A 64-year-old woman presents to her primary
care physician with fatigue, weakness, and a
weight loss of 4.5 kg (10 lb) in the past
4 months. Additionally, she notes that her vision
has deteriorated over that time, and has
had several severe nosebleeds. Physical examination
demonstrates hepatosplenomegaly, and
laboratory tests show an increased total protein
level. Serum protein electrophoresis reveals a
large spike in the gamma region. A skeletal survey
is negative. Which of the following is the
most likely diagnosis?
A. Chronic lymphocytic leukemia B. Diabetes mellitus C. Monoclonal gammopathy of undetermined
signifi cance D. Multiple myeloma E. WaldenstrÃ¶mâ€™s macroglobulinemia
Waldenstrã¶mâ€™s macroglobulinemia-38. the correct answer is e. the disease that is described is waldenstroms macroglobulinemia, which is characterized by weakness, weight loss, a monoclonal m spike on serum protein electrophoresis (seen as a large spike in the gamma region), and a hyperviscosity syndrome (manifesting as nosebleeds, headaches, and vision disturbances). hyperviscosity is caused by the large amount of igm protein in the blood produced by a b-cell neoplasm. these large proteins interfere with microvascular and cellular processes, causing blood vessel damage, which results in headaches due to impaired cranial blood flow and in disturbances in vision due to poor ocular blood flow. additionally, circulating igm proteins can bind to clotting factors and inhibit them, causing increased bleeding. answer a is incorrect. chronic lymphocytic leukemia (cll) typically presents with lymphadenopathy, hepatosplenomegaly, a warm antibody autoimmune hemolytic anemia, and smudge cells in the peripheral blood. the hyperviscosity syndrome is not present in cll. answer b is incorrect. diabetes presents with nocturia, polyuria, and polydipsia. blood tests would demonstrate increased glucose. superficial resemblances between the hyperviscosity syndromes and diabetic retinopathy, and diabetic kidney disease with the renal insufficiency of multiple myeloma, may be misleading. however, bleeding complications due to diabetes alone would be rare. answer c is incorrect. monoclonal gammopathy of undetermined significance (mgus) is similar to the condition described above in that it, too, has a monoclonal spike. an important difference is that mgus is asymptomatic due to a lower level of protein. some patients may experience mild polyneuropathy, but they will not have the bone pain, renal failure, and anemia of multiple myeloma or the hyperviscosity of waldenstroms macroglobulinemia. nonetheless, mgus may be a premalignant lesion that can progress to multiple myeloma. answer d is incorrect. multiple myeloma is similar to the condition described above and it also involves abnormal plasma cells overproducing immunoglobulin, seen as a monoclonal m spike (critical for diagnosis). however, instead of a hyperviscosity syndrome, multiple myeloma typically presents with a collection of other characteristic symptoms. these symptoms include with lytic bone lesions causing bone pain and hypercalcemia, renal insufficiency and azotemia, increased susceptibility to infection, and anemia. additionally, one may find bence jones protein (ig light chains) in the urine and a rouleaux formation of rbcs on peripheral blood smear.