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1.

INTRODUCTION
2. NEOPLASM
3. OSTEOSARCOMA
4. OSTEOCONDROMA
5. EWING SARCOMA
6. CONDROSARCOMA
7. OSTEOARTRITIS
8. GOUTY
9. OSTEOPOROSIS
INTRODUCTION
Anatomical of musculoskletal
Muscle system
Ligamen
Tendon
Skeletal system
Bone ---- skeleton
Cartilage
Joints
Bone-Skeleton Function
Supporting & protecting
Bone marrow
Blood Cell regeneration: HSC
Cell Regeneration: MSC
Reservoir
Ca, PO4, Ion
Movemoent system
HISTOLOGY
Major cell:
Osteum
Osteoblast
osteosit
Cartilage
Condroblast
Condrosit
Connective tissue
Mesencymal stem cell
Extracelluler matrix
Extracelluler Matrix
Basic subtantial
Gylosaminoglican
Proteoglycan
Protein-Carbohydrate
Glycoprotein
Situs for :
integrine molecule
Collagen fiber
Fiber
Collagen
Ellastin
Reticuler
Fetal Bone
Normal Bone
Adult Bone
Adult Bone
CELL REGULATION

Proliferation

Stable baseline
Differentitation
cell population

Apoptosis
POTENTIAL OF CELL
PROLIFERATION

Cell cycle
Biochemical factor
Stimulator
Inhibitor
Basis of regenerative capacity :
1. Continuously dividing cell
2. Quiescent cell
3. Nondiving / permanent cell
GROWHT FACTOR ON CELL REGULATION
Polypeptida serum Locall cell

Growth factor

Signal transduction Pleiotropic effect

Cycle Cell Cell Migration

Diffrentiation
CellularProliferation Tissue remodeling
Moleculer Mechanism of
Signal Transduction

1. Reception of the stimulus


2. Transfer into the cell
3. Amplification of a cytoplasmic
signal
4. Modulation of effector system
Patology of Musculoskeletal
Neoplasm
Gene regulator
Neoplasm pathogenesis
Terminology of neoplasm
Behavioural diffrences of neoplasm
Osteosarcoma
Osteocondroma
Ewing sarcoma
Condrosarcoma
Gene Regulator of Cancer

3 Class Gen :
1. Protooncogenes : Growth promoting
2. Suppressor genes : Growth inhibiting
3. Apoptosis : programmed sel death.
4. DNA repair genes :

Step:
Protooncogen mutation
Suppresor gene disorder
Pathogenesis of Neoplasm

1. Multiple hit mutation:


Proto-onkogen Onkogen
2. Feedback mekanism Disorder
Gen Supressor Tumor
1. Regulation control of proliferation
2. Cell cycle
3. Repair gene
4. Apoptosis mechanism
Oncogeneis by virus
History
Peyton Rous 1911 Chicken sarkoma
(transmition mechanism)
Michael Bishop & Harold 1975
Retroviruses. (Rous Sarcoma virus)
Transforming sequential
Akut Transforming Virus : Mutant
Onkogen Retroviral
Transforming proses
Insertion procees

V-oncs: identicall with normal DNA


Oncogene Virus:
(Transforming Retrovirus)
src,
sis
myc
erbA dan erbB.
Ha-ras
Ki-ras.
Terminology of Neoplasm

Neoplasm : new growth


An abnormality of celluler
The formation of masses of
differentiation.
abnormal tissue (tumors)
An abnormality of maturation.
Loss control of growth

The term tumors : any swelling (one of the cardinal signs of inflamation)

The division of neoplasms is based on : Potential clinical behavior


Benign
Malignant Cancer : Grips the surrounding tissues with
claw (like a crab)
Behavioral Differences of
Neoplasms
Benign Malignant

