SKELETAL AND SOFT TISSUE DISEASE-BONE Achondroplasia Genetic

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SKELETAL AND SOFT TISSUE DISEASE-BONE

• Achondroplasia
• Genetic derangement in epiphyseal cartilaginous
  growth
• Retarded endochondral bone formation,
• Abnormal short long bones but normal width (
  Appositional growth is not affected)
• Resulting in dwarfism,
• Most are acquired mutations (Some are familial)
• FCF3 gene new mutation

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Achondroplasia
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Achondroplasia

• Spine - normal length
• Skull - appears large
• Heterozygotes (AD- MC)
• Normal longevity,
• Mental, sexual and reproductive development are
  normal,
• Homozygous (AR)
• Constricted thoracic cage causes death soon after
  birth
• Thanatophoric dwarfism
• most common lethal form of dwarfism
• respiratory insufficiency
• die at birth or soon after

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SKELETAL AND SOFT TISSUE DISEASE-BONE

• Osteogenesis imperfecta
• Group of closely related genetic disorders
• Caused by qualitative or quantitative abnormal
  synthesis of type I collagen (which constitutes
  90 of bone matrix),
• Based on specific biosynthetic abnormality- four
  major subsets,
• Osteopenia (too little bone)
• marked thickening of the cortices and rarefaction
  of the trabeculae,
• fractures can easily occur

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Osteogenesis imperfecta
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SKELETAL AND SOFT TISSUE DISEASE

• Mucopolysaccharidoses
• Group of lysosomal storage diseases caused by
  deficiencies in enzymes that degrade the various
  Mucopolysaccharides
• Chondrocytes play a role in metabolism of
  Mucopolysaccharides,
• Abnormal hyaline cartilage, including growth
  plates, costal cartilages and articular surfaces,
  
• Short stature and have malformed bones as well as
  other cartilage abnormalities

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SKELETAL AND SOFT TISSUE DISEASE

• Osteoporosis
• Reduction in bone mass owing to small but
  incremental losses incurred in the constant
  turnover of bone,
• Common condition is seen most often in the
  elderly of both sexes
• More pronounced in Postmenopausal women, (
  estrogen reduces bone resorption by modulating
  IL1 and TNF a thus affecting osteoclasts reduce
  and osteoclasts increase activity.)
• Clinically significant when there is increased
  risk of vertebral and other fractures (Hips,
  wrists)

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Osteoporosis

• Causes
• Cause is largely unknown
• Generalized
• in postmenopausal and senile osteoporosis
  (primary forms)
• Idiopathic juvenile
• Idiopathic middle adulthood osteoporosis
• Localized
• due to immobilization or paralysis of an
  extremity

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Osteoporosis

• cortex and trabeculae- thinned and the Haversian
  systems are widened
• Bone - normal composition,
• Genetic factors do determine the size of bone
  mass achieved in young adulthood,
• Aging-related slowing of osteoblastic function
  and increased Osteoclastic activity induced by
  endocrine influences (decreased serum estrogen
  levels, perhaps through interleukin-1, IL-1)

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Osteoporosis

• Net negative balance in the continued turnover of
  bone,
• Rx TO slow or prevent the abnormal loss of bone
• Estrogen replacement therapy coupled with
• Calcium supplementation soon after menopause

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Osteoporosis

• Radiograph of the hip region
• increased lucency of cortical bone
• indicative of osteoporosis in an older woman.

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Osteoporosis

• The femur seen here with the hip
• Severe osteoporosis with marked loss of bone
  density

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Changes in bone density with aging in women
OF FRACTURE

• The normal curve (A) steepens following
  menopause, but even by old age the risk for
  fracture is still low.
• A woman who begins with diminished bone density
  (B) even before menopause is at great risk,
  particularly with a more accelerated rate of bone
  loss. Interventions such as postmenopausal
  estrogen (with progesterone) therapy, the use of
  drugs such as the non-hormonal compound
  alendronate that diminishes osteoclast activity,
  and the use of diet and exercise regimens can
  help to slow bone loss
• (C) but will not stop bone loss completely or
  restore prior bone density. Diet and exercise
  have a great benefit in younger women to help
  build up bone density and provide a greater
  reserve against bone loss with aging.
• Men may also develop osteoporosis, but overall
  are at less risk because they tend to have a
  greater bone density than women of similar age,
  and their bone loss is not as pronounced with
  aging.

