BLOCK B2

Musculoskeletal Disorder
Teaching Assisstant 2015
Afif - Alfin – Azzam – Dika – Fedy – Gerry – Vano – Aisyah – Daisy – Hana –
Irene – Oca – Tere – Yena
▶ Osteosarcoma

▶ Chondroma

▶ Giant Cell Tumor

Of Tendon Sheath

▶ Rhabdomyosarcoma

▶ Lipoma

▷ Osteomyelitis Musculoskeletal
▷ Thopus Disorder
 Content

TRIPLE
DIAGNOSIS
CLASSIFICATION
OSTEOSARCOMA
Osteogenic Sarcoma | Bone Sarcoma
NORMAL BONE

A. Osteoblast

B. Osteocyte

C. Osteoid

D. Cement line

E. Bone
OSTEOGENIC TUMOURS
 Osteoid osteoma 9191/0
 Osteoblastoma 9200/0
 Osteosarcoma 9180/3
▷ Conventional 9180/3
▷ chondroblastic 9181/3

•
▷ fibroblastic 9182/3
Osteoblastic 9180/3
WHO
•
•
Telangiectatic 9183/3
Small cell 9185/3
CLASSIFICATION
• Low grade central 9187/3
• Secondary 9180/3
• Parosteal 9192/3
• Periosteal 9193/3
• High grade surface 9194/3
 Bone-Forming
Malignant Mesenchymal Tumor
Osteosarcoma is an aggressive malignant neoplasma that arises from primitive
transformed cells of mesenchymal origin in bone that produces malignant osteoid

Most common primary 20% of primary Origin : Osteoblast

tumor of the bone after bone cancers
myeloma
Epidemiology
 Occurs in all age, but have bimodal age  8% jaw
distribution  10% shoulder
 Men : woman (1,6 : 1)  15% around hip
 60% knee

Occurs mostly in
Metaphysial region
of long bone

Predilection
 Etiopathogenesis
Associated with :

 tp53 mutation  Li-Fraumeni Syndrome

 RB1 mutation  Retinoblastoma
 Overexpression of MDM2
 Overexpression of CDK4
 INK4 mutation
 RCLQ4 mutation  Rothmun-Thompson Syndrome
 Werner syndrome (WLM Mutation)
 Bloom syndrome (BLM Mutation)
Subtype

 Intramedullary  High
 Intracortical  Low
 Surface

 Osteoblastic
 Primary  Chondroblastic
 Secondary  Fibroblastic
 Teleangictatic
 etc
Clinical Features
 Painful enlarging masses
 First sign : Pathologic fracture
 10-20% pulmonary metastasis
 Systemic symptoms such as
fever, weight loss, and malaise
are generally absent
 Diagnosis

Radiographic Lab test

Periosteal Reaction, Codman Elevated serum alkaline phospatase
Triangle, Sunburst Appereance (no great value for detecting osteosarcoma)

PA Specimen IHC Staining

open biopsy, needle biopsy, vimentin, kolagen type I, II, IV, s-100
FNAB, frozen section (chondroblastic), alkaline phospatase
 Radiologic Finding

Codman Triangle Periosteal reaction Sunburst

Appereance
 Macroscopic
 Gritty, bulk, gray-white, and
contain areas of hemorrhage and
cystic degeneration
 Infiltrating and replacing the
marrow
 Destroy the surrounding cortices,
producing soft tissue masses
Microscopic
 Tumor cells vary in size and shape
 Large hyperchromatic nuclei.
 Bizarre tumor giant cells can be found
 Pathologic mitoses
 Vascular invasion and extensive
necrosis
 The formation of bone by the tumor
cells  OSTEOID MALIGNA
 May produce cartilage or fibrous
tissue
Microscopic variant
 Osteoblastic (50% Cases)
 Chondroblastic
 Fibroblastic (Less common)
 Telangiectatic (Rare)
 Small cell (Rare)
 Fibrohistiocytic
 Anaplastic
 Well differentiated
 Juxtacortical (parosteal)
 Periosteal osteosarcoma
 etc
Osteoblastic
Chondroblastic
Fibroblastic
Telangiectatic
Small Cell
 Treatment
 Amputation/ disarticulation
 Limb sparing procedures
 Adjuvant chemotherapy
 Intensity-modulated radiation therapy
(IMRT); proton beam therapy
 Biphosphonates

