Updated: 12/27/2021

Multiple Myeloma

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  • Snapshot
    • A 65-year-old man presents to his primary care physician with generalized fatigue and lower back bone pain. He reports an unexpected 20-pound weight loss over the course of 3 months. Physical examination is notable for conjunctival pallor and tenderness upon palpation of the lower spine. Laboratory studies are notable for a normocytic, normochromic anemia, hypercalcemia, and renal insufficiency. Urine electrophoresis is notable for Bence Jones proteins.
  • Introduction
    • Overview
      • neoplastic proliferation of plasma cells within the bone marrow
        • leads to the production of monoclonal immunoglobulin (Ig)
          • mostly IgG (52%) and IgA (21%)
        • results in skeletal destruction
  • Epidemiology
    • Demographics
      • older adults
        • median age is 66 years of age
    • Risk factors
      • monoclonal gammopathy of undetermined significance (MGUS)
  • ETIOLOGY
    • Pathophysiology
      • clonal malignant plasma cell proliferation
    • Associated conditions
      • Fanconi syndrome
      • renal tubular acidosis type 2
      • ↑ susceptibility to infection
      • primary amyloidosis
  • Presentation
    • Symptoms
      • fatigue
        • secondary to anemia
      • bone pain
        • especially in the back and chest
      • radiculopathy
        • especially in the thoracic or lumbosacral area
        • it's the most common neurological complication of multiple myeloma
        • secondary to
          • paravertebral plasmacytoma
          • bone collapse
      • peripheral neuropathy
        • rare and usually secondary to amyloidosis
      • sequelae associated with hypercalcemia
        • e.g., constipation, abdominal pain, muscle pain, and frequent urination
      • edema
        • secondary to effects of amyloidosis on kidneys
  • Imaging
    • Radiography
      • indication
        • can be used as an initial imaging study when evaluating bone pain
          • it is the least sensitive method for detecting skeletal lesions
      • findings
        • lytic bone lesions
    • Whole body low-dose CT scan
      • indication
        • used in most cases to have a baseline assessment of how much the bone is involved
    • MRI whole body (or spine and pelvis)
      • indication
        • when CT scan does not demonstrate bone lesions but there is a high suspicion of multiple myeloma
          • most sensitive in evaluating bone involvement
        • when there is concern for cord compression
    • PET scan
      • indication
        • suspected extramedullary disease
          • most sensitive in evaluating extramedullary involvement
  • Studies
    • Serum labs
      • normocytic, normochromic anemia
        • secondary to
          • bone marrow replacement
          • renal damage
          • hemodilution with large M protein
      • elevated serum creatinine
        • secondary to
          • light chain cast nephropathy (myeloma kidney)
            • Bence Jones protein on urine electrophoresis
          • hypercalcemia
      • hypercalcemia
        • from osteolytic bone lesions
      • protein electrophoresis of the serum (SPEP)
        • monoclonal immunoglobulin spike (M protein)
      • peripheral blood smear
        • rouleaux formation of red blood cells
          • "stack of coins" appearance
    • Invasive studies
      • bone marrow aspiration
        • ≥ 10% clonal plasma cells
        • multiple plasma cells with a "clock-face" chromatin pattern
      • renal biopsy
        • amyloid desposits will show apple-green birefringence under polarized light with Congo red stain
    • Imaging
      • punched-out lytic bone lesions on radiograph
  • Differential
    • MGUS
      • differentiating factors
        • < 10% clonal plasma cells
        • absence of lytic lesions
        • serum M protein is low
    • Waldenstrom macroglobulinemia
      • differentiating factors
        • IgM gammopathy
        • absence of hypercalcemia, renal involvement, anemia, and bone lytic lesions
  • Treatment
    • Medical
      • chemotherapy
        • indication
          • treatment of choice
            • optimal treatment has not been established yet
  • Complications
    • May lead to
      • ↑ susceptibility to infection
      • anemia
      • primary amyloidosis (AL)
        • cast nephropathy
          • due to excess light chain production
        • peripheral neuropathy
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(M2.ON.15.4691) A 68-year-old male presents to his primary care physician with complaints of fatigue and pain in his upper arms and lower back for the past 2 months. Physical examination reveals pallor, hepatosplenomegaly, and focal bony tenderness to palpation over the lumbar vertebrae, bilateral humeri, and skull. Laboratory evaluation reveals hemoglobin 9.8 g/dL, serum calcium of 9.4 mg/dL, serum creatinine of 1.4 mg/dL, albumin of 3.7 g/dL, and rouleaux formation on peripheral blood smear. Serum protein electrophoresis reveals an elevated spike of a monoclonal IgG protein, with an M-protein serum concentration of 50 g/L. Which of the following radiographs would most likely be associated with this patient's condition?

QID: 107650
FIGURES:
1

Figure A

10%

(2/21)

2

FIgure B

10%

(2/21)

3

Figure C

5%

(1/21)

4

Figure D

10%

(2/21)

5

Figure E

62%

(13/21)

M 6 D

Select Answer to see Preferred Response

(M2.ON.14.6) A 68-year-old man presents with a 6-month history of worsening fatigue and weight loss. He is especially concerned about a recent episode in which he noticed a blurring of his vision and headache; he also notes that his “memory is not as good as it used to be,” which his wife confirms. Physical exam is notable only for pallor and general weakness. Laboratory studies reveal anemia as well as an elevated erythrocyte sedimentation rate. Serum protein electrophoresis (SPEP) reveals a sharp, narrow spike of monoclonal IgM; serum IgM concentration is 6.3 g/dL. What is the most likely diagnosis in this case?

QID: 104646
1

IgM monoclonal gammopathy of undetermined significance (MGUS)

0%

(0/17)

2

Multiple myeloma

35%

(6/17)

3

Waldenstrom’s macroglobulinemia

59%

(10/17)

4

Non-Hodgkin’s lymphoma

0%

(0/17)

5

Chronic lymphocytic leukemia

0%

(0/17)

M 6 E

Select Answer to see Preferred Response

(M2.ON.14.20) A 57-year-old woman with a history of hypertension presents to her physician with severe mid-back pain. She reports that the pain is sharp and began when she was reaching to retrieve a plate from a cabinet in her kitchen. She denies any major trauma to the back or any history of lifting heavy objects. On exam, she has spinal tenderness over the site, which is not warm or erythematous. On laboratory evaluation, she is found to have a creatinine of 5.6 mg/dL and a calcium of 16 mg/dL. Which of the following bone marrow biopsy findings is most likely to be found in this patient?

QID: 104660
FIGURES:
1

Figure A

81%

(13/16)

2

Figure B

0%

(0/16)

3

Figure C

6%

(1/16)

4

Figure D

6%

(1/16)

5

Figure E

0%

(0/16)

M 6 E

Select Answer to see Preferred Response

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