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Osteoporosis

• Features of osteoporosis
• rarefaction of bone.
• Degenerative changes
• Subluxation at the DIP joints most marked in the
  forefinger.

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Osteoporosis

• This MRI of the spine
• marked kyphosis with compressed fractures.
• consequence of osteoporosis

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Osteoporosis

• Compressed" fracture of the vertebral column.
• The middle vertebral body is greatly reduced in
  size.
• fractures are common in persons with osteoporosis
  
• Particularly in older women, even with minor
  trauma.

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Osteoporosis

• FEATURES
• Bone pain owing to Micro-fractures,
• Loss in height and stability of the vertebral
  column,
• ?RISK of fractures of femoral necks, wrists and
  the vertebrae,
• DIAGNOSIS
• difficult - since it remains asymptomatic until
  skeletal fragility is well advanced,
• X-ray-not reliable if lt30 to 40 bone loss,
• Absorptiometry and quantitative CT,

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Osteoporosis

• DD
• one of a group of osteopenic disorders which are
  hard to distinguish from each other
• Osteomalacia
• Osteogenesis imperfecta
• Osteitis fibrosa/hyperparathyroidism

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SKELETAL AND SOFT TISSUE DISEASE

• Osteopetrosis
• (Brittle Bone disease)
• Rare hereditary overgrowth and sclerosis of bone,
  
• marked thickening of the cortex and
• narrowing or filling of the medullary cavity
  (impairs hematopoiesis)
• Despite too much bone, it is brittle and
  fractures like chalk,
• Visual loss and deafness
• Autosomal recessive form is evident at birth,
• FEATURES
• Anemia
• Neutropenia
• infections
• death

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Osteopetrosis

• AD - benign but predisposes to fractures,
• In all forms - hereditary defect in osteoclast
  function
• resulting in reduced bone resorption and enhanced
  net bone overgrowth,
• Defect in osteoclastic bone solubilizing enzymes

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SKELETAL AND SOFT TISSUE DISEASE

• Paget disease
• (Osteitis deformans)
• Polyostotic MC (85)
• Monostotic - 15
• 3 stages
• a) initial osteolytic stage
• b) mixed osteolytic - osteoblastic stage
• c) burnt-out, quiescent osteosclerotic stage

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Paget disease

• Considered as slow viral infection of osteoblasts
  and then osteoclasts
• Paramyxovirus,
• Virus - identified but cannot be isolated in
  osteoclasts by in situ hybridization
• Osteolytic phase
• numerous overtly large osteoclasts gt100 nuclei
  (normal 10-12) thus resorption

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Paget disease

• Mixed phase
• Osteolysis as well as neo-Osteogenesis of
  predominantly woven bone (but some lamellar)
• Tile-like or mosaic pattern pathognomonic of
  Paget disease
• Burnt-out phase
• marked by bone formation and osteosclerosis,
• disordered and poorly mineralized,
• soft and porous, lacks structural stability
• vulnerable to fracture or deformation under stress

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Paget disease

• Clinically
• fractures, nerve compression, osteoarthritis and
  skeletal deformities (ex. Tibial bowing, skull
  enlargement),
• Coarsening of the facial bones
• Leontiasis ossea (lion-like faces also seen in
  Leprosy)
• Less commonly high-output heart failure
  (vascularity of Polyostotic lesions)
• Secondary Osteosarcoma develops
• (1 of patients- very aggressive)

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SKELETAL AND SOFT TISSUE DISEASE

