BONE &

JOINT

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 BONE DISEASES

A. Congenital Bone Disorders

B. Metabolic Bone Diseases: disorders of
remodeling (formation and
resorption)
C. Hormonal Disorders Affecting Bone
D. Nutritional Disorders Affecting Bone
E. Infectious Bone Disease: Osteomyelitis
F. Idiopathic Bone Disorders
G. Cystic and Neoplastic Bone Lesion
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 A. Congenital Bone Disorders

I. Ostogenesis imperfecta
II. Osteopetrosis

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 Osteogenesis Imperfecta

- Usually transmitted as an autosomal dominant

trait
- Appears after perinatal period
- Bowing extremities, blue sclerae, and other
manifestations of defect in collagen synthesis
- Marked osteopenia with a porous cortex
because osteoblast do not synthesize normal
amount of bone matrix

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 I. Osteogenesis
Imperfecta

Fetus develop
multiple fracture
born in crippling
deformities

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 II. Osteopetrosis
A hereditary disorder charcterized by abnormally dense bone

Clinical features (two forms)

Benign form
Autosomal dominant, and patients may have multiple
fractures
diagnosis often is not made until the 2nd or 3rd of life
common complication: osteomyelitis
Malignant form
Recessive, slow growth, mental retardation, mental
retardation and deafness
affected children
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 Osteopetrosis
A hereditary disorder charcterized by abnormally dense bone

Pathology
Extreme reduction in the size of the medullary
cavity and an increased density and widening of all
cortical bones except membranous bone (cranium)
A large number of osteoclasts are present but are
incapable of resorbing bone because they cannot
release acid phosphatase

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 B. Metabolic Bone Diseases: disorders of
remodeling (formation and resorption)

I. Osteopenia
1. Senile osteopenia
2. Steroid induced osteopenia
II. Osteoporosis
1. Post menopausal osteoporosis
2. Immobilization osteoporosis

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 Osteopenia
1. Senile osteopenia
Increasing age continuous loss of bone (both trabecular &
cortical layers) thinner by internal resorption
2. Steroid induced osteopenia
Catabolic effect of corticosteroid affect trabecular bone
decrease in bone formation
Steroid decreases intestinal absorption and renal resorption
of calcium less calcium reaches the bone

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 Normal & Osteoporosis

Osteoporosis denotes increased porosity of the skeleton resulting

from a reduction in bone mass
Imbalance between resorption and formation in the remodeling
sequence the entire skeleton may show low density with
conspicuous sparsity and thinning of the spongy trabeculae of the
affected bone

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 Pathogenesis

Factors influence pathogenesis of

osteoporosis
Age related changes
Reduced physical activity
Genetic factors
Nutritional state
Hormonal influences

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 Pathophysiology of post-menopausal and
senile osteoporosis

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 Osteoporosis
1. Post menopausal osteoporosis
The decrease in bone volume is due to disorder in
remodeling and decreased amount of bone deposited by
osteoblast
2. Immobilization osteoporosis
In bed longer than 6 months loss of 30% of initial bone
volume
The lack of exercise probably leads to increase resorption of
bone and decrease in bone formation

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 Osteoporotic Fracture

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 Osteoporotic Fracture

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 Osteoporosis

The osteoid tissue are very few

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 Osteoporotic Fracture

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 Osteoporotic Callus

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 C. Hormonal Disorders
Affecting Bone
I. Primary Hyperparathyroidism
II. Secondary Hyperparathyroidism
Renal failure and other conditions hypocalcemia or
hyperphosphatemia compensatory to PTH
III. Hypoparathyroidism
- accidental surgical removal of parathyroid gland
- hypocalcemia with soft issue calcification & ossification,
abnormal dentition, otosclerosis
- Mic: markedly decrease turnover rate, with active
osteoblast
and lack of osteoclast

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 Primary Hyperparathyroidism
Pathogenesis
Elevated PTH (PTH stimulate the active phase of the
remodeling squence) because of parathyroid hyperplasia or
adenoma affects bone
Clinical Features:
Predominantly affects women age 30 50
Hypercalcemia: serum calcium elevated above 11.5 mg/dl,
and phosphorous levels are reduced to less than 2 mg/dl
Bone pain, more severe in lower extremities
Pathologic fractures and bone deformities may be seen
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 Primary Hyperparathyroidism

Pathology
Increased number of osteoclast resorb the walls
of haversian canals of the cortical bone and the
surface of spongy trabeculae replaced with
fibrous tissue
Occasionally proliferation of osteoclasts contain
hemosiderin is prominent within the fibrous stroma
brown tumor (commonly in the jaw)
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 Hyperparathyroidism

Osteoclasts boring into the center of the trabeculum

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 Brown Tumor

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 D. Nutritional Disorders
Affecting Bone
Vitamin D deficiency
1. Children
2. Adults
Vitamin C deficiency
Vitamin A disorders
1. Hypervitaminosis
2. Vitamin A deficiency

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 Vitamin D deficiency

1. Children before epiphyseal

closure rickets pain & bone
deformities: rachitic rosary (swelling at
the osteochondral junction of the ribs),
bowing the legs, fractures, and pelvic
disorders
2. Adults osteomalacia: uncalified
osteoid cartilage increases and
calcified bone decreases
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 Vitamin C deficiency

Causes increased capillary fragility

hemorrhages in the periosteum,
gums, skin
Trabecular bone mass decreases,
osteoblasts are abnormal

