Disorders affecting bone,joint,soft

tissue

BY: Mathewos Tamene(MD, pathologist)

 Outline
Bone
• introduction
• Congenital diseases of the bone
• Acquired diseases of bone and development
• Bone tumors
Joints
• degenerative joint disease (osteoarthritis),
gout, and infectious arthritis
Soft tissue tumors
Skeletal Pathology
Skeletal system
has 206 bones
Anatomy of Bone
BONE
 Introduction
Structure of Bones
• Bone is composed of hard extracellular matrix and spe-
cialized cells responsible for production and mainte-
nance of the matrix.
• Hard Matrix is made of organic protein component known as os-
teoid(35%) and inorganic mineral component (65%).
• The main structural protein-type I collagen makes 90%
of organic component – matrix(osteoid) and its pro-
duced by osteoblast cells.
• Most of the mineral -in the form of a calcium phosphate
complex known as hydroxyapatite
 MICROSCOPIC STRUCTURE OF BONE
• Woven bone – irregular nonmineralized bone, normally seen
only in fetus. In adult is always sign of pathologic process
• Lamellar bone – regular mineralized bone gradually replaces
woven bone during growth and is stronger than woven bone
• Osteoblasts and osteoclasts act in coordination as “basic mul-
ticellular unit” performing bone formation and resorption dur-
ing skeletal growth (modeling) and maintenance of mature
skeleton (remodeling)
 MICROSCOPIC STRUCTURE OF BONE
• Osteoprogenitor cells – pluripotential mesenchymal cells. Un-
der appropriate stimulation can differentiate into osteoblasts
• Osteoblasts – located on the surface of bone, “build” the
bone and initiate process of mineralization. Have receptors for
PTH, vit D and estrogen.
• Osteoblasts surrounded by bone matrix – osteocytes.
• Osteocytes are less active than osteoblasts but play important
role in control of the fluctuations in serum Ca and Ph levels.
• Osteoclasts – responsible for bone resorption, multinucleated
giant cell,derivate of granulocyte-monocyte precursor cell
from bone marrow
Woven bone  

Lamellar bone  
• During development, bone is formed either
–directly in connective tissue, as in the skull (in-
tramembranous ossification) or
–on pre-existing cartilage, as in the limb bones
(endochondral ossification)
Modeling/RE-modeling
CONGENITAL AND HEREDITARY DISEASES
OF BONE
• Congenital disorders of the skeleton are vari-
ous and, depending on the resulting defect,
become manifest at different ages.
• The most severe produce developmental ab-
normalities that are evident from the earliest
stages of skeletogenesis.
 1) MALFORMATIONS AND DISEASES CAUSED BY
DEFECTS IN NUCLEAR PROTEINS AND “TRAN-
SCRIPTION FACTORS”(DNAmRNA)

• Uncommon
Failure of development of a bone (eg. Absence of phalanx,
rib or clavicle)
Formations of extra bones (eg. Supernumerary digits or
ribs)
Fusion of adjacent digits (syndactyly)
Craniorachischisis: failure of closure of vertebral spinal
column and skull; produces meningomyelocoele /en-
cephalocoele
Meningomyeleocele
2) DISEASES CAUSED BY DEFECTS IN HORMONES AND
SIGNAL TRANSDUCTION MECHANISMS

Achondroplasia
• Autosomal dominant disorder
• Characterized by impaired proliferation and maturation of carti-
lage in the developing growth plate.
• is a major cause of dwarfism
• Majority of cases are caused by activating point mutation involv-
ing the gene for fibroblast growth factor receptor 3 (FGFR3) that
inhibits the proliferation and function of growth plate chondro-
cytes; consequently, the growth of normal epiphyseal plates is
suppressed, and the length of long bones is severely stunted,
hence the term “achondroplastic”;
• Achondroplasia affects all bones that develop
by enchondral ossification.
• The most conspicuous changes include dis-
proportionately short extremities but well-
muscled arms and legs and normal trunk size,
normal or enlarged head (bulging forehead,
prominent supraorbital ridges, depression of
root of nose) .
Achondroplasia
Achondroplastic “dwarf” Thanatophoric “dwarf”, often lethal

Short arms and extra folds of skin

3) DISEASES ASSOCIATED WITH DEFECTS IN EX-
TRACELLULAR STRUCTURAL PROTEINS
Osteogenesis Imperfecta(OI)
• "brittle bone disease’’, too LITTLE bone),
• a group of hereditary conditions caused by
deficiencies in the synthesis of type I collagen.
• It is the most common inherited disorder of
connective tissue.
• OI principally affects bone, but also impacts
other tissues rich in type I collagen (joints,
eyes, ears, skin, and teeth).
• The fundamental abnormality in OI is too little bone, resulting
in extreme skeletal fragility.
• Other findings include
• blue sclerae caused by decreased collagen content, making
the sclera translucent and allowing partial visualization of the
underlying choroid;
• hearing loss related to both a sensorineural deficit and im-
peded conduction due to abnormalities in the bones of the
middle and inner ear; and
• Dental imperfections (small, misshapen, and blue yellow
teeth) secondary to a deficiency in dentin.
• Several different genetic defects have been shown to
interfere with the normal synthesis of type I collagen
• the most common variants are inherited as autoso-
mal dominant disorders
• Osteogenesis imperfecta can be separated into four
major clinical subtypes(types 1-4) that vary widely in
severity
• Whatever the subtype, OI is characterized by the
presence of multiple bone fractures
• In the more severe forms of the disease(type 2),
bone fragility causes multiple fractures and fetal
demise in utero or shortly after birth
Osteogenesis Imperfecta

BLUE SCLERA
 4) DISEASES ASSOCIATED WITH DEFECTS IN METABOLIC PATH-
WAYS (ENZYMES, ION CHANNELS, AND TRANSPORTERS)

Osteopetrosis
• Osteopetrosis, also known as marble bone disease and
Albers-Schönberg disease, refers to a group of rare ge-
netic diseases that are characterized by reduced bone
resorption and diffuse symmetric skeletal sclerosis due
to impaired formation or function of osteoclasts.
• Both autosomal recessive infantile and autosomal
dominant adult form have been recognized
• OSTEOPETROSIS, 4 types
• one common one has a carbonic anhydrase deficiency,
i.e., ↓ aciddecreased osteoclast resorption
4) DISEASES ASSOCIATED WITH DEFECTS IN METABOLIC PATH-
WAYS (ENZYMES, ION CHANNELS, AND TRANSPORTERS)

Osteopetrosis
• Defective osteoclastic activity in these patients
results in the deposition of abnormally thick-
ened, heavily mineralized osteoid but de-
posited bone is not remodeled and tends to
be woven in architecture result in abnormally
brittle bone and fracture easily, like a piece of
chalk..
• MORPHOLOGY
• Due to deficient osteoclast activity, bones involved by os-
teopetrosis lack a medullary canal, and the ends of long bones
are bulbous (Erlenmeyer flask deformity) and misshapen (Fig.
26-7).
• Bones are very dense. Bones tend to fracture easily. (often
with a linear fx)
• The primary spongiosa, which is normally removed during
growth, persists and fills the medullary cavity, leaving no room
for the hematopoietic marrow and preventing the formation
of mature trabeculae (Fig. 26-8)..
• The neural foramina are small and compress exiting nerves.
Osteopetrosis

Note
Failure of os- unusual
teoclastosis bone
density

http://www.rad.washington.edu/mskbook/dysplasia.html
OSTEOPETROSIS
 Clinical Features.
• An autosomal dominant adult form present with mild clinical mani-
festations.
• Autosomal recessive infantile form are severe/lethal Phenotype
and usually becomes evident in utero or soon after birth.
• Fracture, anemia, pancytopenia and hydrocephaly are often seen,
resulting in postpartum mortality.
• Affected individuals who survive into their infancy have cranial
nerve defects due to compression of nerves within shrunken cranial
foramina (optic atrophy, deafness, and facial paralysis) and re-
peated, often fatal infections because of leukopenia.
• Hepatosplenomegaly caused by extramedullary hematopoiesis re-
sulting from reduced marrow space.
 ACQUIRED DISEASES OF BONE
• Many nutritional, endocrine, and systemic
disorders affect the development of the skele-
tal system.
 ACQUIRED DISEASES OF BONE

OSTEOPOROSIS
•Osteoporosis is an acquired condition characterized by re-
duction in bone mass in the presence of normal mineraliza-
tion => increased bone porosity => leading to bone fragility
and susceptibility to fractures.
•Normal decline in bone mass is slow
•Osteoporosis is accelerated bone loss
Pathogenesis
• Osteoporosis occurs when the dynamic balance between bone formation by os-
teoblasts and bone resorption by osteoclasts tilts in favor of resorption.
• This can be due to
–increased bone resorption,
–decreased bone formation, or
–Both
• In contrast to osteomalacia , mineralization of bone is normal
• Several factors may tip the scales (Fig. 20–4):
–Age-related changes.
–Physical activity.
–Genetic factors.
–Calcium nutritional state.
–Secondary causes of osteoporosis. These include prolonged glucocorticoid
therapy, which increases bone resorption and reduces bone synthesis. Cigarette
smoking and excess alcohol also can result in reduced bone mass.
Categories of osteoporosis
• 1. Localized eg. disuse osteoporosis of a limb
• 2. Generalized; involve the entire skeleton
–Primary or secondary
–PRIMARY
–Postmenopausal
–Senile
–Idiopathic
–SECONDARY
–Endocrine disorders e.g Hyperparathyroidism
– Drugs - e.g. corticosteroids
– Neoplasia--e.g. Multiple myeloma
– Gastrointestinal- e.g. Malnutrition
–
• Primary forms of osteoporosis are most common and may be asso-
ciated with aging (senile osteoporosis) or the postmenopausal
state in women.
• Normally In both men and women, beginning in the third or fourth
decade of life, bone resorption begins to outpace bone formation.
• The drop in estrogen following menopause tends to exacerbate the
loss of bone that occurs with aging, placing older women at high
risk of osteoporosis relative to men.
• The risk of osteoporosis with aging is related to the peak bone
mass earlier in life, which is influenced by genetic, nutritional, and
environmental factors.
• Bone mass peaks during young adulthood; the greater the peak
bone mass, the greater the delay in onset of osteoporosis.
• MORPHOLOGY
• The hallmark of osteoporosis is a loss of bone.
• The cortices are thinned, with dilated haversian canals, and the
trabeculae are reduced in thickness and lose their interconnec-
tions.
• Osteoclastic activity is present but is not dramatically increased,
and the mineral content of the bone tissue is normal.
• Once enough bone is lost, susceptibility to fractures increases.
• Loss of bone is more rapid in trabecular bone than in cortical
bone as a result spine and femoral neck are common site of
fracture
Osteoporosis-disease characterized
by low bone mass & structural dete-
rioration of bone tissue