• Rickets Osteomalacia
• Rickets in growing children or osteomalacia in
  adults
• Caused by either vitamin D deficiency or
  phosphate depletion resulting in defective matrix
  mineralization,
• Vitamin D deficiency due to
• Dietary deficiency,
• Inadequate exposure to sunlight,
• Malabsorption of vit D, calcium or phosphate,
• Derangements in conversion of vit D to active
  metabolites (ex. renal disease),
• End-organ resistance and rare hereditary or
  acquired disorders of vitamin D metabolism

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Rickets Osteomalacia

• Failure of bone mineralization,
• Excess un-mineralized matrix and abnormally wide
  osteoid
• Growing child
• skeleton is weak with bowing of the legs and
  deformities of ribs, skull and other bones,
• Adults
• no skeletal deformities - only osteopenic
  osteomalacia
• Too little (normal) Bone- Osteoporosis Too little
  mineralization ?Vit D
• Too much bone - osteopetrosis

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SKELETAL AND SOFT TISSUE DISEASE

• Hyperparathyroidism
• (Osteitis fibrosa cystica or Von Recklinghausen
  disease of bone)
• Primary or secondary (to renal failure)
• Demineralization ? ? osteoclastic activity with
  resorption of bone and peri trabecular fibrosis
  (Osteitis fibrosa)
• Marrow fibrosis and more marked resorption ?
  formation of cysts within the marrow cavity

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Hyperparathyroidism

• Now rare because parathyroid hyperfunction is
  detected earlier and controlled
• X-ray-
• Bone loss evident as moth-eaten,
• Rarefied bones of the distal phalanges and
  clavicles and loss of the lamina dura about the
  tooth sockets, so-called Brown tumors (resembling
  reparative giant cell granulomas)
• Paradoxically, soft tissue metastatic
  calcifications sometimes appear, the bone changes
  completely regress after control of
  hyperparathyroidism

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Hyperparathyroidism
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SKELETAL AND SOFT TISSUE DISEASE

• Renal osteodystrophy
• Bone changes with CRF,
• Features of Osteitis fibrosa cystica admixed with
  osteomalacia
• Metastatic calcifications may develop in the
  skin, eyes and arterial walls and around joints,
• Other factors that contribute to the bone changes
  include
• Metabolic acidosis and iron and aluminum
  deposition in bone - derived from dialysate,
  which interferes with mineralization of matrix

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Hypertrophic osteo-arthropathy

• The hand shows periosteal new bone formation at
  the ends of metacarpals and proximal
  interphalangeal joints
• This is accompanied by "clubbing" with increased
  soft tissue and edema of the digits.
• MC with underlying pulmonary malignancies.
• Rarely, - familial phenomenon

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No doubt knowledge is valuable..,but above it
are power, goodness most important Character
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SKELETAL AND SOFT TISSUE DISEASE

• Fractures
• Speed, healing and perfection of fracture repair
  depend on
• type of fracture
• occurred in normal bone or in previously diseased
  bone (ie. pathologic fracture)
• Incomplete (greenstick) and closed (intact skin)
  fractures when aligned heal most rapidly, with
  potentially complete reconstitution of the
  preexisting architecture,
• comminuted (splintered bone) and compound (open
  skin wound) fractures heal much more slowly, with
  poorer end results

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Fractures
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Greenstick Fracture
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Fractures

• Fracture healing
• organization of a hematoma at the site, leading
  to a soft, organizing, weak procallus? conversion
  to a Fibrocartilaginous callus? replacement of
  the later by an Osseous callus, which is
  eventually remodeled along lines of weight
  bearing to complete the repair

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Fractures

• if the fracture has been well aligned and the
  original weight-bearing strains are restored,
  almost perfect repair is accomplished,
• Imperfect results are seen in
• Misalignment,
• Comminution,
• inadequate immobilization of the fracture site,
• infection and
• superimposed systemic abnormality (ex.
  atherosclerosis, Avitaminosis, dietary
  deficiency, osteoporosis)

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Fractures -Malunion
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SKELETAL AND SOFT TISSUE DISEASE

