BONES AND MUSCLES

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BONES AND MUSCLES

• ROBERTO D. PADUA JR., MD, DPSP
• DEPARTMENT OF PATHOLOGY
• FATIMA COLLEGE OF MEDICINE

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SKELETAL DEVELOPMENTAL AND GENETIC DISORDERS

• CHONDRODYSPLASIAS
• Abnormalities in the size and shape of bones
• Disproportionate shortness in stature
• Named after the part of the bone affected
• Other names refer to the appearance of the bone
• Diastrophic (twisted)
• Thanatophoric (death-bearing)
• Metatropic (changing)
• Family history of disease is obligatory
• Radiologic appearance can be confused with other
  metabolic bone diseases
• Serum levels of biochemical markers are normal
• Bone is well mineralized

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SKELETAL DEVELOPMENTAL AND GENETIC DISORDERS

• 1. ACHONDROPLASIA
• Most common cause of disproportionately short
  stature
• 1 of 40,000 live births, autosomal dominant
• Head is large, frontal region is protuberant,
  nasal bridge is depressed
• Lordosis and lumbar kyphosis are present
• Anteroposterior flattening of the pelvic inlet
• Failure of normal endochondral ossification at
  the level of the proliferating and maturing
  cartilage

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SKELETAL DEVELOPMENTAL AND GENETIC DISORDERS

• 2. ACHONDROGENESIS
• Affected infants are either stillborn or do not
  survive the immediate neonatal period
• 2 syndromes
• a) Achondrogenesis I (Parenti-Fraccaro)
• Associated with congenital heart defects
• No ossification in the skull vertebral bodies
• b) Achondrogenesis II (Langer-Saldino)
• Shortened limbs disproportionately large head
• Underdeveloped ossification centers in the
  vertebral bodies and pelvis
• Epiphyseal cartilage is lobulated with increased
  vascularity
• Completely disorganized endochondral ossification
  of the growth plate and there is no column
  formation

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SKELETAL DEVELOPMENTAL AND GENETIC DISORDERS

• 3. THANATOPHORIC DYSPLASIA
• Infants are either stillborn or die of
  respiratory distress during the neonatal period
• Pattern of inheritance is unknown
• Length of trunk is normal but the head is large
  with cranio-facial disproportion
• Common CVS and CNS anomalies
• Pronounced platyspondyly of the lumbar vertebrae
  with an inverted U appearance
• Curvature of femurs with medial and lateral
  spikes at their lower ends short, flared ribs
• Endochondral ossification is disrupted at the
  growth plate, no regular column formation

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SKELETAL DEVELOPMENTAL AND GENETIC DISORDERS

• 4. CHONDROECTODERMAL DYSPLASIA
• Also known as Ellis-van Creveld syndrome
• Short limb dwarfism
• Consanguity is an important factor in the
  etiology of the disease
• Clinical presentation
• Narrowing of rib cage
• Congenital heart disease
• Ectodermal abnormalities
• Acromegalic micromelia (shortening of the distal
  segment of the limb

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SKELETAL DEVELOPMENTAL AND GENETIC DISORDERS

• 5. ASPHYXIATING THORACIC DYSPLASIA
• Jeunes syndrome
• Narrowing of the chest and immobility
• Stippled epiphyses and chondroplasia punctata are
  striking features on x-ray

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SKELETAL DEVELOPMENTAL AND GENETIC DISORDERS

• 6. OSTEOPETROSIS
• Marble bone disease
• Defective osteoclast function that impairs
  skeletal resorption
• Primary spongiosa persists during adult life
• Increased incidence of parental consanguity
• Early symptom is malformation of mastoid and
  paranasal sinuses
• Pathognomonic histologic finding is the failure
  of osteoclast to resorb skeletal tissue

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SKELETAL DEVELOPMENTAL AND GENETIC DISORDERS

• 7. PROGRESSIVE DIAPHYSEAL DYSPLASIA
• Camurati-Engelman disease
• Rare autosomal dominant disorder
• Formation of new bone at both the periosteal and
  endosteal surfaces

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SKELETAL DEVELOPMENTAL AND GENETIC DISORDERS

• 8. ENDOSTEAL HYPEROSTOSIS
• Van Buchem disease
• Autosomal dominant/recessive disorder
• Progressive enlargement of mandible during
  puberty
• Radiographic feature dense and homogenous
  diaphyseal cortex with narrowing of the medullary
  canal

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SKELETAL DEVELOPMENTAL AND GENETIC DISORDERS

• 9. OSTEOPOIKILOSIS
• Presence of numerous foci of sclerosis in
  cancellous bone (spotted bones)
• Autosomal dominant disorder
• Bone changes are asymptomatic
• Found incidentally on radiographs

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SKELETAL DEVELOPMENTAL AND GENETIC DISORDERS

• 10. OSTEOPATHIA STRIATA
• Characterized by linear striations at the ends of
  long bones and in the ilium
• X-ray shows gracile linear striations in the
  cancellous region of the skeleton
• Autosomal dominant trait

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SKELETAL DEVELOPMENTAL AND GENETIC DISORDERS

• 11. MELORHEOSTOSIS
• Characterized by hyperostosis of the limb bones
• X-ray likened to appearance of melted wax that
  is dripped down the side of the candle
• Typical histologic finding is endosteal thickening

