Updated: 10/7/2021

Multiple Myeloma

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Introduction
  • Multiple myeloma is cancer of monoclonal plasma cells
    • produces large amounts of IgG (55%) or IgA (25%)
    • high levels of IL-6 may be present
  • Epidemiology
    • most common primary tumor arising within bone in the elderly
  • If asymptomatic
    • called monoclonal gammopathy of undetermined significance (MGUS)
    • increased gamma globulin on serum electrophoresis but no symptoms of multiple myeloma are present
  • Pathophysiology
    • initial event - abnormal response of B lymphocyte to antigenic stimulation results in monoclonal proliferation of plasma cells -> MGUS
    • additional mutations causes progression from MGUS to multiple myeloma
    • since the plasma cell population in multiple myeloma are clones, they produce the same antibody, resulting in the monoclonal M spike on serum protein electrophoresis
      • though total serum antibody levels increase, these antibodies do not provide protection against pathogens because there is a lack of antibody antigenic diversity 
Presentation
  • Symptoms 
    • bone pain
    • sequelae associated with hypercalcemia
    • sequelae associated with renal failure
Evaluation
  • Serum protein electrophoresis
    • monoclonal immunoglobulin spike (M protein)
  • Urinalysis 
    • Ig light chains (Bence Jones protein)
  • Peripheral blood smear
    • Russell bodies
      • Ig containing inclusion bodies seen in plasma cells
    • RBC rouleaux formation
      • Igs coat RBC and neutralize the ionic charge than normally repels RBCs
  • Bone marrow aspiration
    • proliferation of large monoclonal plasma cells
      • "fried-egg" appearance
  • Serology
    • hypercalcemia  
      • result of bone degradation due to cytokine production that activates RANK receptor on osteoclasts
      • associated with decreased phosphate, increased PTH-rp and decreased vitamin D levels
    • prolonged bleeding time
  • Imaging
    • punched-out lytic bone lesions on x-ray
Prognosis, Prevention, and Complications
  • May lead to
    • renal insufficiency
    • ↑ susceptibility to infection
    • anemia
    • primary amyloidosis (AL) 
  • Poor prognosis

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Questions (7)
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(M1.ON.17.4754) A 68-year-old female presents to her primary care physician with a 7-month history of fatigue and low back pain. Her pain is not improved by over the counter analgesics. Laboratory analysis is notable for a calcium level of 11.5 mg/dL, creatinine level of 2.0 mg/dL, and blood urea nitrogen level of 30 mg/dL. Large eosinophilic casts are seen on renal biopsy. Which of the following findings is most likely to be seen on peripheral blood smear?

QID: 108696
1

Abundant reticulocytes

5%

(3/64)

2

Linear aggregations of red blood cells

62%

(40/64)

3

Schistocytes

6%

(4/64)

4

Leukocytosis with abundant mature myeloid cells

19%

(12/64)

5

Smudge cells

5%

(3/64)

M 2 C

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(M1.ON.15.4671) A 74-year-old man presents complaining of back pain. He has also been feeling fatigued for the last several months and says he has lost about 20 pounds. On laboratory exam, his creatinine has increased from baseline, and his serum calcium is 11.5 mg/dL. He is referred to a nephrologist, and the results of a renal biopsy are shown in Figure A. Microscopic examination of the urine demonstrated the presence of eosinophilic casts. What is the most likely explanation for his renal findings?

QID: 107158
FIGURES:
1

Monoclonal protein overproduction

64%

(69/108)

2

Ischemic tubular injury

13%

(14/108)

3

Acute pyelonephritis

7%

(8/108)

4

Diabetic nephropathy

6%

(6/108)

5

Nephritic syndrome

8%

(9/108)

M 2 E

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(M1.ON.15.75) A 68-year-old male presents to his primary care physician with a complaint of increased fatigue and back pain that has not resolved over the past few months despite adequate rest and treatment with over the counter analgesics. The physician orders basic blood work including a CBC and BMP that demonstrates anemia, renal failure, and hypercalcemia. The physician orders a renal biopsy to evaluate the etiology for the renal failure. Which of the following figures is most likely to be observed on renal biopsy?

QID: 106765
FIGURES:
1

Figure A

35%

(52/147)

2

Figure B

14%

(21/147)

3

Figure C

24%

(35/147)

4

Figure D

12%

(18/147)

5

Figure E

13%

(19/147)

M 1 B

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(M1.ON.15.27) A 74-year-old female presents to her primary care physician complaining of an 8-month history of malaise and lower back pain. Laboratory findings reveal a serum M spike and urinalysis is positive for light chain proteinuria. MRI imaging is obtained (Figure A). Which cellular component is likely to be found in abundance in the dominant cells on bone marrow biopsy in this patient?

QID: 105637
FIGURES:
1

Mitochondria

7%

(3/46)

2

Golgi bodies

7%

(3/46)

3

Rough endoplasmic reticulum

59%

(27/46)

4

Smooth endoplasmic reticulum

9%

(4/46)

5

Lysosomes

13%

(6/46)

M 1 C

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