 MSTS Staging for choosing treatment

 Prognosis

Without metastases/ Metastases or secondary

initial diagnosis. osteosarcoma

60% -70% <20%

5-year survival rates 5-year survival rate
 Tenosynovial GCT | Nodular Tenosynovitis | Fibrous
hystiocytoma of tendon sheath | Fibrous xanthoma

GIANT CELL TUMOR

of Tendon Sheath
Overview
Proliferation of synovial like mononuclear cells with osteoclast-like giant cells, foam
cells, siderophages and inflammatory cells in synovial lining of joints, tendon
sheaths, and bursae

Origin Subtype

Histiocyte localized and diffuse

Epidemiology
 30 – 50 years, peak in 40 – 50 years
 Female : male = 3 : 2
 Predilection :
• Hand and wrist (65-89%) Pain 
• Foot and ankle (5-15%) Locking 
• Pressure Erosions in 15% Swelling 
Usually asymptomatic 
Movement limitation 

Clinical Features
 Pathogenesis
Reciprocal somatic chromosomal translocation t(1;2)(p13;q37)
involving M-CSF gene
 overexpression of M-CSF
 Predilection: flexor surface of middle
or index fingers.
 Characters :  Usually knee (80%); also ankle, hip,
• solitary mass (2-5 cm) shoulder, elbow, foot
• slow growing  Almost always monoarticular, painful
• well-circumsribed swelling
• Painless  Occasionally invades underlying
• Cortical erosion in 15% case bone; may cause bone cyst
• in women (30-50 years) formation, loss of bone and
cartilage
 Locally aggressive; often recurs, but
only rarely has malignant behavior
 Macroscopic
 Localized tumors up to 4 cm in  Brown-yellow spongy tissue
small joints (larger elsewhere)  Firm and nodular
 Circumscribed, lobulated  Often 5 cm or larger
 White-gray-brown  Finger-like projection
 May have shallow grooves along
deep surface due to underlying
tendons
Macroscopic
Macroscopic
Microscopic
 Well circumscribed, lobulated, partially
encapsulated
 Variable proportions of mononuclear
cells (small, round to spindled, with
pale cytoplasm and round or grooved
nuclei), osteoclast-like giant cells with 3
- 50 nuclei, foam cell, siderophages,
epithelioid cells with glassy cytoplasm
and round vesicular nuclei
 Varying amounts of dense collagenous
stroma
 Giant cell

Hemosiderin pigment

GCT of the Sheath

Localized-Type
Microscopic
 Large clefts, pseudoglandular or
alveolar spaces lined by synovial
cells, osteoclast-like multinucleated
(10 - 70 nuclei) giant cells,
epithelioid cells
 Abundant collagen may be present,
but lymphocytes and plasma cells
are sparse
 Also giant hemosiderotic granules
(2 - 3x diameter of RBC), giant
siderophages
 GCT of the Sheath
Diffuse-Type
 Diagnosis

Radiographic Histopathologic IHC : CD68, CD45

Radiologic Finding
 Treatment & Prognosis
 Complete surgical excision
 5-50% recurrence rate
 Operative approach depend on
location and extend of the tumor
 Recurrences can be reexcised
CHONDROMA
Classifiation based on place :
• Enchondroma : intramedullary cavity
(synonym : solitary enchondroma, central
chondroma)
• Juxtacortical chondromas : on the surface of
bone (synonim : periosteal chondroma,
Origin : Chondrocyte
parosteal chondroma

Benign Cartilaginous Tumor

“Usually occur in bones of enchondral origin”
 Usually occurs in long bone, particularly the long bones of the hand, followed by the
humerus and femur
 Typically present during the second decade but can present at any age
 They generally are central, metaphyseal lesions
 Multiple enchondromas can be found in Ollier disease and Mafucci Syndrome.