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SKELETAL DEVELOPMENTAL AND GENETIC DISORDERS

• 12. PACHYDERMOPERIOSTOSIS
• Hypertrophic osteoarthropathy
• Characterized by clubbing of digits,
  hyperhidrosis, thickening of skin around the face
  and forehead and periosteal new bone formation in
  the distal limbs
• Inherited as autosomal dominant trait
• Mengtwomen
• X-ray shows thickening and sclerosis of the
  distal portions of the tubular bones

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SKELETAL DEVELOPMENTAL AND GENETIC DISORDERS

• 13. OSTEOGENESIS IMPERFECTA
• Brittle bone disease
• Hereditary disorder involving defects in the
  synthesis or structure of collagen type I
• Cardinal features osteopenia associated with
  recurrent fracture and skeletal deformity
• Biochemical findings increased AP, increased
  level of hydroxyproline, hypercalciuria
• Histology abnormal skeletal matrix
  cartilaginous bars formed by vascular invasion of
  the metaphyses do not become envelop by bones
  cortical bone is almost non-existent

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METABOLIC BONE DISEASES

• 1. OSTEOPOROSIS
• Loss of normally minerralized bone
• Diagnosed clinically with non-invasive
  radiographic techniques that measures bone
  density
• Changes in the bone
• Structurally weak
• Loss of trabecular bone
• Enlargement of the medullary space
• Cortical porosity
• Reduction in cortical thickness

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METABOLIC BONE DISEASES

• 2. RENAL OSTEODYSTROPHY
• Seen in patients with advanced renal failure
• Clinical presentations
• Bone pain (most common), spontaneous fractures,
  aseptic necrosis of hip, myopathy
• Laboratory findings
• Low levels of 125(OH)2D3, hyperphosphatemia,
  hypocalcemia, alterations in the secretion or
  activity of PTH
• X-ray
• Subperiosteal erosions, patchy osteosclerosis
  (rugger jersey appearance of thoracic vertebral
  spine on lateral views, salt and pepper
  appearance of skull, slipped epiphyses

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METABOLIC BONE DISEASES

• 3. OSTEOMALACIA
• Defective mineralization of the trabecular and
  cortical bone matrix
• Associated with decreased serum calcium phosphate
  product
• A common complication of chronic renal failure in
  adults
• Secondary to Vitamin D deficiency
• Histologically characterized by excessive
  quantities of osteoid because of the failed
  matrix calcification despite continued matrix
  synthesis by the osteoblasts

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METABOLIC BONE DISEASES

• 4. RICKETS
• Defective mineralization of the epiphyseal growth
  plate cartilage
• Clinical features craniotabes, frontal bossing,
  rachitic rosary, pectus excavatum, Harrisons
  groove, thoracic kyphosis, rachitic potbelly,
  genu varum/genu valgum
• Histologic appearance
• Rachitic growth plate is wide and irregular
• Columnar rearrangement of the hypertrophic
  chondrocyts is lost
• Zone of provisional calcification disappears
• Cartilage extends deep into the metaphyses

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TRAUMA

• FRACTURE REPAIR
• Blastema ? wound closure ? scar formation
• Initial repair tissue formed is called a CALLUS
  which is composed of fibrous tissue, woven bone
  and cartilage
• 3 phases of fracture healing
• A) inflammatory phase
• B) reparative phase orderly removal and
  replacement of immature woven bone by cartilage
  differentiation
• C) modeling phase realignment mechanical
  shaping of the bone and callus restoration of
  the medullary cavity and bone marrow
• Complications of fracture healing
• A) nonunions
• B) fibrous union

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INFLAMMATORY BONE DISORDERS

• OSTEOMYELITIS
• Classified according to several factors
• 1. its duration acute, subacute or chronic
• 2. nature of the exudate hemorrhagic, purulent,
  or nonsuppurative
• 3. its location bone, periosteum, or epiphyses
• 4. etiologic agent Staphylococcus, Tb, etc.
• Histologically, inflammatory cells are seen
• Loss of normal marrow architecture
• Hematopoietic elements and fat are replaced by
  leukocytic infiltrates

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INFLAMMATORY BONE DISEASES

• OSTEOMYELITIS..
• Chronic sclerosing osteomyelitis of Garre
• A chronic form of osteomyelitis with findings of
  dense, scarred bone and few clinical symptoms
  without any abscess formation.
• Brodies abscess
• Osteomyelitis sharply limited to one side with
  formation of abscess cavity surrounded by a rim
  of sclerotic bone.
• Causes
• Coagulase () Staph. Aureus (60-90)
• Strep, Pneumococcus, E. coli, Klebsiella,
  Salmonella, Bacteroides

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INFLAMMATORY BONE DISEASES

• OSTEOMYELITIS..
• Causes
• Tuberculosis
• Spread hematogenously
• Characteristic lesion Chronic caseating
  granulomatous inflammation which often involves
  the subchondral part of the joint. Sequestrum
  forms in the subchondral bone and articular
  cartilage resulting in a kissing sequestrum.
• Potts disease Tb of the spine

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OSTEOMYELITIS
X-RAY
GROSS UPPER FEMUR
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INFLAMMATORY BONE DISEASES