normal bone osteoporotic bone

OSTEOPOROSIS
Osteoporosis
Osteoporosis
 Clinical Course.
• More common in females than males and white than blacks
• The clinical manifestations of osteoporosis depend on which bones
are involved.
• Vertebral fragility fractures that frequently occur in the thoracic and
lumbar regions are painful, and, when multiple, can cause signifi-
cant loss of height(most common) and various deformities, including
lumbar lordosis and kyphoscoliosis or 'dowager's hump') due to
wedge fractures of the vertebral bodies which can compromise res-
piratory function.
• Pulmonary embolism and pneumonia are common complications of
fractures of the femoral neck, pelvis, or spine and result in as many
as 50,000 deaths annually.
 MRI of Spine

compression
fractures due
to osteoporosis
that results in
kyphosis

http://www-medlib.med.utah.edu/WebPath/BONEHTML/BONEIDX.htm
Compressed fracture of vertebral
column
 Compression Fx.
Collapse of vertebra

What’s left of vertebral body

http://www-medlib.med.utah.edu/WebPath/BONEHTML/BONEIDX.html
 Herniated disk com-
pressing spinal cord.

http://www-medlib.med.utah.edu/WebPath/BONEHTML/BONEIDX.html
 OSTEOPOROSIS
• The two main biochemical markers for bone
formation are
• serum alkaline phosphatase and serum os-
teocalcin.
• Markers for bone resorbtion include urinary
calcium and urinary hydroxyproline
 OSTEOPOROSIS
Prevention Strategies
• The best long-term approach to osteoporosis is pre-
vention.
• children and young adults, particularly women, with
a good diet (with enough calcium and vitamin D) and
get plenty of exercise, will build up and maintain
bone mass. Exercise places stress on bones that
builds up bone mass.
• This will provide a good reserve against bone loss
later in life.
• Summary of major complications of osteo-
porosis are:
–fracture
–bone pain (usually due to compression fracture)
–skeletal deformity
• Osteoporosis prevention and treatment begin
with adequate dietary calcium intake, vitamin
D supplementation, and a regular exercise reg-
imen—starting before the age of 30—to max-
imize the peak bone mass.
 ACQUIRED DISEASES OF BONE
Paget disease (Osteitis deformans)
•Paget’s is an osteitis deformans of unknown cause characterized by
excessive and abnormal bone remodelling.
•Skeletal disease characterized by repititive episodes of regional, un-
controlled osteoclastic activity and bone resorption (osteolytic
stage), followed by exuberant bone formation (mixed osteoclastic-os-
teoblastic stage), and finally by an apparent exhaustion of cellular ac-
tivity (osteosclerotic stage). The net effect of this process is a gain in
bone mass; however, the newly formed bone is disordered and weak,
so bones may become enlarged and misshapen.
•Paget disease uncommon before 40yrs, but its incidence increases
steadily after that time.
Paramyxovirus

IL1 and IL-6

 ACQUIRED DISEASES OF BONE
Paget disease (Osteitis deformans)
•There are three phases in the development of
Paget disease
–1) Increased osteoclast resorption
–2) Increased “hectic” bone formation (osteoblasts)
–3) Osteosclerosis
•Although any bone may be affected, the spine,
skull, and pelvic bones are especially common sites
of involvement
 Stage 1

Diagramatic representation
of Paget Disease showing Stage 2
The three phases in the
Evolution of the disease

Stage 3
 Paget’s Disease

Note hazy ap-

pearance of
cranium

http://www.amershamhealth.com/medcyclopaedia/Volume%20III%201/Pagets%20disease.asp
PAGET’s DISEASE
Because the bone formation occurs in an erratic pat-
tern, areas of new bone are juxtaposed in a random
pathognomonic mosaic pattern, giving the appear-
ance of a jigsaw puzzle
 Paget disease of the bone

Under polarized light

well organized (normal) irregularities of the bony lamellae (paget)
PAGET’S DISEASE - MICROSCOPY
Clinical features
• Usually asymptomatic
• The clinical findings depend on the extent and site of
the disease.
• Paget disease is monostotic (solitary lesion) in about
15% and remainder polyostotic (multifocal)
• Although any bone may be affected, the spine, skull,
and pelvic bones are especially common sites of in-
volvement
• Back pain (microfractures)
• Transverse fractures of long bones (chalkstick frac-
ture)
Clinical features
• headache, enlargement of the head, visual disturbances, and
deafness, all caused by deformity of the bones of the skull and
impingement on cranial nerves
• Hypervascularity may cause high-output congestive heart fail-
ure
• Benign tumors – giant cell tumor
• Sarcoma (1-5% of polyostotic PD) – osteosarcoma, chon-
drosarcoma, MFH
• Most patients have mild symptoms, treated by calcitonin and
diphosphonates
Rickets and osteomalacia
• characterized by deficient mineralization of the
organic matrix of the skeleton.
• Causes include:
–dietary deficiency of vitamin D
–deficiency of vitamin D metabolites
–intestinal Malabsorption
–renal disease
• Accumulation of unmineralized bone matrix (hy-
perosteoidosis)
Rickets and osteomalacia
• Osteomalacia: in adults
• Malabsorption of calcium and phosphate from
the intestine is the commonest cause of osteoma-
lacia in adults
• bone formed during remodeling is undermineral-
ized, causes osteopenia and fractures
• characteristic pathological feature in adults with
osteomalacia is spontaneous incomplete frac-
tures
Rickets and osteomalacia
• Rickets: occur in children
• When the levels of vitamin D metabolites are low, calci-
fication cannot occur and cartilaginous proliferation
continues.
• This accounts for the enlargement of long bones and
the ribs at growth plates resulting with irregular,
broadened, cup shaped epiphyseal growth plates
around knee and wrist and costochondral swelling.
• Inadequate mineralization of bone reduces its normal
strength and allows deformities to develop.
• Diagnosis
• The characteristic clinical deformities of rickets in-
clude:
–bowing of the long bones of the leg
–pronounced swelling at the costochondral junctions
–flattening or 'bossing' of the skull
• The main symptoms are bone pain and tenderness,
and weakness of proximal limb muscles
• Serum calcium levels may be reduced and serum
alkaline phosphatase is increased
Wrist enlargment
Rib beading (rachitic rosary)
Rickets: frontal bossing
RICKETS
X-ray in rickets
 HYPERPARATHYROIDISM
• Hallmark of PTH excess is increased osteoclastic ac-
tivity with bone resorption.
• 10 or 20
• Primary hyperthyroidism
–Only 25% have bone disease,
–affects entire skeleton
–Marked hypercalcemia and hypophosphatemia
–Gross: thin bone cortices, loss of lamina dura around
teeth; rarely associated with brown tumor .
–Detected early or lately “osteitis fibrosa cystica” (Reck-
linghausen’s disease)
• secondary hyperparathyroidism
–Skeletal abnormalities with secondary hyperparathy-
roidism are typically mild
PRIMARY HYPERPARATHYROIDISM

OSTEITIS FIBROSA “BROWN” “TUMOR”

CYSTICA
“Brown tumor”
 Osteonecrosis
(Avascular bone necrosis )
• Ischemic necrosis with resultant bone infarction occurs rela-
tively frequently..
• Mechanisms contributing to bone ischemia include.
Mechanical vascular interruption ( fracture )
Corticosteroids
Thrombosis and embolism
Vessel injury ( vasculitis )
Increased intraosseus pressure
Venous hypertension
Sickle cell anaemia
Most cases of bone necrosis are due to fracture or occur after corti-
costeroid use, but in many instances the etiology is unknown.
MORPHOLOGY
Medullary infarcts – necrosis is geographic and involves the can-
cellous bone and marrow ( cortex is spared because of collateral
supply )
Subchondral infarcts – wedge shaped

