bone and soft tissue.ppt

Pathology of the bones, joints and soft
tissue tumors

Introduction
Structure of Bones
• hard matrix
– Made of matrix proteins and mineral
• The main structural protein-type I collagen
• Most of the mineral -in the form of a calcium
phosphate complex known as hydroxyapatite

• Bone cells two distinct types:
• Osteoclasts - bone- resorbing cells
• The osteoblast family : osteoblasts- bone
forming cells; osteocytes, form an
interconnecting network throughout bone
matrix
• All are involved in bone remodeling

• During development, bone is formed either
– directly in connective tissue, as in the skull
(intramembranous ossification) or
– on pre-existing cartilage, as in the limb bones
(endochondral ossification)

Woven bone  
Lamellar bone  

CONGENITAL AND HEREDITARY DISEASES OF BONE
Achondroplasia
• Autosomal dominant disorder
• characterized by impaired maturation of
cartilage in the developing growth plate
• is a major cause of dwarfism
• majority of cases are caused by dominant
mutations involving the gene for fibroblast
growth factor receptor 3

• Achondroplasia affects all bones that are
formed from cartilage
• normal head and trunk size, and
disproportionately short but well-muscled
arms and legs
• The face usually has a large forehead,
prominent supraorbital ridges, and deep-set
root of the nose

Malformations and diseases caused by defects in nuclear
proteins and transcription factors
• 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)
 Development of long spider like digits(Arachinodactyly)

Craniorachischisis
• failure of closure of the vertebral column and
skull
  meningomyelocele or
myeloencephalocele
Meningomyeleocele

Osteogenesis Imperfecta
• "brittle bone disease’’
• a group of hereditary conditions characterized by
abnormal development of type I collagen
• Type I collagen is present in many different
tissues, including skin, joints, and eyes, and it is a
major component of normal osteoid
• Several different genetic defects have been
shown to interfere with the normal synthesis of
type I collagen

• Four major forms have been identified
• the most common variants are inherited as
autosomal dominant disorders
• 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

Subtype Inheritance Collagen defect Major C/F
OI I
Postnatal
fracture, blue
sclerae
Autosomal dominant Decreased synthesis
proα1(1)
Compatible
Normal stature,
skeletal fragility, DI,
hearing
impairment,joint
laxity,blue sclera
OI II
Perinatal lethal Most are autosomal
recessive ; some are
autosomal dominant
? New mutations
Abnormal short pro-
α1(1) chain;
Unstable triple helix
Abnormal or
insufficient pro-α2(1)
Death in utero or
within days of birth
Skeletal deformity with
excessive fragility &
multiple fractures.
Blue scera
OI III
Progressive
deforming
Autosomal
dominant(75%)
Autosomal
recessive(25%)
Altered structure of
pro-peptides of pro-
α2(1)
Impaired triple helix
formation
Compatible with survival
GR, ≠s, blue sclera which
become white,
deformities,hearing
impairment,dentinogenesi
s imperfecta
OI IV
Postnatal
fractures,
normal scerae
Autosomal dominant Short pro-α2(1) chain
Unstable triple helix
Compaible with
survival; moderate
skeletal
fragility,short

Osteopetrosis
• "marble bone disease’’
• encompasses a group of uncommon hereditary
disorders caused by deficient osteoclastic activity
• Both autosomal recessive and autosomal
dominant variants have been recognized
• Defective osteoclastic activity in these patients
results in the deposition of abnormally thickened,
heavily mineralized, abnormally brittle bone

• In addition to an increased incidence of fractures,
patients with osteopetrosis also suffer from anemia,
thrombocytopenia, pancytopenia
• Abnormally thickened bone may also compress nerve
roots, accounting for a high frequency of cranial
nerve palsies in these patients

Osteoporosis and Acquired metabolic diseases
Osteoporosis
• reduction in bone mass in the presence of
normal mineralization
• diagnosed by radiological assessment of bone
mineral density

Age related bone loss-senile osteoporosis
Most commonly post menopausal

PRIMARY
Postmenopausal
Senile
Idiopathic
SECONDARY
Endocrine disorders
e.g Hyperparathyroidism
Drugs
e.g. corticosteroids
Neoplasia
e.g. Multiple myeloma
Miscellaneous
e.g. Immobilization
Gastrointestinal
e.g. Malnutrition
Categories of generalized osteoporosis(read about specific mechanisms)