• SARCOIDOSIS
• Noncaseating granulomatous process
• Manifest as small lytic and sclerotic foci in the
  bones of the hand
• Large areas of destruction are not typically found

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INFLAMMATORY BONE DISEASES

• PAGETS DISEASE OF BONE (OSTEITIS DEFORMANS)
• A chronic osteolytic and osteosclerotic disease
  of uncertain cause
• May involve one or more bones
• Presents with pain, skeletal deformities, and
  occasionally sarcomatous transformation
• Usually affects 3 of white population over 40
  y/o
• Incidence increases with age mengtwomen
• Most patients are asymptomatic (80-90)

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INFLAMMATORY BONE DISEASES

• PAGETS DISEASE OF BONE..
• Common skeletal sites of involvement are the
  sacrum, spine, pelvis, skull, femur, clavicle,
  tibia, ribs, and humerus
• Histopathology
• Normal marrow is replaced by a richly vascular,
  loose fibrous connective tissue
• Isolated clusters of inflammatory cells may be
  seen
• Osteoclasts aggregate on the existing bone
  trabeculae and within the cortex
• Innumerable small, irregularly shaped bone
  fragments (mosaic pattern)
• Grossly resembles the gritty but brittle texture
  of pumice or lava rock

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INFLAMMATORY BONE DISEASES

• PAGETS DISEASE OF BONE.
• X-RAY flocculant, radiopaque deposit likened to
  cotton wool. Pelvis is the most common site of
  involvement.
• Elevated AP and osteocalcin level
• Elevated urinary excretion of hydroxyproline,
  pyridinoline and deoxypyridinoline
• Malignant transformation are also observed
• Osteosarcomas
• Fibrosarcomas
• Giant cell malignant fibrous histiocytoma

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PAGETS DISEASE OF BONE
EARLY CHANGES SHOWING PROMINENT OSTEOCLASTIC
ACTIVITY
X-RAY OF TIBIA SHOWING BONE DESTRUCTION AND BONE
FORMATION
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DEGENERATIVE DISEASES OF BONE

• OSTEONECROSIS
• Infarction of bone typically involving the
  femoral head
• 3 generic categories postfracture, idiopathic,
  and renal transplant associated
• Also known as avascular necrosis of bone
• Earliest histologic changes are death of the bone
  and the surrounding hematopoietic fatty marrow
• X-ray Crescent sign , a separation of
  fracture cleft forms between the impacted
  fragments and the overlying subchondral plate.
  Increased density within the necrotic bone.

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BONE TUMORS

• Most malignant tumors arise de novo
• Benign bone lesions that predispose to the
  development of skeletal malignancies
• Pagets disease, chondromatosis,
  osteochondromatosis, fibrous dysplasia, and
  osteofibrous dysplasia
• Five basic parameters in the diagnosis of bone
  tumors
• Age of the patient
• Bone involved
• Specific area within the bone
• Radiographic appearance
• Microscopic appearance

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BONE FORMING TUMORS

• 1. OSTEOMA
• Seen almost exclusively in the flat bones of
  skull and face
• Microscopically composed of dense, mature,
  predominantly lamellar bone
• Benign
• Associated with Gardners syndrome

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BONE-FORMING TUMORS

• 2. OSTEOID OSTEOMA
• Benign neoplasm seen in patients between 10 and
  30 y/o
• 21 male-female ratio
• Intense pain is the most prominent symptom
• Reported in practically every bone, most are
  centered in the cortex (85), spongiosa (13), or
  subperiosteal region (2)
• X-ray typical finding is a radiolucent nidus
  that is seldom larger than 1.5 cm and may or may
  not contain a dense center. This nidus is
  surrounded by a peripheral sclerotic reaction.
• Microscopic sharply delineated central nidus
  composed of more or less calcified osteoid lined
  by plump osteoblast and growing within
  vascularized connective tissue, without evidence
  of inflammation.

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OSTEOID OSTEOMA
MICROSCOPIC
GROSS
X-RAY
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BONE-FORMING TUMORS

• 2. OSTEOBLASTOMA
• Benign osteoblastoma, giant osteoid osteoma
• Closely related to osteoid osteoma both
  microscopically and ultrastructurally
• It has a larger size of the nidus, absence of
  surrounding area of reactive bone formation, and
  the lack of intense pain
• A cartilaginous matrix is present in some cases
• Most cases arise in the spongiosa of the bone
  involving the spine or major bones of the lower
  extremity
• Osteomalacia can be seen as a complication

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BONE-FORMING TUMORS

• 3. OSTEOSARCOMA
• The most frequent primary malignant tumor,
  exclusive of hematopoietic malignancy
• Usually occurs in patients between 10 and 25
  years of age and is rare in pre-school children
• Another peak age incidence occurs after the age
  of 40, in association with other disorders
• Most osteosarcomas arise de novo, but others
  arise within the context of a preexisting
  condition
• Pagets disease, radiation exposure,
  chemotherapy, preexisting benign bone lesions,
  foreign bodies, trauma

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BONE-FORMING TUMORS

• OSTEOSARCOMA..
• Located in the metaphyseal area of long bones,
  particularly the lower end of femur, upper end of
  the tibia, and the upper end of the humerus
• Large majority arise within the medullary cavity
  from which they extend into the cortex
• Gross appearance varies depending on the relative
  amounts of bone, cartilage, cellular stroma and
  vessels ? bony hard to cystic, friable, and
  hemorrhagic
• From its usual origin in the metaphysis of a long
  bone, the tumor may spread along the marrow
  cavity, invade the adjacent cortex, or elevate or
  perforate the periosteum (Codmans triangle)

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BONE-FORMING TUMORS

• OSTEOSARCOMA..
• Extend into the soft tissues, extend into the
  epiphysis, extend into the joint space, form
  satellite nodules independent from the main tumor
  mass proximal to the primary lesion (skip
  metastases), metastasize through the blood
  stream to distant sites particularly the lung.