←
Clinical Course
•Pts present with pain of variable intensity
•Symptoms depend on the size and location of injury.
•Subchondral infarcts initially present with pain during physical
activity that becomes more persistent with time.
•Medullary infarcts usually are silent unless large in size (as may
occur with Gaucher disease, caisson disease, or sickle cell dis-
ease).
•Medullary infarcts usually are stable, but subchondral infarcts
often collapse and may lead to severe osteoarthritis and Rare
risk of malignant transformation.
 OSTEOMYELITIS
• Inflammation of bone (osteitis) or bone marrow
space (myelitis)
• Inflammation in bone is most likely due to infection,
however, one must also consider other etiologies
such as trauma, metabolic conditions such as gout
and malignancy.
• Although any microorganism can cause osteomyeli-
tis, the most common etiologic agents are pyogenic
bacteria and Mycobacterium tuberculosis.
 PYOGENIC OSTEOMYELITIS
• Most cases of acute osteomyelitis are caused by bacteria.
• In as many as 50% of cases, no organisms can be iso-
lated.
• Routs of organism entry to the bone by one of three root:
1. Hematogenous spread: most common cause.
–In many cases arises in a previously healthy individual
–Hematogenous osteomyelitis mostly affect children, and the
preferential sites of infection are areas of rapid growth (growth
plates of long bones such as the distal femur, proximal femur,
proximal tibia, proximal humerus and distal radius).
–Interestingly, children have large caliber metaphyseal veins
where blood flows more slowly, thus, placing them at a higher
risk of thrombosis and seeding of microbes when bone tissue is
injured.
 PYOGENIC OSTEOMYELITIS
Routs of organism entry to the bone……..cont:
•2. Extension from a contiguous site of infected joint or
soft tissue : less common
•3. Direct implantation: may be associated with trauma
(compound fracture) or rarely iatrogenic implantation
of infectious material /orthopedic surgical procedures.
–Mixed bacterial infections, including anaerobes-in many
cases after bone trauma
 Pyogenic osteomyelitis
• The culprit organism in children is usually Staphylococcus aureus, followed
by Streptococcus pyogenes and Haemophilus influenzae.
• Staphylococcus aureus -the most common causative organism which pro-
duces receptors to bone matrix components
• E. coli and group B streptococci are important causes of acute osteomyeli-
tis in neonates
• In patients with sickle cell disease, Salmonella is often the causative organ-
ism and affects multiple sites.
• In debilitated adults, the most common organism is also Staphylococcus
aureus, however, gram-negative bacteria and yeasts can be a cause in IV
drug users.
• Note that whereas the knee is the most common site of infection in chil-
dren, the spine is most commonly affected in adults.
• In hospitalized patients on multiple antibiotics, Pseudomonas aeruginosa
can enter the spine and cause spinal osteomyelitis.
• In diabetics with foot ulcers, the infections are often polymicrobial.
 Pyogenic osteomyelitis
Morphology
• The morphologic changes in osteomyelitis depend on the lo-
cation and chronicity of the infection.
• The location of infection varies with age
–In infants<1yr, the existence of loose periosteal attachments and
connections between the vessels in the metaphysis and epiphysis al-
lows the infection to spread to the epiphysis and joint capsule
–Neonates may have considerable subperiosteal spread
–In children>1yr-metaphyses of long bones are typically involved,
sparing of joint.
–In adults-primarily affects vertebral bodies that remain quite vascu-
lar
 Pyogenic osteomyelitis
Morphology
• Causal bacteria proliferate, inducing an acute inflammatory
reaction, with consequent cell death.
• Initially neutrophilic inflammation with edema, fibrin, and
hemorrhage
• Within days, entrapped bone rapidly becomes necrotic with
empty lacunae ; this non-viable bone is called a sequestrum.
• In long bones, the infection spreads along medullary cavity
within shaft or through harvesian canal of the cortical bone
and may reach the periosteum, sometimes creating a subpe-
riosteal abscess.
• Neonates may have considerable subperiosteal spread
Morphology
• Subperiosteal abscesses further impair blood supply
=> which causes more necrosis and Rupture of the
periosteum can lead to abscess formation in the sur-
rounding soft tissue that may lead to a draining sinus.
Morphology
• After the first week of infection, chronic inflamma-
tory cellsl(ymphocytes and plasma cells)become
more numerous.
• Leukocyte cytokine release stimulates osteoclastic
bone resorption, fibrovascular granulation tissue in-
growth, and reactive periosteal bone formation in
the periphery.
• Reactive woven or lamellar bone created by perios-
teum which is deposited around sequestrum, it is
called an involucrum (Fig. 20–7).
• Viable organisms can persist in the sequestrum for
years after the original infection.
Morphology
• May evolve to chronic osteomyelitis:
–Established (>6weeks)
–Chronicity may develop when:
•delay in diagnosis, ineffective treatment, large area of
necrosis, weakened host defense or as a result of infections by an
indolent pathogens like TB.
–Morphologically
•Prominent Fibrosis of marrow with chronic in-
flammatory infiltrate; lymphocytes, plasma cells, and
macrophages.
•Plasma cell predominance
•Fragments of necrotic bone with multinucleated
giant cells
Morphology
• May evolve to chronic osteomyelitis:
–Morphologically ….cont
•Chronic disease is accompanied by promi-
nent Periosteal new bone deposition (involu-
crum)
•appositional deposition of new bone on
existing trabeculae can also be seen.
•The formation of sequestrum is part of the
reason chronic ostemyelitis can be refractory to
antibiotics; this necrotic bone protects bac-
terium from antibiotic penetration.
Pyogenic osteomyelitis
Prominent periosteal bone prolifera-
tion(involucrum)
A key feature of acute osteomyelitis
is necrotic bone (no viable osteocytes) sur-
rounded by a neutrophilic infiltrate.
Healed osteomyelitis
 Pyogenic osteomyelitis
Special forms/types
•Brodie abscess:
–Small intraosseous abscess in cortex, walled off by reactive
bone with no periosteal reaction
–Cavity may contain infectious organisms or be sterile
–May have late recrudescence
–Therapy: total surgical excision
•Sclerosing osteomyelitis of Garré:
–In jaw, associated with extensive new bone formation that
obscures underlying osseous structure
–Also called periostitis ossificans
• Variants of chronic osteomyelitis
–Brodie’s abscess
 Pyogenic osteomyelitis
Clinical feature
– Can present as acute, subacute or chronic
• Initially systemic manifestations such as fever, malaise, and leukocytosis
• local pain, swelling, and redness may occur in some adults.
• Diagnosis;
– X-ray ;-Lytic & sclerotic lesion(prominent periosteal reaction resembling neoplasm)
– Blood culture
– Biopsy
• It is worth mentioning that the diagnosis of acute or chronic osteomyelitis
can only be made after integrating clinical, radiographic and histologic
data.
• The terms acute, subacute and chronic osteomyelitis refer to the duration
of the disease and not the composition of the inflammatory infiltrate.
• Neutrophils, lymphocytes and plasma cells in varying proportions can be
seen in both acute and chronic osteomyelitis.
 Pyogenic osteomyelitis
Treatment
• combination of Antibiotics of adequate coverage and suffi-
cient duration and Surgical removal of the infected se-
questrum is usually curative. but up to a quarter of cases do
not resolve and persist as chronic infections.
• If treated inadequately with antibiotics, it may continue for
many years with recurrent episodes of local infection, which
may be accompanied by sinus tract formation connecting
bone to the overlying cutaneous surface .
• These tracts are lined by squamous epithelium and may
progress into squamous cell carcinoma, although this long-
term complication is quite rare.
 Pyogenic osteomyelitis
• Chronic osteomyelitis may be complicated by:
–Pathologic fracture.
–Secondary amyloidosis
–Endocarditis
–Sepsis
–acute bacterial arthritis
–Squamous cell carcinoma from draining sinus tract.
•Approximately 1% of patients develop squamous cell carci-
noma, and it may be as long as 40 years after the original infection
–Rarely sarcoma in the affected bone
 Tuberculous Osteomyelitis
• Bone infection complicates an estimated 1% to 3% of cases
of pulmonary tuberculosis.
• The organisms usually reach the bone through the blood-
stream(Hematogenously born)
• Rarely direct extension from a contiguous focus of infection
(eg. From the lung to the ribs or mediatinal nodes to the verte-
brae)
• With hematogenous spread, long bones and vertebrae are fa-
vored sites.
• The spine ( esp. thoracic and lumbar ) is the most common site;
followed by the knees and hips
• More destructive and resistant to control than Pyogenic cases
• Bone infection is usually solitary but can be multiple/multifocal
in HIV/AIDS
 Tuberculous Osteomyelitis
• Because the tubercle bacillus is microaerophilic, the synovium,
with its higher oxygen pressures, is a common site of initial in-
fection. The infection then extends/spreads to the adjacent
epiphysis, where it elicits typical granulomatous inflammation
with caseous necrosis and extensive bone destruction.
• Tuberculosis of the vertebral bodies is a clinically serious form of
osteomyelitis. Infection extends through intervertebral discs to
involve multiple vertebrae and may produce vertebral deformity,
collapse, and posterior displacement (Pott disease), leading to
neurologic deficits.
• The infection breaks through the invertebral discs and extends
into the adjacent soft tissues with the development of psoas
muscle abscesses is fairly common.
• Sequestration and the formation of an involucrum are uncom-
mon.
POTT’s DISEASE
 Tuberculous Osteomyelitis
Clinical feature and complications
Pain on motion
Swelling
Symptom complex of tuberculosis
Bone destruction.
Vertebral deformities
May form an inguinal mass ‘which represents a cold fluctuant
psoas abscess.
Tuberculous arthritis.
sinus tract formation
amyloidosis
 Clinical features and complications:
• Pain
• Fever weight loss
• May form an inguinal mass ‘which represents
a cold fluctuant psoas abscess.
• Tuberculous arthritis.
• sinus tract formation
• amyloidosis
 SYPHILITIC OSTEOMYELITIS
• Bone involvement more common in congenital syphilis; appears
at 5th month of gestation in areas of active endochondral ossifi-
cation (osteochondritis) and periostitis
• Acquired syphilis involves bone in 3 0 phase, usually nose, palate,
skull, tibia, vertebrae, hands/feet
• Saddle nose deformity is a condition associated with syphilis and
also other disease; It is characterized by a loss of height of the
nose, because of the collapse of the bridge
• Spirochetes can demonstrated in the inflammatory tissue with
special silver stains
• Gummata also occur in the bone lesions
• Edematous granulation tissue containing numerous plasma cells
and necrotic bone
Bone tumors and tumor-like lesions
 BONE TUMORS
• Secondary is more common than primary bone tumor
• Primary neoplasms of the skeleton are rare, amounting
to only 0.2% of the overall human tumour burden; most
primary are benign
• However, children are frequently affected and the aeti-
ology is largely unknown
• Bone tumors may result in amputation
• Disfigurement and great physical challenge
 Diagnosis of BONE TUMORS
• Clinical symptoms are usually not helpful in making a diagnosis
• Important to be aware of:
• 1. patient age
–May be the most important clinical clue:
–primary osteosarcoma and Ewing Sarcoma are tumors of children and young
adults.
–After 40 – bone metastases , Multiple myeloma and chondrosarcoma are most
common.
• 2. Location of tumor
–area of bone involved (epiphysis, metaphysis, diaphysis; cortex, medulla or pe-
riosteum).
• 3. Radiological appearance
–X-rays are important to define the tumor’s location & aggressiveness, and
are necessary to diagnose low grade cartilaginous tumors and see next
page
• 4. Histological features.
RADIOLOGICAL EXAMINATION SHOULD ANSWER THE FOLLOW-
ING QUESTIONS:

• The exact location of the lesion

• Evidence of any underlying bone abnormality(bone
infarct,Paget’s disease
• Is the lesion multifocal?
• Does the tumor have a well defined margin?The rim of scle-
rotic bone?(signs of benign lesions).
• Is there evidence of cortical destruction or expansion?(signs
of aggressive behavior).
• Does the tumor produce mineralized matrix(osteoid or carti-
lage)?
• Is there a soft tissue mass?
 Bone tumors
• Classification: tissue of origin or distinct clinico-pathologi-
cal features
• Bone tumors are classified as:
–Benign or malignant (sarcoma)
–Primary bone tumors or Secondary bone tu-
mors
Most Primary bone tumors are classified accord-
ing to the normal cell of origin and apparent pattern of
differentiation
• Secondary tumors can be further subdivided into:
–Metastatic tumors
–Tumors resulting from contiguous spread of adjacent soft tis-
sue neoplasms
–Tumors representing malignant transformation of the pre-ex-
 Metastatic bone cancers
• Are the most frequent malignant tumors found in bone.
• They are by far more common than primary bone tumors and are
characterized by the following:
• Predominant occurrence in two age groups: adults over 40 years of
age and children in the first decade of life.
• Most are predilection for the hematopoietic marrow sites in the ax-
ial skeleton (vertebrae, pelvis, ribs and cranium) and proximal long
bones.
• Metastases to long bones distal to the elbows and knees are un-
usual. Metastases to the small bones of the hands and feet are even
rarer.
• Typically Multifocal
• Occasionally, metastases may appear as solitary lesions (particularly
true for the kidney and thyroid cancer).
 METASTATIC BONE TUMORS
• Pathways of spread include (1) direct extension, (2)
lymphatic or hematogenous dissemination, and (3)
intraspinal seeding.
• MOST COMMON MALIGNANCIES,PRODUCING BONE
METASTASES are:
• ADULTS:-- More than 75% of skeletal metastases orig-
inate from Cancer of the prostate, breast, kidney and
lung. Others are thyroid, colon and melanoma!
• IN CHILDREN- neuroblastoma,, retinoblastoma, Ew-
ing sarcoma and rhabdomyosarcoma. And also
Wilms tumor, osteosarcoma
 RADIOGRAPHIC APPEARANCE OF
METASTATIC TUMORS
• X-ray finding– purely lytic, purely blastic or mixed
• → Kidney, lung, GI, and melanoma – lytic lesions
• → Prostatic adenocarcinoma – blastic lesions
• -> Most metastases induce a mixed lytic and blastic
reaction.
 Bone metastases of spine & pelvis
dark spots indicate osteolytic lesions (destroy bone)
http://www-medlib.med.utah.edu/WebPath/BONEHTML/BONEIDX.html
 MRI scan of spine
demonstrates
metastatic lesion
destroying C7

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Ill-defined lytic lesion in
midshaft of fibula pro-
duced by metastasis of
lung carcinoma
Renal cell carcinoma of clear cell type metastatic to bone. Notice the marked
fresh hemorrhage that is a characteristic feature of this tumor.
 PRIMARY BONE TUMORS
• Primary neoplasms of the skeleton are rare.
• More common in first 3 decades of life (skeletal growth activity) and the ae-
tiology is largely unknown.
• The commonest sites for both benign and malignant – distal femur and prox-
imal tibia – the bones with the highest growth rate
• Relatively specific radiologic presentation
• Benign tumors are by far more common than malignant
• The most common benign tumors are osteochondroma, non-ossifying fi-
broma, and enchondroma.
• Among primary malignant neoplasms, osteosarcoma and multiple myeloma
have the highest incidence, followed by chondrosarcoma and Ewing's sar-
coma.
• Some primary bone tumors are difficult to classify as benign or malignant.
For example, giant cell tumor of bone is very aggressive locally but only
rarely metastasizes.
 Bone tumors: cause
• Although the cause of most bone tumors is unknown.
• Risk factors:-
• Bone infarcts
• Pagets disease
• Radiation
• Chronic osteomyelitis
• Fibrous dysplasia and metal prostheses are also associated
with increased incidence of bone neoplasia
• Hereditary
– e.g. Bone osteosarcomas in the li-fraumeni and heredi-
tary retinoblastoma which are linked to mutations in p53
and rb genes.
–Several bone tumours occur in the setting of inherited
tumour syndromes, but their histology differs little from
the respective sporadic counterparts.
 Two important features of bone
tumors:
• The ability of some to dedifferentiate (eg., en-
chondroma or a low-grade chondrosarcoma
transforming into a high-grade sarcoma)
• Tendency of high-grade sarcomas to arise in
damaged bone, at the sites of bone infarcts,
radiation osteitis and Paget's disease.
 Primary Bone tumors
Can be:
•Bone-forming tumors
•Cartilage-forming tumors
•Fibrous tumors
•Hematopoietic tumors
•Miscellaneous tumors
Bone-Forming Tumors
• characterized by the production of osteoid by
the tumor cells
• Benign
•osteoma
•Osteoid Osteoma
•Osteoblastoma
• Malignant
•Osteogenic sarcoma
Osteoma
• Rare; slow growing BENIGN tumor of skull & facial
bones
• 40-50 years, 2/3 male, usually solitary
• Multiple in Gardner syndrome
• May obstruct sinus cavity, impinge on brain/eye, inter-
fere with oral cavity function, cause cosmetic problems.
Doesn’t transform in to osteosarcoma
• Gross: well circumscribed, bossilated round/oval sessile
tumor which projects from subperiosteal or endosteal
surfaces of cortex
• Micro: dense, mature, predominantly lamellar bone
rimmed by osteoblasts
Osteoma :formed of bone
 Osteoid osteoma and Osteoblastoma
• Identical histology but different size ,site and symp-
toms
 Osteoid osteoma and Osteoblastoma
Morphology
• Diaphysis is common sites of involvement
• On gross inspection, both lesions are round-to-oval masses of
gritty-appearing tan hemorrhagic tissue.
• A rim of reactive sclerotic bone is present at the edge of both
types of tumors; however, it is much more conspicuous in osteoid
osteomas leaving the tumor as a central nidus.
• On microscopic examination, both neoplasms are composed of
Well circumscribed interlacing trabeculae of woven bone lined by
osteoblasts (Fig. 20–8). The intervening stroma is loose, well vas-
cularized connective tissue containing variable numbers of giant
cells.
Osteoid osteoma

NIDUS
 Osteoid osteoma
Central hemorrhagic nidus
surrounded by dense rim of
sclerotic bone
 OSTEOID OSTEOMA AND OSTEOBLASTOMA
TREATMENT AND PROGNOSIS

