Musculoskeletal

Pathology
Alemwosen T(MD,pathology)
 Bone
Structure of Bones
Bone is characterised by its hard matrix
matrix consists of two components, matrix proteins
and mineral
The main structural protein in bone matrix is
type I collagen
Most of the mineral deposited in bone is in the
form of a calcium phosphate complex known as
hydroxyapatite
 Inorganic elements- calcium hydroxyapatite(65%)
Store house of 99% of bodys calcium, 85% of bodys
phosphorus and 65% of bodys sodium and magnesium
Organic elements (35%) - Cells and proteins of the
matrix
Cells of the bone
Bone forming cells - Osteoprogenitor cells,
osteoblasts and osteocytes
Bone resorbing cells - Osteoclasts, monocyte
origin
 Osteoclasts - the bone-resorbing cells, are mono
or multinucleated cells
Involved in bone remodelling
The osteoblast family consists of:
Osteoblasts- bone forming cells
Osteocytes - form an interconnecting network
throughout bone matrix
 CELLS of BONE
OSTEOPROGENITOR (STEM)(TGF)
OSTEOBLASTS (surface of spicule)
under control of calcitonin to take blood calcium and put it into
bone
OSTEOCYTES - are osteoblasts which are now completely
surrounded by bone)
OSTEOCLASTS (macrophage lineage)
under control of PTH to chew up the calcium of bone and put it
into blood
Proteins
Type 1 collagen- 90%
Noncollagenous proteins-adhesion proteins, ca-binding
proteins, enzymes, cytokines ,growth factors..
 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)
Epiphysis
from subarticular plate to epiphyseal cartilage
Metaphysis
Area between epiphyseal plate to the area where bone
develops its funnel or flute shape
Diaphysis
Body of bone, between metaphyses
Congenital and hereditary diseases of bone
1. Defects in nuclear proteins and transcription
factors
2. Defects in hormones and signal transduction
pathways
3. Defects in extracellular structural proteins
4. Defects in metabolic pathways
 Malformations and diseases caused by defects in
nuclear proteins and transcription factors
Uncommon
Failure of development of a bone (e.g. Absence of phalanx, rib or clavicle)
Formations of extra bones (e.g. Supernumerary digits (polydactyly) 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 meningoencephalocele
Meningomyeleocele
CONGENITAL AND HEREDITARY DISEASES OF BONE
Achondroplasia
caused by defects in hormones and signal
transduction mechanisms
inherited disorder characterized by impaired
maturation of cartilage in the developing growth
plate
a major cause of dwarfism
majority of cases of achondroplasia are caused by
dominant mutations involving the gene coding for
fibroblast growth factor receptor 3
 Achondroplasia affects all bones that are formed
from cartilage
The skeletal abnormalities are not associated with
changes in longevity, intelligence or reproductive
status
An autosomal dominant condition (but often a new
mutation)
The patient has a head and trunk of normal size,
and disproportionately short but well-muscled
arms and legs
The face usually has a large forehead, prominent
supraorbital ridges, and deepset root of the nose
 Thanatophoria, dwarf (lethal)
micromelic shortening of the limbs
frontal bossing with relative macrocephaly,
a small chest cavity, and
a bell-shaped abdomen
underdeveloped thoracic cavity leads to
respiratory insufficiency, and the patients
frequently die at birth or soon after
thanatophoric dwarf
Osteogenesis Imperfecta
Aka "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 of OI 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, bone
fragility causes multiple fractures and fetal
demise in utero or shortly after birth
 Subtype Inheritance Collagen defect Major C/F
Postnatal Autosomal dominant Decreased synthesis Compatible
fracture, blue pro1(1) Normal stature,
OI I sclerae skeletal fragility, DI,
hearing
impairment,joint
laxity,blue sclera
Perinatal lethal Most are autosomal Abnormal short pro- Death in utero or
recessive ; some are 1(1) chain; within days of birth
OI II autosomal dominant Unstable triple helix Skeletal deformity with
excessive fragility &
? New mutations Abnormal or
multiple fractures.
insufficient pro-2(1) Blue scera

