1. Case Study
Multiple Myeloma

2. Amy 54 year old female
One year history of :-
Fatigue shortness of breath, and dizziness
Weight loss
Increasingly severe back pain.
Bone fractures
Skin lesions
Enlarged tongue
Infections

3. Amy wented to the doctor, and make physical examination:- - She appeared pale - but otherwise her physical exam was within normal limits

4. Asked the doctor several tests include :-

5. Aspirate differential .
CBC
Bone marrow biopsy:
Aspirate differential .
Chemistry:
Total protein .
Serum protein electrophoresis .
Immunoglobulins, quantitative
Radiography

6. Parameters Result Normal Rang Observation
RBC
2.85 x1012/L
4.7 to 6.1 x 1012/L
low HB
7.6 g/dL
g/dL
Low
HCT
23.9 %
40-52 %
MCV fl fl
Normal
MCH pg
27-31 pg
Low -nearly normal
MCHC
31.8 g/dL
32-36 %
Low –nearly normal
RDW
16.8
13 ± 1.5 %
high
WBC
8.4 x109/L
4,5-11 x 109/L
normal N
60 %
40-75% L
26 %
20-45% M
12 %
2-10% E
1 %
1-6% B
0-1%
PLT
418 x 109/L
x 109/L
High - near normal

7. calcium >11.5 mg/dL high
Chemistry
Observation
Parameters
high
AlT
AST
High >2 mg/dL
creatinine
Uric acid
calcium >11.5 mg/dL high
HyperCalcemia

8. Chemistry Observation Normal Rang Result Parameters high 5.2-8.3 g/dL
Total protein
low
g/dL
2.8 g/dL
Albumin
normal
g/dL
0.4 g/dL
Alpha1 Globulins
g/dL
1.0 g/dL
Alpha2 Globulins
g/dL
0.8 g/dL
Beta Globulins
g/dL
5.6 g/dL
Gamma Globulins

9. Immunoglobulins, quantitative
Observation
Normal Rang
Result
Parameters
seen in gamma fraction
5.5 g/dL
Monoclonal protein
low
mg/dL
9 mg/dL
IgA
high
mg/dL
5800 mg/dL
IgG
mg/dL
25 mg/dL
IgM

10. Bone marrow biopsy: Aspirate differential
Eccentric : ليست في المركز

11. Radiography:
Multiple lytic lesions of the skull, spine, pelvis, and femurs.

12. Question
What is the most likely diagnosis?

13. Multiple myeloma (IgG, kappa type)

14. Discussion :
Anemia occurs when the red blood cell count is low. It can cause fatigue, shortness of breath, and dizziness.
Bone loss from myeloma causes an excess of calcium to be released into the bloodstream, Hypercalcemia can also be caused by overactive parathyroid glands.
Excess protein and calcium in the blood put a strain on the kidneys as they try to keep up with filtering all of the unwanted material out of the blood.
The kidneys try to process all of the calcium and protein, but they can’t, and they get overworked. If the kidneys are overworked for too long, kidney failure occurs.
raised serum creatinine due to reduced kidney function,

15. Uric acid levels may be elevated as a complication of multiple myeloma
Uric acid levels may be elevated as a complication of multiple myeloma. Serum viscosity, a measure of how "thick" the fluid portion of the blood is; when levels of the abnormal protein become very high, serum viscosity may increase and cause symptoms.
↑ M protein in serum, may have ↓ levels of normal antibodies
A monoclonal protein
M spike
β2-microglobulin ↑ Levels (measure of tumor burden)
Staging is an evaluation of how much abnormal immunoglobulin is being produced, how much calcium is in the blood, how extensive and severe the bone damage is, and how anemic the affected person is. Staging helps to determine a person's prognosis.

16. Clinical Course :
The patient was treated with chemotherapy and radiation therapy.
Her bone pain lessened, and her serum protein levels gradually decreased to within normal ranges.
After several months, however, she was again experiencing bone pain and abnormal protein levels.
She continued to be followed in Hematology Clinic, and at her last visit--four years after the original diagnosis--the disease still appeared to be progressing slowly.