• Both are treated by conservative surgery

• Incomplete excision – may recur
• Malignant transformation is very rare,usually after ir-
radiation
• Prognosis is good
 Osteosarcoma (osteogenic sarcoma)
• A malignant mesenchymal tumor in which the neoplastic cells produce bone ma-
trix(ostoid)
• osteosarcoma is the most common primary malignant tumor of bone(after
myeloma and lymphoma); accounting for approximately 20% of primary bone can-
cers.
• Osteosarcomas occur in all age groups, but about
• 75% of patients are younger than 20 years of age(Primary osteosarcoma ).
• M>F
• Primary osteosarcoma mostly arise in the metaphyseal regions of long bones
• 60% occur around the knee(Common sites are distal end of femur or proximal
tibia); 15% around the hip, 10% at the shoulder, and 8% in the jaw.
• second peak occurring in elderly persons(secondary osteosarcoms); usually in as-
sociation with other conditions, including Paget disease, bone infarcts, and/or prior
irradiation, fibrous dyplasia and benign tumors .
• After the age of 25,the incidence in flat bones and long bones is almost
equal.
 Pathogenesis;
• Mutations are very important in development of OSa
• In particular, RB gene mutations occur in 60% to 70% of
sporadic tumors, and persons with hereditary retinoblastomas
(due to germline mutations in the RB gene) have a thousand-
fold greater risk for development of osteosarcoma. .
• Mutations in p53 gene in spontaneous OSA.
• Many osteosarco -mas develop at sites of greatest bone
growth, perhaps because rapidly dividing cells provide a
fertile soil for mutations.
 CLASSIFICATION OF OSTEOSARCOMA
• According to anatomic origin: --
–intramedullary, intracortical, surface
• No. of involved sites
–Solitary, multiple
• Degree of defferentiation/Grade of malignancy
–low and high grade
• Presence of underlying disease
–Primary or secondary
• Histologic variants:
–osteoblastic,chondroblastic,fibroblastic,telangioectatic etc.
• The most common type of osteosarcoma is primary, soli-
tary, intramedullary, and poorly differentiated, osteoblastic
producing a predominantly bony matrix and which arises in
metaphysis of the long bones in young patients
• Radiographs
Imaging
–characteristic mixed destructive and blastic lesion
•sun-burst or hair on end pattern of matrix mineralization due to
the tumor spicules of calcified/mineralized bone radiating in right angles
–periosteal reaction (Codman's triangle)
•The tumor often elevates the periosteum to produce the so-called
Codman triangle on radiographs
–large soft tissue mass with maintenance of bone cortices
• CT
–chest CT is required at presentation to evaluate for pulmonary
metastases
• Labs
–Elevated alkaline phosphatase
–may be 2-3 times normal value
• The tumor often elevates the periosteum to produce
the so-called Codman triangle on radiographs
Morphology
• Grossly,
–osteosarcomas are bulky tumors that are gritty, gray white, and often
contain areas of hemorrhage & cystic degeneration.
–The tumors frequently destroy the surrounding cortices and produce
soft tissue masses
–Is potentially infiltrating extending in all directions
• Microscopy–
–the hallmark of osteosarcoma is the formation of osteoid by malignant
mesenchymal cells!
–Histologically mesenchymal cells can have a range of morphologies
such as spindle cells, epithelioid, plasmacytoid, fusiform, ovoid, small
round, clear and multinucleated.
–Conventional OS: osteoblastic, chondroblastic and fibroblastic,
–Variants: telangiectatic, small cell and giant cell rich variants.
 Osteosarcoma (osteogenic sarcoma)
Clinical Features
•Osteosarcomas typically manifest as painful enlarging masses,
although a pathologic fracture can be the first sign.
•Conventional osteosarcomas are aggressive lesions that metas-
tasize through the bloodstream early in their course
•The lungs are common sites of metastases.
•Despite aggressive behavior, standard treatment with chemo-
therapy and limb salvage therapy currently yields long-term sur-
vivals of 60% to 70%.
•Like primary osteosarcomas, secondary osteosarcomas are
highly aggressive tumors, but they do not respond well to ther-
apy and are usually fatal.
 Cartilage-Forming Tumors
• Cartilage-forming tumors produce hyaline or myxoid carti-
lage; fibrocartilage and elastic cartilage are rare com-
ponents.
• Like the bone-forming tumors, cartilaginous tumors con-
stitute a spectrum from benign, self-limited growths to
highly aggressive malignancies; again, benign cartilage
tumors are much more common than malignant ones.
• Only the more common types are discussed here.
Cartilaginous Tumors
• Benign:
•Osteochondroma
•Chondroma and enchondroma
•Chondroblastoma
•Chondromyxoid Fibroma
• Malignant:
•Chondrosarcoma
Osteochondroma ( Exotosis)
• benign proliferations composed of mature bone and
a cartilaginous cap
• Account for about one third of all benign tumors of
the bone
• May occur in any bone; usually metaphysis of long
bones (lower end of femur, upper end of humerus
and upper end of tibia are most frequent)
• In children
• <1% risk of sarcomatous transformation
 Morphology

•Osteochondromas are mushroom shaped and range in size from 1 to 20 cm.

•The outer layer of the head of the osteochondroma is composed of benign
hyaline cartilaginouus cap varying in thickness(usually less than 2 cm)
•Newly formed bone forms the inner portion of the head and stalk, with the
stalk cortex merging with the cortex of the host bone and central region
merging with medullary cavity of the host bone
Chondroma ( enchondroma)
• Benign tumor of mature hyaline cartilage
• Develop from the rests of cells of the growth plate
cartilage and/or genetic alterations in mesenchymal
stem cells.
• Most arise within medulla of bone (enchondroma);
few on the bone surface, they are called juxtacortical
chondromas.
• Most common intraosseus tumors occurring in pa-
tients aged between 20 and 50yrs.
Types:
• Solitary Enchondroma
–Usually solitary involving the metaphyseal region
of tubular bones especially short bones of hand and
feet.
• Multiple Enchondromas
–Ollier's Disease: multiple encochondromas pref-
erentially involving one side of the body
–Maffucci Syndrome (multiple chondromas asso-
ciated with soft tissue spindle cell hemangiomas)
 Composed of mature lobules of
hyaline cartilage with foci of myx-
oid degeneration, calcification
and endochondral ossification;
may be quite cellular
Clinical course
•Most are asymptomatic but can be painful or patholog-
ical fractures may occur
•Deformities are common in multiple cases
•Growth potential is limited and most remain stable
•Incomplete resection results in recurrence
•Rare sarcomatous change is seen
Chondrosarcoma
• Second most common malignant matrix(cartilage)
producing tumor
• Patients are usually ≥40years of age.
• M:F=2:1
• Significant cases occur in association with a pre-exist-
ing enchondroma and few develop in cases of Osteo-
chondroma, chondroblastoma, fibrous dysplasia or
Paget disease.
• Patients present with painful progressively en-
larging masses
• They arise in central portions of the skeleton;
common sites of origin include the shoulder
area, pelvis, proximal femur, and ribs
• Anatomy/Site-
–Intramedullary and Juxtacortical
• Histologic types-
–Conventional (hyaline or myxoid ).
–Clear cell.
–Dedifferentiated, and
–Mesenchymal variants
• Microscopically, nodular pattern is seen and malignant features
depend on grade of tumor
• 3 grades- depending on the cellularity , nuclear atypia and mi-
tosis
• There is direct correlation between the grade and biologic be-
havior of the tumor
• Five-year survival for grade I – 90%; grade II – 81%; grade III –
43%
• Most conventional chondrosarcomas are grade I-II and have rel-
atively indolent course
• Tumor’s size is also significant prognostic feature – tumors
>10cm behave more agressively, than those <10cm
• Metastases show predilection for lungs and skeleton
GRADE I GRADE II GRADE III
Ill-defined margins;
fusiform thickening of
shaft; perforation of
cortex
Other Tumors of Bone
Giant cell tumor of bone (osteoclastoma)
• GCT is a relatively common benign but locally aggres-
sive bone tumor,
• usually arising in persons in their 20s to 40s.
• F>M
• Most common primary epiphyseal tumor of adults
• 50% around knee with most in distal femur
• Monocyte-macrophage lineage
MORPHOLOGY
• Gross-tumors are large & red brown masses that fre-
quently undergo cystic degeneration
• Microscopy- two components
→ mononuclear cells – proliferating cells with oval
nuclei and indistinct membrane
• → Osteoclast like giant cells uniformly distributed
( similar nuclei of the mononuclear cells )
• Necrosis, hemorrhage, hemosiderin deposition & re-
active bone formation can be seen
Giant Cell Tumor
Gross

Fig. 10 Curetted fragments from GCT lesion

are soft and friable, color varies from gray-
brown to reddish with some yellow.
 Giant Cell Tumor
Microscopic

Histologically, giant cell tumors of bone as seen here on right are com-
posed of osteoclast-like multinucleated giant cells in a sea of round to
oval mononuclear stromal cells. There may also be foamy
macrophages and hemosiderin deposition in the stroma. Though these
tumors are biologically benign, they can expand and cause pain, de-
formity, or fracture. They are treated by curettage or resection, but
when radiated, they may undergo malignant transformation.
 Clinical course
• Majority of GCT arise in the epiphysis and Involve the
metaphysis in adults and, the metaphysis in adoles-
cents.
• Arthritic symptoms ,pathological fracture
• Most are solitary
• Unpredictable biologic behavior
• Recurrence is common after local curettage
• 2% spread to the lungs as localized lesions that are
cured by local excision.
• Rare sarcomatous transformation
 Miscellaneous Bone Tumors
Ewing’s family of tumors
• Primary malignant small round cell tumors of bone and
soft tissue.
• Highly aggressive neoplasm that must be differentiated
from other pediatric tumors composed of "small blue
cells’’
• Two groups of Ewing’s family of tumors are identified dif-
fer in their degree of neural differentiation.
• Neural differentiation  PNET
• Undifferentiated  EWING SARCOMA
• Both arise from the medullary cavity and invade the cor-
tex & periosteum => to produce soft tissue masses
• Ewing sarcoma accounts for 6% to 10% of primary
malignant bone tumors.
• Ewing sarcoma is second to osteosarcoma in children
• Ewing sarcoma has the youngest age affection of ma-
lignant tumors (b/n 10 & 15yrs)
• The femur, tibia, and pelvis are favored sites of origin
• Usually arise in the diaphysis
• Radiologic finding
• X-ray shows lytic lesions with permeation in to
soft tissue.
• There is a characteristic periosteal reaction
with deposition of bone in an onion-skin pat-
tern.
Morphology
•Grossly tumors are tan white with areas of hemor-
rhage and necrosis
•Microscopically, sheets of small round cells that are
slightly larger than lymphocytes with scanty clear cyto-
plasm ( glycogen rich )
•Rosettes ( Homer-wright rosettes )  neural differen-
tiation
•Stroma is scanty but fibrous septa is seen
•Few mitotic figures are seen
The tan-white tumor fills most of the medullary cavity of the meta-
physis and proximal diaphysis. It has infiltrated through the cortex,
lifted the periosteum, and formed soft tissue masses on both sides
of the bone.
Clinical feature
• Painful enlarging mass the site is tender, warm and
swollen.
• Systemic symptoms may be seen suggestive of infec-
tion
• Treatment is chemotherapy and surgical excision
with or without radiotherapy
• 5yr survival reaches up to 75%
Fibrous dysplasia
• A benign lesion likened to a localized developmental
arrest ( failed maturation )
• Can be monostotic(70%) or polyostotic
• Can be seen in association with endocrinopathies
• Long bones , jaw bones and vertebra are affected
• seen mostly in early adolescence and growth stops
when the growth plate closes.
Morphology
• Gross & microscopy-lesions are well circumscribed ,
intramedullary and vary greatly in size
• They are tan white, gritty and composed of curvilin-
ear trabeculae of woven bone forming “Chinese let-
ters” with surrounding fibroblastic proliferation(no
osteoblastic rimming)
• Cystic degeneration, hemorrhage and foamy
macrophages are common
Clinical course
• Asymptomatic
• Recurrent fractures, severe swellings and disfigure-
ments can occur
• Treatment is conservative surgery
• Rare malignant transformation ( esp. in those that
are irradiated)
Diseases of the Joints
SYNOVIAL JOINTS
 Diseases of the Joints

