Updated: 9/25/2018

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
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
    • 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 (5)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.ON.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? Review Topic

QID: 108696
1

Abundant reticulocytes

6%

(3/47)

2

Linear aggregations of red blood cells

55%

(26/47)

3

Schistocytes

9%

(4/47)

4

Leukocytosis with abundant mature myeloid cells

23%

(11/47)

5

Smudge cells

2%

(1/47)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 2

(M1.ON.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 is shown in Figure B and notably also shows the presence of eosinophilic casts. What is the most likely explanation for his renal findings? Review Topic

QID: 107158
FIGURES:
1

Monoclonal protein overproduction

61%

(46/75)

2

Ischemic tubular injury

15%

(11/75)

3

Acute pyelonephritis

8%

(6/75)

4

Diabetic nephropathy

4%

(3/75)

5

Nephritic syndrome

9%

(7/75)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1

(M1.ON.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? Review Topic

QID: 106765
FIGURES:
1

Figure A

38%

(38/99)

2

Figure B

13%

(13/99)

3

Figure C

18%

(18/99)

4

Figure D

14%

(14/99)

5

Figure E

14%

(14/99)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1

(M1.ON.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? Review Topic

QID: 105637
FIGURES:
1

Mitochondria

9%

(3/33)

2

Golgi bodies

6%

(2/33)

3

Rough endoplasmic reticulum

55%

(18/33)

4

Smooth endoplasmic reticulum

9%

(3/33)

5

Lysosomes

12%

(4/33)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 3
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