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 Vitamin A disorders
1. Hypervitaminosis A
Causes abundant mineralization of periosteum and
abnormal bone formation.
In children premature epiphyseal closure
permanent skeletal deformities
2. Vitamin A deficiency
Remodeling ceases, osteoclastic activity disappears
The bones are short and thick, with a predominance
of new cancellous periosteum
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 E. Infectious Bone Disease:
Osteomyelitis
- Causative agent : Staphylococcus aureus, occasionally other
bacteria or fungi
- Destroyed bone repair and remodeling with new bone
formation
- Risk: sickel cell anemia, hemodialysis, joint prosthesis, iv drug
abuses
- Occasionally inflammation may persist in a region of relative
avascularity
- The bone infection is a result of several conditions

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 The bone infection is a result
of:
1. Most commonly: hematogenous spread of
bacteria from distant focus of sepsis
2. Invasion of bone from adjecent septic arthritis
or soft tissue abscess
3. Penetrating trauma
4. Complication of fractures
5. Complication of surgery

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 Types of Osteomyelitis
Pyogenic osteomyelitis
- most commonly in children & young adult: femur, tibia,
humerus, radius
- causative agent: S. aureus, but often no source of
infection is obvious
- chronicity occur when the acute process is not properly
treated
Tuberculous osteomyelitis
- granulomatous (specific) inflammation
- Potts disease
- Scoliosis

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 SCOLIOSIS

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 Chronic Osteomyelitis

The bone marrow shows chronic inflammatory cells infiltration

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 F. Idiopathic Bone Disorders

1. Pagets disease of the bone (Osteitis deformans)

2. Avascular necrosis
3. Legg-Calve-Perthes disease

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 Pagets Disease of the Bone
3 4 % of the population >40 year old, mostly men
Usually polyostotic, with predilection: skull, pelvis, tibia, femur
Chronic focal lysis of bone tissue replaced by a soft, fibrotic matrix
marked medullary fibrosis
Numerous oteoclast appear abnormal (increased number of nuclei)
Lytic and formative phases rapidly succeed one another local
increase of bone mass and disorganization of the normal trabecular
pattern
High turn over of bone (numerous osteoclast and osteoblast,
increased calcification rate, accumulation of woven bone) mosaic
pattern
May develop pathologic fracture
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 Pagets Disease of the Bone

Mosaic pattern of lamellar bone

pathognomonic of Paget disease

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 2. Osteonecrosis
(Avascular Necrosis)
Relatively common event and can occur in the medullary
cavity of the metaphysis & diaphysis, and subchondral
region of epiphysis
All forms of bone necrosis results from ischemia:
1. Mechanical vascular interruption (fracture)
2. Corticosteroids
3. Thrombosis and embolism (caissons disease)
4. Vessel injury (vasculitis, radiation therapy)
5. Increased intraosseus pressure with vascular compression
6. Venous hypertension
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 2. Osteonecrosis

Femoral head with subchondral, wedge-shaped pale yellow area of osteo-

necrosis (caused by trabecular compression fracture without repair)

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 3. Legg-Calve-Perthes disease

Childhood disorder of the head, and is

similar to avascular necrosis of adulthood
The typical age of onset is 5 to 9 years
The earliest manifestations are intermittent
limp and pain

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 Pathology of the
JOINT
Diseases

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 JOINTS
A. Inflammatory Disorders
1. Non-specific inflammation
(bacterial arthritis)
2. Specific inflammation
(tuberculous arthritis)
B. Arthritis of probable autoimmune
origin
1. Rheumatoid arthritis
2. Juvenile rheumatoid arthritis
3. Seronegative arthritis
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 JOINTS
C. Degenerative joint disease
Osteoarthritis
D. Arthritis of metabolic origin
1. Gout
2. Chondrocalcinosis
(pseudogout)
E. Tumors and Tumor-like Lesions
1. Ganglion
2. Synovial cyst
3. Synovial sarcoma
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 A.1. Bacterial (pyogenic, septic)
Arthritis
An acute inflammatory process, usually
monoarticular
Etiology: mostly gono-staphylo-strepto-and
pneumococci
Usually acquired from hematogenous spread of
primary septic focus such as: pneumonia, otitis
media, endocarditis, gonorrhoeal infection

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 A.1. Bacterial (pyogenic,
septic) Arthritis
Clinical features:
- most susceptible: age 20-40, with fever & maleise
with limitation of joint movement
- acute pain, swelling, tenderness, and redness of
the involved joint
- radiologically: shows prominent accumulation of fluid

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 A.1. Bacterial (pyogenic, septic)
Arthritis
Pathology:
- early stage: congestion & edema of the
synovial membrane collection of fluid in
the joint space suppurative inflammation
purulent exudate necrosis in the
synovium and articular cartilage
- if the disease is uncontrolled fibrosis &
calcification ankylosis
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 A.2. Tuberculous Arthritis
Chronic specific inflammatory process
(granulomatous inflammation), predominantly
in children as complication of pulmonary
tuberculosis
Most common location: spine
Clinical manifestations are the same as other
infectious arthritis, but they present late (after
the joint destruction occurred)

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 A.2. Tuberculous Arthritis

Microscopically characterized by the present of

granulomatous inflammation with caseous
necrosis and Langhans giant cells
Destruction and obliteration of the joint are
common
Erosion of articular cartilage and bone
ankylosis