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BONE-FORMING TUMORS

• OSTEOSARCOMA..
• Microscopic features
• May destroy preexisting bone trabeculae or grow
  around them in an appositional fashion
• Key feature is the presence of osteoid and or
  bone produced directly by tumor cells without
  interposition of cartilage
• Osteoblastic areas are often mixed with
  fibroblastic and chondroblastic foci
• Tumor cells may grow in diffuse, nesting or
  pseudopapillary arrangements

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BONE-FORMING TUMORS

• OSTEOSARCOMA..
• OS cells usually exhibit strong AP activity,
  regardless of their appearance
• Ultrastructurally, tumor cells resemble normal
  osteoblasts
• Consistently expresses Vimentin
• In some cases, they are positive for smooth
  muscle actin, desmin, EMA, S-100 protein
• Osteonectin, osteocalcin, osteopontin bone
  morphogenetic protein and bone GLA protein have
  been identified immunohistochemically

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BONE-FORMING TUMORS

• OSTEOSARCOMA..
• Microscopic variants
• Telangiectatic
• Small cell
• Fibrohistiocytic
• Anaplastic
• Well-differentiated intramedullary
• Others parosteal (juxtacortical), periosteal

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OSTEOSARCOMA
GROSS SHOWING SKIP METASTASIS
MICROSCOPIC APPEARANCE
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OSTEOSARCOMA
TELANGIECTATIC VARIANT OF OSTEOSARCOMA
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OSTEOSARCOMA
JUXTACORTICAL OSTEOSARCOMA
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BONE-FORMING TUMORS

• OSTEOSARCOMA..
• Diagnosis characteristic radiographic
  appearance, open biopsy, needle biopsy, FNAB,
  frozen section.
• Therapy amputation or disarticulation. At
  present, limb-sparing procedures coupled with
  other therapeutic modalities.
• Prognosis
• Poor presence of Pagets disease, multifocal
  OS, chondroblastic type, Telangiectatic variant,
  elevated AP, low postchemotherapy tumor necrosis,
  loss of heterozygosity of the RB gene, HER2/neu
  expression, expression of P-glycoprotein

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CARTILAGE-FORMING TUMORS

• 1. CHONDROMA
• A common benign cartilaginous tumor that occurs
  most frequently in the small bones of the hands
  and feet, particularly the proximal phalanges
• 30 are multiple
• Microscopically, they are composed of mature
  hyaline cartilage. Foci of myxoid degeneration,
  calcification, and endochondral ossification are
  common
• Enchondromas begins in the spongiosa of the
  diaphysis from which they expand and thin out the
  cortex
• Lesions with predominantly unilateral
  distribution are referred to as Olliers disease
• Its association with soft tissue hemangiomas is
  known as Maffuccis syndrome

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CHONDROMA
MICROSCOPIC
X-RAY
GROSS
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CARTILAGE-FORMING TUMORS

• 2. OSTEOCHONDROMA
• Most frequent benign tumor
• Usually asymptomatic, but may lead to deformity
  or interfere with the function of adjacent
  structures such as tendons and blood vessels
• Most common locations are metaphyses of the lower
  femur, upper tibia, upper humerus and pelvis
• Average age of onset is 10 y/o, majority appears
  before the age of 20
• Average greatest diameter is 4 cm but may reach
  10 cm or more
• A cap of cartilage covered by fibrous membrane
  continous with the periosteum of the adjacent
  bone
• Microscopically, the cells resemble those of
  normal hyaline cartilage. Eosinophilic, PAS-()
  inclusions may be seen in the cytoplasm. The bulk
  of the lesion is composed of mature bone
  trabeculae located beneath the cartilaginous cap
  and containing normal bone marrow.

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OSTEOCHONDROMA
GROSS, CUT SECTION
MICROSCOPIC
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CARTILAGE-FORMING TUMORS

• 3. CHONDROBLASTOMA
• Occurs predominantly in males under 20 y/o
• Usually arises in the epiphyseal end of long
  bones before the epiphyseal cartilage has
  disappeared, particularly in the distal end of
  femur, proximal end of humerus, and proximal end
  of tibia
• X-ray tumor is fairly well delimited and
  contains areas of rarefaction
• Microscopic
• the basic tumor cell is an embryonic
  chondroblast with only a limited capacity for the
  production of cartilaginous matrix.
• Presence of occasional scattered giant cells