Pathogenesis
• is caused by a loss of coupling in the bone
remodeling process net loss of bone volume
• This can be due to
– increased bone resorption,
– decreased bone formation, or
– Both
• In contrast to osteomalacia , mineralization of bone
is normal

Complications
• The major complications of osteoporosis are:
– skeletal deformity
– bone pain (usually due to compression fracture)
– fracture

Clinical
• more common in females than males and
white than blacks
• fragility fracture , progressive loss of
height(most common), or stooping deformity
(kyphosis or 'dowager's hump') due to wedge
fractures of the vertebral bodies

Paget disease (Osteitis deformans)
• characterized by episodes of localized,
frenzied osteoclastic activity and bone
resorption, followed by exuberant bone
formation
• ‘Collage of matrix madness’
• There are three phases in the development of
Paget disease:

Diagramatic representation
of Paget Disease showing
The three phases in the
Evolution of the disease
Stage 1
Stage 2
Stage 3

• uncommon before 40yrs, but its incidence
increases steadily after that time
Morphology
• a solitary lesion (monostotic) or may be
multifocal (polyostotic)
• Although any bone may be affected, the spine,
skull, and pelvic bones are especially common
sites of involvement

Because the bone formation occurs in an erratic
pattern, areas of new bone are juxtaposed in a
random mosaic pattern, giving the appearance of a
jigsaw puzzle

Clinical features
• Usually asymptomatic
• high-output congestive heart failure
• headache, enlargement of the head, visual
disturbances, and deafness, all caused by
deformity of the bones of the skull and
impingement on cranial nerves
• Back pain

• Transverse fractures of long bones (chalkstick
fracture)
• In about 1% of the cases osteosarcoma
develops

Rickets and osteomalacia
• characterized by deficient mineralization of the organic
matrix of the skeleton
• Rickets - in children
• Osteomalacia -in adults
• Causes include:
– dietary deficiency of vitamin D
– deficiency of vitamin D metabolites
– intestinal Malabsorption
– renal disease
• Malabsorption of calcium and phosphate from the
intestine is the commonest cause of osteomalacia in
adults

Diagnosis
• The characteristic clinical deformities of rickets
include:
– bowing of the long bones of the leg
– pronounced swelling at the costochondral junctions
– flattening or 'bossing' of the skull
• Inadequate mineralization of bone reduces its
normal strength and allows deformities to
develop

• When the levels of vitamin D metabolites are
low, calcification cannot occur and
cartilaginous proliferation continues
• This accounts for the enlargement of long
bones and the ribs at growth plates
• characteristic pathological feature in adults
with osteomalacia is spontaneous incomplete
fractures

• 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

Bone Diseases Associated With
Hyperparathyroidism
–Revise your endocrinology note

Osteonecrosis (Avascular necrosis )
• Can occur in the medullary cavity of metaphysis or diaphysis
and the Subchondral regions of the epiphysis.
• All cases result from ischemia
 Mechanical vascular interruption ( fracture )
 Corticosteroids
 Thrombosis and embolism
 Vessel injury ( vasculitis )
 Increased intraosseus pressure
 Venous hypertension
 Sickle cell anaemia

• Pts present with pain of variable intensity.
• Causes are diverse but in many cases are
idiopathic

MORPHOLOGY
 Medullary infarcts – necrosis is geographic and involves the
cancellous bone and marrow ( cortex is spared because of
collateral supply )
 Subchondral infarcts – wedge shaped
↓
←

•The dead bone is recognized as an empty lacunae
surrounded by necrotic adipocytes - creeping
substitution
•In Subchondral infarcts creeping substition is slow
and infarctions result fractures & even sloughing of
articular surface
•Rare risk of osteoarthritis and malignant
transformation

• It can be complicated by salmonella
osteomyelitis esp.osteonecrosis due to sickle
cell anemia

Osteomyelitis
• Inflammation of bone and marrow cavity
• Routs of organism entry to the bone:
1. hematogenous
2. direct extension from infected joint or soft tissue
3. Direct implantation after compound fractures or
orthopedic surgical procedures