Progressive Autosomal Altered structure of Compatible with survival

GR, s, blue sclera which
deforming dominant(75%) pro-peptides of pro- become white,
OI III Autosomal 2(1) deformities,hearing
recessive(25%) Impaired triple helix impairment,dentinogenesi
formation s imperfecta

Postnatal Autosomal dominant Short pro-2(1) chain Compaible with

fractures, Unstable triple helix survival; moderate
OI IV normal scerae skeletal
fragility,short
Osteogenesis Imperfecta
Osteogenesis Imperfecta
Other features
Hearing loss
Blue sclera
Dental imperfections
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
 Fracture like a piece of chalk
In addition to an increased incidence of
fractures, patients with osteopetrosis also suffer
from anemia, thrombocytopenia
Increased susceptibility to infections caused by a
dramatic decrease in the amount of marrow
space available for hematopoiesis
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
is a disease in which there is a reduction in bone
mass in the presence of normal mineralisation
is diagnosed by radiological assessment of bone
mineral density
Clinically, osteoporosis may present as a fragility
fracture, loss of height, or stooping deformity
(kyphosis or 'dowager's hump') due to wedge
fractures of the vertebral bodies
The most common forms are senile
and postmenopausal osteoporosis
Categories of generalized osteoporosis(read about specific mechanisms)

PRIMARY SECONDARY
Postmenopausal Endocrine disorders
Senile e.g Hyperparathyroidism
Drugs
Idiopathic e.g. corticosteroids
Neoplasia
e.g. Multiple myeloma
Miscellaneous
e.g. Immobilization
Gastrointestinal
e.g. Malnutrition
 Characterized by increased porosity of the
skeleton
often results from a combination of age-related
bone loss and additional bone loss from another
cause; by far the most common such cause is
post-menopausal estrogen withdrawal
Pathogenesis
caused by a loss of coupling in the bone
remodelling process
 This can be due to
increased bone resorption,
decreased bone formation, or
Both
The loss of coupling results in a net loss of
bone volume
In contrast to osteomalacia , mineralisation of
bone is normal
 Osteoporosis is commoner in females than males
and is less common in blacks
Complications
The major complications of osteoporosis are:
skeletal deformity
bone pain (usually due to compression fracture)
fracture
The commonest clinical feature of osteoporosis is
the progressive loss of height that occurs with age
Diseases caused by osteoclast dysfunction
Paget disease (Osteitis deformans)
Characterized by episodes of localized, frenzied osteoclastic
activity and bone resorption, followed by exuberant bone
formation
Collage of matrix madness
Usually begins during mid-adult life and increases steadily
after that time
 There are three phases in the development of Paget disease:
An initial osteolytic stage
A mixed osteoclastic-osteoblastic stage with dominance of
osteoblastic activity
A burnt-out quiescent osteosclerotic stage
 Stage 1

