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Difficulty: HardDiagnostic Workup and Test Sequencing

A 6868-year-old man is evaluated in the clinic for a 33-month history of progressively worsening lower back pain, generalized fatigue, and recent-onset constipation. He has no prior history of malignancy or significant chronic medical conditions. His temperature is 37.1∘C37.1^\circ\text{C} (98.8∘F98.8^\circ\text{F}), blood pressure is 138/86 mmHg138/86\text{ mmHg}, pulse is 84/min84/\text{min}, and respiratory rate is 14/min14/\text{min}. Physical examination reveals midline tenderness over the lower lumbar spine with no focal neurologic deficits. Muscle strength and deep tendon reflexes are symmetric and intact in both lower extremities.

Laboratory studies show:

Laboratory TestResult
Hemoglobin9.4 g/dL9.4\text{ g/dL}
Mean corpuscular volume88 fL88\text{ fL}
Leukocyte count6,200/mm36,200/\text{mm}^3
Platelet count180,000/mm3180,000/\text{mm}^3
Calcium, serum11.5 mg/dL11.5\text{ mg/dL}
Creatinine, serum2.2 mg/dL2.2\text{ mg/dL}
Protein, total9.2 g/dL9.2\text{ g/dL}
Albumin, serum3.5 g/dL3.5\text{ g/dL}

Based on these findings, which of the following diagnostic studies are the most appropriate concurrent next steps in this patient's evaluation? (Select two)

  1. Serum protein electrophoresis and serum free light chain assayAnswer
  2. Whole-body low-dose computed tomography (CT) scanAnswer
  3. C
    Technetium-99m bone scintigraphy
  4. D
    Bone marrow aspiration and biopsy
  5. E
    Magnetic resonance imaging (MRI) of the lumbar spine without contrast

Answer

The most appropriate concurrent next steps are Serum protein electrophoresis and serum free light chain assay AND a Whole-body low-dose computed tomography (CT) scan.
This patient's presentation of hypercalcemia, renal insufficiency, anemia, and bone pain (CRAB criteria) coupled with an elevated protein gap (total protein minus albumin >4 g/dL> 4\text{ g/dL}) is highly suspicious for multiple myeloma (MM). The initial diagnostic workup for MM requires two parallel pathways: biochemical identification of the monoclonal protein and radiologic assessment of skeletal involvement. Serum protein electrophoresis (SPEP) and a serum free light chain (SFLC) assay are the most sensitive initial non-invasive biochemical tests. Concurrently, systemic skeletal imaging is required. Whole-body low-dose CT has superseded conventional plain-film skeletal surveys as the standard of care due to its higher sensitivity for detecting small osteolytic lesions.

Step-by-Step Solution

1
Analyze the clinical presentation and laboratory findings to establish a primary differential diagnosis.
The patient exhibits hypercalcemia, acute kidney injury, normocytic anemia, and bone pain (CRAB criteria), alongside a significantly elevated protein gap (9.2−3.5=5.7 g/dL9.2 - 3.5 = 5.7\text{ g/dL}).
This constellation of findings strongly suggests a plasma cell dyscrasia, most notably multiple myeloma.
2
Determine the optimal initial biochemical diagnostic workup.
Serum protein electrophoresis (SPEP) and a serum free light chain (SFLC) assay must be ordered.
These highly sensitive, non-invasive tests identify and quantify the monoclonal immunoglobulin (M-protein) before escalating to invasive bone marrow sampling.
3
Determine the most appropriate concurrent imaging modality.
A whole-body low-dose CT scan should be ordered alongside the laboratory workup.
Systemic evaluation of the skeleton is necessary to identify osteolytic lesions. Whole-body low-dose CT has replaced conventional X-ray skeletal surveys as the gold standard due to its superior sensitivity.

Key Concept

The initial evaluation of suspected multiple myeloma requires concurrent non-invasive biochemical screening for a monoclonal protein (SPEP and serum free light chain assay) and systemic skeletal imaging (whole-body low-dose CT) prior to performing a confirmatory bone marrow biopsy.
Estimated Time:1m 30s
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Diagnostic Workup and Test Sequencing

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