• hematogenous most common route
• In many cases arises in a previously healthy
individual
• Staphylococcus aureus -the most common causative
organism
• Other common pathogens include pneumococci,
Escherichia coli and group B streptococci

• Salmonella-especially common in sickle cell disease
• Mixed bacterial infections, including anaerobes-in
many cases after bone trauma
Morphology
• intense, neutrophilic inflammatory infiltrate at the
site of bacterial invasion

• In long bones, the infection spreads through the
cortical bone and may reach the periosteum,
sometimes creating a subperiosteal abscess
• From the subperiosteal area, the infection may
spread into adjacent soft tissues to create draining
sinuses

• The location of infection varies with age
• In children-metaphyses of long bones are typically
involved
• In adults-primarily affects vertebral bodies that
remain quite vascular
• The involved bone becomes necrotic

• In infants, the existence of loose periosteal
attachments and connections between the
vessels in the metaphysis and epiphysis allows
the infection to spread to the epiphysis and
joint capsule

Chronic osteomyelitis
• develops as a sequel of acute infection
• Over time-a repair reaction (osteoclast
activation, fibroblastic proliferation, and new
bone formation)

• Sequestrum-residual necrotic bone may be resorbed
by osteoclastic activity
• involucrum-new reactive bone surrounding
sequestrum
• When a well-defined rim of sclerotic bone surrounds
a residual abscess, the lesion is sometimes
designated a Brodie abscess
• Chronic osteomyelitis may be complicated by the
development of draining sinuses and pathologic
fractures

• Other complications- septicemia, acute
bacterial arthritis, squamous cell carcinoma,
amyloidosis
Clinical feature
• Initially systemic manifestations such as fever,
malaise, and leukocytosis
• local pain,swelling, and redness may occur in
some adults

Tuberculous Osteomyelitis
• Hematogenously born
• Rarely direct extension eg. From the lung to the ribs
or from the tracheobronchial nodes to the
vertebrae
• Bone infection is usually solitary but can be
multiple in HIV/AIDS
• 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.
• Spreads through large areas of medullary cavity and
causes extensive necrosis.
• Pott disease – in the spine, infection extends through
intervertebral discs to involve multiple vertebrae &
extends into soft tissues, forming abscess( psoas
abscess)

Clinical feature
 Pain on motion
 Swelling
 Symptom complex of tuberculosis
 Vertebral deformities

Skeletal Syphilis
• Acquired or congenital
• Bones commonly involved- nose, palate, skull &
extremities(esp tibia)
• Osteochndritis and periostitis
• 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
• Benign or malignant
• Malignant- primary(de novo) or secondary
• risk factors- Paget diseases , radiation ,fibrous
dysplasia, hereditary (p53 and RB genes)

Can be
• Bone forming
• Cartilage forming
• Others

Bone-Forming Tumors
• characterized by the production of osteoid by
the tumor cells
• Benign
• osteoma
• Osteoid Osteoma
• Osteoblastoma
• Malignant
• Osteogenic sarcoma

Osteoma
• Involve skull and facial bones as a bossolated, round
mass
• Usually solitary
• Middle age adults
• Multiple in Gardner syndrome
• Histology-composed of woven and lamellar bone in a
cortical pattern with haversian-like symptoms

• Slowly growing impinge on brain or eyes or
bring cosmetic problems
• Doesn’t transform in to osteosarcoma

Osteoid osteoma and Osteoblastoma
• Identical histology but different size ,site and
symptoms

Morphology
• Gritty tan hemorrhagic tissue
• Well circumscribed, trabeculae of woven bone lined
by osteoblasts, well vascularised, hemorrhagic
stroma , surrounding marked reactive bone leaving
the tumor as a central nidus

Central hemorrhagic nidus
surrounded by dense rim of
sclerotic bone

Osteosarcoma (osteogenic sarcoma)
• a malignant mesenchymal tumor in which the
neoplastic cells produce bone matrix
• 75% of cases are < 20yrs of age
• in the elderly it usually follows paget disease, bone
infarcts and/or prior irradiation
• mostly arise in the metaphyseal regions of long
bones ( 60% occur around the knee )

• Conventional osteosarcomas are aggressive lesions
that metastasize through the bloodstream early in
their course
• M > F
• The lungs are common sites of metastases

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– osteoblastic, chondroblastic,
fibroblastic, telangiectatic, small cell and giant
variants
• The most common variant is that which arises
in the metaphysis of long bones; is primary,
solitary, intramedullary and poorly
differentiated with production of bone matrix

• The tumor often elevates the periosteum to produce the so-
called Codman triangle on radiographs
• the hallmark of osteosarcoma is the formation of osteoid by
malignant mesenchymal cells!