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 B.1. Rheumatoid Arthritis

Inflammatory joint disease that affect approximately 4% of

the American population, and 1% of world population
Women : Man is 3 to 1, peak incidence in the twenties and
forties
Is a chronic systemic inflammatory disorder that may
affect many tissues:
- principally: joints non-suppurative proliferative
synovitis progress to destruction of articular cartilage
and ankylosis (usually fingers, metacarpophalangeal,
metatarsophalangeal, any joints, and usually symmetrical
- systemic involvement: skin, blood vessel, heart, lungs,
muscle

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 B.1. Rheumatoid Arthritis
Pathogenesis
RA is triggered by exposure of an immunogenetically
susceptible host to an arthritogenic microbial antigen

Factors involved
(1) Genetic susceptibility (major determinant)
(2) Primary exogenous arthritogen (microbial agents)
(3) An autoimmune to joint components (T cells chronic
destructive nature of RA)
(4) Mediators of the joint damage
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 Immunopathogenesis of Rheumatoid Arthritis

-Usual suspected cytokins (TNF, IL-1,

IL-6, IL-16, interferon-)
-Growth factors (GM-CSF, TGF-)
HLA-DR4 / DR1 / both -Proteases & elastases (leukocytes &
synoviocytes)

TNF- , IL-1
IgM

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 Rheumatoid arthritis (RA)

Ankylosis and deformities

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 RA: Morphology
1. Dense perivascular infiltration in synovial stroma
lymphoid follicles (mostly CD4+ helper T cells), plasma
cells, macrophages
2. Increased vascularity (vasodilatation & angiogenesis),
with superficial hemosiderin deposits
3. Aggregation of organizing fibrin covering part of
synovium, and floating in the joint spaces (rice bodies)
4. Accumulation of neutrophils in the synovial fluid and
along synovial surface (not deep in the stroma)
5. Osteoclastic activity in underlying bone juxta articular
erosion, subchondral cyst, osteoporosis
6. Pannus formation
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 Rheumatoid Arthritis: Clinical course
Fatigue, maleise, low grade fever Joint symptoms apparent
In the morning upon waking

Most frequently the proximal inter-

The joints are usually symetrically
Phalangeal & metacarpophalangeal
affected, enlarged, reddened, painful
joints

Advance: erotion of the entire

Progress and become chronic
articular surface, obliteration of
joint space, fibrous adhesion
bony ankylosis Progressive joint deformity
ankylosis (permanent & disabling)

Pannus formation Claw hand ulnar deviation

The joint: acute non-specific inflammation

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 RA: Morphology

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 RA: Morphology

Marked synovial hypertrophy with villi formation, and

dense lymphoid aggregate are seen in the sub synovial area.

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 Pannus

Fibrocellular mass of synovium and synovial stroma consisting

of inflammatory cells, granulomatous tissue, and fibroblasts
destroy the underlying cartilage bridging the apposing bones
ossification ankylosis
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 RA: Radiography

Early More advance

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 Rheumatoid Nodule

The most common cutaneous lesion of RA (25% of patients)

Locations: skin regions that are subjected to pressure: lunar-
aspect of fore-arm, elbow, occiput, lumbosacral
Firm, nontender, round to oval, arise in the subcutaneous tissue

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 Rheumatoid Nodule

Central zone of fibrinoid necrosis surrounded by a prominent rim of

epitheloid histiocytes and numerous lymphocytes & plasma cells
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 RA: Diagnosis
Primarily made on the clinical feature at least 4 criteria:
Morning stiffness
Arthritis in 3 or more joint areas
Arthritis of hand joints
Symmetric arthritis
Rheumatoid nodules
Serum rheumatoid factor
Typical radiographic changes

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 B.2. Juvenile RA
One of common connective tissue disease in children
By definition it begins before 16 years
Female is approximatley twice as much than male
Classified into:
- oligoarticular: less than 5 joints are involved
- polyarticular: 5 or more joints are involved
- systemic variants

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 B.2. Juvenile RA,
differs from adult RA

1. Oligoarthritis is more common

2. Large joints are affected more than small joints
3. Systemic onset is more frequent
4. Rheumatoid nodules & Rh. factors are usually absent
5. Antinuclear antibody seropositivity is common

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 B.3. Seronegative Arthritis
(Spondyloarthropathy)

Characteristic
1. Absence of rheumatoid factor
2. Extremely high incidence in HLA-
B27-positive individual
3. Peripheral arthritis
4. Sacroiliitis

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 B.3. Seronegative Arthritis
(Spondyloarthropathy)

Types
1. Ankylosing spondylitis
- HLA-B27 associated (up to 90% of patients)
- Spine & sacroiliac joint bone fusion rigidity &
fixation (ankylosis)
2. Reiter syndrome
- urethritis, conjunctivitis, arthritis
- often associated with venereal or intestinal infection
3. Psoriatic arthritis
- occurs in approximately 10% of patients with
psoriasis
4. Arthritis associated with inflammatory bowel
disease
- peripheral arthritis or ankylosing spondylitis
complicating of ulcerative colitis or Crohns disease

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 C. Osteoarthritis
Chronic non-inflammatory joint disease characterized by
degeneration of articular cartilage accompanied by new
bone formation subchondrally & at the margins of the
affected joints
The most common form of arthritis
Higher incidence in women, beginning after age 50
Is most often related to mechanical trauma to the
affected joints