Macroscopic : Macroscopic :
Smooth surface (capsule) Irreguler surfice (uncapsule)
Slow growth rate Rapid growth rate
High survival rate Poorly survival rate
Microscopic : Microscopic
No infiltration,just compression Infiltration
Well differentiated
Poorly differentiated (Anaplastic)
Uniform appearance (Polarity)
Pleomorphism apperearance
No Mitotic
Increased mitotic
No Necrosis
Necrosis, Haemorrhagic
No metastasis
Metastasis
Differentiation-Anaplastic
Differentiated : Morphologic grades of neoplasms cell resemble to
original cell
Differentiation parenchymal cell : refer to benign or malignant
Benign neoplasms : Well differentiated cell (very closely with their tissue of
origin)
Malignant neoplasms : wide range (well-poor/undifferentiated).
Undifferentiated cell : Anaplastic (a Hallmark of malignancy)
Anaplastic : to form backward
Dedifferentiation
Loss of the structural and functional
Fail to develop recognizable patterns of orientation
Lose normal polarity
Pleomorphism (Marked variation in size and shape)
Hyperchromatic nuclei,coarse and clumped
Large nuclei (nuclear-cytoplasmic ratio 1:1).
Giant cells : one enormous or several nuclei
Between the two extremes lie tumors : Moderatly well differentiated
Osteosarcoma
Most common bone sarcoma
third most common malignancy in children,
adolescents.
( Multiple myeloma and Tumor of B cell )
In patients 10 to 20 years old
80 % nonmetastatic (at the time of presentation).
High-grade bone sarcoma.
Sites :
Distal femur,
Proximal tibia
Proximal humerus.
Most patients present with localized disease
Osteosarcoma
Increased risk

1. Positive family history

2. Elderly with Paget's disease


of bone
3. Previous radiation

Suspect the disease

1. Teenage boy develops knee pain


2. Persons with pain at a site of prior
radiation therapy
Factors Influencing Tumor Development

Ionizing radiation
Chemical carcinogens
Foreign bodies
Pre-existing skeletal abnormalities : healed fractures.
Genetic predisposition ( family lines )
Aberrations of the p53 tumor suppressor gene.
Viruses
DNA Virus (polyomavirus and SV-40 virus)
RNA viruses (type C retroviruses)
Biologic Growth Pattern of Osteosarcoma
Grows radially Compresses
Cell Canser
soft tissues
Penetrates bony cortex
surrounding muscles

Pseudocapsular layer

Reactive Zone."

microextensions
primary mass

Bone sarcoma Satellite


Metastases
Mass Tumor

Skip metastaes Transartikuler Intraosseous ball-like mass.


Metastases

Metastases
Regional : the same bone intraosseous
Distant sites : transarticular skip metastases
Systemic metastases : lungs.
The bones are the second most common, Latest stage
Associated with the poorest
Rare regional lymph node metastases
Prognosis worsens
The entire tumor mass (satellites) : resected to ensure removal of all
gross tumor.
Surgical margin must be wide
Clinical Presentation

Dull aching pain of several months,


Increase in pain severity
Penetration to cortical bone
Irritation of the periosteum,
Night pain, awaken the patient from sleep
Chronic indolent night pain should not be dismissed as "growing
pains," especially unilateral
Swelling localized enlargement
Pathologic fracture (occasionally)
Frequently
History of a minor injury,
Sprain or muscle
Pathology
Microscopically :
1. Destruction of normal bony architecture ( by malignant cell )
2. Stimulation of reactive bone production
3. Deposition of osteoid (Tumor osteoid production)
Divided into
high-grade
low-grade variants
Depending on
Cellularity
Pleomorphism
Anaplasia
Number of mitoses.
Microscopically,
conventional osteosarcomas are composed of malignant-
appearing spindle cells that produce osteoid.
Enneking System
for Staging Osteosarcomas
Stage Grade and anatomic extent
I. Low-grade tumor
IA Intracompartmenta
lIB Extracompartmental

II. High-grade tumor


IIA Intracompartmental
IIBExtracompartmental

III. Either grade with metastases

Most conventional osteosarcomas present as stage IIB tumors


(i.e.,nonmetastatic with an associated soft tissue mass).
Histopathology

Biopsy for the definitive diagnosis


Jamshidi needle that removes a core of the osseous neoplasm.
A core biopsy taken from the center of the lesion
Multiple core samples
Heterogeneous Appearance
Histologically

1. Poorly differentiated
2. Fibroblastic
3. Osteoblastic
4. Telangectatic
5. Giant cell, or chondroblastic
Heterogeneous Appearance
Histologically
Poorly differentiated
Telangectatic
Pleomorphic- fusiform cell
Rare neoplasm
Minimal deposition osteoid Variably sized blood
Highly aggressive neoplasm. Mitoses
Fibroblastic lytic, destructive
Widespread metastasis
Pleomorphic- fusiform cell
Rapid growth and fatal.
Lytic tumor. Difficult to differentiate from
Most favorable prognosis hemangiosarcoma
Osteoblastic Giant cell
Anaplastic osteoblasts Expansive, lytic
Non-productive osteoblastic
Plump to spindle shaped
Giant cells predominate
Lytic or non-productive.
Microskopis

cancer cells
Pleomorphism (irregular
odd in size and shape).

