Case Presentation: A 61-year-old female with hypertension was sent to the hospital after anemia was noted on routine outpatient blood tests. Her hemoglobin was 6.8 g/dL with an MCV of 97.1 fL/red cell and an RDW of 19.2%. Platelet count was 146 k/μL and white blood cell count was 4.0 k/μL. She denied chest pain, dyspnea, melena, hematochezia, back pain or hematuria. She was also noted to have an elevated globulin gap of 8.4 g/dL between total protein and albumin. Vitamin B12, SPEP, UPEP, and free kappa/lambda ratio were sent. Vitamin B12 level was low. Intrinsic factor antibody was subsequently sent and was positive. The patient was started on Vitamin B12 for treatment of pernicious anemia and discharged home.
After discharge, SPEP resulted with elevated IgM Kappa, concerning for Waldenström macroglobulinemia. The patient was referred to hematology. Bone marrow biopsy demonstrated hyper-cellular marrow with CD5/CD10 negative small B-cell lymphoma with plasmacytic differentiation, consistent with Waldenström macroglobulinemia. The patient was treated with bendamustine, rituximab, and plasmapheresis.

Discussion: Pernicious anemia is a type of megaloblastic anemia due to Vitamin B12 deficiency in which the body lacks intrinsic factor. It is often caused by autoimmune destruction of parietal cells, and may be associated with atrophic gastritis and H. Pylori infection. Other autoimmune diseases such as primary adrenal insufficiency or type 1 diabetes are associated with increased risk of pernicious anemia. Symptoms of pernicious anemia include weakness and paresthesia. Pernicious anemia is treated with oral or intravenous Vitamin B12.

Waldenström macroglobulinemia occurs when clonally related lymphocytes, lymphoplasmacytic cells, and plasma cells producing IgM accumulate in the bone marrow. It is defined as a lymphoplasacitic lymphoma associated with serum IgM monoclonal protein. Symptomatic presentation of Waldenström macroglobulinemia is related to tumor infiltration, circulating IgM, or IgM tissue deposition. Age-adjusted incidence of Waldenström macroglobulinemia is 3.4 per million among US males and 1.7 per million among US females. Asymptomatic patients may be monitored without therapy, though splenomegaly or anemia with hemoglobin < 10 g/dL may justify treatment. It has been suggested that chronic immune stimulation may be associated with Waldenström macroglobulinemia. Landgren et al. assessed a Swedish population registry of 2470 case patients with Waldenström macroglobulinemia and found an association between personal history of certain immune-related conditions and Waldenström macroglobulinemia. However, no significant association with pernicious anemia was found, suggesting that the two processes contributing to anemia in our patient are unrelated.

Conclusions: 1. Consider multiple concurrent processes in a patient presenting with anemia.
2. Patients are often discharged from the hospital with unresulted lab tests; it is essential to ensure that these results are followed-up.
3. While Waldenström macroglobulinemia has been associated with immune-related conditions, pernicious anemia and Waldenström macroglobulinemia are unlikely to be associated with one another.