• The joints are subject to a wide variety of disorders,

including
• degeneration,
• immune-mediated injury,
• metabolic derangements,
• Infections and
• neoplasms
 DEGENERATIVE JOINT DISEASE (OSTEOARTHRI-
TIS)
• is the most common disorder of the joints.
• fundamental feature -Progressive erosion of articular cartilage and
structural changes in the underlying subchondral bone with os-
teosclerosis.
• Intrinsic disorder of articular cartilage ( biochemical & metabolic al-
terations) => breakdown.
• Primary osteoarthritis due to aging process and without apparent ini-
tiating cause (most cases ).
• In such cases the disease usually is oligoarticular (i.e., affecting only a
few joints).
• Usually age 50+ years (present in 80% at age 65 years)
• Sites: Wt. bearing joints – hips (men), knees & hands (women), ver-
tebrae
 DEGENERATIVE JOINT DISEASE (OSTEOARTHRI-
TIS)
• Secondary osteoarthritis-usually in younger pa-
tients with predisposing condition(previous
trauma, congenitally deformed joints, or in some
metabolic disorders (obesity, diabetes, ochrono-
sis, hemochromatosis), such as knees of basket-
ball players and often involves one or several
predisposed joints.
Pathogenesis
• Articular cartilage : major target
• Normally balanced articular cartilage degradation
and replacement
• Cartilage degradation may be mediated by IL-1, TNF
& NO
• Attempts to repair by deep chondrocytes
• In osteoarthritis, this process is disturbed by a variety
of influences
• the most important of these influences are aging and
mechanical effects
• characterized by significant changes in both the
composition and the mechanical properties of carti-
lage; Early changes include , increased water and de-
creased proteoglycans=> reduce tensile strength &
the resilience of the articular cartilage
Morphology
• fibrillation (splitting) at the articular surface
• Erosion of the articular cartilage
• Thickened Subchondral bone with osteosclerosis
• Fragments of cartilage and bone are often dislodged to
form free-floating "joint mice“
• The fracture gaps allow synovial fluid to be forced into
the subchondral regions to form fibrous walled cysts.
• bone proliferation occurs at the margins of the joints to
produce bony excrescences, termed osteophytes
Femoral head
 Normal femoral
head removed after
fracture.

Note smooth articu-

lar cartilage.

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http://www-medlib.med.utah.edu/WebPath/BONEHTML/BONEIDX.html

Arthritic femoral
head removed due to
disease.

Note rough articular

surface.
 Osteoarthritis
(proximal femur)

Note rough, irregular surface on

femoral head and greater
trochanter.

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 Osteoarthritis
anterior/superior
patella & posterior
tibia

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OSTEOARTHRITIS
Cracking and fibrillation of cartilage
 Osteoarthritis of
vertebral column

Osteophytes

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Mic: osteoarthritis
 Osteoarthritis
Clinical courses
• Osteoarthritis is an insidious disease, predominantly affecting
patients beginning in their 50s and 60s.
• the hips, knees, lower lumbar and cervical vertebrae, proximal
and distal interphalangeal joints of the fingers commonly in-
volved
• Asymptomatic or common complaints include joint stiffness
and deep, aching pain, particularly in the morning which exac-
erbated by use, crepitus (grating or popping sensation in the
joint), and limitation in range of movement.
• Some degree of joint swelling is common, and small effusions
may develop.
 Osteoarthritis
• Osteophyte impingement on spinal foramina
can cause nerve root compression with radicu-
lar pain, muscle spasms, muscle atrophy, and
neurologic deficits
• Characteristic in women, but not in men, are
Heberden nodes in the fingers, representing
prominent osteophytes at the distal interpha-
langeal joints.
Heberden nodes- in
females,not in males
Prominent osteophytes
 Rheumatoid arthritis
• Rheumatoid arthritis (RA) is a chronic systemic in-
flammatory disorder affecting synovial lining of joints,
bursae and tendon sheaths; also skin, blood vessels,
heart, lungs ,muscles..
• principally attacks the joints;- producing a nonsuppurative
proliferative and inflammatory synovitis that often pro-
gresses to destruction of the articular cartilage and anky-
losis of the joints.
• F:M (3:1), 40-70yrs
• Sites: small bones of hand and feet affected first (MCP, PIP
joints of hands and feet) then wrist, elbow, knee
 Etiology and Pathogenesis:
• Etiology :
• Genetic Susceptibility:
–HLA DR4, or DR1 in 65% to 80% cases.
• Microbial inciting agent:
–Epstein-Barr virus, Borrelia & Mycoplasma..?
• Autoimmunity:
–Triggered by exposure of genetically susceptible host to
arthitogenic microbial antigen
–Autoimmune reaction then occurs with:
• Activated CD4+ T – helper cells & B – lymphocytes
 Pathophysiology:
• CD4+ T – helper cells against type II collagen & cartilage:
stimulate other cells in joint(macrophages & synovial
cells) to release cytokines esp.TNF & IL -1 => stimulate
synovial cells to releases various mediators of inflamma-
tion;protease, PG, osteoclasts.
• B – lymphocytes : immune complex deposition
• Circulating immune complexes deposit in cartilage, acti-
vate complement, cause cartilage damage=> destroy
joints
• 80% have IgM autoantibodies to Fc portion of IgG
(Rheumatoid factor)
 Morphology
Joints : On histologic examination, the affected joints show
chronic papillary synovitis, characterized by:
• 1,Synovitis-Infiltration of synovium by dense inflammatory
infiltrates (plasma cells , lymphocytes , macrophages)
• 2,Increased vascularity in synovium
• 3,Aggregates of fibrin on synovium and floating in joint
space as rice bodies
• 4,Accumulation of neutrophilsin the synovial fluid but not
deep in the stroma
• 5,Osteoclastic activity in underlying bone => allows syn-
ovium to penetrate in to the bone => juxta articular ero-
sions, osteoporosis and Subchondral cysts,
• 6. Pannus formation-a mass of synovium and synovial
stroma consisting of inflammatory cells , granulation
tissue,& fibroblasts growing over articular cartilage
and eroding it
• After cartilage destruction it bridges the apposing
bones forming fibrous ankylosis => ossifies bony
ankylosis
• Other changes frequently occur around the joint.
–Atrophy of muscles
–Muscle spasms caused by inflammation and pain
–Bone alignment shifts
–Contractures and deformity develop.
7/24/2014 233
7/24/2014 235
7/24/2014 236
Pannus destorying the articular
cartilage
• Skin-rheumatoid nodules(25%)
–Regions subjected to pressure: ulnar aspect of
forearm, elbow, occiput, lumbosacral area
–Gross: Firm, non tender, round to oval in SubCu-
taneous tissue
–Microscopy: Central fibrinoid necrosis sur-
rounded by epitheloid granuloma
• Blood vessels-
–obliterative endarteritis…..peripheral neuropa-
thy ,ulcers and gangrene
7/24/2014 239
Rheumatoid nodules at pressure points
of elbows
7/24/2014 241
Clinical course
• Variable
• Insidious onset ; malaise, fatigue, musculoskeletal
pain, then joint involvement;
• 10% have acute onset of severe symptoms, but usu-
ally joint involvement occurs over months to years;
50% have spinal involvement
• Generally small joints are involved before the larger
ones; the hip joints involved late, if at all.
• The lumbosacral region is typically spared
• Fusiform hot swollen joints, morning stiffness
improves with activity.
• Symmetrical involvement of joints
• Narrowing of joint space; destruction of ten-
dons, ligaments and joint capsules produce
radial deviation of wrist, ulnar deviation of dig-
its, swan neck finger abnormalities
• Baker cysts : synovial cyst in the popliteal fossa
Acute rheumatoid arthritis
Chronic rheumatoid arthritis
 Chronic rheumatoid arthritis