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CARTILAGE-FORMING TUMORS

• CHONDROBLASTOMA..
• Microscopic
• Cells are usually polyhedral with round to
  indented nuclei. Reticulin fibers surround each
  individual cell.
• Presence of small zones of focal calcification
  (chicken wire)
• Diagnosis can be made by fine needle aspiration
  which will show neoplastic chondroblast,
  multinucleated osteoclast-like giant cells, and
  chondroid myxoid fragments
• Treatment is by curettement with bone grafting

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CHONDROBLASTOMA
X-RAY
GROSS
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CHONDROBLASTOMA
MICROSCOPIC
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CARTILAGE-FORMING TUMORS

• 4. CHONDROMYXOID FIBROMA
• An unusual benign tumor
• Usually occurs in long bones of young adults
• Radiographically, it is sharply defined and may
  attain a large size
• Grossly, it is solid and yellowish white or tan,
  replaces bone and thins the cortex.
• Microscopically, shows hypocellular lobules with
  a chondromyxoid appearance separated by
  intersecting bands of fibroblast-like spindle
  cells and osteoclasts
• Strong positivity to S-100 protein
• Treatment is by curettage with a recurrence rate
  of 25

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CHONDROMYXOID FIBROMA
X-RAY
GROSS
MICROSCOPIC
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CARTILAGE-FORMING TUMORS

• 5. CHONDROSARCOMA
• A malignant tumor of cartilage-forming tissues
• Divided into conventional and variants
• Conventional chondrosarcoma can be
• Central located in the medullary cavity,
  usually of flat or long bone. X-ray show
  osteolytic lesion with splotchy calcification
  with ill-defined margins, fusiform thickening of
  the shaft, and perforation of the cortex
• Peripheral may arise de novo or from the
  cartilaginous cap of a preexisting osteochondroma
• Juxtacortical (periosteal) involves the shaft
  of a long bone characterized by a cartilaginous
  lobular pattern with areas of splotchy
  calcification and endochondral ossification

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CARTILAGE-FORMING TUMORS

• CHONDROSARCOMA..
• Microscopically, there is production of
  cartilaginous matrix and the lack of direct bone
  formation by the tumor cells
• Soft tissue implantation following biopsy is a
  well known complication
• Chondrosarcoma variants
• Clear cell chondrosarcoma
• Myxoid chondrosarcoma
• Dedifferentiated chondrosarcoma
• Mesenchymal chondrosarcoma

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CHONDROSARCOMA
GROSS APPEARANCES OF CHONDROSARCOMA
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CHONDROSARCOMA
X-RAY, FEMUR
60
CHONDROSARCOMA
WELL-DIFFERENTIATED
CLEAR CELL VARIANT
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GIANT CELL TUMOR

• Osteoclastoma
• Patients are over 20 years of age
• More common in women then men
• More frequently in Oriental than Western
  countries
• Classic location is epiphysis of long bone
• Affects more commonly the lower end of femur,
  upper end of tibia, and lower end of the radius.
  It also occurs in the humerus, fibula, and skull
  particularly the sphenoid bone.
• Multicentricity has been reported particularly in
  young patients and in the small bones of hands
  and feet

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GIANT CELL TUMOR

• X-ray
• The typical appearance is that of an entirely
  lytic, expansile lesion in the epiphysis, usually
  without peripheral bone sclerosis, or periosteal
  reaction
• Gross
• The size of the tumor varies when large, it may
  be associated with a pathologic fracture
• The cut surface is solid and tan or light brown,
  traversed by fibrous trabeculae, and often
  contains hemorrhagic areas
• The cortex is thinned, but periosteal new bone
  formation is rare

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GIANT CELL TUMOR

• Microscopic
• Two main components are stromal cells and giant
  cells
• The giant cells are usually large and have over
  twenty or thirty nuclei, most of then are
  arranged toward the center.
• They resemble osteoclasts at all levels
  ultrastructurally, enzyme histochemically and
  immunohistochemical
• Result of fusion of circulating monocytes that
  have been recruited into the lesion
• Possible mechanisms
• Autocrine or paracrine loop mediated by
  transforming growth factor beta

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GIANT CELL TUMOR

• Microscopic..
• Possible mechanisms.
• 2. Production of osteoprotegerin ligand (a factor
  essential for osteoclastogenesis)
• 3. Expression of the ligand for RANK (receptor
  activator of nuclear factor Kappa B)
• Mononuclear stromal cells is the only
  proliferating element in the lesion and the one
  exhibiting atypia in the rare cytologically
  malignant examples of this tumor
• These changes may be focal, hence a thorough
  sampling is required
• Produces type I III collagen and has receptors
  for PTH

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GIANT CELL TUMOR
X-RAY
GROSS APPEARANCE
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GIANT CELL TUMOR
MICROSCOPIC APPEARANCE
67
GIANT CELL TUMOR

• Frequent positivity for S-100 protein
• Many benign lesions with giant cells have been
  diagnosed as giant cell tumor in the past
• A diagnosis of a lesion other than GCT should be
  favored if
• 1. patient is a child
• 2. lesion is located in the metaphysis or
  diaphysis of a long bone
• 3. lesion is multiple
• 4. lesion is located in the vertebrae, jaw, or
  bones of the hands or feet

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GIANT CELL TUMOR

• Treatment
• Surgical consists of curettage with bone
  grafting or en bloc resection with allograft or
  artificial material
• Use of radiation therapy should be reserved only
  for cases in which surgical removal is impossible