Enchondroma
Solitary Enchondroma | Central Chondroma
Can be found in these disease:

 Ollier disease : multiple chondroma

preferentially involving one side of the
body

 Mafucci Syndrome : multiple

chondroma associated with spindle cell
hemangiomas

Enchondromatosis
A Condition when people have multiple chondroma
 Arise from the surface of the cortex,
deep to the periosteum, and erode into
the cortex
 The most common site is the proximal
humerus
 Histologically and clinically resembles an
enchondroma

Juxtacortical Chondroma
Periosteal Chondroma | Parosteal Chondroma
 Point mutation in IDH1 or IDH2 that
create a new enzyme activity

IDH1 or IDH2  produce isositrate dehydrogenase  synthesis of 2-

hydroxyglutarate ( inhibits alpha-Ketoglutarat)  inhibit TET activity  interfere
DNA methylation (Epigenetic Change).

Pathogenesis
Point mutation in IDH1 or IDH2
Diagnosis Clinical Features
 Clinical Findings Usually asymptomatic and detected as 
 Radiology incident findings
X-Ray, Bone Scan, CT scan, MRI
Occasionally painful 
 Biopsy  Histopathology
Cause pathologic fractures 

May be numerous and large, 

producing severe deformity
Radiologic Finding

 The unmineralized nodules of

cartilage produce well-
circumscribed oval lucencies
surrounded by thin rims of
radiodense bone (O-ring sign).
 Calcified matrix manifests as
irregular opacities.
Macroscopic

 Solid nodule < 3 cm, gray-blue and

translucent
 Frequently multinodular
 Well-demarcated if intact
 Yellow or red foci represent areas of
calcification or ossification
 Microscopic
 Nodule of hyaline cartilage

 Nodule containing benign cytologically

chondrocyte
 The peripheral portion of nodules undergo
enchondral ossification
 The center can calcify and intact

 Necrosis is common because of avascular

cartilage
 Mitotic activity is very low

 Cytoplasm  granular osinophilic

 Nuclei  small, round, condensed chromatin

Treatment Prognosis
Observation Growth potential is limited 
Excision, may recur if incompletely excised. Occasionally, an enchondroma will recur 
many years later, and rarely recur as a
low grade chondrosarcoma.
Solitary chondromas rarely undergo 
malignant transformation.
Enchondromatoses are at increased risk 
for malignant transformation.
Individual with mafucci syndrome are 
also at risk for ovarian carcinomas and
brain gliomas
RHABDOMYOSARCOMA
Malignant rhabdomyoma | Rhabdopoietic sarcoma
Overview
 Primitive malignant soft tissue sarcoma with skeletal muscle
phenotype
 Most common soft tissue sarcoma of
childhood/adolescence
 Twothirds of cases are diagnosed in children younger than
six years of age
 There is a small male predominance (M/F Ratio 1.3 : 1.5).
 Origin : Rhabdomyoblast
 Subtype
 Head and neck RMS are more common in
younger children; when they arise in the orbit,
they are almost always of the embryonal type Pleomorphic;
 Nearly 80 percent of genitourinary tract RMS 20%
are embryonal
 Extremity tumors present more commonly in
Alveolar ; 20%
adolescents and are frequently of the alveolar Embryonal ;
type 60%
 Relatively rare in adults, who often have
pleomorphic
Predilection
 Children 2-6 years : head, neck or
GU tumor

 Teenagers : paratesticular, trunk or

abdominal tumors
Pathogenesis
1. Rearrangements : (2;13) or(1;13) translocations.

2. Fusions of the FOXO1 gene to either the PAX3 or the PAX7 gene.

3. PAX3-FOXO1 fusion protein interferes gene expression program that drives

differentiation.

4. Most embryonal RMS have loss of heterozygosity (LOH) at the 11p15 locus, the site
of the IGFII gene.
 Clinical Features
Depend on type and location of tumor

Alveolar and Embrional Pleomorphic

 Paranasal : proptosis or cranial nerve deficits Rapid growing masses 

 Perirectal : constipation Painful 

 Paraspinal : nerve root abnormalities

(parestesia, hyperestesia, paresis)

 N.cranialis  diplopia

 Vesica urinaria  urine retention

Diagnosis
 Laboratory Finding

 Imaging/Radiology

 Histopathology

 One of the small round blue-cell tumors

RMS in left orbital Myogenin Staining
of childhood.