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 C. Osteoarthritis

Primary osteoarthritis
Idiopathic
May results from interplay of genetic predisposition with a
variety of mechanical or inflammatory mechanism
Secondary osteoarthritis
Occurs in joint by known mechanism: mechanical factors,
metabolic disorders (ochronosis), inflammatory disorders

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 C. Osteoarthritis

Characteristic morphologic changes

1. Loss of elasticity, pitting, and fraying ofn cartilage;
fragments may float into synovial fluid
2. Eburnation: polished, ivory-like appearance of bone,
resulting from erotion of overlying cartilage
3. Cystic change in subchondral bone
4. New bone formation
- increased density of subchondral bone
- osteophyte formation

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 C. Osteoarthritis
Characteristic morphologic changes
5. Osteophyte fracturing floating into synovial fluid
6. Heberden nodes: osteophyte at the distal
interphalangeal joint of the fingers (only in women)
7. Bouchard nodes: osteophyte at the proximal
interphalangeal joint of the fingers

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 C. OSTEOARTHRITIS

Left: marked erotion of the articular Osteoarthritis: characteristic fibril-

cartilage: very little shiny cartilage lation of the articular cartilage
remain.
Right: a more advanced case, all
cartilage is lost

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 C. Severe osteoarthritis
Eburnated articular surface

Subechondral cyst

Residual articular cartilage

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 Comparative Features

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 D.1. Gout
General characteristics
Hyperuricaemia deposition of urate crystals
in tissues especially joints
Intense inflammatory reaction: opsonization
of crystals by IgG followed by neutrophils and
phagocytic cells that eventually release
proteolytic enzymes and inflammatory
mediators extremely painful acute arthritis
& bursitis

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 D.1. Gout
General characteristics
Podagra: acute gouty arthritis in
metatarsophalangeal joint of great toe
Tophi: urate crystals in a protein matrix
surrounded by fibrous connective tissue,
inflammatory cells, and giant cells
Often precipitated by a large meal or alcohol
intake
Diagnosis: hyperuricaemia, istopathological
diagnosis

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 Pathogenesis of Acute Gouty Arthritis

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Pathogenesis of hyperuricemia

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 Urate crystal

Urate crystals are negatively birefringent under polarized light

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 Tophus

Aggregates of urate crystals are surrounded by reactive fibroblast,

mononuclear inflammatory cells, and giant cells.

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 Gout Arthritis

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 Chronic gout

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080613TUMS-BONE 82
 D.2. Pseudogout
(chondrocalcinosis)
Is caused by deposition of calcium pyrophosphate
dihydrate crystals inflammatory reaction in cartilage
Clinically resemble gout
CPPD: calcium pyrophosphate crystal deposition
disease, is frequently asymptomatic
Occasionally it is a great simulator produce acute,
subacute, chronic arthritis mimic osteoarthritis or RA

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 Pseudogout Ca pyrophosphate

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 Smear preparation of Ca pyrophosphate
crystal, from synovial fluid

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 E. Tumors and tumor like lesion: 1. Ganglion
Small cyst (11.5 cm), appears as a firm fluctuant, pea-
sized translucent nodule
Common location is around wrist joint, near the joint
capsule or tendon sheath
It arises as a result of miyxoid or cystic degeneration
pseudocyst
No communication with joint space

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E. Tumors and tumor like lesion: 2. Synovial cyst

Herniation of synovium through the joint capsule, or

massive enlargement of a bursa
Baker cyst : cyst in popliteal space in the setting of RA
The synovial lining may be hyperplastic, contain
inflammatory cells and fibrin

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 E. Tumors and tumor like lesion:
Giant cell tumor of tendon sheath

Another name: Villonodular synovitis, localized nodular

tenosynovitis (because it was considered as reactive
synovial proliferation)
Develop in the synovial lining of joints, tendon sheaths,
and bursae
Other type: Pigmented Villonodular Synovitis (PVNS)

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 Giant cell tumor of tendon sheath

Sheets of proliverating cells is bulging the synovial lining

The tumor cells are polyedral, moderately sized, resemble synoviocytes
Other frequent findings: hemosiderin deposits, foamy macrophages,
and giant cells
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 Giant cell tumor of tendon sheath

Localized, well circumscribed, resembles small walnut

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080613TUMS-BONE 91
 BONE TUMORS
Totok Utoro
Department of Pathology
Gadjah Mada University School of Medicine

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 BONE DISORDERS & LESIONS
Congenital Bone Disorders
Metabolic Bone Diseases: disorders of
remodeling (formation and resorption)
Hormonal Disorders Affecting Bone
Nutritional Disorders Affecting Bone
Infectious Bone Disease: Osteomyelitis
Idiopathic Bone Disorders
Cystic and Neoplastic Bone Lesion

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 Bone:

Cystic & Neoplastic

Lesions
1. Cystic Lesions: Solitary bone cyst, Aneurysmal bone cyst
2. Benign disorders: Fibrous dysplasia, chondroma
enchondroma), osteochondroma, chondroblastoma,
chondromyxoid fibroma, osteoma osteoid osteoma,
osteoblastoma
3. Malignant tumor (0.2% from all malignancies):
osteosarcoma, chondrosarcoma, giant cell tumor
(osteoclastoma), Ewings sarcoma
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 BONE TUMORS I
Tumor Age Sex Bones more commonly
(yr) (M:F) affected (in order of frequency)