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MARROW TUMORS

• 1. EWINGS SARCOMA/PRIMITIVE NEUROECTODERMAL
  TUMOR (PNET)
• Undifferentiated type of bone sarcoma in children
• Related to the neoplasm originally described in
  the soft tissues as primitive (peripheral)
  neuroectodermal tumor
• Usually seen in patients between the ages of 5
  and 20 years
• Clinically, the tumor may simulate OM because of
  pain, fever, and leukocytosis

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EWINGS/PNET

• Occurs most often in long bones (femur, tibia,
  humerus, and fibula) and in the bones of the
  pelvis, rib, vertebrae, mandible and clavicle
• It generally arises in the medullary canal of the
  shaft, from which it permeates the cortex and
  invade the tissues
• Can present clinically as a soft tissue neoplasm
  with a normal appearance of the underlying bone
  on plain x-ray films
• X-ray cortical thickening and widening of the
  medullary canal. With progression of the lesion,
  reactive periosteal bone may be deposited in
  layers parallel to the cortex (onion-skin
  appearance) or at right angle to it (sun-ray
  appearance)

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EWINGS SARCOMA/PNET

• Microscopic
• Consists of solid sheets of cells divided into
  irregular masses by fibrous bands
• Individual cells are small and uniform
• The cells outline are indistinct, resulting in a
  syncitial appearance
• The nuclei are round, with frequent indentations,
  small nucleoli and variable but usually brisk
  mitotic activity
• There is well developed vascular network
• Pseudorosettes and rosettes arrangement of cells
  may be seen

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EWINGS SARCOMA/PNET
X-RAY
GROSS APPEARANCE
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EWINGS SARCOMA/PNET
MICROSCOPIC APPEARANCE
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EWINGS SARCOMA/PNET

• Cells contains large amounts of cytoplasmic
  glycogen --- () PAS
• Ultrastructurally, a few dense core granules will
  be found either in the cell cytoplasm or in cell
  prolongations
• Immunohistochemically, positive for vimentin, LMW
  keratin, NSE, protein gene product 9.5, Leu7, and
  neurofilaments
• Over 95 of cases show a reciprocal translocation
  1122 (q24q12), which results in the fusion of
  EWS gene with FLI or ERG genes

75
EWINGS SARCOMA/PNET

• Metastatic spread is to the lungs and pleura,
  other bones (particularly the skull), CNS, and
  (rarely) regional LN
• About 25 of the patients have multiple bone
  and/or visceral lesions at the time of
  presentation
• Treatment
• Combination of high-dose irradiation and
  multidrug chemotherapy sometimes combined with
  limited surgery

76
MARROW TUMORS

• 2. MALIGNANT LYMPHOMA
• Can involve the skeletal system primarily or as a
  manifestation of a systemic disease
• LARGE CELL LYMPHOMA
• More common in adults than in children
• 60 of cases occurring in patients over 30 y/o
• No sex predilection
• Most cases involve the diaphysis or metaphysis og
  long bones or vertebrae producing patchy cortical
  and medullary destruction associated with minimal
  to moderate periosteal reaction
• The tumor is pinkish gray and granular,
  frequently extends into the soft tissues and
  invades the muscle

77
MALIGNANT LYMPHOMA

• LARGE CELL LYMPHOMA..
• Radiographically, a combination of bone
  production and bone destruction often involves a
  wide area of a long bone
• Microscopically, the appearance is similar to
  that of the large cell lymphoma in nodal and
  other extranodal sites, some cases are
  accompanied by prominent fibrosis
• The 5-year survival rate for localized B-cell
  lymphoma of bone has ranged from 30-60
• The stage of the disease is the single most
  important prognostic determinator

78
MALIGNANT LYMPHOMA
MICROSCOPIC APPEARANCE
X-RAY
79
MALIGNANT LYMPHOMA

• HODGKINS LYMPHOMA
• Produces radiographically detectable bone lesions
  in approximately 15 of the patients
• Involvement is multifocal in about 60 of cases,
  most frequent sites being vertebrae, pelvis,
  ribs, sternum, and femur
• Osseous lesions are often asymptomatic and in
  half of the cases are not demonstrable
  radiographically

80
MALIGNANT LYMPHOMA

• Anaplastic large cell lymphoma
• Burkitts lymphoma
• Lymphoblastic lymphoma

81
ACUTE LEUKEMIA

• Associated with radiographic abnormalities in the
  skeletal system in 70-90 of cases
• Destructive bone lesions are extremely rare in
  the chronic leukemias

82
VASCULAR TUMORS

• 1. HEMANGIOMA
• Often seen in the vertebrae as an incidental
  post-mortem finding
• The most common locations are the skull,
  vertebrae, and jaw
• Cut section has a currant jelly appearnce
• Microscopically, there is a thick-walled
  lattice-like pattern of endothelial lined
  cavernous spaces filled with blood
• Multiple hemangiomas are mainly seen in children
  and are associated in about half of the cases
  with cutaneous, soft tissue, or visceral
  hemangiomas

83
VASCULAR TUMORS

• 2. MASSIVE OSTEOLYSIS
• Gorhams disease
• Not a vascular neoplasm
• Has microscopic similarities with skeletal
  angiomatosis
• It has a destructive character
• It results in reabsorption of a whole bone or
  several bones and the filling of the residual
  spaces by a heavy vascularized fibrous tissue