 IHC (+) results for muscle-specific

markers, such as desmin and myogenin.

SRBCT
Staining Algorithm
for Small Round Blue Cell Tumor
Radiologic Finding
 Macroscopic

Alveolar Embryonal Sarcoma Botryoides

 Microscopic
 Composed of primitive mesenchymal cells that
show variable degrees of skeletal muscle
differentiation
 Sheets of small, stellate, spindled or round cells
with scant or deeply eosinophilic cytoplasm
and eccentric, small oval nuclei with a light
chromatin pattern and inconspicuous nucleoli
 Can occasionally identify tumor cells that
contain generous amounts of eosinophilic
cytoplasm, a feature of rhabdomyoblastic
differentiation (so called "strap" cells) or also
known as cells with elongated tails of
cytoplasm (tadpole cells)
 Botryoid variant frequently shows a "cambium
layer," a hypercellular zone immediately
beneath the epithelial surface
TADPOLE CELL
Cambium layer
Alveolar RMS
Pleomorphic RMS
Treatment Prognosis

Combination of Rhabdomyosarcoma are aggresive tumor 

Sarcoma botyroides has the best prognosis 
 Surgery and Chemotherapy Pleomorphic subtype has the worst prognosis 
 +/- Radiotherapy Prognosis factor 
Tumor origin •
Tumor size •
Histology subtype Variant* •
Genetic •
LIPOMA
 Benign tumor composed of mature white adipocytes with uniform nuclei
resembling normal white fat

Most common soft Adults, age 40+ Origin : Adipocyte

tissue tumor

No gender or ethnic
Associated with obesity Rare in children
preference
 Patogenesis

Rearragement of chromosome 12 and abnormality in the HMGA2-LPP fusion

gene
Predilection
 Usually trunk, back, shoulder,
neck, proximal extremities
 Rare on hands, feet, face,
lower leg, retroperitoneum
 Usually subcutaneous
 Unusual sites include oral
cavity, pancreas, breast,
intestines
Clinical Features
 Relatively static growth after
initial growth period
 Does not regress even with
starvation
 Becomes hard after
application of ice
 Soft, mobile, and painless
except angiolipoma
Diagnosis
 Lab studies : D-dimer Level
 Radiology  USG
 Biopsy  Excision (Treatment) 
Histopathology w/ staining
• Simple  Oil Red O & Sudan Black
• IHC  Vimentin, S100
Macroscopic
 Bright yellow homogeneous
fat with fine fibrous capsule
(superficial lesions only) and
trabeculae
 May be very large (particularly
if deep)
 Greasy cut surface
 Rubbery consistency
 Microscopic
 Mature white adipose tissue without
atypia
 2 - 5x variation in cell size (more than
normal white adipose tissue), with
obvious large cells up to 300 microns
 Cytoplasmic vacuoles are relatively
uniform
 May have intranuclear vacuoles,
thickened fibrous septa in buttocks, foot
or hand
 May contain areas of fat necrosis with
histiocytes, infarct or calcification
 Rarely contains bone or cartilage
 No mitotic figures
Fibrolipoma
Angiolipoma
Spindle Cell Lipoma
Intramuscular Lipoma
Treatment
 Excision
 Liposuction
 Lipolysis
OSTEOMYELITIS
Overview

Inflammation of bone and marrow

May be complication of any systemic infection, but frequenly

manifest as a primary solitary focus of disease

Most common caused by pyogenic bacteria and mycobacteria

Etiology

50% cases are unknown

Most cases are due to Staphylococcus aureus

Specific bacteria for sickle cell patients, neonates, and post-

traumatic cases

Other known organisms are E. coli, Pseudomonas and Klebsiella

Rute of Infection

Hematogenous spread

Extension from contagious site ( joint

or other soft tissue)

Direct implantation caused by trauma

(open fracture)
Type of Osteomyelitis

Pyogenic osteomyelitis

Mycobacterial osteomyelitis

Fungal ostemyelitis ( rare)