Osteosarcoma 10-25 3:2 Femur tibia humerus pelvis jaw

fibula
Chondrosarcom 30-60 3:1 Pelvis ribs femur humerus
a vertebrae
Mesenchymal 20-60 1:1 Ribs skull & jaw vertebrae pelvis
chondrosarcoma soft tissue
Giant cell tumor 20-40 4:5 Femur tibia radius

Ewings sarcoma 5-20 1:2 Vertebrae pelvis ribs sternum

/ PNET skull

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 BONE TUMORS II
Tumor Usual location Behavior
within long bone
Osteosarcoma Medulla of metaphysis Malignant: 20% 5-year
survival rate
Chondrosarcoma Central medulla of Malignant 5 ysr:
diaphysis; peripheral Low grade 78%
cortex of periosteum of Moderate grade 53%
metaphysis
High grade 22%
Mesenchymal Medulla or cortex of Malignant; extremely poor
chondrosarcoma diaphysis prognosis
Giant cell tumor Epiphysis and Potentially malignant; 50%
metaphysis recur; 10% metastasize
Ewings sarcoma / Medulla of diaphysis or Malignant; diffuse form
PNET metaphysis uniformly fatal, localized form
often controlled with radiation
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 ONKOLOGIE
KWF Nederlandse Kankerbestrijding
(from all bone malignancies)

Insidence (%)
Tumor White Black

Osteosarcoma 43 32.6 57.9

Chondrosarcoma 28 27.0 19.1

Ewings sarcoma / PNET 14 17.3 3.8
Fibrosarcoma & MFH 12 5.5 7.1

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 Relative frequency of malignancy
in male and female, 1994-1997
Male Female
Malignancy Indonesia Yogya Indonesia Yogya

1 Nasopharynx 3392 364 1669 170

(10.22 %) (7.97 %) (2.79 %) (2.10 %)
2 Prostate 1863 281
(5.61 %) (6.15 %)
3 Breast 11582 2091
(19.34 %) (25.78 %)
4 Soft tissue 1871 269 1530 215
(5.64 %) (5.89 %) (2.55 %) (2.65 %)
5 Bone 688 99 482 58
(2.07) (2.17 %) (0.80 %) (0.71 %)
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 Etiology Factors
Radiation
Chronic Inflammation
Chromium, nickel, cobalt, alluminium,
titanium, methylmetacrylate and
polyethylene
Implanted metallic hardware
Joint prosthesis

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 Diagnosis

1. Clinical symptoms (age is

important)
2. Radiologic : location, tumor size,
periosteal reaction, form of bone
destruction (geografi, moth-eaten,
permeative)
3. Histological feature

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 Clinical symptoms

Swelling and painful

General discomfort
Limited movement
Spontaneous fracture

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 Grading of bone sarcoma
Cellularity
Nuclei features
Mitosis
Necrosis
G1 = low malignancy
G2 = high malignancy

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Musculoskeletal tumour society staging
of malignant bone lesions
Stage
IA Low grade, intracompartmental
IB Low grade, extracompartmental
IIA High grade, intracompartmental
IIB High grade, extracompartmental
III Any grade, metastatic

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WHO CLASSIFICATION OF BONE TUMOR
CARTILAGE TUMOR
Osteochondroma 9210/0
Chondroma 9220/0
Enchondroma 9220/0
Periosteal chondroma 9221/0
Multiple chondromatosis 9220/1
Chondroblastoma 9230/0
Chondromyxoid fibroma 9241/0
Chondrosarcoma 9220/3
cental, primary and secondary 9220/3
Peripheral 9221/3
Dedifferentiated 9243/3
Mesenchymal 9240/3
Clear cell 9242/3
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WHO CLASSIFICATION OF BONE TUMOR
OSTEOGENIC TUMORS
Osteoid osteoma 9191/0
Osteoblastoma 9200/0
Osteosarcoma 9180/3
Conventional 9180/3
Chondroblastic 9181/3
Fibroblastic 9182/3
Osteoblastic 9180.3
Telangiectatic 9183/3
Small cell 9185/3
Low grade central 9187/3
Secondary 9180/3
Parosteal 9192/3
Periosteal 9193/3
High grade surface 9194/3

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WHO CLASSIFICATION OF BONE TUMOR
Fibrogenic tumours
Desmoplastic fibroma 8823/0
Fibrosarcoma 8810/3
Fibrohistiocytic tumors
Benign fibrous histicytoma 8830/0
Malignant fibrous histiocytoma 8830/3
Ewing sarcoma/PNET
Ewing sarcoma 9260/3
Haemopoeitic tumours
Plasma cell myeloma 9732/3
Malignant lymphoma, NOS 9590/3
Giant cell tumour
Giant cell tumour 9250/1
Malignancy in giant cell-tumour 9250/3

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WHO CLASSIFICATION OF BONE TUMOR

Notochordal tumours
Chordoma 9370/3
Vascular tumours
Hemangioma 9120/0
Angiosarcoma 9210/3
Smooth muscle tumours
Leiomyoma 8890/0
Leiomyosarcoma 8890/3
Lipogenic tumours
Lipoma 8850/0
Liposarcoma 8850/3