84
VASCULAR TUMORS

• 3. LYMPHANGIOMAS
• Most cases are multiple and associated with soft
  tissue tumors of similar appearance
• 4. GLOMUS TUMOR
• May erode the underlying bone
• 5. HEMANGIOPERICYTOMA
• Can present as a primary bone lesion, most common
  location is the pelvis

85
VASCULAR TUMORS

• 6. EPITHELIOID HEMANGIOENDOTHELIOMA
• A borderline type of vascular neoplasm
  characterized microscopically by the presence
  epithelial- or histiocyte-like endothelial cells
  with abundant acidophilic and often vacuolated
  cytoplasm, large vesicular nucleus, modest
  atypia, scanty mitotic activity, inconspicous or
  absent anastomosing channels, recent and old
  hemorrhage and an inconstant but sometimes
  prominent inflammatory component rich in
  eosinophils

86
VASCULAR TUMORS

• 7. ANGIOSARCOMA
• Malignant hemangioendothelioma,
  hemangioendothelial sarcoma
• Exhibits obvious atypia of the tumor cells,
  formation of solid areas alternating with others
  with anastomosing vascular channels, and foci of
  necrosis and hemorrhage
• Multicentricity is common
• Distant metastasis are common, particularly lungs

87
VASCULAR TUMORS
CAVRNOUS HEMANGIOMA OF BONE
88
VASCULAR TUMORS
EPITHELIOID HEMANGIOENDOTHELIOMA
89
METASTATIC TUMORS

• In most cases the lesions are multiple
• More than 80 arises from the breast, lung,
  prostate, thyroid, or kidney
• These metastases can be accompanied by visceral
  deposits or represent the only apparent site of
  dissemination
• Soft tissue sarcomas rarely metastasize to the
  bones except embryonal rhabdomyosarcoma in
  children
• They are usually osteolytic but maybe
  osteoblastic or mixed

90
Metastatic tumors

• The mechanism is thought to be the production of
  bone growth factors by tumor cells, such as
  TGF-beta, fibroblast growth factor, and bone
  morphogenetic proteins
• Symptoms is usually pain
• Treatment is relief of pain and to prevent
  fracture of weight-bearing bones

91
TUMORLIKE LESIONS

• 1. SOLITARY BONE CYST
• Unicameral bone cyst
• Usually occur in long bones, most often in the
  upper portion of the shaft of the humerus and
  femur
• Also seen in the short bones, calcaneus
• Mostly affects males and are seen in patients
  under 20 years
• Usually are advanced when first seen, most are
  centered in the metaphysis and they migrate away
  from the epiphyseal line

92
TUMORLIKE LESIONS

• SOLITARY BONE CYST.
• The cysts contains a clear or yellow fluid that
  is lined by a smooth fibrous membrane
• Maybe hemorrhagic if previous fracture occurred
• Microscopic well-vascularized connective tissue,
  hemosiderin and cholesterol clefts are frequent
• Treatment of choice is curettement and
  replacement of the cyst with bone chips

93
SOLITARY BONE CYST
X-RAY
GROSS APPEARANCE
94
TUMORLIKE LESIONS

• 2. ANEURYSMAL BONE CYST
• Usually seen in patients between 10 and 20 years
  of age
• More common in females
• Occurs mainly in the vertebrae and flat bones but
  can also arise in the shaft of long bones
• Multiple involvement is common in the vertebral
  lesions
• X-ray shows eccentric expansion of the bone with
  erosion and destruction of the cortex and a small
  area of periosteal new bone formation

95
TUMORLIKE LESIONS

• ANEURYSMAL BONE CYST.
• GROSS it forms a spongy hemorrhagic mass covered
  by a thin shell of reactive bone, which may
  extend into the soft tissue
• Microscopic
• show large spaces filled with blood
• They do not contain endothelial lining but are
  rather delimited by cells with similar features
  to fibroblast, myofibroblasts, and histiocytes
• A row of osteoclasts is often seen immediately
  beneath the surface
• There is significant deposition of generated
  calcifying fibromyxoid tissue.

96
TUMORLIKE LESIONS

• ANEURYSMAL BONE CYST.
• Pathogenesis is still unknown
• In a few cases, the lesion is preceded by trauma
  with fracture or subperiosteal hematoma
• It may also arise in some preexisting bone lesion
  as a result of changed hemodynamics
• Insulin-like growth factor-I may play in its
  pathogenesis
• Ddx chondroblastoma, GCT, fibrous dysplasia,
  nonossifying fibroma, osteoblastoma,
  chondrosarcoma
• Treatment en bloc resection or curettage with
  bone grafting

97
ANEURYSMAL BONE CYST
GROSS APPEARANCE
X-RAY
98
ANEURYSMAL BONE CYST
MICROSCOPIC APPEARANCE
99
TUMORS OF SKELETAL MUSCLES

• RHABDOMYOSARCOMA
• Most common soft tissue sarcoma of childhood and
  adolescence
• Usually appears before the age of 20
• Commonly occurs in the head and neck or
  genitourinary tract, extremities
• Cytogenic abnormalities
• t(213)(q35q14)
• t(113)(q3614)