• Osteo-necrosis
• (avascular necrosis)
• Infarction of bone and marrow
• Occur in
• Medullary cavity of the metaphysis or diaphysis
• Subchondral region of the epiphysis,
• Mechanisms that lead to
• local ischemia include vascular interruption
  (fracture),
• Thrombosis and embolism (caisson disease),
• Vessel injury (vasculitis, radiation therapy),
• Vascular compression (steroid-induced necrosis -
  most common cause)
• Venous HTN

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Osteonecrosis (avascular necrosis)

• Wedge-shaped area of avascular necrosis
  (Osteonecrosis) at the upper right of this
  femoral head.
• pain with activity, progressing to pain at rest.
• Eventually, the necrotic bone collapses,
  distorting the overlying articular cartilage and
  producing secondary osteoarthritis

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Osteonecrosis (avascular necrosis)

• In the marrow, a local geographic area of pale
  yellow infarction,
• Cortex - not affected because of its collateral
  blood flow,
• the focus is marked by death of osteocytes, empty
  lacunae and necrotic fat cells, sub-chondral
  infarcts, the articular cartilage may collapse
  into the softened necrotic bone,
• Asymptomatic, but subchondral lesions often cause
  joint pain and osteoarthritis later

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SKELETAL AND SOFT TISSUE DISEASE

• Pyogenic osteomyelitis
• Results from bacterial seeding of bone
  (hematogenous, contiguous infection, open
  fracture, surgical procedure),
• Developing countries,
• MC- Blood-borne infections
• Staphylococcus aureus (often penicillin
  resistant) is most often implicated,
• Developed countries-
• Extension of the infection or traumatic
  inoculation is more common
• mixed infections- most often responsible
• Patients with sickle cell anemia are prone for
  Salmonella infection,

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Pyogenic osteomyelitis

• Suppurative reaction is associated with ischemic
  necrosis, fibrosis and bony repair,
• Necrosis of bone segment sequestrum ( in
  acute),
• Sub-periosteal new bone involucrum ( in
  chronic)
• if new bone formation continues, the focus
  becomes sclerotic - Garré sclerosing
  osteomyelitis ( in jaw bone)

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Pyogenic osteomyelitis

• Clinically
• an acute febrile illness with pain, tenderness
  and heat referable to the local lesion,
• subtle lesions, present as
• unexplained fever in infants or
• localized pain without fever in adults

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Pyogenic osteomyelitis

• Chronic cases may lead to
• bone deformity,
• sinus tracts
• secondary amyloidosis
• less severe cases -heal or be localized and
  walled off to create a Brodies abscess
  (sometimes sterile)

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Pyogenic osteomyelitis

• Diagnosis
• first 10 days, x-ray changes may be minimal, but
• Radionuclide studies often show localized uptake
  of tracers,
• Complications include
• Acute fare-ups
• Pathologic fracture,
• Amyloidosis,
• Bacteremia with endocarditis and
• Squamous cell carcinoma in the sinus tract
• Rarely Osteosarcoma

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SKELETAL AND SOFT TISSUE DISEASE

• Tuberculous osteomyelitis
• Rare in developed countries but more common in
  developing countries where pulmonary and GI TB
  are still common,
• blood-borne insidious infection, much more
  destructive and resistant to control than
  suppurative diseases,
• Spine - Pott disease, produces atypical
  granulomatous reaction

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SKELETAL AND SOFT TISSUE DISEASE

• Syphilis
• Rare in the US,
• Occur in either congenital or acquired forms,
• Congenital syphilis appears at birth and is
  marked by periostitis, on x-ray a 'crew
  haircut'-like appearance of new bone formation on
  the cortex is produced, Saber shin results when
  the tibia is involved,
• Acquired syphilis appears in the tertiary stage
  of the disease, it may be manifested as
  periostitis but more often by Gummas in bone

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SKELETAL AND SOFT TISSUE DISEASE Tumors of Bone

• The most common neoplasm in bone is a metastasis.
  