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WHO CLASSIFICATION OF BONE TUMOR
Neural tumours
Neurilemmoma 9560/0
Miscellaneous tumours
Adamantimoma 9261/3
Metastatic malignancy 9261/3
Miscellaneous lesions
Aneurysmal bone cyst
Simple cyst
Fibrous dysplasia
Osteofibrous dysplasia
Langerhans cell histiocytosis 9751/1
Erdheim-Chester disease
Chest wall hamartoma
Joint lesions
Synovial chondromatosis 9220/0

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 Bone Tumors
Cystic Chondroblastic Osteoblastic Other

Benign
Bone cyst: Chondroma Osteoma Fibrous dysplasia
- solitary Osteochondroma Osteoid osteoma
- aneursmal Chondroblastoma Osteoblastoma
Chondromyxoid-
fibroma

Malignant Chondrosarcoma Osteosarcoma Giant cell tumor-

of bone
Plasma cell myeloma
Ewings sarcoma
Lymphoma
Metastatic tumors

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 Bone Cyst

Solitary / Bone Cyst

Aneurysmal Bone Cyst

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 Bone Cyst

Solitary Bone Cyst

Benign lesion of unknown etiology, predominantly
occur in the distal end of the long bones of young
males
Pain of the affected area and swelling of the soft
tissue
Multiloculated cyst filled with clear or bloody fluid
Treatment: curettage followed by insertion of bone
chips

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 Solitary Bone Cyst

Imaging
Radiolucent from
metaphysis epiphysis
Bone expansion (-) or
few
marginal sclerosis (-)
or thin

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 Solitary Bone
Cyst

Histopathologic
Cyst wall of connective
tissue with giant cells,
hemosiderin pigment,
some times with bone
formation

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 Aneurysmal Bone Cyst

Aneurysmal Bone Cyst

Metaphysis of the long bones and vertebrae,
female>male, 3rd decade
Swelling & pain of the affected area, from few to 20 cm
Spongy appearance filled with blood
Micros: cavernous spaces with walls that lack normal
epithelial lining
The most successful treatment is removal of the entire
lesion recurrences up to 21%

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 Aneurysmal Bone Cyst

Multiloculated space filled with blood

in different stage of organization
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 Aneurysmal Bone Cyst

Cavernous spaces with walls lack normal endothelial linings

DD: - giant cell tumor of the bone
- teleangiectatic osteosarcoma

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 Aneurysmal Bone Cyst

Large cavernous space filled with blood

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 OSTEOGENIC TUMORS
Osteogenic tumors are defined as neoplasms
that produced an osteoid or bony matrix
According to their biological behaviour, they are
divided into benign and malignant lesions
Benign bone-forming neoplasms very rarely
undergo malignant transfomation
Osteomas are not considered neoplasms
Osteoid osteomas and osteoblastomas share
many clinical and rontgenographical similarities
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 BONE-FORMING TUMORS
Osteoma
Osteoid Osteoma & Osteoblastoma
Osteosarcoma (Osteogenic sarcoma)

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 OSTEOID OSTEOMA
Clinical
In children and adults
Location
Long bones, mostly close to proximal
of the femur
Close to joint joint effusion
arthritis
Gross pathology
Lesion in cortex les than 1 cm, red,
granular, surrounded by sclerotic bone

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 Osteoid Osteoma

Microscopic
Central Vascularized connective tissue
Osteoblast cells, osteoid, bone

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 OSTEOBLASTOMA

Clinical
Rare, 1% of all bone tumors
Mostly male, young adult and adult
Location
Vertebra sacrum
Proximal and distal femoral bone, proximal
tibia metaphysis

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 OSTEOBLASTOMA

Gross pathology
Abundant blood vessels reddish brown
Concistency like sands
The tumor is round or ovoid with thin cortex
Some times with Aneurysmal Bone Cyst
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 OSTEOBLASTOMA

Histopathological
Similar with osteoid osteoma
Trabeculae surrounded by a
layer of osteoblasts
Abundant blood vessels
Mitosis could be (+), non-
atypical
Osteoclasts are frequently
found similar with GCT

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 Osteosarcoma

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 OSTEOSARCOMA
Intramedullar primary tumor
Osteoid producing high grade tumor
Other names:
Classical Osteosarcoma
Osteogenic sarcoma
Osteoblastic sarcoma
Chondroblastic osteosarcoma
Fibroblastic osteosarcoma
Medullary Osteosarcoma
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 OSTEOSARCOMA
Clinical
The most frequent primary malignant
tumor
Age: 2nd decade
60% below 25 years old
30% > 40 years old
Male > female
Pathological fracture

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 Conventional Osteosarcoma
Conventional osteosarcoma is a primary intramedullary
high grade malignant tumor in which the neoplatic cells
produce osteoid, even if only in small amount
Synonym: conventional osteosarcoma, classical
osteosarcoma, osteogenic sarcoma, osteosarcoma not
otherwise specified, osteochondrosarcoma, osteoblastic
sarcoma, chondroblastic osteosarcoma, fibroblastic
osteosarcoma, osteofibrosarcoma, central osteosarcoma,
central osteogenic sarcoma, conventional central
osteosarcoma, medullary osteosarcoma, sclerosing
osteosarcoma

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 ICD-O codes
Osteosarcoma, NOS 9180/3

Chondroblastic osteosarcoma 9181/3

Fibroblasrtic osteosarcoma, 9182/3

osteofibrosarcoma
Central osteosarcoma, conventional 9180/3
central osteosarcoma, medullary
osteosarcoma
Intracortical osteosarcoma 9195/3

