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Difficulty: MediumDiagnostic Workup and Test Sequencing

A 71-year-old man comes to the clinic reporting a 2-month history of worsening mid-to-lower back pain. The pain is constant, does not improve with rest, and occasionally awakens him at night. Over the same period, he has experienced progressive fatigue, constipation, and increased urinary frequency. His past medical history is notable only for mild osteoarthritis, for which he takes acetaminophen as needed. He does not use tobacco, alcohol, or illicit drugs. Vital signs are within normal limits. Physical examination reveals tenderness to palpation over the lumbar spine but no focal neurological deficits.

Laboratory results are as follows:

Hemoglobin: 9.2 g/dL9.2 \text{ g/dL}
Leukocyte count: 6,500/μL6,500/\mu\text{L}
Platelet count: 140,000/μL140,000/\mu\text{L}
Calcium: 11.8 mg/dL11.8 \text{ mg/dL}
Creatinine: 2.1 mg/dL2.1 \text{ mg/dL}
Alkaline phosphatase: 95 U/L95 \text{ U/L}

Which of the following diagnostic tests should be ordered concurrently as the most appropriate next steps in this patient's initial workup? (Select all that apply)

  1. Serum protein electrophoresis with immunofixationAnswer
  2. Serum free light chain assayAnswer
  3. C
    Bone marrow aspiration and biopsy
  4. D
    Radionuclide bone scintigraphy
  5. E
    Prostate-specific antigen testing

Answer

The most appropriate initial diagnostic steps are serum protein electrophoresis with immunofixation and a serum free light chain assay.
This patient presents with the classic 'CRAB' manifestations of multiple myeloma: hyperCalcemia (constipation, polyuria), Renal insufficiency (elevated creatinine), Anemia (fatigue, low hemoglobin), and Bone pain (lumbar tenderness). The correct sequencing of diagnostic tests begins with non-invasive identification of a monoclonal paraprotein. Current guidelines recommend ordering serum protein electrophoresis with immunofixation, urine protein electrophoresis, and a serum free light chain assay concurrently to maximize initial screening sensitivity.

Step-by-Step Solution

1
Analyze the patient's clinical and laboratory presentation.
The patient exhibits hypercalcemia, renal insufficiency, anemia, and bone pain (CRAB symptoms).
Identifying this specific constellation of findings is necessary to formulate a focused differential diagnosis.
2
Identify the most likely underlying condition.
The clinical picture strongly suggests multiple myeloma.
Multiple myeloma classically presents in older adults with the CRAB criteria, along with a normal alkaline phosphatase level indicating purely osteolytic rather than osteoblastic bone involvement.
3
Determine the optimal sequencing for the initial diagnostic workup.
Order non-invasive serologic screening tests, specifically serum protein electrophoresis (SPEP) with immunofixation and a serum free light chain assay.
Guideline-concordant test sequencing requires establishing the presence of a monoclonal protein non-invasively before proceeding to invasive confirmatory procedures like a bone marrow biopsy.

Key Concept

The initial diagnostic workup of suspected multiple myeloma requires concurrent non-invasive screening with serum/urine protein electrophoresis and serum free light chain assays prior to invasive confirmatory testing.
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Diagnostic Workup and Test Sequencing

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