Cartilaginous Tumors
• Benign:
• Chondroma
• Osteochondroma
• Chondroblastoma
• Chondromyxoid Fibroma
• Malignant:
• Chondrosarcoma

Chondroma ( enchondroma)
• Benign tumor of mature hyaline cartilage
• Most within bone (enchondroma)
• Most common intraosseus tumors occurring in
patients aged between 20 and 50yrs.
• Usually solitary involving the metaphyseal region of
tubular bones especially short bones of hand and
feet.

• Multiple enchondromatoses - Ollier disease, in
maffuci’s syndrome
• Develop from the rests of cells of the growth plate
cartilage and/or genetic alterations in mesenchymal
stem cells.

Composed of mature lobules of
hyaline cartilage with foci of myxoid
degeneration, calcification and
endochondral ossification; may be
quite cellular

• Most are asymptomatic but can be painful or
pathological 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

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

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-
existing enchondroma and few develop in cases of
Osteochondroma, chondroblastoma, fibrous
dysplasia or Paget disease.

• They arise in central portions of the skeleton;
common sites of origin include the shoulder area,
pelvis, proximal femur, and ribs
• Site- Intramedullary and Juxtacortical
• Microscopy-Conventional (hyaline or myxoid ), Clear
cell, Dedifferentiated, and Mesenchymal variants

Ill-defined margins;
fusiform thickening of
shaft; perforation of cortex

• Microscopically, nodular pattern is seen and
malignant features depend on grade of tumor
• 3 grades- depending on the cellularity , nuclear
atypia and mitosis
• Prognosis depends on grade
• Patients present with painful progressively enlarging
masses
• Metastases show predilection for lungs and skeleton

Other Tumors and Tumor-like Conditions of
Bone
Giant cell tumor of bone (osteoclastoma)
• An uncommon benign but locally aggressive tumor
• 80% of patients > 20 years
• 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
frequently 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 &
reactive bone formation can be seen

• Involve the epiphysis and metaphysis in adults and,
the metaphysis in adolescents
• Arthritic symptoms ,pathological fracture
• Most are solitary
• Unpredictable biologic behavior
• Rare sarcomatous transformation
• Recurrence is common after local curettage

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
curvilinear trabeculae of woven bone with
surrounding fibroblastic proliferation(no osteoblastic
rimming)
• Cystic degeneration, hemorrhage and foamy
macrophages are common

Clinical course
• Asymptomatic
• Recurrent fractures, severe swellings and
disfigurements can occur
• Treatment is conservative surgery
• Rare malignant transformation ( esp. in those that
are irradiated)

Ewing’s family of tumors
• Primary malignant small round cell tumors
• Differ in their degree of neural differentiation.
• Neural differentiation  PNET
• Undifferentiated  EWING SARCOMA
• 6-10% of primary malignant bone tumors.
• highly aggressive neoplasm that must be
differentiated from other pediatric tumors
composed of "small blue cells’’

• Ewing sarcoma is second to osteosarcoma in children
• Ewing sarcoma has the youngest age affection of
malignant tumors (b/n 10 & 15yrs)
• Both arise from the medullary cavity and invade the
cortex & periosteum  to produce soft tissue
masses
• Tumors are tan white with areas of hemorrhage and
necrosis

• The femur, tibia, and pelvis are favored sites of
origin
• Usually arise in the diaphysis

• Microscopically, sheets of small round cells that are
slightly larger than lymphocytes with scanty clear
cytoplasm ( glycogen rich )
• Rosettes ( Homer-wright rosettes )  neural
differentiation
• Stroma is scanty but fibrous septa is seen
• Few mitotic figures are seen

Clinical feature
• Painful enlarging mass the site is tender, warm and
swollen.
• Systemic symptoms may be seen
• X-ray shows lytic lesions with permeation in to soft
tissue
• Treatment is chemotherapy and surgical excision
with or without radiotherapy
• 5yr survival reaches up to 75%

