Hematology Oncology · Year 2 · from Hematology Oncology
Case 3: Waldenstrom Macroglobulinemia with Hyperviscosity
Patient Presentation
Demographics: 72-year-old male
Chief Complaint: Blurred vision, headache, and nosebleeds
History of Present Illness: The patient has had progressive fatigue for several months. Over the past 2 weeks, he developed blurred vision, headaches, and recurrent nosebleeds. He reports his gums bled significantly during a recent dental cleaning. He also notes numbness and tingling in his feet.
Physical Examination:
- Blood pressure: 148/92 mmHg
- General: Pale
- HEENT: Retinal exam shows dilated, tortuous veins ("sausage-link" appearance), flame hemorrhages, papilledema
- Lymph nodes: Cervical lymphadenopathy
- Abdomen: Splenomegaly (4 cm below costal margin)
- Neurologic: Decreased sensation in stocking distribution
Workup and Results
Laboratory Studies:
- Hemoglobin: 8.8 g/dL
- WBC: 6,200/mcL
- Platelets: 125,000/mcL
- ESR: 125 mm/hr
- Serum viscosity: 6.2 cP (normal <1.8)
Serum Studies:
- SPEP: M-spike 4.8 g/dL
- Immunofixation: IgM kappa
- IgM level: 6,200 mg/dL (markedly elevated)
Bone Marrow Biopsy:
- Infiltration by lymphoplasmacytic cells (35%)
- CD20+, CD19+, CD138 partial+
- MYD88 L265P mutation: Positive
CT Imaging:
- Lymphadenopathy (cervical, axillary, retroperitoneal)
- Splenomegaly
Clinical Image
Fundoscopic examination demonstrating hyperviscosity syndrome findings: dilated, tortuous "sausage-link" retinal veins, flame hemorrhages, and papilledema.
Diagnosis
Waldenstrom Macroglobulinemia with Hyperviscosity Syndrome
Features:
- IgM monoclonal gammopathy
- Lymphoplasmacytic bone marrow infiltration
- MYD88 L265P mutation (present in >90%)
- Symptomatic hyperviscosity
Discussion
This case demonstrates Waldenstrom macroglobulinemia:
- IgM Paraprotein: The lecture distinguishes WM from myeloma by the IgM isotype. IgM is a large pentameric molecule prone to causing hyperviscosity even at moderate concentrations.
- MYD88 Mutation: The lecture notes that the MYD88 L265P mutation is present in over 90% of WM cases, making it diagnostically useful.
- Hyperviscosity Syndrome: The lecture describes hyperviscosity as most commonly associated with WM due to the large IgM molecule. Symptoms include visual changes, bleeding, neurological symptoms, and cardiac failure.
- Fundoscopic Findings: "Sausage-link" veins (segmental dilation) are characteristic of hyperviscosity and visible on fundoscopic exam.
Treatment Plan
- Emergency Treatment for Hyperviscosity:
- Plasmapheresis (immediate)
- Typically 1-2 sessions achieve symptomatic relief
- Avoid RBC transfusion before pheresis (worsens viscosity)
- Systemic Therapy:
- Rituximab-based regimen (avoid initial rituximab "flare")
- Options: Bendamustine + rituximab, or BTK inhibitor (ibrutinib/zanubrutinib)
- Avoid rituximab monotherapy initially if IgM very high (flare risk)
- Monitoring:
- Serial IgM levels
- Serum viscosity
- Peripheral neuropathy assessment
- Peripheral Neuropathy:
- May be due to anti-MAG antibodies or cryoglobulinemia
- Gabapentin/pregabalin for symptom management
Teaching Points
- Waldenstrom macroglobulinemia is characterized by IgM M-protein
- MYD88 L265P mutation present in >90% of cases
- Hyperviscosity most common with IgM due to large pentameric structure
- Plasmapheresis is emergency treatment for hyperviscosity
- "Sausage-link" retinal veins are characteristic of hyperviscosity
Image Reference
For visual reference of plasma cell disorder concepts, see:
- Radiopaedia: Multiple myeloma - Skeletal findings
- Wikipedia: Amyloidosis - Congo red staining
- Radiopaedia: Cardiac amyloidosis - Echo findings
Learning Points
- CRAB Criteria: Calcium, Renal, Anemia, Bone - define symptomatic myeloma
- M-Protein Screening: SPEP detects M-spike; immunofixation identifies type
- AL Amyloid Diagnosis: Congo red stain with apple-green birefringence under polarized light
- Cardiac Amyloid Prognosis: Most important factor; avoid digoxin
- WM and Hyperviscosity: IgM (pentamer) causes viscosity; plasmapheresis is emergency treatment