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

Stage 3
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 , incidental radiographic findings
Pain localized to the affected bone-most common
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, kyphosis
High-output congestive heart failure
Transverse fractures of long bones (chalkstick fracture)
In about 1% of the cases osteosarcoma develops
Rickets and osteomalacia
characterized by deficient mineralisation of the organic
matrix of the skeleton
Rickets is the name given to osteomalacia affecting the
growing skeleton of children
Causes of osteomalacia, or rickets, 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 mineralisation 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
Other features
craniotabes
frontal bossing and a squared appearance to the head
rachitic rosary."
pigeon breast deformity
Harrison's groove
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
 When the levels of vitamin D metabolites are
low, calcification cannot occur and
cartilagenous 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
Bone Diseases Associated With
Hyperparathyroidism
Dicussed on endocrinology
OSTEOMYELITIS
Inflammation of bone and marrow cavity
caused by an infectious organism
offending organisms reach the bone by one of
three routes:
1. hematogenous dissemination,
2. direct extension from a focus of acute infection in the
adjacent joint or soft tissue, or
3. traumatic implantation after compound fractures or
orthopedic surgical procedures
 In most patients, osteomyelitis is hematogenous in
origin
In many cases the infection arises in a previously
healthy individual
other cases are associated with a more obvious
source of infection
Staphylococcus aureus is the most common
causative organism
Other common pathogens include pneumococci
and gram-negative rods,Escherichia coli and group
B streptococci
 Salmonella is an especially common pathogen
responsible for osteomyelitis occurring in
patients with sickle cell disease
Mixed bacterial infections, including anaerobes,
are responsible for many cases of osteomyelitis
developing after bone trauma
MORPHOLOGY
intense, neutrophilic inflammatory infiltrate at
the site of bacterial invasion
 The location of infection varies with age
In children, metaphyses of long bones are typically involved
In adults, hematogenous osteomyelitis primarily affects
vertebral bodies that remain quite vascular
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
The involved bone becomes necrotic
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
Chronic osteomyelitis
develops as a sequel of acute infection
Over time, an influx of chronic inflammatory cells into
the focus of osteomyelitis initiates a repair reaction
(osteoclast activation, fibroblastic proliferation, and
new bone formation)
Residual necrotic bone, termed the sequestrum, may
be resorbed by osteoclastic activity
Larger sequestra are eventually surrounded by a rim
of reactive bone, termed the involucrum
 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 include septicemia, acute
bacterial arthritis, squamous cell carcinoma,
amyloidosis
Clinical feature
Initially causes systemic manifestations similar
to those seen in any other acute infection,
such as fever, malaise, and leukocytosis
local pain, swelling, and redness may occur in
some adults
Tuberculous Osteomyelitis
Hematogenously born
Rarely direct extension e.g. 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 or cold abscess)
POTTs DISEASE
Clinical feature
Pain on motion
Swelling
Symptom complex of tuberculosis
Vertebral deformities (scoliosis , kyphosis)
Neurological deficits secondary to spinal cord and nerve
compression
 BONE TUMORS
Primary bone tumors are considerably less common
than are metastatic lesions
most common originating sites for bone metastases,
in descending order of frequency, are the
prostate,
breast,
lung,
kidney,
gastrointestinal tract, and
thyroid
 Metastases may be destructive (osteolytic) or associated
with reactive new bone formation (osteoblastic)
Most metastasis are osteolytic , some tumors e.g. prostate can
be osteoblastic
Some conditions are associated with increased risk of
bone tumors e.g. Paget disease of bone, chronic
osteomyelitis, and exposure to radiation
Few cases are associated with hereditary tumor
syndromes
Gardner syndrome (osteomas)
familial retinoblastoma (osteogenic sarcomas)
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
benign lesions of bone that (may be developmental aberrations
or reactive growths)
commonly encountered in the head and neck, including the
paranasal sinuses
present as localized, usually solitary, hard, exophytic growths
attached to the surface of the bone
Histologically, osteomas are composed of a bland mixture of
woven and lamellar bone, which may be difficult to distinguish
from normal bone
Osteoma
Involve skull and facial bones as a bossolated, round mass
Usually solitary
Middle age adults
Multiple in Gardner syndrome
Slowly growing ,impinge on brain or eyes or bring cosmetic
problems
Doesnt 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
Radiologic findings
well-circumscribed lesions, which usually involve the cortex