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 OSTEOSARCOMA
Major Sites of Origin of
Osteosarcoma

Location
Metaphysis (90%), diaphysis
(,9%) femur distal, tibia prox,
humerus prox
Jaws, skull, pelvis, vertebra
Lab
Alkaline phosphatase
Lactic acid dehydrogenase

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 OSTEOSARCOMA
Etiology: unknown
Injury?
Pagets disease of the bone
Radiation
Other bone tumors
Non-neoplastic conditions (osteomyelitis,
prosthesis)

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 OSTEOSARCOMA
Microscopic
Tumor cells
Pleomorphic
Anaplastic CD 99
Epitheloid, plasmacytoid, spindle cell, ovoid,
small round cells, clear cells, multinucleated
cells
Osteoid
Dense amorphous mass
pink color: - osteocalcin
- osteonectin

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 Osteosarcoma

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 Osteosarcoma

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 Prognostic Factors
Without treatment fatal
Pulmonary metastasis is the most frequent bad
Response to pre-operative therapy is the most
sensitive survival indicator
Tumor necrosis > 90% (responsive) long term
survival 80-90%
Tumor necrosis <90% (non-responsive) survival <
15%

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 CARTILAGE-FORMING TUMOR
Osteochondroma
Chondroma/Enchondroma
Chondroblastoma
Chondromyxoid fibroma
Chondrosarcoma

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 OSTEOCHONDROMA
Definition
Growing bone layered by cartilage on the surface of the
bone and filled with bone marrow inner side
Clinical
First 3 decades
Male = female
15% multiple
Location
Femoral metaphysis of distal part
Humerus: proximal part
Tibia: proximal
Fibula: proximal

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 OSTEOCHONDROMA

080613TUMS-BONE 138
 OSTEOCHONDROMA

Gross pathologhy
Size less than 3 cm
Irregular grayish white mass
When calcification (+), looks and feels
like sands

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 OSTEOCHONDROMA

Imaging
Pedunculated
sessile

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 OSTEOCHONDROMA

Gross pathology
Cartilage cap less than 2 cm
> 2 cm malignant?

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 ENCHONDROMA

Benign cartilage tumor of the medulla of bone

10-25% of all benign bone tumors
Age: 5-80 tahun
May be multiple in the same bone
Location:
Hands and feet: small tubular bone
Humerus: proximal
Femur: proximal and distal

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 CHONDROMA / ENCHONDROMA

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 ENCHONDROMA

Imaging
Well defined
Can be radiolucent
Often in metaphysis,
central or exentric
No destruction of the
cortex
No invasion to the soft
tissue

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 ENCHONDROMA

Histopatologik
Generally hypocellular,
avasular
Hyalin matrix, myxoid or
chondroid
Some time multinodular
In small bone (hands and
feet) can be more cellular
no radiological examination
misleading to malignancy

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 CHONDROBLASTOMA
Benign tumor producing cartilage in epiphysis of
immature bone
Clinical
Less than 1% of all benign bone tumor
Age: 10-25 tahun
Male > female
Location
Epiphysis and metaphysis
Femur: proximal and distal
Tibia: proximal
Humerus: proximal

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 CHONDROBLASTOMA

Radiologic
Lytic lesion in central
or exentric
Size: 3-6 cm
Well circumscribed

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 CHONDROBLASTOMA

Microscopical
The cells are uniform, rounded-polygonal
Cytoplasm thin and eosinophilic
The nuclei are rounded or ovoid (chondroblast)
Nuclear groove
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 CHONDROMYXOID FIBROMA

Microscopical
Well circumscribed
Lobular, sel spinde or stelate cells with mixoid matrix
In the center hypocellular, bordered by hypercelular area
20-30% of cases: nuclei are pleomorphic and
hyperchromatic looks like malignant
19%: content cartilage hyalin
Mitosis is rare (not atypical)
10% with ABC
calcification and osteoclast is possible

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 CHONDROMYXOID FIBROMA

Imaging
Lesions are found in the metaphysis, exentric, well
circumscribed
Ekspansion to cortex, parallel along the length of bone

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 CHONDROMYXOID FIBROMA
Benign tumor with spindle or stellate cells lobules,
and matrix mixoid or chondroid
Clinical
Less than 1% of all bone tumors
More often in male
2nd 3rd decades
Location
All types of bones
Mostly in proximal tibia and distal femur

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 CHONDROSARCOMA

Malignant cartilaginous tumor that may arise de novo

(primary chodrosarcoma) or originate from a pre-existing
benign cartyilaginous lesion (secondary chondrosarcoma.
May be followed by myxoid change, calcification, or
ossification
080613TUMS-BONE 152
 CHONDROSARCOMA
Primary chondrosarcoma (convensional)
Originate from the center of normal bone
Clinical
25% dari tumor ganas tulang
Menduduki urutan ketiga (mieloma-osteosarkoma-
kondrosarkoma)
90% primer
>50 tahun, sedikit lebih sering pada pria
Location
Pelvis femur proximal humerus proximal
femur distal iga
Metafisis atau diafisis

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 Chondrosarcoma

080613TUMS-BONE 154
 CHONDROSARCOMA

Imaging: very important

Radiolucent feature
with calcification patch
or ringlike opacities
Erotion/destruction of
the cortex

