomen and pelvis. Radiology. 1993 Sep;188(3):669-73.