and rarely the medullary cavity of bone
Radiologic findings
well-circumscribed lesions, which usually
involve the cortex and rarely the medullary
cavity of bone
 Central hemorrhagic nidus
surrounded by dense rim of
sclerotic bone
Osteosarcoma (osteogenic sarcoma)
The most common primary malignant bone tumor
(exclusive of myeloma and lymphoma)
Malignant cells must produce osteoid
Peak in 2nd decade with gradual decrease thereafter
75% of cases are < 20yrs of age
M> F
Secondary osteosarcomas occur in an older age group
than do primary conventional osteosarcomas
Signs/Symptoms:
Pain and swelling
Pathologic fracture is uncommon
 Conventional osteosarcomas are aggressive lesions that
metastasize through the bloodstream early in their
course
The lungs are a common site of metastases
Anatomic Distribution:
60% arise around the knee
Metaphysis of long bones
 Characteristically destroys the cortex and frequently
extends inward into the marrow cavity and outward into
adjacent soft tissues
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
 Microscopy Osteoblastic, chondroblastic,
fibroblastic, telangiectatic, small cell and giant cell
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
Cartilaginous Tumors
Benign:
Chondroma
Osteochondroma
Chondroblastoma
Chondromyxoid Fibroma
Malignant:
Chondrosarcoma
 Osteochondroma
Also called exostoses
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)
Osteochondromas are mushroom shaped and range in size from
1 to 20 cm
First diagnosed in late adolescence and early adulthood
<1% risk of sarcomatous transformation
 Chondroma(enchondroma)
Benign tumor of mature hyaline cartilage
Most within bone (enchondroma)
Two syndromes characterized by multiple chondromas:
Olliers disease
Multiple enchondromas, usually unilateral
Maffuccis syndrome
Multiple enchondromas associated with soft tissue
hemangiomas
 Usually solitary involving the metaphyseal region of
tubular bones especially short bones of hand and feet
Enchondroma is the most common tumor of the
bones of the hand
Incomplete resection results in recurrence
Rare sarcomatous change is seen
Localized central lytic lesion surrounded
by sharp rim of sclerosis; cortex usually
not involved, though may be thin
 Composed of mature lobules of
hyaline cartilage with foci of myxoid
degeneration, calcification and
endochondral ossification; may be
quite cellular
 CHONDROBLASTOMA
RARE, in teenagers
M>>F
KNEES, usually
Epiphyses
MUCH LESS matrix than a chondroma
Chondrosarcoma
malignant neoplasms populated by mesenchymal cells
that produce a cartilaginous matrix
M:F -2:1
occur in older patients, with a peak incidence in the
sixth decade
They arise in central portions of the skeleton; common
sites of origin include the shoulder area, pelvis, proximal
femur, and ribs
 CHONDROSARCOMA
ANATOMY
INTRAMEDULLARY
JUXTACORTICAL
HISTOLOGY
CONVENTIONAL
HYALINE
MYXOID
CLEAR
DE-DIFFERENTIATED
MESENCHYMAL
 Ill-defined margins;
fusiform thickening of
shaft; perforation of cortex
Other Tumors and Tumor-like Conditions of Bone
Giant cell tumor of bone
Aka osteoclastoma
Signs/Symptoms:
Pain, loss of mobility, fracture
Age:
80% of patients > 20 years
Sex:
F>M
Anatomic Distribution:
Epiphysis of long bones
50% around knee with most in distal femur
Most common primary epiphyseal tumor of adults
 Grossly, a dark-brown appearance due to abundant vascularity
Histologically, they are composed of two major cell populations
Multinucleatede giant cells (osteoclast like)
Mononuclear cells
Behavior of these neoplasms is somewhat unpredictable
Recurrences are common after local curettage
Rarely sarcomatous transformation can occur
 Ewings family of tumors
Ewing sarcoma and PNET are primary malignant small
round cell tumors of bone and soft tissue
Viewed as the same tumor, differing only in their degree
of neural differentiation
identical chromosome translocation
Ewing sarcoma occurs predominantly in children and
adolescents
Peak incidence in the second decade of life
Highly aggressive neoplasm that must be differentiated
from other pediatric tumors composed of "small blue
cells
 Arises within the medullary cavity of the affected bone
to produce a soft, expansile mass
The femur, tibia, and pelvis are favored sites of origin
The tumor usually extends beyond the medullary cavity
into the cortical bone and periosteum
Usually arise in the diaphysis
Classically presents as pain, often accompanied by local
inflammation
 METASTATIC DISEASE
Most common form of skeletal malignancy
The pathways of spread include
direct extension
lymphatic or hematogenous dissemination, and
intraspinal seeding (Batson plexus of veins)
Skeletal metastases are typically multifocal
however, carcinomas of the kidney and thyroid are
notorious for producing solitary lesions
Red marrow with its rich capillary network, slow blood
flow, and nutrient environment facilitates implantation
and growth of the tumor cells
 FRACTURES, adjectives
Complete, incomplete
Closed, open (communicating)
Communited (splintered, greenstick)
Displaced (NON-aligned)
Pathogenic, (non-traumatic, 2 to other
disease, often metastases)
 FRACTURES
THREE PHASES
HEMATOMA, minutes days PGDF, TGF-, FGF
SOFT CALLUS (PRO-CALLUS), ~1 week
HARD CALLUS (BONY CALLUS), several weeks