Osteoid
Non-mineralized bone

osteocytes
lacunar cells with white halo
Osteoid

Osteoid, surrounded by cancer cells.

large blood vessel, the lumen is filled with erythrocytes


Can you identify the cancer cells
and the nonmineralized bone ?
Poorly differentiated with a homogeneous
population of spindle cells, scattered mitoses, and
a few pink deposits of osteoid , hematoxylin and
eosin stain).
a

Pleomorphic : round, plump, or fusiform a. Mitosis cell


,Wright stain). b. Plasmacytoid appearance.
c. anisocytosis and
anisokaryosis,Wright-Leisman stain
Osteoclasts are large cells that are Pleomorphic population of
multinucleate (Wright-Leishman stain). neoplastic osteoblasts are
surrounded by pink osteoid matrix
Wright-Leishman stain).
Microscopis of Osteosarcoma
Microscopis Osteosarcoma
Osteosarcoma
OSTEOCONDROMA
a benign (noncancerous) that develops during childhood or
adolescence.
Abnormal growth that forms on the surface of a bone near the
growth plate.
Growth plates are areas of developing cartilage tissue near
the ends of long bones in children.
Bone growth occurs around the growth plate, and when a
child becomes full-grown, the growth plates harden into solid
bone.
an outgrowth of the growth plate and is made up of both bone
and cartilage.
As a child grows
Grow larger.
Once a child has reached skeletal maturity,
the osteochondroma typically stops growing.
In most cases of osteochondroma, no
treatment is required other than regular
monitoring of the tumor to identify any
changes and complication
OSTEOCONDROMA
Osteochondroma
Differential Diagnosis
Based on Radiographic

1. Osteosarcoma
2. Ewing's sarcoma
3. Osteomyelitis
4. Osteoblastoma
5. Giant cell tumor
6. Aneurysmal bone cyst
7. Fibrous dysplasia
Ewing's Sarcoma
Prevalence
7% of all primary bone malignancies
More common in males and is rare in blacks

Source
Every bone of the foot ( uncertain origin )
Located in the hindfoot
20% in the calcaneous
From primitive reticulum cells of marrow
common karyotypic translocation between chromosomes 11 and 22
Age
Children & young adults, 10 - 20 years
3% in children < 3 years of age
64% in the second decade
The mean age :17 years
Genetics
Expresses p30/32 MIC2 antigen (cell surface glycoprotein)
85% contain chromosomal translocation at the (11;22)(q24;q12)
Clinical Presentation

Femoral diaphysis > pelvis, Tibia,Humerus, fibula, Ribs


Pain accompanied by significant diffuse swelling
Inflamed-misdiagnosis of infection can be made.
Elevated
WBCl count,
Eerythrocyte sedimentation rate
Temperature
Anemia
Enlarging, Tender, bony prominence (soft tissue mass)

Symptoms for an average : 14 months prior to diagnosis.


Hindfoot lesions : 22 months
Forefoot lesions : 7 months
Metastases
Highly aggressive tumor with frequent metastasis
Tumors in pelvis: poorer prognosis
Peculiar predilection for shaft of fibula
Little or no hematopoietic marrow
In extraosseous sites ("soft-tissue, Ewing's")
Distant metastases 20% of cases

Prognosis
Survival is highly dependant on the stage and location.
Patients without metastasis had 88% survival,
Non-pulmonary and pulmonary metastasis had 10% and 0% survival.
In the forefoot had 70% survival and in the hindfoot had 33% survival.
Tumor size and delay before diagnosis also vary by site,
Greater impact on prognosis than the difference in site alone.
Radiographs

Diaphyseal tumor w/ mottled, or patchy density


Cortical involvement : Periosteal reaction "onion skin" pattern

Highly variable
Small lytic lesion - Permeative apperance, no matrix or soft tissue calcification.
Permeative lysis accompanied by marked sclerosis .
In an unusual case involving the distal fibula, the lesion appeared entirely cystic
and was mistaken for a unicameral (simple) bone c
Ewing Sarcoma
Ewing Sarcoma
Microscopic Features:
Chondrosarcoma

20% of primary malignant bone tumours (2nd most common after


osteosarcoma).
Majority (80-90%) are low grade malignant tumour.
Solitary (single) tumour is commoner than multiple (as seen in
familial osteochondromatosis & familial enchondromatosis - Ollier's
disease).
Chondrosarcoma occurs in two forms :
Primary (de novo) 75%

Secondary (in association with)


Multiple enchondromatosis eg. Ollier's disease & Maffuci's
syndrome
Exostosis (osteochondromatosis)
Condroblastoma
Clinical presentation

The clinical behaviour is variable


Age : 30 - 60 years
Sex : Male > female (2:1)
Graduallly enlarging painfull mass (low grade type)
Metastasis occurs relatively late
Sites :
central (axial) skeleton - pelvic girdle,
ribs,
shoulder girdle
vetebrae & sternum
Microscopic Appearance

Chondrosarcoma arrising from the vetebral column.