Metastatic Disease
• Most common form of skeletal malignancy
• Direct extension or Lymphohematogeneous
dissemination
• 75% of cases originate from cancers of the prostate,
breast, kidney and lung
• In children- neuroblastoma, Wilms tumor,
osteosarcoma, Ewing sarcoma and rhabdomyosarcoma
• Typically Multifocal
• Thyroid and kidney carcinomas -solitary

• Most are in the axial skeleton ( vertebral column,
pelvis, ribs, skull & sternum ) – marrow
• Metastasis to small bones of hands and feet is
uncommon
• X-ray – lytic, blastic or mixed
→ Kidney, lung, GI, and melanoma – lytic lesions
→ Prostatic adenocarcinoma – blastic lesions

Renal cell carcinoma of clear cell type metastatic to bone. Notice the marked fresh
hemorrhage that is a characteristic feature of this tumor.

Ill-defined lytic lesion in midshaft of
fibula produced by metastasis of lung
carcinoma

• Mesenchymal proliferations in the extraskeletal ,
non-epithelial tissues of the body which recapitulate
muscle , fat, fibrous tissue, vessels and nerves
• Benign, malignant and intermediate (low-grade
malignant – locally aggressive, can recur, no
metastatic potential)

• Originate from primitive mesenchymal stem cells
• Classification according to their differentiation lines
(e.g. liposarcoma is not a tumor arising from lipoblast
but exhibiting lipoblastic differentiation)

Classification of soft tissue tumors
Lipomatous tumors
Lipoma
Liposarcoma
Smooth muscle tumors
Leiomyoma
Leiomyosarcoma
Skeletal muscle tumors
Rhabdomyoma
Rhabdomyosarcoma
Fibroblastic tumors
Nodular fasciitis
Fibromatoses
Fibrosarcoma
Fibrohistiocytic tumors
Benign fibrous histiocytoma
Malignant fibrous histiocytoma
Vascular tumors
Hemangioma
Angiosarcoma
Tumors of peripheral
nerves
Schwannoma
Neurofibroma
Malignant peripheral nerve
sheath tumor
Tumors of uncertain
origin
Synovial sarcoma

Lipoma
• The most common benign soft tissue tumor of
adulthood
• 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 feature
Subtypes:
• Well-differentiated, myxoid, round cell, pleomorphic
liposarcoma with decreasing prognosis and increased
risk of recurrence and metastasis

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

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

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
margins
• Microscopy-plump immature fibroblasts arranged in
randomly or short bundles, numerous mitoses,
cellular pleomorphism not present , lymphocytes
and extravasated blood
• ‘ pseudosarcomatous fasciitis’

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):
abnormal curvature of penis

• All forms are common in males than females
• May have stable course , recur or resolve
spontaneously
• 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
period, sometimes in surgical scars
• Intra-abdominal: young adults, mesentery, association with
Gardner’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
excision

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
pattern“), frequent mitoses
• Infantile fibrosarcoma: within the first two years of
life, much better prognosis

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
pattern (storiform pattern)

Malignant fibrous histiocytoma (MFH)
• Deep soft tissues of limbs, retroperitoneum
• Irregularly arranged plump, eosinophilic, spindle-
shaped cells ,bizarre nuclei, numerous mitoses,
storiform pattern in some areas
• MFH represents merely a morphological pattern
shared by wide variety of poorly differentiated
malignant neoplasms , it is a heterogeneous group of
unrelated lesions
• MFH (synonymous designation: undifferentiated
pleomorphic sarcoma) - diagnosis of exclusion

• Hemangioma
• Angiosarcoma
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 interlacing
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
neurofibromatosis
• 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
major nerve
• Microscopy :relatively uniform spindle-shaped cells
with hyperchromatic nuclei and high mitotic activity

Ganglion and synovial cyst
• 1-1.5cm cyst almost always located near a joint
capsule or tendon sheath
• Common in the wrist joint area
• Firm , fluctuant, pea-sized translucent nodule
• As a result of cystic or myxoid degeneration of
connective tissue
• Cyst wall with no lining epithelium, no
communication with the joint space

Synovial cyst
• Herniation of synovium through a joint capsule or
massive enlargement of bursa
• E.g baker cyst in RA
• Synovial lining may be hyperplastic and contain
inflammatory cells and fibrin

