A 68-year-old man presents to the clinic with a 4-month history of persistent, dull low back pain that is worse with movement and partially relieved by rest. He also reports generalized weakness and a 10-pound unintentional weight loss. He denies any recent trauma. Past medical history is significant for hypertension which is managed with amlodipine. Vital signs are within normal limits. Physical examination reveals tenderness to palpation over the lumbar spine but no focal neurological deficits.
Laboratory studies show the following:
Hemoglobin: 9.2 g/dL
Calcium: 11.4 mg/dL (Normal: 8.5–10.5)
Creatinine: 2.1 mg/dL (Baseline: 1.0)
Total Protein: 10.5 g/dL (Normal: 6.0–8.0)
Albumin: 3.2 g/dL (Normal: 3.5–5.0)
A peripheral blood smear shows red blood cells stacked like coins. A 24-hour urine collection reveals increased excretion of monoclonal light chains. Which of the following is the most likely additional finding in this patient?
The correct answer is:
B) Plasma cells constituting 15% of the bone marrow aspirate
This patient is presenting with multiple myeloma (MM), a malignant proliferation of plasma cells in the bone marrow. It is a disease of older adults and is characterized by the CRAB clinical tetrad:
Calcium elevation (hypercalcemia) due to increased osteoclast activity.
Renal insufficiency caused by the filtration of toxic Bence-Jones proteins (monoclonal light chains) through the kidneys.
Anemia: Normocytic anemia due to bone marrow infiltration.
Bone disease: Punched-out lytic lesions and pathologic fractures.
The diagnosis of multiple myeloma requires the presence of ≥10% clonal bone marrow plasma cells or biopsy-proven extramedullary plasmacytoma, plus one or more myeloma-defining events (like the CRAB features). The stacked coin appearance on the peripheral smear refers to Rouleaux formation. This occurs because high levels of monoclonal protein (M-protein) decrease the negative charge between red blood cells, causing them to sediment more quickly.
Answer choice A: Osteoblastic lesions on a radionuclide bone scan, is incorrect. Multiple myeloma causes osteolytic (radiolucent) lesions due to osteoclast activation. Radionuclide bone scans, which detect osteoblastic activity, are often falsely negative in MM. A skeletal survey (X-rays) or CT/MRI is preferred.
Answer choice C: Positive direct antiglobulin (Coombs) test for IgG, is incorrect. While MM causes anemia, it is typically a non-hemolytic anemia of chronic disease or marrow replacement. A positive Coombs test is seen in autoimmune hemolytic anemia, which is more commonly associated with CLL.
Answer choice D: "Starry sky" appearance on lymph node biopsy, is incorrect. This is the classic histological finding for Burkitt lymphoma, caused by tingible body macrophages.
Answer choice E: t(14;18) translocation involving the BCL2 gene, is incorrect. This translocation is the hallmark of follicular lymphoma. While MM involves the 14q32 (IgH) locus in about 50% of cases, it typically translocates with different partners (e.g., t(4;14)or t(11;14)).
Key Learning Point
Multiple myeloma should be suspected in an elderly patient with bone pain, hypercalcemia, and renal failure. The hallmark laboratory findings include an M-spike on serum protein electrophoresis (SPEP), Bence-Jones proteins in the urine, and Rouleaux formation on peripheral smear. Diagnosis is confirmed by ≥10% plasma cells on bone marrow biopsy.