COMPLICATIONS
PSEUDOARTHROSIS
INFECTION (especially OPEN [communicating]
fractures)
FRACTURES
 OSTEONECROSIS
Also called AVASCULAR necrosis
Also called ASEPTIC necrosis
CAUSE: ISCHEMIA
Trauma
Steroids
Thrombus/Embolism
Vessel injury, e.g., radiation
INCREASED intra-osseous pressurevascular
compression
 OSTEONECROSIS
Disorders Associated with Osteonecrosis
Idiopathic Pregnancy

Trauma Gaucher disease

Corticosteroid Sickle cell and other

anemias
administration
Infection Alcohol abuse
Dysbarism Chronic pancreatitis
Radiation therapy Tumors
Connective tissue Epiphyseal disorders
disorders
OSTEONECROSIS
 JOINTS
Joints are constructed to provide both
movement and mechanical support
classified as solid (nonsynovial) and cavitated
(synovial)
SYNOVIAL JOINTS
 Diseases of the Joints
Osteoarthritis
Also termed degenerative joint disease
Is the most common disorder of the joints
characterized by the progressive erosion of
articular cartilage
May arise without any obvious predisposing
factors (primary)
Secondary osteoarthritis refers to degenerative
changes developing 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
OA is characterized by significant changes in both
the composition and the mechanical properties of
cartilage
Early changes include , increased water and decreased
proteoglycans
Attempts for repair
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
Clinical features
Signs and symptomes develop gradually
The joints commonly involved include the hips,
knees, lower lumbar and cervical vertebrae,
proximal and distal interphalangeal joints of the
fingers
May be asymptomatic ,common complaints
include joint stiffness and deep, aching pain,
particularly in the morning
Some degree of joint swelling is common, and
small effusions may develop
HANDSWRISTELBOWS