Pigmented villonodular synovitis and giant cell
tumor of the tendon sheath
• Several closely related benign neoplasms in the
synovial lining of joints, tendon sheaths and bursae
• PVNS-involves synovium of a joint
• GCT of the tendon sheath-localized nodular
tenosynovitis
• Both in the 20s and 40s
• PVNS involves one or more joints

PVNS
• Usually solitary
• 80% the knee joint
• Pain, locking and recurrent swelling
• Joint stiffness , palpable mass
• Erosion of adjacent bone and soft tissue
• Significant risk of recurrence

GCT
• Solitary , painless , slowly growing mass
• Tendon sheaths along the wrists and fingers
• The most common mesenchymal neoplasm of
the hand
• cortical bone erosion in 15%
• Can recur

• Gross-both red brown to mottled orange-yellow
• The smooth synovium is converted in to a tangled
mat by finger-like projections and nodules
• GCT-localized well circumscribed
• Microscopy- synoviocyte-like cells , infiltrate the
subsynovial compartment
• Hemosiderin deposits , foamy macrophages,
multinucleated giant cells and zones of sclerosis

Diseases of the Joints
Osteoarthritis (degenerative joint disease)
• is the most common disorder of the joints
• fundamental feature -degeneration of the articular
cartilage
• May arise without any obvious predisposing factors
as an aging process (primary or idiopathic)
• secondary osteoarthritis-usually in young in a
previously deformed joints or in some metabolic
disorders

Pathogenesis
• Normally balanced articular cartilage degradation
and replacement
• 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
cartilage
• Early changes include , increased water and
decreased proteoglycans
• Attempts to repair by deep chondrocytes

Morphology
• fibrillation (splitting) at the articular surface
• Erosion of the articular cartilage
• Thickened Subchondral bone
• Fragments of cartilage and bone are often
dislodged to form free-floating "joint mice“
• bone proliferation occurs at the margins of the
joints to produce bony excrescences, termed
osteophytes

Heberden nodes-
infemales,not in males
Prominent osteophytes

Clinical features
• Gradual onset of symptoms
• the hips, knees, lower lumbar and cervical vertebrae,
proximal and distal interphalangeal joints of the
fingers commonly involved
• Asymptomatic or common complaints include joint
stiffness and deep, aching pain, particularly in the
morning which worsens with use
• Some degree of joint swelling is common, and small
effusions may develop

Rheumatoid arthritis
• A systemic, chronic, inflammatory disorder
characterized by progressive arthritis , production of
rheumatoid factor, and extra-articular manifestations
• nonsuppurative proliferative and inflammatory
sinovitis that often progresses to destruction of the
articular cartilage and ankylosis of the joints

• Unknown cause
• Autoimmunity plays a role in chronicity and
progression
• 1% Of world population affected
• F:M=3:1
• In 40-70yrs

Morphology
Joints
• Perivascular mononuclear inflammation of the
synovial stroma , edema and hyperplasia…bulbous
fronds
• Granulation tissue
• ‘Rice bodies’ and organization of synovial fibrin
• Neutrophils in the synovial fluid but not deep in the
stroma

• Juxta-articular erosions , Subchondral cysts, and
osteoporosis
• Pannus formation….fibrous ankylosis…..ossification
and bony ankylosis
• Pannus-a mass of synovium and synovial stroma
consisting of inflammatory cells , granulation
tissue,& fibroblasts which grows over articular
cartilage and causes erosion

• Skin-rheumatoid nodules(25%)….elbows
,occiput and lumbosacral area
• Blood vessels- obliterative
endarteritis…..peripheral neuropathy ,ulcers
and gangrene

Pathogenesis
• An autoimmune diseases triggered by
exposure of a genetically susceptible host to
an unknown arthritogenic antigen

Clinical course
• Variable
• Insidious onset
• 10% acute onset with severe symptoms
• 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
• Radial deviation of the wrist and ulnar
deviation of the fingers
• ‘swan neck’ deformity
• Baker cysts : synovial cyst in the popliteal
fossa

• Elevated ESR and hypergammaglobulinemia
• Rheumatoid factor positive in 80% of RA
• Felty syndrome-RA+ neutropenia+
splenomegaly
• Caplan syndrome…..in pneumoconiosis
• Amyloidosis