It appears as a large lobulated destructive mass with a characteristic
translucent whitish appearance due to the chondroid stroma
Microscopic High grade
condrosarcoma
Apprearance

Low grade
condrosarcoma
High grade condrosarcoma - cellular atypia & crowding ( X 400)
Chondrosarcoma consist of malignant chondrocytes in a chondroid matrix
Chondrosarcoma
Chondrosarcoma
X-ray

Radiologically shows a circumscribed tumour mass punctuated by


mottled densities from calcification & ossification ('snow storm' appearance)
Prognosis

Generally the prognosis depends on the histological grade

Tumour histological grade 5 years survival rate

Grade I 90 %

Grade II 80 %

Grade III 80 %
Chordoma

Appear anywhere in the spinal column


at the ends of the spine at the occipital cervical junction or in the
sacrococcygeal region.
Rare.
Sacrococcygeal chordoma appears more often in males
and usually develops during middle ages, but can
develop any time
Imaging studies x-rays and MRIs may be suspicious,
Treatment is surgical resection of the tumor.
Myeloma

The most common primary malignant tumor of bone.


Adults greater than 40 years of age.
Multiple bones, but back pain and involvement of the
spine is the most common presenting complaint.
Treatment is palliative; meaning that disease can be
controlled, but not completely cured.
Chemotherapy is used to control the pain and slow the
progression of the disease.
Surgery may be required if pathological fractures
develop or there is compression of the spinal cord.
Rhabdomiosarcoma
Malignant tumor of mesenchymal origin thought to arise from
cells committed to a skeletal muscle lineage.
With approximately 250 cases diagnosed yearly in the United
States,
it is the third most common extracranial solid tumor of childhood
after Wilms' tumor and neuroblastoma.
Common sites:
Head and neck region, genitourinary tract, and extremities.
Tumor-nodes-metastasis staging system
for assessing prognosis and assigning therapy in
conjunction with the traditional surgicopathologic clinical
grouping system.
Significant improvements in outcome, especially for patients
with local or locally extensive disease for whom a 60%-70%
disease-free survival can be expected.
surgery, dose-intensive combination chemotherapy, and
radiation therapy,
Outcome for patients with metastatic disease remains poor.
less toxic therapy for patients with localized disease and new
approaches for patients with metastatic disease.
Rhabdomysarcoma
Rhabdomysarcoma
Gouty Arhritis
an inflammatory disease of the joints that are
affected by the intake of foods high in purines.
The prevalence
Increase in younger age (productive age).
Levels of uric acid in the blood increases due
to an imbalance between production and
excretion.
Gouty Arthritis
Gouty Arthritis
Gouty Arthritis
OSTEOARTHRITIS
a condition that affects the joints, causing pain
and stiffness.
Most common form of joint disease
the knee is one of the most commonly
Symptom of Osteoarthritis
Pain
stiffness
Grating or grinding sensation when the joint moves
(crepitus)
Swelling (either hard or soft).
Sometimes the knee may either lock or give way when
you put weight on it.
Predispotition
40 years old or older
Overweight
Woman
Family
Previously had a severe knee injury
Have been damaged by another disease, for example
rheumatoid arthritis or gout.
Osteoarthritis
Rhematoid Arthritis
Condition that mainly affects the bodys joints,
causing pain and swelling.
Autoimmune disease that causes inflammation
in joints.
Main symptoms are joint pain and swelling.
Second most common form of arthritis in the UK.
Have joint pain and morning stiffness.
Rheumatoid Arthritis
Rheumatoid Arthritis
Rheumatoid Module
Osteoporosis
Systemic disorder characterized by
decreased bone mass and microarchitectural
deterioration of bone tissue, leading to bone
fragility and increased susceptibility to
fractures of the hip, spine, and wrist.
Associated with disability and pain.
Pathophysiology
Imbalance between bone resorption and bone formation. I
Bone resorption takes place to a greater extent than bone
formation---- negative balance occurs with a net loss of bone
accompanying increasing risk of fractures,
resulting in deformity and chronic pain.
Nociceptive pain is considered to be chronic when it has been
present for at least 3 months.
occur as a result of one or a combination of the following
factors:
Increased bone resorption within a remodeling unit.
Decreased bone formation within a remodeling unit
(incomplete coupling).
Osteoporosis
Osteoporosis
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