• The most common primary bone tumors are benign.
• The most common malignant primary bone tumors are
  Multiple myeloma
• The most common malignant primary bone forming
  tumors are Osteosarcoma.

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Tumors of Bone

• Magnetic resonance imaging (MRI) scan of the
  spine in sagittal view
• Metastatic lesion destroying C7 (the first
  cervical vertebra is not visible in this view,
• Partial congenital fusion of C5-C6).

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Tumors of Bone

• Osteoma
• Bosselated round protuberances or swellings,
  sessile tumor attached to a bone surface
• Composed of densely sclerotic, well- formed bone
• Osteomas protrude from cortical surfaces, most
  often the skull and facial bones,

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Multiple osteomas

• congenital familial osteomatosis.
• Bumpy appearance

• little clinical significance unless their
  location
• (ex. the inner table of the skull)
• compromises local organ function,
• disturbing cosmetically,
• associated with Gardner syndrome ( a familial AD
  syndrome of polyposis of the rectum and colon,
  associated with cysts and tumors of the skin and
  bone. Carcinomas of the colon develop in more
  than 50 of cases by age 40. colectomy is
  recommended

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Tumors of Bone

• Osteoid osteoma
• Small benign neoplasm without malignant
  potential,
• teens and twenties (90)
• 1 cm in diameter,
• most often located near the ends of the Tibial
  and femur (all bones can be involved),
• Painful
• X-ray - small radiolucent nidus within cortex
  surrounded by densely sclerotic bone,
• Histologically
• radiolucent Nidus consists of delicate trabeculae
  of woven bone rimmed by numerous osteoblasts and
  surrounded by highly vascular, spindled stroma in
  turn enclosed by dense bone

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Tumors of Bone

• Osteoblastoma
• Giant osteoid osteoma
• Lytic tumor - same histologic appearance as
  osteoma
• but without the surrounding sclerotic rim,
• larger than osteoma (gt2cm),
• Osteoblastoma tends to be located in the vertebra
  or long bones and
• does not cause much pain,
• considered benign,
• aggressive forms associated with repeated local
  recurrences,
• rarely some transform into osteosarcoma

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SKELETAL AND SOFT TISSUE DISEASE

• Osteosarcoma
• Malignant cells form Osteoid, bone or both,
• 2nd most common form of primary bone cancer
• Primary
• absence of underlying bone disease
• lt 20 years old
• Metaphyseal regions of Long bones
• Secondary
• older people,
• both flat and long bones,
• preexisting bone pathology (ex. Paget disease,
  enchondromas, exostoses, osteomyelitis, fibrous
  dysplasia, infarcts, fractures) or
• exposure to oncogenic influences (previous
  irradiation)

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Osteosarcoma

• Pathogenesis
• Genetic, constitutional and environmental
  influences
• familial retinoblastoma have a greatly increased
  risk of osteosarcomas and have a hereditary
  mutation of the suppressor Rb gene on chromosome
  13,
• patients who survive hereditary retinoblastoma
  have continued risk of developing osteosarcoma,
  often in an irradiated area,
• Sporadic osteosarcomas - p53 suppressor gene
  mutations on chromosome 17 (Li-Fraumeni syndrome)

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Osteosarcoma

• Favored sites of greatest bone growth (ex. at the
  base of the femoral growth plate)
• 80 to 90 arise in the medullary cavity of the
  Metaphyseal ends of long bones (proximal tibia,
  distal or proximal femur, and proximal humerus)
• Irradiation - predispose to secondary
  osteosarcoma
• After 25 yrs.,
• Flat bones (jaws and pelvis) equals that in long
  bones
• superimposed on underlying bone disease

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SKELETAL AND SOFT TISSUE DISEASE Osteosarcoma

