Are lytic lesions in Waldenstrom's (Waldenström's macroglobulinemia) macroglobulinemia the same as in multiple myeloma?

Lytic Lesions in Waldenström's Macroglobulinemia vs Multiple Myeloma

No, lytic bone lesions are NOT the same in Waldenström's macroglobulinemia (WM) and multiple myeloma (MM)—in fact, the presence of lytic lesions is a key distinguishing feature that typically indicates MM rather than WM. 1

Key Distinguishing Features

Multiple Myeloma

• Lytic bone lesions are a hallmark feature of MM and represent one of the defining CRAB criteria (hypercalcemia, renal insufficiency, anemia, bone lesions) used for diagnosis 1
• The presence of lytic lesions in a patient with IgM monoclonal protein strongly suggests IgM MM rather than WM 1, 2
• When lytic lesions are present alongside an IgM paraprotein, the diagnosis of IgM MM requires ≥10% plasma cells on bone marrow biopsy plus either lytic bone lesions and/or t(11;14) translocation 1

Waldenström's Macroglobulinemia

• Lytic bone lesions are characteristically ABSENT in WM and serve as a major differentiating feature from MM 3
• WM is diagnosed by bone marrow infiltration with lymphoplasmacytic cells and presence of monoclonal IgM protein, but without the destructive bone lesions seen in myeloma 3
• The MYD88 L265P mutation (present in ~90% of WM patients) helps differentiate WM from MM when diagnostic uncertainty exists 3

Critical Clinical Pitfall: Rare WM Cases with Lytic Lesions

Important caveat: While extremely rare, isolated case reports document WM patients presenting with lytic bone lesions, creating a diagnostic dilemma 4, 5

• These exceptional cases complicate the differential diagnosis and require careful application of International Criteria for WM diagnosis 4
• When lytic lesions are present with IgM paraprotein, you must systematically evaluate:
  • Bone marrow morphology (plasma cells vs lymphoplasmacytic cells) 1
  • Immunophenotyping (CD19, CD20, CD22, CD79a expression favors WM) 3
  • FISH for t(11;14) (presence suggests IgM MM) 1
  • MYD88 L265P mutation testing (presence favors WM) 3

Prognostic Implications

• Patients with IgM MM (defined by lytic lesions) have a median overall survival of 30 months, which is significantly shorter than typical WM patients and similar to non-IgM myeloma 1
• This survival difference underscores why accurate differentiation is clinically critical—the diseases require different therapeutic approaches 1, 6

Practical Diagnostic Algorithm

When encountering an IgM monoclonal gammopathy with bone lesions:

1. Document bone marrow morphology: Plasma cell predominance (≥10%) suggests MM; lymphoplasmacytic infiltration suggests WM 3, 1
2. Perform FISH cytogenetics: Presence of t(11;14) strongly supports IgM MM diagnosis 1
3. Test for MYD88 L265P mutation: Presence favors WM (found in ~90% of cases) 3
4. Assess immunophenotype: CD19/CD20 positivity favors WM over MM 3

The bottom line: Treat lytic lesions as a red flag for myeloma rather than WM, but recognize that rare exceptions exist requiring comprehensive diagnostic workup to avoid misclassification and inappropriate therapy 1, 4, 5.