• RA Diagnostic criteria:
1.morning stiffness
2.arthritis in 3 or more joints
3.symmetric arthritis
4.rheumatoid nodules
5.serum rheumatoid factor
6.typical radiologic changes
7.Arthritis of typical hand joints

Juvenile rheumatoid arthritis (JRA)
• Occurs in children younger than 16 years of age
• More common in girls
• RF is usually absent
• Oligoarthritis is more common
• Frequent systemic onset
• often large joints are affected
• Antinuclear positivity is common

• Polyarticular JRA
– Disabling arthritis predominates
– > 5 joints involved
• Pauciarticular JRA
– Arthritis limited to a few joints
– Uveitis with the potential for blindness

• Infectious arthritis
Suppurative arthritis
• Routes of infection
Hematogenous route
-Most common
-Seeding of joint during bacteremia
Spread from adjacent site of infection
Direct inoculation

• Gonococci, satph. aurous, streptococci,
H.influenza, G-negative bacilli
• Usually monoarticular , tender , painful ,
swollen, erythematous large joints
• Joint aspiration- cloudy ,clots easily , high
neutrophil count , positive G-stain and culture
in 50-70% of cases

Tuberculous arthritis
• Chronic progressive monoarticular disease
• All age especially in adults
• Hematogenous or from adjoining TB osteomyelitis
• Systemic symptoms may or may not be present

• Confluent granulomas and Pannus
• Severe destruction with fibrous ankylosis and
obliteration of the joint space
• Hips ,knees and ankles commonly affected

Gout and gouty arthritis
• group of diseases characterized by an
increased serum uric acid level and deposition
of monosodium urate crystals in joints ,soft
tissue around joints and skin

• Gout is the common end point of a group of
disorders that produce hyperuricemia
• Leads to- acute arthritis ,Chronic gouty arthritis and
tophi
• Most , but not all patients with gout also develop
urate nephropathy
• Hyperuricemia is a sine qua non , but not a sole
determinant

• Primary(90%)-Unknown cause ,gout is the initial
manifestation
-overproduction or decreased excretion
• Secondary(10%)-known cause ,gout is not the main
clinical dysfunction
-over production e.g in leukemias or underexcretion
e.g renal disease

Factors which favor the development of arthritis
• Age and duration of hyperuricemia
• Genetic predisposition
• Heavy alcohol consumption
• Obesity
• Drugs e.g thiazides
• Lead toxicity

• Central to the pathogenesis of the arthritis is
precipitation of monosodium urate crystals
into the joints

Pathogenesis of hyperuricemia
• uric acid is the end product of the catabolism of
purines derived either from diet or synthesized
denovo
• uric acid is eliminated from the body mostly through
urine
• values of >7.0mg/dl exceeds blood saturation at
body temperature
• Hyperuricemia can result from overproduction of
uric acid, decreased urinary excretion or a
combination of both

Morphology
• Acute arthritis-acute inflammation against needle
shape crystals
• Chronic Tophaceous arthritis- repetitive episodes
ending in chronic inflammation, Pannus formation
and complicated by fibrous and bony ankylosis
• Tophi are hallmark of gout
• Gouty nephropathy- interstitial or renal uric acid
stones and obstruction

Tophi
• Extracellular deposits of these crystals ( tophi) are
surrounded by foreign body giant cells
• macroscopically it appears as chalky which deposits
on the surfaces of extraarticular structures and soft
tissues
• Classic locations are ear, head, olecranon bursa and
in the Achilles tendon

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
polyarticular with fever
3. Intercritical gout
Asymptomatic interval b/n attacks
4. Chronic tophaceous gout

Pseudogout (calcium pyrophosphate crystal
deposition disease , chndrocalcinosis)
• In over age 50yrs
• Idiopathic(sporadic),hereditary and secondary types
• Secondary- in damaged joints, hyperparathyroidism ,
hemochromatosis…

• Early neutrophilic response against intraarticular
crystal later chronic inflammation and fibrosis
• Geometric shape crystal, may form masslike
aggregates simulating tophi
• Mono or polyarticular
• Acute , subacute or chronic arthritis
• May simulate osteoarthritis or rheumatoid arthritis

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