• focal hemorrhages and necrosis
• Composed of anaplastic mesenchymal cells,
  fibroblastic, osteoblastic, chondroid ,highly
  vascular (telangiectatic),
• osteoid incorporating or bone-incorporating
  malignant cells,
• Cortical penetration of tumor with periosteal
  elevation can cause a Codman triangle
  presentation on x-ray, (rarely penetrates the
  epiphyseal plate)
• Extra skeletal osteosarcoma also can occur

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Osteosarcoma

• Metastasize widely, lung first but also organs
  and bones (lymph node mets. are rare),
• local pain, tenderness and swelling,
• surgery alone results in 20 5-year survivals,
• surgery, radiation and chemotherapy yield 60
  5-year survivals,
• Better prognosis - jaw, parosteal (juxtacortical)
  and intraosseous low-grade types

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Osteosarcoma

• parosteal variant
• Femur has a large eccentric tumor mass arising in
  the metaphyseal region.
• These tumors most often occur in young persons
  (note that the epiphysis seen at the right is
  still present).

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Osteosarcoma
Sun burst
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Osteosarcoma

• Arising in the metaphysis at the upper tibia of a
  teenage boy
• breaks through the bone cortex and extends into
  soft tissue.

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Osteosarcoma

• very pleomorphic cells, often with a spindle
  shape.
• One large cell with very large nuclei
• There are islands of reactive new bone

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Osteosarcoma

• The neoplastic spindle cells of osteosarcoma are
  seen to be making pink osteoid here.
• Osteoid production -diagnostic

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SKELETAL AND SOFT TISSUE DISEASE

• Osteochondroma
• Also called exostosis
• solitary sporadic lesions
• AD- multiple hereditary exostosis,
• displacement of the lateral portion of the growth
  plate,
• Proliferates in a direction diagonal to the long
  axis of the bone
• Away from the nearby joint,
• Males females 31

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Osteochondroma

• Bony projection (exostosis).
• Solitary, incidental
• Excised if they cause local pain.
• Rarely- multiple osteo-chondromatosis marked by
  bone deformity ?risk of chondro-sarcoma.

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Osteochondroma

• Sites
• MC-Metaphysis of long bones,
• occasionally the pelvis, scapula and ribs are
  involved
• rarely the small bones of the hands and feet
• Morphologically
• mushroom-shaped lateral protrusions,
• capped by hyaline cartilage,
• cortices and medullary cavities in continuity
  with the underlying marrow cavity,
• Age
• late childhood or adolescence,
• benign lesions -incidental x-ray findings
• Hereditary condition- lead to Chondrosarcomas

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SKELETAL AND SOFT TISSUE DISEASE

• Chondroma
• Benign tumors of mature hyaline cartilage,
• Enchondromas -Within the bone
• Enchondromatosis or Ollier disease-
• Single or multiple,
• a nonfamilial multiple form
• Maffucci syndrome -familial form with multiple
  chondromas associated with hemangiomas
• Solitary, sporadic malignant change is rare
• Multiple, in the systemic syndromes- sarcomatous
  transformation (usually chondrosarcoma) is
  frequent

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Chondroma

• Asymptomatic but may cause bone deformity, pain
  and fracture,
• Lesions of the hands and feet are almost always
  innocuous but may recur when incompletely
  removed,
• In long bones (DD - well differentiated
  chondrosarcoma)

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SKELETAL AND SOFT TISSUE DISEASE

• Chondroblastoma
• Uncommon
• almost invariably found in Epiphyses of
  skeletally immature individuals
• DD with GCT or clear cell chondrosarcoma,
• both occurring in the same location but usually
  in older patients)

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Chondroblastoma

• Tumor cells
• resembling embryonic chondroblasts
• polygonal, arranged in sheets, and sometimes
  surrounded by a lace-like pattern of hyaline
  cartilage,
• nuclei are often deeply indented or
  longitudinally grooved,
• multinucleated osteoclast-like giant cells may be
  present and abundant enough to suggest giant cell
  tumor of bone,
• great majority are benign

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SKELETAL AND SOFT TISSUE DISEASE

