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Prepared by:

Maribec V. Pagaduan

69 year old male complained of pain


in his lower back upon bending over in
his garage.
He worked in a petroleum plant for 15
years.
He also complained of easy fatigability.

radiograph of the spine shows a


compression fracture of the lumbar
vertebrae at L2 L3.
Further evaluation reveals
normocytic anemia, hypercalcemia,
and a high globulin fraction. Bone
marrow biopsy was also done.

Other

name: Plasma cell myeloma

Second

most common hematologic


malignancy.

It

affects osseous and non-osseous


tissues.

The

cause of myeloma is unknown

High

occurrence among the following:

- Those exposed to radiation


warheads
- Myeloma has been seen more
commonly than expected among farmers,
wood workers, leather workers, and those
exposed to petroleum products.

Occurrence:
Age:

2-4/100,000

Increases with age

Median Age of Px: 65 y/o


Gender:
Race:

More men than women

More common in Blacks than in


Caucasians, Asians low incidence.

Composition
1.The PARENCHYME
2.The STROMA

RED
BONE
MARROW

Continuous
replacement of
old bone tissue
by new bone
tissue
-

2 types of cells
1.Osteoblasts
2.Osteoclasts

Used

to determine
size and shape of
RBCs, WBCs and
platelet precursors
and to examine
various
maturational
abnormalities.
Gold standard for
diagnosing MM

Non

destructive
method of inspection
Each specimen under
evaluation will have
differences in density,
thickness, shapes,
sizes, or absorption
characteristics

L2-L3
Compression

Randomly distributed, rounded, punched out lytic


lesions throughout the skull.

Patient

Normal

3.4 X 103/uL

(3.3-11.0)

Neut

9%

(44-88)

Lymph

27%

(12-43)

Mono

4%

(2-11)

Eos

0%

(0-5)

Baso

0%

(0-2)

RBC

3.2 X 106/uL

(3.9-5.0)

Reticulocytes

1.%

(0.5-1.5)

Hgb

8.6 g/dL

(11.6-15.6)

HCT

26.1 %

(37.2-50.4)

MCV

81.5 fL

(79-99.0)

MCH

26.8 pg

(26.0-32.6)

MCHC

32.9 g/dL

(31.0-36.0)

Plts

110 thousands/uL

(130-400)

WBC

Test

Patient

Normal

Glucose

90 mg/dL

(65-110)

Creatinine

1.9 mg/dL

(0.7-1.4)

BUN

29 mg/dL

(7-24)

Uric Acid

9 mg/dL

(3.0-8.5)

Cholesterol

199 mg/dL

(150-240)

Calcium

12 mg/dL

(8.5-10.5)

Protein

10.9 g/dL

(6-8)

Albumin

3.7 g/dL

(3.7-5.0)

LDH

270 U/L

(100-225)

Alk. Phos.

210 U/L

(30-120)

AST

50 U/L

(0-55)

GGTP

35 U/L

(0-50)

Bilirubin/Bil. Direct

0.7 mg/dL/(.11 mg/dL)

(0.0-1.5)/(.02-18)

Patient

Normal

pH

(5.0-7.5)

Protein

3+

(Neg)

Glucose

Neg

(Neg)

Ketone

Neg

(Neg)

Occult blood

Neg

(Neg)

Color

Yellow

(Yellow)

Clarity

Clear

(Clear)

Sp. Grav.

1.050

(1.010-1.055)

WBC

3/HPF

(0-5)

RBC

1/HPF

(0-2)

Test

A process of separating
electrically
charged particles in solution by
passing an electric current
through the solution

Particularly used to
determine
whether the humoral
immunity
function normally or not.

Albumin 1

MAJOR CRITERIA
I.Plasmacytoma by biopsy
II.>30% marrow plasmacytosis
III.Monoclonal gammopathy
Serum: IgG > 3.5 g/dL, IgA >2 g/dL
Urine:
>1 g/d of Bence Jones Proteins
MINOR
CRITERIA
A.10-30% marrow plasmacytosis
B.Monoclonal gammopathies with lower values
than above
C.Lytic bone lesions
D.Suppressed normal immunoglobulins

Stage
I

II
III

Durie-Salmon Staging System


Criteria

All of the following:


1. Hemoglobin >100 g/L (>10 g/dL)
2. Serum calcium <3 mmol/L (<12 mg/dL)
3. Normal bone x-ray or solitary lesion
4. Low M-component production
a. IgG level <50 g/L (<5 g/dL)
b. IgA level <30 g/L (<3 g/dL)
c. Urine
lightI chain
Fitting
neither
nor III<4 g/24 h
One or more of the following:
1. Hemoglobin <85 g/L (<8.5 g/dL)
2. Serum calcium >3 mmol/L (>12 mg/dL)
3. Advanced lytic bone lesions
4. High M-component production
a. IgG level >70 g/L (>7 g/dL)
b. IgA level >50 g/L (>5 g/dL)
c. Urine light chains >12 g/24 h

Estimated Tumor
Burden, x 1012 cells/m2

<0.6 (low)

0.61.20
(intermediate)

>1.20 (high)

Age: 69 y/o, Male, Hx of working in a petroleum plant


DNA is damaged during the development of stem cell into a B cell
Development of malignant plasmablasts
Produce adhesive molecules and bind to Bone Marrow Stromal Cells
Malignant plasmablast grows into malignant plasma cells
Uncontrolled proliferation of malignant plasma cell clones

Formation of
Plasmacytomas

Production of
Paraproteins
(M-protein)

Production of
Bence Jones
Protein

Formation of
Plasmacytomas
Compression of
surrounding bone
tissue, bone marrow
and nerve endings
Destruction of
Bone marrow
stem cells

osteoblast
s

PAIN

Release of IL-6 and TNF


Recruitment and
activation of osteoclasts

HYPERCALCEMIA

Osteoclasts attach to
bone tissue

Protein digesting enzyme


Digestion of collagen and fibers

Acids

Calcium is released
and enters the
bloodstream

Dissolves bone minerals

bone

deposition

PUNCHED-OUT
OSTEOLYTIC LESIONS
Hematopoesis

Continuous bone destruction


PATHOLOGIC
FRACTURE

Hematopoiesis

RBC

ANEMIA

Megakaryocytes

Platelets

Easy fatigability

WBC

Leukopenia

Susceptibility to
infection
THROMBOCYTOPENIA

Susceptibility to
bleeding

Age: 69 y/o, Male, Hx of working in a petroleum plant


DNA is damaged during the development of stem cell into a B cell
Development of malignant plasmablasts
Produce adhesive molecules and bind to Bone Marrow Stromal Cells
Malignant plasmablast grows into malignant plasma cells
Uncontrolled proliferation of malignant plasma cell clones

Formation of
Plasmacytomas

Production of
Paraproteins
(M-protein)

Production of
Bence Jones
Protein

Production of
Paraproteins
(M-protein)
Serum Monoclonal
Antibodies
Binds with other serum
protein

HYPERVISCOSITY
SYNDROME
Susceptibility to
bleeding

Normal Plasma cell


breakdown
Disrupted antibody
mediated immunity
Normal Antibody
production
Susceptibility to
infection

Age: 69 y/o, Male, Hx of working in a petroleum plant


DNA is damaged during the development of stem cell into a B cell
Development of malignant plasmablasts
Produce adhesive molecules and bind to Bone Marrow Stromal Cells
Malignant plasmablast grows into malignant plasma cells
Uncontrolled proliferation of malignant plasma cell clones

Formation of
Plasmacytomas

Production of
Paraproteins
(M-protein)

Production of
Bence Jones
Protein

Production of Bence
Jones Protein

Glomeruli filters large


amounts of BenceJones Protein

ANEMIA
RBC
Production
erythropoietin

UREMIA
elimination of
nitrogenous
waste

Cellular degeneration and


impairment of kidney/tubular
function

Proteinaceous
inclusion bodies
accumulates in
the tubules

Excreted in
urine

Blockage of tiny kidney


tubules
PROTEINURIA

Chronic

Pain
Activity intolerance
Risk for Infection
Fear/Anxiety

Trials of Arsenic Trioxide in Multiple Myeloma


Mohamad A. Hussein, MD

Anatomy and Physiology by Tortora, 11th ed.

Clinical Physiology by Moran Campbell

Pathophysiology By Porth, 4th ed.

Harrisons Principles of Internal Medicine, 17th ed.

Wintrobes Clinical Hematology,

Blood and Bone Marrow Pathology by Wickramasinghe


and McCullough