A 67-year-old man presents to the clinic with a 3-month history of progressively worsening… — USMLE Step 3

A 67-year-old man presents to the clinic with a 3-month history of progressively worsening fatigue, generalized weakness, and severe, aching mid-back pain. The pain does not radiate and is not relieved by over-the-counter analgesics. He has no history of trauma, weight loss, or constitutional symptoms. His temperature is $37.1^\circ\text{C}$ ( $98.8^\circ\text{F}$ ), blood pressure is $135/85 \text{ mmHg}$ , pulse is $88/\text{min}$ , and respiratory rate is $14/\text{min}$ .

Physical examination reveals conjunctival pallor and point tenderness to percussion over the T10 and T11 spinous processes. Neurologic examination of the lower extremities shows $5/5$ motor strength, intact sensation to light touch and pinprick, and $2+$ bilateral patellar and Achilles reflexes.

Initial laboratory studies obtained yesterday reveal:

Laboratory Test	Result	Reference Range
Hemoglobin	$9.6 \text{ g/dL}$	$13.5-17.5 \text{ g/dL}$
Mean corpuscular volume	$90 \text{ fL}$	$80-100 \text{ fL}$
Serum creatinine	$2.1 \text{ mg/dL}$	$0.6-1.2 \text{ mg/dL}$
Serum calcium	$11.4 \text{ mg/dL}$	$8.5-10.5 \text{ mg/dL}$
Alkaline phosphatase	$95 \text{ U/L}$	$40-120 \text{ U/L}$

The physician suspects a plasma cell dyscrasia. Which of the following diagnostic investigations should be ordered concurrently as the most appropriate next steps in this patient's diagnostic workup? (Select exactly two)

Serum and urine protein electrophoresis with immunofixation, and serum free light chain assayAnswer
Whole-body low-dose computed tomography without contrastAnswer
C
Radionuclide bone scintigraphy with technetium-99m
D
Unilateral bone marrow aspiration and biopsy
E
Magnetic resonance imaging of the thoracic and lumbar spine with intravenous gadolinium

Answer

The most appropriate concurrent initial diagnostic steps are ordering biochemical screening (serum and urine protein electrophoresis with immunofixation and serum free light chain assay) and skeletal imaging (whole-body low-dose computed tomography without contrast).

This patient's presentation of bone pain, fatigue, and classic CRAB criteria (Hypercalcemia, Renal failure, Anemia, Bone lesions) is highly suspicious for multiple myeloma. The initial diagnostic workup for suspected multiple myeloma requires concurrent biochemical screening and preliminary skeletal imaging. The correct approach includes serum and urine protein electrophoresis with immunofixation alongside a serum free light chain assay to detect monoclonal paraproteins. Concurrently, whole-body low-dose computed tomography without contrast is the gold standard initial imaging modality to detect osteolytic bone lesions. It has replaced conventional skeletal surveys due to superior sensitivity and does not require intravenous contrast, protecting the patient's compromised renal function.

Step-by-Step Solution

Analyze the patient's clinical and laboratory presentation.

The patient exhibits bone pain, normocytic anemia, acute kidney injury, and hypercalcemia, which aligns perfectly with the CRAB criteria for multiple myeloma.

Establishing a high pre-test probability dictates the required specific diagnostic pathway.

Determine the appropriate non-invasive biochemical screening tests.

Serum and urine protein electrophoresis with immunofixation (SPEP/UPEP) and a serum free light chain (SFLC) assay are selected.

These tests provide a highly sensitive, non-invasive method for detecting and quantifying the monoclonal paraproteins characteristic of plasma cell dyscrasias.

Select the most appropriate initial skeletal imaging modality.

Whole-body low-dose computed tomography (CT) without contrast is selected.

Guidelines mandate whole-body low-dose CT to detect osteolytic lesions due to its superior sensitivity compared to plain radiography, while avoiding the nephrotoxic risks of intravenous contrast.

Evaluate the appropriateness of invasive testing in the current sequence.

Bone marrow biopsy is deferred until the non-invasive screening returns positive.

Proper test sequencing dictates performing non-invasive, high-sensitivity screening prior to invasive confirmatory procedures to minimize patient harm.

Key Concept

The initial diagnostic workup for suspected multiple myeloma requires concurrent non-invasive biochemical screening for monoclonal proteins and whole-body low-dose CT for osteolytic lesions, preceding any invasive confirmatory bone marrow biopsy.

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