Waldenström macroglobulinemia

Epidemiology, pathogenesis, clinical manifestations, & Dgx of Waldenström macroglobulinemia

 

Epidemiology, pathogenesis, clinical manifestations, & Dgx of Waldenström macroglobulinemia

 

Waldenström macroglobulinemia (WM) is a rarely observed clinicopathologic subset showing the bone marrow infiltration by clonal lymphoplasmacytic cells + monoclonal IgM gammopathy in the blood. Ptns often present in their 7^th decade with Sms related to the infiltration of the hematopoietic tissues or the impact of monoclonal IgM in the blood. WM mostly seen with Sms related to anemia (e.g., pallor, weakness, fatigue), systemic C/O (e.g., weight loss, fever, night sweating), + organomegaly (e.g., lymph nodes enlargement, spleen, and/or liver). In contrary to ptns with MM (multiple myeloma), involvement of the bone or kidneys is uncommonly observed.  

 

An important presentation includes CNS Sns & Sms owing to the hyperviscosity syndrome (e.g., blurred, or lost vision, headache, ataxia, dementia, stroke, or coma). These may be intense enough to ask for a medical emergency, that requires urgent plasmapheresis. Classic findings seen with hyperviscosity in WM is the finding of oronasal bleeding + dilated, segmented, & tortuous retinal veins, showing a "sausage link" appearance. Another fundamental presentation is that of peripheral neurologic Sms e.g. paraesthesia & weakness. Other neurologic finding may include Bing-Neel syndrome and present with cranial nerve palsy, atypical neuropathic complaint, headach, low back pain & motor deficit.

 

Ptns with WM who’re NOT symptomatizing could be considered as having smoldering WM. The Dgx of WM can be made if the following criteria have been assured:

(1)  The finding of an IgM monoclonal paraprotein on serum immunofixation.  

(2)  Bone marrow biopsy sample must show ≥10 % infiltration by small lymphocytes that exhibit plasmacytoid or plasma cell differentiation (lymphoplasmacytic features or lymphoplasmacytic lymphoma) + intertrabecular pattern. The infiltrate should show typical immunophenotype (e.g., surface IgM+, CD5-/+, CD10-, CD19+, CD20+, CD22+, CD23-, CD25+, CD27+, FMC7+, CD103-, CD138-).  

(3)  MYD88 L265P mutations can also be detected in > 90 % of ptns & can help DD WM from other diseases. MYD88 L265P mutations can also be observed in about 50 % of ptns with monoclonal gammopathy of undetermined significance (MGUS).

  

DD: Differential diagnosis may include other monoclonal gammopathies & lymphomas. Specifically, WM must be DD from IgM MGUS, multiple myeloma, chronic lymphocytic leukemia, marginal zone lymphoma, & mantle cell lymphoma.

 

Kidney involvement: Renal dysfunction is reported in about 3 % of WM ptns. Nevertheless, deposits of IgM in the GBM (glomerular basement membrane) may be prominent & infiltration of lymphocytes or plasmacytoid cells can be observed. Light chain cast nephropathy & NS (nephrotic syndrome) (owing to deposited amyloid) have also been reported in WM. Immune-mediated GN that is typically due to IgM deposition or cryoglobulinemia, and nonamyloid NS (with a minimal change-like appearance), have been observed. Kidney biopsy may be warranted in ptns with recent unexplained renal dysfunction. Urinary monoclonal light chains (Bence Jones protein) can be identified via immunofixation in 70 % of ptns, but its amount is much less as compared to MM (multiple myeloma).

 

REFERENCES

1. Fonseca R, Hayman S. Waldenström macroglobulinaemia. Br J Haematol 2007; 138:700.
2. Castillo JJ, Olszewski AJ, Kanan S, et al. Overall survival and competing risks of death in patients with Waldenström macroglobulinaemia: an analysis of the Surveillance, Epidemiology and End Results database. Br J Haematol 2015; 169:81.
3. Benjamin M, Reddy S, Brawley OW. Myeloma and race: a review of the literature. Cancer Metastasis Rev 2003; 22:87.
4. Sud A, Chattopadhyay S, Thomsen H, et al. Analysis of 153 115 patients with hematological malignancies refines the spectrum of familial risk. Blood 2019; 134:960.
5. Royer RH, Koshiol J, Giambarresi TR, et al. Differential characteristics of Waldenström macroglobulinemia according to patterns of familial aggregation. Blood 2010; 115:4464.
6. Giordano TP, Henderson L, Landgren O, et al. Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus. JAMA 2007; 297:2010.
7. Koshiol J, Gridley G, Engels EA, et al. Chronic immune stimulation and subsequent Waldenström macroglobulinemia. Arch Intern Med 2008; 168:1903.