A 68-year-old male is evaluated in the ambulatory care center for a 3-month history of wor… — USMLE Step 3

A $68$ -year-old male is evaluated in the ambulatory care center for a $3$ -month history of worsening lower back pain and generalized fatigue. He reports the pain is deep and aching, does not improve with rest, and frequently awakens him from sleep. His past medical history is notable for localized prostate cancer treated with a radical prostatectomy $4$ years ago, as well as essential hypertension. Current medications include lisinopril and over-the-counter ibuprofen. Vital signs are within normal limits. Physical examination reveals point tenderness over the lumbar spine, but neurologic examination of the lower extremities is unremarkable. Laboratory studies reveal the following:

Hemoglobin: $10.1$ g/dL
Mean corpuscular volume: $89$ fL
Platelet count: $180,000$ /mm $^3$
Leukocyte count: $6,500$ /mm $^3$
Blood urea nitrogen: $28$ mg/dL
Serum creatinine: $1.7$ mg/dL (baseline $0.9$ mg/dL)
Total serum calcium: $11.6$ mg/dL
Total serum protein: $8.4$ g/dL
Serum albumin: $3.9$ g/dL
Alkaline phosphatase: $80$ U/L
Prostate-specific antigen: $<0.1$ ng/mL

Which of the following is the most likely diagnosis in this patient?

Multiple myelomaAnswer
B
Metastatic prostate cancer
C
Monoclonal gammopathy of undetermined significance
D
Primary hyperparathyroidism
E
Paget disease of bone

Answer

Multiple myeloma

The correct diagnosis is multiple myeloma. This patient's presentation features the classic CRAB criteria: Calcium elevation, Renal insufficiency, Anemia, and Bone pain. The discrepancy between his total serum protein (

8.4

g/dL) and albumin (

3.9

g/dL) reveals a substantial "protein gap" (difference

>4

g/dL). This gap strongly suggests the overproduction of monoclonal immunoglobulins (paraproteins) by neoplastic plasma cells. The deep, aching back pain with point tenderness is highly characteristic of osteolytic bone lesions or a pathologic vertebral compression fracture, which are hallmark complications of multiple myeloma.

Step-by-Step Solution

Analyze the clinical presentation and past medical history.

The patient is an older adult presenting with worsening, rest-independent back pain and fatigue, with a history of prostate cancer.

Identifying red flags (night pain, point tenderness) helps distinguish sinister causes of back pain (e.g., malignancy) from mechanical causes.

Evaluate the laboratory findings for patterns.

Findings include normocytic anemia (Hgb

10.1

g/dL), acute kidney injury (Cr

1.7

mg/dL), hypercalcemia (

11.6

mg/dL), and a significant protein gap (Total protein

8.4

minus Albumin

3.9

4.5

g/dL).

A protein gap

>4

g/dL strongly suggests elevated globulins, such as monoclonal antibodies produced in a plasma cell dyscrasia.

Synthesize the data to formulate a differential diagnosis and select the most likely etiology.

The combination of hypercalcemia, renal failure, anemia, bone pain, and a protein gap is diagnostic for multiple myeloma.

Although he has a history of prostate cancer, the undetectable PSA, normal alkaline phosphatase, and hypercalcemia point away from osteoblastic prostate metastases and toward osteolytic lesions of multiple myeloma.

Key Concept

The classic presentation of multiple myeloma includes the CRAB criteria (Hypercalcemia, Renal insufficiency, Anemia, Bone lesions) accompanied by a serum protein gap.

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