The rheumatoid nodule shows palisading

fibroblasts
 JUVENILE RHEUMATOID ARTHRITIS (JRA)
Heterogeneous group of chronic arthritides that is a
major cause of functional disability
Types of JRA
oligoarticular (<5 joints involved)
polyarticular (5 or more joints involved) and
systemic variants
2:1 female predominance
By definition, it begins before age 16 and the
arthritis must be present for a minimum duration
of 6 weeks
 JRA differs from RA in adults in the following
ways:
oligoarthritis is more common
systemic onset is more frequent
large joints are affected more often than small
joints
rheumatoid nodules and rheumatoid factor are
usually absent, and
antinuclear antibody seropositivity is common
 Commonly targeted joints in JRA are the knees,
wrists, elbows, and ankles
They become warm and swollen and are often
involved symmetrically
Pericarditis, myocarditis, pulmonary fibrosis,
glomerulonephritis, uveitis, and growth
retardation are potential extra-articular
manifestations
 Clinical Features
Four steps in the clinical course
1. Asymptomatic hyperuricemia
-precedes clinical evident gout by many yrs
2. Acute gouty arthritis
-Initially monoarticular involvement later
polyarticular with fever
3. Intercritical period
Asymptomatic interval b/n attacks
4. Tophaceous gout
 In untreated patients in the form of tophi in
the cartilage, synovial membrane tendons and
soft tissue.
Tophus is a chalky yellow white deposit of
monosodium urate crystals
Classic locations are ear, heads, olecranon
bursa and in the Achilles tendon
 JOINT TUMORS
BENIGN
GANGLION (SYNOVIAL CYST)
GIANT CELL TUMOR of TENDON SHEATH, aka
PVNS, Pigmented VilloNodular Synovitis
MALIGNANT
SYNOVIAL SARCOMA
GANGLION
 Soft tissue tumors
Benign, malignant and intermediate
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 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
nerves
Rhabdomyoma Schwannoma
Rhabdomyosarcoma Neurofibroma
Fibroblastic tumors Malignant peripheral nerve
Nodular fasciitis sheath tumor
Fibromatoses Tumors of uncertain
Fibrosarcoma origin
Synovial sarcoma
 Lipoma
Very common benign tumor
Subcutaneous tissue of the trunk and limbs in the middle-
aged and elderly
Soft, slowly growing mass
Microscopic features: well-defined lobules of mature adipose
tissue
 Liposarcoma
Adults (peak incidence 40-60 years)
Site: lower limb and retroperitoneal space
Key diagnostic feature: multivacuolated lipoblast (two
or more lipid droplets within the cytoplasm)
Subtypes:
Well-differentiated, lipoma-like liposarcoma
(atypical lipomatous tumor):
Myxoid liposarcoma:
Pleomorphic liposarcoma:
Leiomyoma
Skin, subcutaneous tissue, uterus, gastrointestinal
tract
Microscopic features: 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
Rhabdomyoma
Extremely rare lesions
Rhabdomyosarcoma
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 of rhabdomyosarcoma:
Embryonal rhabdomyosarcoma:
most common, early childhood, head and neck region
and genitourinary system, small rounded or spindle-
shaped cells within a myxoid matrix
Bothryoid rhabdomyosarcoma (grape-like):
embryonal rhabdomyosarcoma with polypoid configuration
and myxoid consistency, occur in mucosa-lined organs
Alveolar rhabdomyosarcoma:
ages of 10 to 20 years, muscles of limbs and trunk
Pleomorphic rhabdomyosarcoma:
limbs of adults, large cells with eosinophilic cytoplasm
and either single or multiple highly atypical nuclei
Fibrous Tumors and Tumor-Like Lesions
1.Nodular fasciitis
Benign fibroblastic proliferation
Adolescents and young adults
Rapidly growing nodule within subcutaneous
tissue, forearm is the most common site
Microscopic features: plump immature
fibroblasts arranged in short bundles, numerous
mitoses, cellular pleomorphism not present
2.Superficial fibromatoses
Palmar fibromatosis (Dupuytrens contracture): middle-aged
men, nodular thickening of palmar aponeurosis leading later
to flexion deformities of fingers
 Plantar fibromatosis (Ledderhoses disease):
nodular thickening of plantar aponeurosis
 Penile fibromatosis (Peyronies disease):
abnormal curvature of penis
 Microscopic features: nodules of well-
differentiated fibroblasts arranged in long
sweeping bundles
 3. Deep fibromatoses (desmoid tumors)
Abdominal:
abdominal wall, young adults, particularly women
who have give birth, often detected in peripartum or
postpartum period, sometimes in surgical scars
Intra-abdominal:
young adults, mesentery, association with Gardners
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
4. Fibrosarcoma
Relatively uncommon malignant neoplasm
Middle aged adults
Deep soft tissues of lower limbs and trunk
Microscopic features: bundles of spindle
shaped cells arranged at angles to one another
(herring-bone pattern), frequent mitoses
Infantile fibrosarcoma: within the first two
years of life, much better prognosis
Fibrohistiocytic Tumors
1.Benign fibrous histiocytoma
(dermatofibroma)
Common lesion, most frequently on the skin of
lower leg
Papule or nodule, often deeply pigmented
Microscopic features: situated within the mid-
dermis, spindle cells arranged in curious whorled
pattern (storiform pattern)
2. 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
Synovial sarcoma
so named because it was once believed to
recapitulate synovium
but the cell of origin is still unclear
less than 10% are intra-articular
majority develop in the deep soft tissue in the
vicinity of the large joints of the extremities
The histologic hallmark of biphasic synovial
sarcoma is the dual line of differentiation of the
tumor cells (i.e., epithelial-like and spindle cells)
Tumors of peripheral nerve
1.Schwannoma (neurilemmoma)
Smooth lobulated lesion usually attached to a
nerve
Microscopic features: two patterns recognized:
Antoni A
compact areas formed by regular interlacing bundles of
uniform spindle-shaped cells, often foci of nuclear
palisading
Antoni B
looser open areas, small cells with rounded nuclei
 2.Neurofibroma
Not infrequently multiple, sometimes part of
neurofibromatosis
Infiltrates and expands the affected nerve
Microscopic features: spindle-shaped cells with
elongated wavy nuclei set in myxoid stroma
 Neurofibromatosis Type 1 (NF1)
autosomal-dominant disorder
NF1 gene, located at 17q11.2, has been identified
and encodes a protein termed neurofibromin
characterized by
neurofibromas (plexiform and solitary)
gliomas of the optic nerve
pigmented nodules of the iris (Lisch nodules)
cutaneous hyperpigmented macules (caf au lait spots)
 Neurofibromatosis Type 2 (NF2)
autosomal-dominant disorder
patients develop a range of tumors, most
commonly bilateral VIII nerve schwannomas
and multiple meningiomas
Gliomas, typically ependymomas of the spinal
cord, also occur in these patients
NF2 gene is located on chromosome 22q12,
and the gene product, merlin
3.Malignant peripheral nerve sheath
tumor (MPNST)
Adults, most common locations: neck,
forearm, lower leg, buttock
Large mass producing fusiform enlargement of
a major nerve
Microscopic features: relatively uniform
spindle-shaped cells with hyperchromatic
nuclei and high mitotic activity
Skeletal muscle & peripheral
nerve pathology
 The motor unit