Mycobacterial Osteomyelitis

Approximately 1-3% person with

pulmonary or extrapulmonary TB have
osseous infection
Histologic finding : casseous necrosis
and granuloma
More destructive and resistance to
control than pyogenic osteomyelitis
Tuberculosis spondylitis is particularly
destructive. 40% happen in person with
mycobacterium osteomyelytis
Pyogenic Osteomyelitis

50% of suspected cases, no organism can be found

80-90% of cases are due to Staphylococcus aureus
E.Coli, Pseudomonas, and Klebsiella are more frequently isolated in
person with UTI
Haemophylus influenza common in children
Mixed bacteria common in direct spread or direct inoculation cases
Location of Infection
influenced by osseous vascular circulation, varies w/ age.

Neonate : metaphysis, epiphysis, or both

Children : metaphysis
Adult : epiphyses and subchondral regions

Clinical Features
Malaise Leukocytosis
Fever Bone pain
Chills Swelling and redness
Pathogenesis
of
Osteomyelitis
Radiologic
Findings
Diagnosis
Clinical features Blood test (leucocytosis)
Radiologic finding : inflammation in bone Culture
Bone biopsy (Gold Standard)

Macroscopic
Sequestrum Sinus drainage
Involucrum Brodie abcess
Subperiosteal abcess Cloaca
Macroscopic
Features 1
2
3
Marjolin Ulcer
Microscopic
Infiltration of inflammatory
cells from cortex to medulla
Involucrum (new bone Osteocyte
formation) Infiltration of
inflamation
Sequestrum (necrotic bone) cells
Hemorrhage and necrosis

Bone Fibrous tissue

trabeculae

Involucrum
Treatment

Surgery to remove dead bone

(sequestrum)

Antibiotics; often Cloxacillin, Nafcillin,

third generation cephalosporins

Local antimicrobials
TOPHUS
Overview
A deposit of uric acid crystal, in the form monosodium urate
crystals in hyperuricemia people

Predilection
Most common di distal joint
May appear in articular cartilage, ligament, tendons,
and bursae
Less frequently occur in soft tissue (earlobe, fingertips)
and kidney
Gout
Disease that occurs in response to the presence of monosodium urate
(MSU) crystals in joints, bones, and soft tissues.
Marked by transient attack of acute arthritis
2 forms : Primary and Secondary
• Primary gout (90%) :underexcretion or overproduction of uric acid
• Secondary gout (10%) is related to medications or conditions that cause
hyperuricemia, such as : chronic renal disease, leukemia (increase leukocyte
turnover), etc
Pathogenesis
Risk Factor
Hyperuricemia (at age > 30 y.o) Alcohol use
Diets rich in meat and seafood content Obesity
Familial history of gout Thiazide administration.

Diagnosis
Clinical Findings
Blood Test
Synovial Fluid Analysis
Radiology
AP
Clinical Feature
Accute attack
pain, warmth, redness, swelling, onset more often
at night, lower-extremity involvement
Intercritical : Asymptomatic
Chronic tophaceous gout
not painful, enlargement, yellow or white colour
Macroscopic
Chalky white appearance
of gouty deposits
Microscopic
Tophi (large aggregates of urate crystals, granulomatous inflammation,
hyperplastic fibrotic synovium); gout crystals are long, slender, needle shaped
but difficult to visualize with routine staining because they are dissolved during
formalin processing (crystals are water soluble); easier to identify on scrape or
with alcohol fixation
With chronic disease, urate deposits may be present in soft tissue, ligaments,
skin
Gouty deposits may be surrounded by fibrous tissue and be rimmed by
histiocytes and giant cells
Treatment
Gout is managed in the following 3 stages:
 Treating the acute attack.
 Providing prophylaxis to prevent acute flares.
 Lowering excess stores of urate to prevent flares of gouty arthritis and to prevent tissue
deposition of urate crystals.

The target serum uric acid level is <6 mg/dL (355 μmol /L).
Allopurinol is the first-line urate-lowering therapy.
Complications : pain, soft tissue damage and deformity, joint destruction and
nerve compression syndromes such as carpal tunnel syndrome.
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