100
TUMORS OF SKELETAL MUSCLES

• RHABDOMYOSARCOMA
• In the more common translocation, t(213), the
  PAX3 gene on chromosome 2 fuses with the FKHR
  gene on chromosome 13
• PAX3 gene functions upstream of genes that
  control muscle differentiation
• Pathogenesis of tumor involves dysregulation of
  muscle differentiation by the chimeric PAX3-FKHR
  protein

101
TUMORS OF SKELETAL MUSCLES

• RHABDOMYOSARCOMA MORPHOLOGY
• EMBRYONAL
• ALVEOLAR
• PLEOMORPHIC
• Diagnostic cell is the RHABDOMYOBLAST
• contains eccentric eosinophilic granular
  cytoplasm rich in thick and thin filaments
• may be round or elongated (tadpole or strap
  cells
• Ultrastructurally, contain sarcomeres
• Immunohistochemically, they stain with
  antibodies to the myogenic markers desmin,
  MYOD1 and myogenin

102
TUMORS OF SKELETAL MUSCLES

• RHABDOMYOSARCOMA MORPHOLOGY
• EMBRYONAL RHABDOMYOSARCOMA
• Most common type, accounting to 60
• Includes Sarcoma Botryoides
• Occurs in children under 10 years of age
• Typically arises in the nasal cavity, orbit,
  middle ear, prostate and paratesticular region
• Allelic loss of chromosome 11p15.5 as its major
  genomic abnormality

103
TUMORS OF SKELETAL MUSCLES

• RHABDOMYOSARCOMA MORPHOLOGY
• EMBRYONAL RHABDOMYOSARCOMA
• Grossly,they present as a soft gray infiltrative
  mass
• Microscopically, the tumor cells mimic skeletal
  muscle cells at various stages of embryogenesis
  and consist of sheets of both malignant round and
  spindled cells in a variably myxoid stroma
• Sarcoma botryoides grows in a polypoid fashion,
  producing the appearance of a cluster of grapes
  protruding into a hollow structure such as the
  bladder or vagina

104
TUMORS OF SKELETAL MUSCLES

• RHABDOMYOSARCOMA MORPHOLOGY
• ALVEOLAR RHABDOMYOSARCOMA
• Most common in the early and mid-adolescence and
  usually arises in the deep musculature of the
  extremities
• Histologically, the tumor is traversed by a
  network of fibrous septae that divide the cells
  into clusters or aggregates as the central cells
  degenerate and drop out, resembles pulmonary
  alveolae
• Tumor cells are moderate in size and have little
  cytoplasm

105
TUMORS OF SKELETAL MUSCLES

• RHABDOMYOSARCOMA MORPHOLOGY
• ALVEOLAR RHABDOMYOSARCOMA
• Cells with cross-striations are identified in
  about 25 of cases
• Cytogenetic studies show a t(213) or t(113)
  chromosomal translocations

106
TUMORS OF SKELETAL MUSCLES

• RHABDOMYOSARCOMA MORPHOLOGY
• PLEOMORPHIC RHABDOMYOSARCOMA
• Characterized by numerous large, sometimes
  multinucleated, bizarre eosinophilic tumor cells
• This variant is rare
• Arises in the deep soft tissue of adults
• Resemble malignant fibrous histiocytoma
  histologically

107
TUMORS OF SKELETAL MUSCLES

• RHABDOMYOSARCOMA
• Usually treated with a combination of surgey and
  chemotherapy with or without radiation
• Histologic variant and location of the tumor
  influence survival
• Sarcoma botryoides have the best prognosis,
  followed by embryonal, pleomorphic, and alveolar
  variants
• Overall prognosis for children is good 65
  less for adults

108
TUMORS OF SMOOTH MUSCLE

• LEIOMYOMA
• Benign smooth muscle tumor, commonly arises in
  the uterus
• May also arise in the erector pili muscles found
  in the skin, nipples, scrotum and labia and less
  in the deep soft tissues
• Multiple lesions is thought to be hereditary and
  transmitted as an autosomal dominant trait
• Occur in adolescence and early adult life

109
TUMORS OF SMOOTH MUSCLE

• LEIOMYOMA
• Tumors are usually not larger than 1 to 2 cm in
  greatest dimension
• Composed of fascicles of spindle cells that tend
  to intersect each other at right angles
• Tumor cells have blunt-ended, elongated nuclei
  and show minimal atypia and few mitotic figures
• Treatment is surgical

110
TUMORS OF SMOOTH MUSCLE

• LEIOMYOSARCOMA
• Account for 10 to 20 of soft tissue sarcomas
• Occurs in adults, womengtmen
• Most develop in the skin and deep soft tissues of
  the extremities and retroperitoneum
• Present as painful, firm masses
• Retroperitoneal tumors may be large and bulky and
  cause abdominal symptoms

111
TUMORS OF SMOOTH MUSCLE

• LEIOMYOSARCOMA
• Histologically, characterized by malignant
  spindle cells that have cigar-shaped nuclei
  arranged in interweaving fascicles
• Immunologically, they stain with antibodies to
  vimentin, actin, smooth muscle actin and desmin
• Treatment depends on the size, location and grade
  of the tumor

112
Thank You