Neurone Axon
NMJ

Diseases of neuromuscular
transmission
Diseases of Peripheral
neuropathies
motor neurones
Primary muscle
disease: myopathies
 General Reactions of the Motor Unit
The two main responses of peripheral nerve to injury are
based on the target of the insult:
Schwann cell or
the axon
Diseases that affect primarily the Schwann cell lead to a
loss of myelin, referred to as segmental demyelination
In contrast, primary involvement of the neuron and its
axon leads to axonal degeneration
Two principal pathologic processes seen in skeletal muscle
are
denervation atrophy follows loss of axons
Myopathy due to a primary abnormality of the muscle fiber
itself
 GENERAL Reactions
NERVE MUSCLE FIBER
DEMYELINATION NECROSIS
(segmental) VACUOLIZATION
AXONAL REGENERATION
DEGENERATION ATROPHY
NERVE HYPERTROPHY
REGENERATION
REINNERVATION
Sites of lesions producing neuromuscular pathology

Either the upper (1,2,3)

or lower motor
neurone pathway (4,5),
N-M-J (6) or muscle (7)
may be responsible
Spinal cord

M
Peripheral nerve

myelin
axon Node of ranvier
 Muscle disease

NMJ
UMN LMN
M

~ Muscle weakness and wasting the distribution of which depends

on the type of disease but strong tendency to involve proximal muscles
i.e trunk and limb girdles

~ Various causes
Classification

Inherited Acquired

Muscular dystrophies Endocrinopathies

Myotonic dystrophy Drug induced
Congenital myopathis Idiopathic
inflammatory
myopathy
Metabolic myopathies Metabolic
myopathy
Channelopathies Myasthenia Gravis
/LEMS
POLYMYOSITIS, usually endo-myseal
INCLUSION BODY MYOSITIS, rimmed vacuoles
 Myasthenia Gravis

NMJ
UMN LMN
M

~ Muscle weakness without wasting

~ Fatiguability
~ Ocular and bulbar muscles commonly involved
~ Responds well to treatment
 Common causes of peripheral neuropathy
1. Deficiency Vit B1 alcoholic
Vit B6 in pts taking isoniazid
Vit B12 in patients with PA and bowel disease

2. Toxic Alcohol
Drugs isoniazid, vincristine

3. Metabolic DM, CRF

4. Post-infectious Guillain- Barre syndrome

5. Collagen vascular RA, SLE, PA

6. Hereditary Charcot- Marie Tooth disease

7. Idiopathic Perhaps up to 50% cases

 NEUROPATHY, Inflammatory
Guillain-Barr
Preceded by influenza-like illness
NO actual specific etiologic agent isolated, autoimmune
disease to myelin gangliosides most likely
Inflammation of a peripheral nerve
DEMYELINATION
ASCENDING paralysis
Guillain-Barr, (AIDP), Acute Inflammatory Demyelinating Polyradiculoneuropathy
 NEUROPATHY, Infectious
Leprosy
Diphtheria
V/Z (Varicella-Zoster)