A 64-year-old woman comes to the office due to a bitemporal headache that has slowly worsened over the past week. The patient has also had dizziness, blurry vision, and tingling and numbness of her feet. She has had no fever or jaw pain. The patient has a history of hypertension, for which she takes lisinopril. She does not use tobacco or alcohol. Temperature is 37.2 C (99.0 F), blood pressure is 140/90 mm Hg, pulse is 70/min, and respirations are 16/min. Physical examination shows moist mucous membranes, normal tympanic membranes, and no sinus or temporal area tenderness. Bilateral pupils are equal and reactive. Visual acuity is decreased in both eyes, and funduscopic examination reveals dilated, segmented, and tortuous retinal veins. Facial sensation and strength are normal. Bilateral upper and lower extremity muscle strength is normal. There is decreased pinprick sensation and loss of ankle reflex bilaterally in the feet. Laboratory results are as follows:
| Complete blood count | |
| Hemoglobin | 11.2 g/dL |
| Platelets | 180,000/mm3 |
| Leukocytes | 8,000/mm3 |
| Serum chemistry | |
| Creatinine | 0.8 mg/dL |
| Calcium | 9.6 mg/dL |
| Total protein | 10.5 g/dL |
| Albumin | 3.7 g/dL |
| Erythrocyte sedimentation rate | 80 mm/hr |
Which of the following is the best next diagnostic study for this patient?
Waldenström macroglobulinemia | Multiple myeloma | |
Major manifestations |
|
|
Monoclonal antibody | IgM | IgG, IgA, light chains |
Peripheral smear | Rouleaux | Rouleaux |
Bone marrow biopsy | >10% clonal B cells | >10% clonal plasma cells |
This patient with a week of headaches, dizziness, and blurry vision has a large gamma gap (difference between total protein and albumin) and "sausage-link" retinal changes, suggesting hyperviscosity syndrome due to Waldenström macroglobulinemia (WM).
WM is a B-cell malignancy characterized by the excessive production of monoclonal IgM antibody. IgM is a large immunoglobulin, and high levels can clog the microvasculature, resulting in hyperviscosity syndrome. Symptoms typically include vision changes, headaches, vertigo, dizziness, and/or ataxia; rarely, stroke or coma may occur. Other IgM-mediated conditions commonly seen in patients with WM include peripheral neuropathy, cryoglobulinemia, and renal insufficiency. Physical examination typically shows "sausage-link" (dilated, segmented, tortuous) retinal veins, and laboratory studies usually reveal anemia, a gamma gap, and elevated erythrocyte sedimentation rate (ESR).
The screening test for WM is serum protein electrophoresis (SPEP), which can identify a monoclonal IgM spike. If positive, bone marrow biopsy is performed (lymphocytic infiltration with certain immunophenotype markers). This patient would also require serum viscosity testing as urgent plasmapheresis may be required.
(Choice A) Antineutrophil cytoplasmic antibody is associated with microscopic polyangiitis and granulomatosis with polyangiitis. Patients often have ear, nose, throat, upper airway, and renal manifestations. These conditions are usually associated with a marked elevation in ESR, but a sizable gamma gap and "sausage-link" retinal veins would be uncommon.
(Choice B) Diabetes mellitus is associated with elevated hemoglobin A1c levels and commonly causes peripheral neuropathy and retinopathy. Funduscopic examination in patients with diabetic retinopathy typically reveals hemorrhages and cotton wool spots (not "sausage-link" changes). In addition, a large gamma gap would be atypical.
(Choice C) MRI of the brain may be useful for multiple sclerosis, which can cause vision changes, sensory symptoms, and elevated ESR. However, this patient with "sausage-link" retinal changes and elevated gamma gap has neurologic symptoms likely due to hyperviscosity syndrome. She requires a SPEP and serum viscosity measurement; MRI of the brain is likely to be normal.
(Choice E) Temporal artery biopsy helps diagnose giant cell arteritis, which usually manifests in older individuals with headaches, visual changes, jaw claudication, fever, anemia, and elevated ESR. This patient has peripheral neuropathy, a gamma gap, and no jaw symptoms, making WM more likely.
Educational objective:
Waldenström macroglobulinemia is a B-cell neoplasm associated with elevated monoclonal IgM. High levels of IgM may cause hyperviscosity syndrome (vision changes, headaches, vertigo, dizziness, ataxia), peripheral neuropathy, cryoglobulinemia, and/or renal insufficiency. Diagnosis requires serum protein electrophoresis and bone marrow biopsy.