Prepare for USMLE Step 1 with this case! Learn about a USMLE Step 1 question involving a 62-year-old man with headaches, blurry vision, and numbness in his hands. The case study reveals the diagnosis of Waldenstrom macroglobulinemia, focusing on its pathophysiology, symptoms, and diagnostic criteria. Understand the significance of elevated IgM levels, blood viscosity, and the importance of cold agglutination in this hematologic malignancy.
A 62 year-old man presents to his outpatient provider’s office because of two months of persistent headaches, blurry vision, and numbness in the hands bilaterally. The headache is unresponsive to over the counter pain-killers. He also reports 10 lbs (4.5 kg) weight loss over the same period. Past medical history is notable for hypertension. Family history is significant for multiple sclerosis in his mother. His temperature is 37.1°C (98.8°F), pulse is 75/min and blood pressure is 148/97 mmHg. Cardiopulmonary examination is noncontributory. Abdominal examination reveals hepatosplenomegaly. On peripheral smear, red blood cells are seen to clump together when placed in a 5°C (41°F) refrigerator. Which of the following best explains the pathophysiology of the patient’s condition?
A. Neoplastic proliferation of IgM-secreting plasma cells
B. Erythropoietin-independent proliferation of red blood cells
C. Autoimmune destruction of myelin in the central nervous system
D. Malignant proliferation of cells of myeloid lineage
E. Infection by a double-stranded DNA virus
Scroll down for the correct answer!
The correct answer to today’s USMLE® Step 1 Question is…
A. Neoplastic proliferation of IgM-secreting plasma cells
Before we get to the Main Explanation, let’s look at the incorrect answer explanations. Skip to the bottom if you want to see the correct answer right away!
Incorrect answer explanations
B. Erythropoietin-independent proliferation of red blood cells
Incorrect: This answer describes polycythemia vera, a myeloproliferative neoplasm characterized by elevated red blood cell mass. Patients with the condition may present with constitutional symptoms (e.g., fatigue, weight loss) and symptoms secondary to increased blood viscosity (e.g., visual disturbances, headaches, thrombosis). While the patient in this vignette has some of the aforementioned symptoms, it would be atypical for polycythemia vera to cause rouleaux formation on peripheral smear.
C. Autoimmune destruction of myelin in the central nervous system
Incorrect: This answer describes multiple sclerosis, which may cause symptoms including vision impairment, incontinence, paresthesia, and impaired coordination. The patient presents with vision changes and has a family history of multiple sclerosis. However, the disease typically affects young adults between 20-40 years-old. Moreover, multiple sclerosis would not explain the cold-agglutination of RBCs.
D. Malignant proliferation of cells of myeloid lineage
Incorrect:Malignant proliferation of cells of myeloid lineage (e.g. acute or chronic myeloid leukemia) can present with constitutional symptoms, lymphadenopathy, and hepatosplenomegaly. However, it would be uncommon for either AML or CML to present with headaches, visual impairments, and peripheral neuropathy. In addition, peripheral smear finding of rouleaux formation cannot be accounted for by AML or CML.
E. Infection by a double-stranded DNA virus
Incorrect: Base excision repair plays an important role in the repair of spontaneous or toxic deamination (removal of amino groups from nitrogen bases) that results from chemicals like nitrites or nitrosamine. A defect in base excision repair can increase the risk of developing colorectal cancer but is not associated with xeroderma pigmentosum.
Main Explanation
This patient most likely has Waldenstrom macroglobulinemia, a malignant proliferation of IgM-producing plasma cells. The elevated serum IgM levels result in increased blood viscosity. Many patients with the condition are asymptomatic, However, symptomatic patients present with constitutional symptoms (e.g., fatigue, fever, weight loss) and symptoms secondary to increased blood viscosity/decreased blood flow (e.g., vision impairment, leg cramps, neuropathy).
Diagnostic workup involves obtaining a complete blood count, peripheral blood smear, serum protein electrophoresis, and bone marrow biopsy. Cold agglutination, the clumping of red blood cells at low temperatures, can be seen on peripheral smears. A diagnosis of Waldenstrom macroglobulinemia can be made if serum protein electrophoresis demonstrates elevated IgM levels and bone marrow biopsy shows greater than 10% plasma cells.
Asymptomatic patients do not need treatment but should be followed closely. Patients with symptoms secondary to elevated blood viscosity should undergo plasmapheresis, which filters out the excess IgM. Chemotherapeutic agents such as rituximab and fludarabine can be utilized to destroy malignant plasma cells.
Major Takeaway
Waldenstrom macroglobulinemia is the malignant proliferation of IgM-producing plasma cells. Symptomatic individuals present with a mix of constitutional symptoms and symptoms secondary to increased blood viscosity. A diagnosis can be made based on bone marrow biopsy and protein electrophoresis results.
References
- Gertz, M.A. (2017) Waldenstrom macroglobulinemia: 2017 update on diagnosis, risk stratification, and management. Annual Clinical Updates in Hematological Malignancies. 92(2), 209-217. Doi: 10.1002/ajh.24557.
- Michels, T.C., Petersen, K.E. (2017) “Multiple Myeloma: Diagnosis and Treatment.” American Family Physician. Web Address: www.aafp.org/afp/2017/0315/p373.html#afp20170315p373-t3.
- Smith, T., Wong, M., Goldson, T.M., Forjuoh, S.N. (2019) Diagnosis of Waldenstrom macroglobulinemia. Baylor University Medical Center Proceedings. 32(3), 394-396. Doi: 10.1080/08998280.2019.1596681.
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