Waldenstrom Macroglobulinemia: Optimal Diagnostic Workup

Jorge J. Castillo, MD:The diagnostic workup for a patient with Waldenström macroglobulinemia includes multiple steps, and I think initially it involves bloodwork. The bloodwork can give us a good idea of the patient’s status. The most common manifestation in patients with Waldenström macroglobulinemia is anemia, such as in this case. Thrombocytopenia and leucopenia are also seen, but they are less common. Once we have that, we need to make sure that the anemia is actually related to the disease. There are many other causes for anemia, specifically in an aging population, so we typically rule out other common causes such as iron deficiency, vitamin B12 deficiency, or folic acid deficiency. We always make sure that the patient has no evidence of hemolysis, which is the destruction of red blood cells. In this scenario, if all those tests were negative and we performed a bone marrow biopsy that showed there’s extensive involvement of the bone marrow space by this lymphoma, then it’s easy to attribute that anemia to the disease.

The next step is actually evaluating the patient’s serum IgM [immunoglobulin M]. In this case, the serum IgM is elevated to the point that we could be concerned, to some degree, of a condition called hyperviscosity. Hyperviscosity occurs when the viscosity of the serum gets to be so thick that it can cause problems for the patients. Now, IgM is a large molecule and as the IgM increases, the viscosity of the serum also increases. But there is not a linear relation between those 2 factors. Actually, the risk of hyperviscosity to become symptomatic starts at about an IgM of 3000 mg/dL. It is logarithmic in that specific scenario, so levels of 4000, 5000, or 6000 mg/dL are really a much higher risk than 2000 mg/dL or 1000 mg/dL in that specific scenario.

In this patient, we have a viscosity of 3.7 centipoise and an IgM of about 4700 mg/dL. Those are concerning for hyperviscosity, but the patient does not really have classic symptoms of hyperviscosity, which include recurrent headaches, recurrent nosebleeds that are spontaneous and hard to control, and slow mentation. These patients, for example, would be those for whom I would recommend having a formal retinal examination to make sure that there is not evidence of asymptomatic hyperviscosity. In the patient’s retinas, we can see the vessels become engorged or being more torn than we would expect. In later stages, we can actually see sausaging: it’s similar to sausage link formation. In clear cases of hyperviscosity, we see evidence of microhemorrhages in the retina fundus.

I think this is, in general, the way we look at this. There are other patients with Waldenström macroglobulinemia who present with other conditions, which sometimes makes it challenging to diagnose and treat, such as patients with neuropathy or pleural effusions. There is a rare complication in which patients can have amyloidosis with leptomeningeal involvement called Bing-Neel syndrome. Those are very rare situations, and in those situations, I think seeing specialists who treat a large quantity of patients with Waldenström macroglobulinemia would potentially be beneficial.

Transcript edited for clarity.

Case: A 65-Year-Old Female With Newly Diagnosed Waldenström Macroglobulinemia

September 2016

• A 65-year old female presented to her PCP with slowly progressing anemia for the last couple of years
• Several months prior to that, she began experiencing drenching night sweats, distended abdomen, and 15 lb weight loss
• SH: Married, exercises regularly, social drinker, non-smoker, no illicit drug use
• FH: Maternal aunt — breast cancer age 51
• Laboratory results:
  • Hemoglobin; 7 g/dL (11-13 g/dL), platelets; 55,000/mm³(155,000-410,000/mm³), and leukocyte count 1,700/mm³(3,800-9,200/mm³).
  • M-protein; 2991.3 mg/dL; IgM 4710 mg/dL (45—281 mg/dL)
  • Serum viscosity; 3.7 centipoise (cP) (1.6—1.9 cP)
  • Beta-2; 3 mg/L (0-2.7 mg/L)
  • IPSSWM: 2 Intermediate
• Bone marrow aspiration and biopsy; 40—50% B cells
• Flow cytometry; Lambda-restricted B cells that expressed CD19 and CD20
• B cells were negative for CD5, CD10, CD43, bcl-1, and bcl-6
• Allele-specific PCR; MYD88^L265Pmutation
• Diagnosis; Waldenström’s macroglobulinemia (WM)

Treatment

• Patient was started on ibrutinib (420 mg) daily with monthly follow-up visits
• After three months, her IgM was 1500 mg/dL and her serum viscosity was 1.5 cP
• Her CBC showed improvements: WBC, 5000/mm³, Hgb 15.5g/dL; platelets 180,000/mm³
• The patient was last seen on follow-up last month and she continues on ibrutinib 2 years after her initial presentation