7/24/2014 246
 Rheumatoid arthritis
• X-ray: joint effusions, juxta-articular osteopenia, erosions and
narrowing of joint space
 Rheumatoid Arthritis
• Diagnosis is based on:
A. Clinical findings, :
–Morning stiffness; mean age 45 yrs .
–Arthritis in 3 or more joint areas.
–Arthritis of small hand joints.
–Symmetric arthritis.
–Rheumatoid nodules .
B. Laboratory testing.
–Serum rheumatoid factor . Rheumatoid factor positive in
80% of RA
C. Typical radiographic changes
• At least four of above features needed for diagnosis
7/24/2014 249
 JUVENILE RHEUMATOID ARTHRITIS
• Common connective tissue disease occurs in children
younger than 16 years of age
• More common in girls
• Compared to classic rheumatoid arthritis, oligoarthri-
tis, systemic and large joints are involved
• Sites: knees, wrists, elbows, ankles
• Rheumatoid nodules & rheumatoid factors are ab-
sent, but often positive ANA
• Associated with HLA-DRB1, infections by mycobacte-
ria, bacteria, viruses
Gout and gouty arthritis
• Gout affects about 1% of the population, and shows a
predeliction for males.
• It is caused by excessive amounts of uric acid within tis-
sues and body fluids.
• Monosodium urate crystals precipitate from supersatu-
rated body fluids and deposited in joints ,soft tissue
around joints and skin; induce an acute inflammatory
reaction.
• Gout is marked by recurrent episodes of acute arthritis,
sometimes accompanied by the formation of large
crystalline aggregates called tophi, and eventual per-
manent joint deformity.
Pathogenesis of hyperuricemia
• uric acid is the end product of the catabolism of
purines derived either from diet or synthesized den-
ovo
• uric acid is eliminated from the body mostly through
urine
• Hyperuricemia can result from overproduction of uric
acid, decreased urinary excretion or a combination of
both
• 10% of population has hyperuricemia (>7 mg/dl), ex-
ceeds blood saturation at normal body temperature ,
but only 1/20 of these has gout
• Hyperuricemia is a sine qua non , but not a sole determi-
nant of gout
• Factors which favor the development of gout from
asymptomatic hyperuricemia
–Age of the individual and duration of the hyperuricemia are
factors. Gout rarely appears before 20 to 30 years of hyper-
uricemia. M>>F
–Genetic predisposition is another factor. HGPRT deff=>decr
purine production=>increase urate
–Heavy alcohol consumption predisposes to attacks of gouty
arthritis.
–Obesity increases the risk of asymptomatic gout.
–Certain drugs (e.g., thiazides) Reduced renal excretion pre-
dispose to the development of gout.
–Lead toxicity increases the tendency to develop gout
• Gout traditionally is divided into primary and secondary
forms, accounting for about 90% and 10% of cases, re-
spectively
• Primary(90%)-
–Unknown cause or (less commonly) in which the disorder is
due to an inborn metabolic defect that causes hyperuricemia.
–gout is the initial manifestation
–overproduction or decreased excretion
• Secondary(10%)-
–known cause , but gout is not necessarily the main or even
dominant clinical disorder.
–over production e.g in leukemias or underexcretion e.g renal
disease
 Morphology
• Distinctive morphologic changes are
1.Acute arthritis
2.Chronic tophaceous arthritis
3.Tophi at various sites
4.Gouty nephropathy
 Pathogenesis
• Central to the pathogenesis of the arthritis is precipita-
tion of monosodium urate crystals into the joints .
• Synovial fluid poorer solvent than plasma.
• Supersaturated => micro tophi & Urate crystals develop
in synovium & joint catilage
• => release of crystals(? trauma) in to synovial fluid at-
tracts neutrophils and complement,releases free radi-
cals, releases lysosomal enzymes=> acute arthritis ( tis-
sue injury)
• => repeated attacks of acute arthritis cause chronic
arthritis and formation of tophi in synovial membranes
and periarticular tissue, which eventually damages joints
 Acute arthritis :
• Sites: 50% have initial attack in first metatarsopha-
langeal joint; also ankles, heels, knees, wrists, fingers,
elbows
• Dense neutrophilic infiltrate in synovium and synovial
fluid
• monosodium urate crystals: Long , needle
shaped ,slender in cytoplasm of neutrophils aswell as
small cluster in synovium.
• Synovium: edematous , congested , scattersd lympho-
cytes , plasma cells and macrophages
• Crystalization abates and resolubilized : acute attacks
remits
Acute Gout from sodium urate crystals
deposited in joints.
Urate crystals
 Chronic tophaceous arthritis
• Repetitive precipitation of crystals during acute
attacks
• Urate form visible deposits in synovium
• Synovium: hyperplastic, fibrotic, thickened , infil-
trated by inflammatory cells => pannus => de-
stroys underlying cartilage =>juxta articular bone
erosion
• Fibrous / bony ankylosis in severe cases => loss
of joint function
 Chronic gout eventually destroys bone.

Early stage of gout. More advanced stage.

http://www-medlib.med.utah.edu/WebPath/BONEHTML/BONEIDX.html
 X-ray
• Late Early
Chronic gout
 Tophi at various sites
• Pathognomonic of gout
• Extracellular deposits of large aggregates of urate crystals
surrounded by intense chronic inflammatory infiltrates
with foreign body type giant cells
• Macroscopically it appears as chalky which deposits on ar-
ticular Cartilage and in the periarticular ligaments, ten-
dons(achilles),olecranon bursa and soft tissues, including
the ear lobes, nasal cartilages, sole, palms and skin of the
fingertips
• Superficial tophi can lead to large ulcerations of the over-
lying skin.
Tophi
Mic: tophi
Mic: tophi
 Gouty nephropathy
• Renal complications associated with urate de-
position, variously forming medullary tophi,
intratubular precipitations, or free uric acid
crystals and renal calculi.
• Secondary complications such as pyelonephri-
tis can occur, especially when there is urinary
obstruction.
Clinical Features
Four steps in the clinical course
1. Asymptomatic hyperuricemia
-precedes clinically evident gout by many yrs
2. Acute gouty arthritis
-Initially monoarticular involvement later polyarticu-
lar with fever
3. Intercritical gout
Asymptomatic interval b/n attacks
4. Chronic tophaceous gout
Pseudogout (calcium pyrophosphate crystal de-
position disease , chndrocalcinosis)
• In over age 50yrs
• Idiopathic(sporadic),hereditary and secondary types
• Secondary- in damaged joints, hyperparathyroidism ,
hemochromatosis…
Morphology
•Early neutrophilic response against intraarticular crys-
tal later chronic inflammation and fibrosis
•Geometric shape crystal, may form masslike aggre-
gates simulating tophi
•Mono or polyarticular
•Acute , subacute or chronic arthritis
•May simulate osteoarthritis or rheumatoid arthritis
 Arthritis
Infectious arthritis
• All kinds of microorganisms
• Hematogenous
• Direct inoculation
• Contagious spread from ST abscess or fo-
cus of osteomyelitis
• Rapid destruction of joints => permanent
deformities
 SUPPURATIVE ARTHRITIS
• Bacterial infection
• Routes: hematogenous(most common) , direct inoculation
or contiguous infections
• Most commonly due to Staphylococcus, Streptococcus,
gram negative rods; rarely syphilis
• Neonates: often due to osteomyelitis
• H.influenza (< 2yrs)
• Young women: most commonly due to gonorrhea (gram
negative intracellular diplococci, which is associated with
multiple joint involvement, including the knee)
• Sickle cell disease: Salmonella
• Risk factors: immune deficiencies, severe illness,
joint trauma, chronic arthritis, intravenous drug
abuse
• Symptoms: Sudden development of acutely painful
and swollen tender erythematous large joint with re-
stricted range of motion, systemic findings
• Sites: usually single joint (knee, hip, shoulder)
• Micro: Joint aspiration- cloudy ,clots easily , high
neutrophil count , positive G-stain and culture in 50-
70% of cases
Gram stain of joint fluid
 TUBERCULOUS ARTHRITIS
• Chronic progressive arthritis, usually monoarticulars (weight bear-
ing join) hip,knee , ankel ;
• Usually from hematogenous spread or adjoining TB osteomyelitis
• Insidious , gradual progressive pain, Systemic symptoms may or
may not be present
• Causes severe destruction Leading to fibrous ankylosis of joint with
obliteration of joint space
• X-rays: marginal erosion of hip and knee joints, with destruction of
sub chondral bone on both sides of joint and loss of joint space
• Micro: confluent granulomas with caseous necrosis on epiphysial
plate
Tumors & tumor-like lesions of
the joints
 Non neoplastic lesions of the joints
Synovial cyst
• Due to herniation of synovial membrane through poste-
rior joint capsule or massive enlargement and escape of
joint fluid from bursae.
• Any joint disease leading to increased intra-articular
pressure => degenerative joint disease, neuropathic
arthropathy, rheumatoid arthritis
• E.g baker cyst in RA
• The cyst is lined by true synovium and may have carti-
lage in its wall
• Synovial lining may be hyperplastic and contain inflam-
matory cells and fibrin
 BURSITIS
• Pain, erythema, swelling around bursae that
lie between muscles, tendons , skin and bony
prominences
• Usually due to chronic trauma; associated
with cysts, fluid and loose bodies.
 Non neoplastic lesions of the joints
Ganglion
• Small cyst-like mass(1-1.5cm) almost always located near
a joint capsule or tendon sheath
• Common in the wrist joint area
• As a result of cystic or myxoid degeneration of connective
tissue
• May be due to injury or overuse of joint (typists , pianists)
• May cause pain, weakness, bone changes, partial disabil-
ity of joint
• Popliteal – foot drop or pain compression of common
popliteal nerve
 Non neoplastic lesions of the joints