18. Multiple Myeloma: Abnormal Proliferation of Malignant Plasma Cells
Angiogenesis : تكوين الاوعية .

19. Epidemiology Second most common hematological malignancy.
Incidence and rates :
1% of all cancers.
US incidence: 19,900 new cases per year.
US prevalence: 100,000 patients.
Deaths: estimated 10,790 per year.
More than 80% of affected patients >age 60.
Affects slightly more men than women (1.6:1).

20. Clinical Manifestations of Multiple Myeloma
Over proliferation of plasma cells can cause :
Risk of infection
Osteolytic bone lesions
Hypercalcemia
Bone marrow suppression (pancytopenia)
Renal complication risk

21. 2- Production of monoclonal M proteins causes :
Decreased levels of normal immunoglobulins
Hyperviscosity

22. Major Symptoms at Diagnosis
Bone pain - 58%
Fatigue - 32%
Weight loss - 24%
Asymptomatic - 11%

23. Common Sites for Bone Involvement
Skull
Spine :
Thoracic
Lumbar
Vertebrae
Pelvis
Long bones
Spinal cord :
- compression can occur 23

24. Diagnostic Evaluation of Multiple Myeloma
Test
Finding (s) With Myeloma
CBC with differential counts
↓ Hgb, ↓ WBC, ↓ platelets
Electrolytes
↑ Creat, ↑ Ca+, ↑ Uric acid, ↓ Alb
Serum electrophoresis with quantitative immunoglobulins
↑ M protein in serum, may have ↓ levels of normal antibodies
Immunofixation
Identifies light/heavy chain types M protein
β2-microglobulin
↑ Levels (measure of tumor burden)
24-hour urine protein electrophoresis
↑ Monoclonal protein (Bence Jones)
Bone marrow biopsy
≥ 10% plasma cells
Skeletal imaging
Osteolytic lesions, osteoporosis
Serum free light chain
↑ Free light chains
MRI
Evaluation of involvement of disease
The early stages of multiple myeloma are often asymptomatic and the disease may be discovered on routine laboratory testing
When myeloma is suspected (ie, older patients with unexplained pain, fracture, anemia), the diagnostic evaluation should include:
Laboratory tests of both serum and urine
Radiographic imaging
Bone marrow biopsy
The alterations associated with myeloma are listed here
Quantitative immunoglobulins measure the antibodies IgG, IgA, IgM, IgE, and IgD with normal ranges: (IgG mg/dL; IgA ( mg/dL; IgM mg/dL; IgE IU/ml)
Beta 2 microglobulin is a standard measure of tumor burden for myeloma (normal range, 2.0–2.5 µg/mL)
C-reactive protein is a surrogate marker for IL-6, a growth factor for myeloma cells
A 24-hour urine protein electrophoresis (UPEP) measures the presence and amount of myeloma protein in the urine
A serum-based assay (Freelite™) detects and quantifies free light chains, which may help predict the risk of progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma. This test is also easier for patients to complete than a 24-hour urine collection.
Emerging evidence suggests that use of magnetic resonance imaging (MRI) is more sensitive and specific than x-ray and scintigraphy for detecting bone metastases in multiple myeloma patients. Thus, MRI may also be used for initial assessment of multiple myeloma.
Alb = albumin; Creat = creatinine; Hgb = hemoglobin;
MRI = magnetic resonance imaging .

25. Stem cell transplantation:
MM Treatment Options
Conventional chemotherapy:
Melphalan
Doxorubicin
Cyclophosphamide
Steroid therapy:
Dexamethasone
Prednisone
Stem cell transplantation:
Autologous
Allogenic
Radiation therapy

26. Prepration : Presentation : Asmaa Ashour Noor Al-Safadi
Areej Abuzubaida
Nermeen Al-Ashi