A 74-year-old man comes to the office due to 3 months of "problems of old age." He has daily temporal headaches and feels quite fatigued. Intermittently, the patient's ears ring and his eyes become blurry. Both feet feel as if someone is "sticking them with electric pins." The patient used to smoke cigarettes but now uses vaporized nicotine. His medical history is unremarkable. Temperature is 36.6 C (97.8 F), blood pressure is 128/74 mm Hg, and pulse is 88/min. He is well appearing. There is moderate cervical lymphadenopathy. Cardiopulmonary examination is normal. Hepatosplenomegaly is present. Funduscopy shows dilated, segmented, and tortuous retinal veins. There are sensory deficits in his feet, but reflexes and strength are intact. Laboratory results are as follows: Serum protein electrophoresis reveals a sharp IgM spike. Which of the following is the most likely diagnosis for this patient?

Question

A 74-year-old man comes to the office due to 3 months of "problems of old age."  He has daily temporal headaches and feels quite fatigued.  Intermittently, the patient's ears ring and his eyes become blurry.  Both feet feel as if someone is "sticking them with electric pins."  The patient used to smoke cigarettes but now uses vaporized nicotine.  His medical history is unremarkable.  Temperature is 36.6 C (97.8 F), blood pressure is 128/74 mm Hg, and pulse is 88/min.  He is well appearing.  There is moderate cervical lymphadenopathy.  Cardiopulmonary examination is normal.  Hepatosplenomegaly is present.  Funduscopy shows dilated, segmented, and tortuous retinal veins.  There are sensory deficits in his feet, but reflexes and strength are intact.  Laboratory results are as follows:  Serum protein electrophoresis reveals a sharp IgM spike.  Which of the following is the most likely diagnosis for this patient?

Quizplus · Accepted Answer

11ec25c8_d43b_5e03_bc81_71be1dd6a6eb_MD0003_00 Waldenstrom macroglobulinemia (WM) is a lymphoplasmocytic malignancy characterized by the excessive production of monoclonal IgM antibody. Clinical manifestations of WM stem from elevated serum IgM (hyperviscosity syndrome, neuropathy, cryoglobulinemia) and neoplastic infiltration of tissue (hepatosplenomegaly, lymphadenopathy, cytopenias). Peripheral blood smear may show rouleaux formation (or erythrocyte agglutination) due to elevated serum protein. Serum protein electrophoresis (SPEP) is an important screening study; patients with WM have a monoclonal spike (M-spike) of IgM. Diagnosis is then confirmed by bone marrow biopsy showing >10% clonal B cells with specific cytogenetic features. erythrocyte agglutination This patient presents with manifestations of hyperviscosity syndrome (diplopia, tinnitus, headache, dilated/segmented funduscopic findings), neuropathy (electric sensation), and evidence of infiltrative disease (hepatosplenomegaly, anemia, thrombocytopenia), suggesting WM. (Choice A) A minority of patients with chronic lymphocytic leukemia (CLL) have high levels of monoclonal IgM. However, patients with CLL tend to have a dramatic lymphocytic predominant leukocytosis (often >100,000/mm³) on complete blood count. (Choice B) Patients with monoclonal gammopathy of undetermined significance (MGUS) also have M spikes, but they are most commonly due to IgA, IgG, or IgD (IgM is seen in 15% of cases). MGUS is marked by smaller M spikes (<3 g/dL), bone marrow biopsy with <10% monoclonal plasma cells, and, unlike this patient, no end-organ effects (no anemia, hepatosplenomegaly, lymphadenopathy, or systemic symptoms). (Choice C) Multiple myeloma (MM) is also a plasma cell neoplasm that produces a monoclonal antibody spike by SPEP; however, patients with MM rarely (<0.5%) produce monoclonal IgM. MM is typically characterized by monoclonal IgG, IgA, or light chains. In addition, patients with MM tend to present with bone pain rather than hyperviscosity, neuropathy, and tissue infiltration. (Choice D) Non-Hodgkin lymphoma (NHL) usually presents with lymphadenopathy, splenomegaly, and B symptoms (fevers, night sweats, weight loss). SPEP tends not to show monoclonal spikes with NHL. In addition, hyperviscosity syndrome is not a feature of this disease. Educational objective: Waldenstrom macroglobulinemia (WM) is a lymphoplasmocytic neoplasm characterized by excessive monoclonal IgM, end-organ damage, and >10% clonal lymphocytes by bone marrow biopsy. Hyperviscosity syndrome, neuropathy, and cryoglobulinemia are common consequences of elevated serum IgM in patients with WM.

A 74-Year-Old Man Comes to the Office Due to 3