Ganglion
• Gross
–Firm , fluctuant, pea-sized translucent nodule
• MICroscopy
–Cyst wall with no lining epithelium, no communication with
the joint space
Ganglion
Ganglion
 Joint Tumors
• Primary neoplasms of joints are uncommon and usu-
ally benign; in general, they reflect the cells and tis-
sue types (synovial membrane, vessels, fibrous tis-
sue, and cartilage) native to the joints.
• Benign tumors are much more frequent than their
malignant counterparts.
• Common neoplasms are:
• Tenosynovial Giant Cell Tumor
– Pigmented villonodular synovitis(PVNS) and giant cell
tumor of the tendon sheath(GCT)
• Synovial chondromatosis (synovial chondrometaplasia, syn-
ovial osteochondromatosis)
 Joint Tumors
Tenosynovial giant cell tumor (TGCT)
•is a catchall term for several closely related benign neoplasms
of synovium.
•Classic examples are
•Diffuse tenosynovial giant cell tumor, previously known as pig-
mented villonodular synovitis (PVNS), involving joint synovium,
and
•Localized tenosynovial giant cell tumor, also known as giant cell
tumor of tendon sheath.
•Both types typically arise in people in their 20s to 40s, without
gender predilection
 TGCT
Morphology
•Gross;-Both red brown to mottled orange-yellow
•PVNS-the smooth synovium is converted in to a tan-
gled mat by finger-like projections and nodules
•GCT-localized well circumscribed
•Microscopy- synoviocyte-like cells , infiltrate the sub-
synovial compartment
•Hemosiderin deposits , foamy macrophages, multinu-
cleated giant cells and zones of sclerosis
 Clinical features
PVNS
• Usually solitary mimics a monoarticular arthritis.
• affects the knee joint in 80% of cases, followed by
the hip and ankle.
• Patients typically complain of pain, locking, and re-
current swelling.
• Tumor progression with Joint stiffness limits the
range of movement of the joint and palpable mass
• Erosion of adjacent bone and soft tissue
• Significant risk of recurrence
 Clinical features
GCT
• Solitary, slow-growing, painless nodule on ten-
don sheaths of flexor surfaces of wrists/fingers,
ankle/toes
• The most common mesenchymal neoplasm of
the hand
• cortical bone erosion in 15%
• Can recur
Soft tissue tumors
 Soft tissue tumors
• Mesenchymal proliferations in the extraskeletal , non-epithelial tis-
sues of the body which recapitulate muscle , fat, fibrous tissue, ves-
sels and nerves
• Originate from primitive mesenchymal stem cells
• Most soft tissue tumors arise without antecedent causes; rare radia-
tion, burn, virus, genetics, parts of many syndromes, many translo-
cations (cytogenetics)
• Benign, malignant and intermediate (low-grade malignant – locally
aggressive, can recur, no metastatic potential)
• Benign soft tissue tumors outnumber their malignant counterparts
by at least a hundred-fold. In the United States, sarcomas represent-
ing less than 1% of all invasive malignancies.
• soft tissue tumors are classified based on recognizable lines of dif-
ferentiation as follows.
 Classification of soft tissue tumors
Lipomatous tumors Fibrohistiocytic tumors
Lipoma Benign fibrous histiocytoma
Liposarcoma Malignant fibrous histiocytoma
Smooth muscle tumors Vascular tumors
Leiomyoma Hemangioma
Leiomyosarcoma Angiosarcoma
Skeletal muscle tumors Tumors of peripheral
Rhabdomyoma
nerves
Schwannoma
Rhabdomyosarcoma Neurofibroma
Fibroblastic tumors Malignant peripheral nerve
Fibromatoses sheath tumor
Fibrosarcoma Tumors of uncertain ori-
gin
Synovial sarcoma
 Prognosis futures of soft tissue sarcoma:
• Several features of soft tissue sarcomas influence prognosis:
• Diagnostic classification. This is based not only on histology, but
also on IHC, EM, cytogenetics, and molecular genetics, which are
indispensable in assigning the correct diagnosis in some cases.
• Grading. Grading, usually on a scale of I to III, is based cellularity,
pleomorphism, Mitotic counts and necrosis are the most important
predictors.
• Staging. With tumors larger than 20 cm, metastases develop in 80%
of cases; by contrast, for tumors 5 cm or smaller, metastases occur
in only 30% of cases.
• Location. In general, tumors arising in superficial locations (e.g.,
skin) have a better prognosis than deepseated lesions; overall, the
10-year survival rate for sarcomas is approximately 40%.
• Clinicopathological correlation is essential.
 TUMORS OF ADIPOSE TISSUE
Lipoma
• The most common benign soft tissue tumor of adult-
hood
• Subcutaneous tissue of the trunk and limbs in the
middle-aged and elderly
• Soft, slowly growing mass
• Microscopy-well-defined lobules of mature adipose
tissue
• variants:
• Angiolipoma: thin-walled small blood vessels occupy
significant portion of the lesion
• Spindle-cell lipoma: mixture of mature adipocytes,
short bundles of collagen and small uniform spindle
cells
Liposarcoma
• The most common malignant soft tissue tumor
• Adults (peak incidence 40-60 years)
• lower limb and retroperitoneal space
• multivacuolated lipoblast and chicken wire vessels
are key diagnostic histologic features.
Subtypes:
• Well-differentiated, myxoid, round cell, pleomorphic
liposarcoma with decreasing prognosis and increased
risk of recurrence and metastasis
 FIBROUS TUMORS AND
TUMOR-LIKE LESIONS
Nodular fasciitis
• Benign reactive fibroblastic proliferation
• Adolescents and young adults
• Rapidly growing nodule within subcutaneous tissue,
forearm is the most common site
• Preceding trauma in 10-15% of cases
• Dermis,subcutis or muscle
• Several centimeters , nodular , poorly defined mar-
gins
• Microscopy-plump immature fibroblasts arranged in
randomly or short bundles, numerous mitoses, cellu-
lar pleomorphism not present , lymphocytes and ex-
travasated blood
• ‘ pseudosarcomatous fasciitis’
 Myositis Ossificans
• Myositis ossificans is reactive lession distin-
guished from other fibroblastic proliferations
by the presence of metaplastic bone.
• It usually develops in the proximal muscles of
the extremities in athletic adolescents and
young adults after trauma.
• The affected area initially is swollen and
painful, and subsequently evolves into a pain-
less, hard, well-demarcated mass.
 Fibromatoses
• The fibromatoses are a group of fibroblastic
proliferations distinguished by their tendency
to grow in an infiltrative fashion but do not
metastasize and, in many cases, to recur after
surgical removal.
• The fibromatoses are divided into two major
clinicopathologic groups: superficial and deep.
Superficial fibromatoses
• Palmar fibromatosis (Dupuytren’s contracture): middle-aged
men, nodular thickening of Palmar aponeurosis leading to
flexion deformities of fingers
• Plantar fibromatosis (Ledderhose’s disease):
nodular thickening of plantar aponeurosis
• Penile fibromatosis (Peyronie’s disease): ab-
normal curvature of penis
• All forms are common in males than females
• May have stable course , recur or resolve sponta-
neously
• Gross and microscopy: irregular margin,nodules of
well-differentiated fibroblasts arranged in long
sweeping bundles
Deep fibromatoses (desmoid tumors)
• Abdominal: abdominal wall, young adults, particularly women who
have given birth, often detected in peripartum or postpartum pe-
riod, sometimes in surgical scars

• Intra-abdominal: young adults, mesentery, association with Gard-

ner’s syndrome (intestinal polyposis)

• Extra-abdominal: the most aggressive, adults in the third and

fourth decades, pectoral and pelvic girdles

• General features: deep intramuscular location, large size (up to 10-

15cm), infiltrative growth pattern, high risk of recurrence after exci-
sion
Fibrosarcoma
• Relatively uncommon malignant neoplasm
• Middle aged adults
• Deep soft tissues of lower limbs and trunk
• Microscopy: bundles of spindle shaped cells arranged
at right angles to one another (“herring-bone pat-
tern“), frequent mitoses
• Infantile fibrosarcoma: within the first two years of
life, much better prognosis
 FIBROHISTIOCYTIC TUMORS
Benign fibrous histiocytoma (dermatofibroma)
• Common lesion, most frequently on the skin
of lower leg
• Papule or nodule, often deeply pigmented
• Microscopy: situated within the mid-dermis,
spindle cells arranged in curious whorled pat-
tern (storiform pattern)
Malignant fibrous histiocytoma (MFH)
• Deep soft tissues of limbs, retroperitoneum
• Irregularly arranged plump, eosinophilic, spindle-
shaped cells ,bizarre nuclei, numerous mitoses, stori-
form pattern in some areas
• MFH represents merely a morphological pattern
shared by wide variety of poorly differentiated ma-
lignant neoplasms , it is a heterogeneous group of
unrelated lesions
• MFH (synonymous designation: undifferentiated
pleomorphic sarcoma) - diagnosis of exclusion
 SMOOTH MUSCLE TUMORS
Leiomyoma
• Skin, subcutaneous tissue, uterus, gastrointestinal tract
• Microscopy-interlacing bundles of well-differentiated
smooth muscle cells
Leiomyosarcoma
• Mesentery, retroperitoneal space, wall of large veins,
skin, subcutaneous tissue, deep soft tissues of limbs
• Signs of malignancy: large size, high mitotic rate, areas
of necrosis, marked cellular pleomorphism
Leiomyoma
Leiomyosarcoma
 SKELETAL MUSCLE TUMORS
Rhabdomyoma
• Extremely rare lesions
Rhabdomyosarcoma
• The most common malignant soft tissue tumour
in infants and young children
• Diagnosis depends on the demonstration of
rhabdomyoblasts (round, elongated or oval cells
with eccentric eosinophilic cytoplasm, in which
fibrillated appearance may be noted – “tadpole
cells, strap cells, racket cells“)
Subtypes:
• Embryonal rhabdomyosarcoma
-most common, early childhood
-head and neck region and genitourinary system
-small rounded or spindle-shaped cells within a
myxoid matrix
• Botryoid rhabdomyosarcoma (grape-like)
-Embryonal rhabdomyosarcoma with polypoid
configuration and myxoid consistency
-occur in mucosa-lined organs
• Alveolar rhabdomyosarcoma
-between the ages of 10 to 20 years
-muscles of limbs and trunk
• Pleomorphic rhabdomyosarcoma
-rare
-limbs of adults,
-large cells with eosinophilic cytoplasm and either
single or multiple highly atypical nuclei
 Peripheral nerve sheath tumor
Schwannoma (neurilemmoma)
• Smooth lobulated lesion usually attached to a
nerve
• Gross and microscopy: well circumscribed , two
patterns recognized:
• Antoni A – compact areas formed by regular in-
terlacing bundles of uniform spindle-shaped cells,
often foci of nuclear palisading
• Antoni B – loose open areas, small cells with
rounded nuclei(hypocellular area)
Neurofibroma
• Not infrequently multiple, sometimes part of neu-
rofibromatosis
• Infiltrates and expands the affected nerve
• Microscopy: spindle-shaped cells with elongated
wavy nuclei set in myxoid stroma with scattered mast
cells
Malignant peripheral nerve sheath tumor (MPNST)
• Adults, most common locations: neck, forearm,
lower leg, buttock
• Large mass producing fusiform enlargement of a ma-
jor nerve
• Microscopy :relatively uniform spindle-shaped cells
with hyperchromatic nuclei and high mitotic activity
 SYNOVIAL SARCOMA
• Synovial sarcoma was originally believed to recapitulate syn-
ovium; however, the phenotype of the neoplastic cells bears
no resemblance to a synoviocyte, and despite the name, less
than 10% of tumors are intra-articular.
• Synovial sarcomas account for approximately 10% of all soft
tissue sarcomas, typically occurring in persons in their 20s to
40s.
• They usually develop in deep soft tissues around the large
joints of the extremities, with 60% to 70% occurring around
the knee; many have been present for several years at the
time of presentation.