080613TUMS-BONE 155
 CHONDROSARCOMA

Microscopical
Grayish blue matrix (chondroid/myxoid) with irregular cartilage
lobules separated by connective tissue or bone trabecules
More cellular than enchondroma
Atypical cells with enlargement of the nuclei and
hyperchromatic, and some time with benucleation
Infiltrating cortex and medulla different with enchondroma
Matriks kondroid/miksoid
High grade mitosis (+), necrosis (+)

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 CHONDROSARCOMA

Gr I Gr III

Grading prognosis
Celularity
Nuclear size
hyperchromatics
Gr II

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 FIBROUS & FIBRO-OSSEOUS TUMORS
Fibrous Cortical Defect & Nonossifying Fibroma
Fibrous Dysplasia
Fibrosarcoma & Malignant Fibrous Histiocytoma
(MFH)

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 FIBROUS DYSPLASIA

Benign medullary fibro-osseous lesion,

affected one bone or more
Location
Jaw, ribs, skull
Male: more in long bones

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 FIBROUS DYSPLASIA

Microscopical
Consists of bone of connective tissue components
C letter-like trabecule without osteoblastic rimming
cementum-like bone or rounded psammomatous bodies
are some time found

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 Ewing Sarcoma
PNET
ICD-O code:
- Ewing sarcoma : 9260/3
- PNET : 9364/3
- Askin tumor : 9365/3
Synonyms: Ewing tumor, peripheral neuroepi-
thelioma, peripheral neuroblastoma, Askin tumor

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 MISCELANEOS TUMORS
Ewing Sarcoma & Primitive Neuroectodermal
Tumor (PNET)
Giant Cell Tumor
Multiple myeloma, & Lymphoma
Metastatic Tumors

080613TUMS-BONE 162
 Ewing sarcoma / PNET

Ewing described firstly as diffuse endothelioma

PNET describes a small cell malignancy which
is considered by some to be similar to, but distinct
from, Ewing tumor.
Imunohistochemistry & cytogenic studies indicate
that PNET and Ewing tumor are the same entity,
and should be considered to be neuroectodermal
derivation
The prognosis has improved dramatically since
the introduction of radiation & chemotherapy

080613TUMS-BONE 163
 Ewing Sarcoma
Primitive NEuroectodermal Tumor (PNET)

Ewing sarcoma and PNET are defined as round

cell sarcomas that show varying degrees of
neuroectodermal differentiation
The term Ewing sarcoma has been used for
those tumors that lack of evidence of neuroecto-
dermal differentiation as assesed by light
microscopy, immunohistochemistry, and EM
The term PNET has been employed for tumors
that demonstrate neuroectodermal features as
evaluated by one or more of these modalities

080613TUMS-BONE 164
 Ewings Sarcoma

-A rare primary malignant tumor originates in the medullary cavities of the

long bones predominantly
-<2% of all bone malignancies
-Age: 10n 30 years old
-Clinical features: destructive lesion seen radiologically broke the cortex
reactive new bone produced onion skin appearance
080613TUMS-BONE 165
 Ewings Sarcoma

Microscopically:
Undifferentiated small round cells (smaller than lymphocyte with
prominent nuclei and scanty cytoplasm) arranged in sheet or
cord
Rich of vascular background and fibrous tissue is visible
080613TUMS-BONE 166
 Giant Cell Tumor

080613TUMS-BONE 167
 GIANT CELL TUMOR
Benign bone tumor, locally aggressive, consists of
neoplastic ovoid mononuclear cell Intermingled with
giant cell osteoclast osteoclastoma
Clinical feature:
4-5%
20% from primary benign bone tumor
Ages: 20-45 years old
Male > female

080613TUMS-BONE 168
 GIANT CELL TUMOR

Round, polygonal, and spindle cells,intermingled with

osteoclast-like giant cells that can be so big (50-100
nuclei)

080613TUMS-BONE 169
 GIANT CELL TUMOR
Location:
Distal end of femoral tibia proximal
humerus proximal
5%: pelvis, sacrum
<5%: tubular bone of hands and feet
May be very in frequently multicentric

080613TUMS-BONE 170
 IMAGING OF GIANT CELL TUMOR
Type 1 = quiescent
Well circumscribed, sclerotic arround
Cortical involvement minimal or -
Type 2 = active
Well circumscribed, no sclerosis arround
Cortex is thin, expansion +
Type 3 = aggressive
Poorly defined border
Often with cortex destruction and extension
to soft tissue

080613TUMS-BONE 171
 GIANT CELL TUMOR

No correlation between
radiological grading
and histological
features
Some time soap
bubble appearance is
found

080613TUMS-BONE 172
 MALIGNANCY IN GCT

Primary malignant GCT GCT which content high grade sarcoma

part of conventional GCT tissue is still found
Secondary malignant GCT = high grade sarcoma occuring in
recurrent GCT no GCT tissue left
GCT with malignant transformation <1%, female > male

080613TUMS-BONE 173
 Metastatic Tumors

The most frequent malignancy in bone

More than primary tumors of bone

080613TUMS-BONE 174
 Normal Spine

080613TUMS-BONE 175
 Normal Spine

080613TUMS-BONE 176
 Normal Spine

080613TUMS-BONE 177
 Bone Metastasis of Carcinoma

080613TUMS-BONE 178
 Bone Metastasis of Carcinoma

080613TUMS-BONE 179
 Bone Metastasis of Carcinoma

080613TUMS-BONE 180
 Bone Metastasis of Carcinoma

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