• Chondromyxoid Fibroma
• Uncommon benign tumor composed of chondroid,
  fibrous and myxoid tissues,
• Metaphyses - long bones, about the knee,
• MgtF
• teens and twenties
• x-ray - circumscribed lucent area with scattered
  calcifications,
• Focal atypia is marked, (misconstrued as
  sarcomas)
• Rx. by curettage and despite possible recurrence,
  pose no threat

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SKELETAL AND SOFT TISSUE DISEASE

• Chondrosarcoma
• 75 - (primary) arise de novo
• in the central skeleton (ribs, shoulder and
  pelvic girdle) around the knee
• 25- (secondary) arise from
• Enchondromas
• Osteochondromas and
• chondroblastomas (rarely)
• middle to later life

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Chondrosarcoma

• rare beyond the ankles and wrists,
• Lobulated translucent tumors, with necrosis and
  spotty calcification
• DD from endochondroma may be difficult in grade I
  (well differentiated) tumors
• Hyperchromatic nuclei,
• two or more cells per lacuna,
• multinucleate cells and
• anaplasia point toward chondrosarcoma

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Chondrosarcoma

• DD of chondrosarcomas with ossification from
  osteosarcoma with chondroid differentiation
• in chondrosarcomas bone formation occurs within
  cartilage
• X-ray - diagnostic,
• localized area of bone destruction
• punctuated by mottled densities from
  calcification or ossification,
• Rx. All require total removal
• 5 year survival rates for grades I, II and III
  (increasing cytologic anaplasia) are 90, 81 and
  43,
• None of the G- I lesions and 70 of G- III
  lesions disseminate

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Chondrosarcoma

• chondrosarcoma involving the ischium of the
  pelvis.
• lobulated glistening white to bluish-white tissue
  
• In general
• peripheral cartilagenous tumors (e.g., fingers)
  are benign
• those arising in the central axial skeleton are
  malignant.

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Chondrosarcoma

• chondrosarcoma of pelvis.
• Extensive nodules of white to bluish-white
  cartilagenous tumor
• Eroding and extending outward from the bone
• wide age range, and slight malegtF
• Many are slow growing,
• symptoms present for a decade or more.

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Chondrosarcoma

• This radiograph reveals a chondrosarcoma
  involving the right pelvic wing.
• Area of bone destruction accompanied by partial
  calcification, with no periosteal reactive new
  bone, but extension of the tumor into the
  adjacent soft tissue.

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Chondrosarcoma

• This pelvic CT scan
• chondrosarcoma pelvic wing and extending into the
  adjacent soft tissue.
• Area of bone destruction accompanied by partial
  calcification,
• no periosteal reactive new bone.

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Chondrosarcoma

• Pelvic MRI - mass lesion in the right iliac wing
• chondrosarcoma.

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Chondrosarcoma

• Bright area of uptake in the right iliac wing
• (chondrosarcoma)
• No metastases.

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Chondrosarcoma

• Irregular tumor mass composed of islands of
  bluish-white cartilagenous tissue.
• Metaphysis or diaphysis.
• Cortex is thickened, eroded,
• Little periosteal reaction.

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Chondrosarcoma

• Tumor tissue is recognizable as cartilage,
• Chondrocytes in clear spaces, but there is no
  orderly pattern.
• Neoplasm can be seen invading and destroying bone

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Chondrosarcoma

• pleomorphic chondrocytes that are grouped
  together in a haphazard arrangement.
• chondrosarcomas occur over a wider age range than
  osteosarcomas, including older adults

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SKELETAL AND SOFT TISSUE DISEASE Fibrous
cortical defect

• Non-ossifying Fibroma
• Non-neoplastic developmental lesion
• sharply defined, radiolucent lesions of the
  metaphyseal cortex
• Femur, tibia and fibula, single (50) or multiple
  and bilateral (50),
• No risk of malignancy,
• Generally asymptomatic (when large, lead to
  fracture)
• Extremely common (1/3rd of normal children),
• also disappear spontaneously

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SKELETAL AND SOFT TISSUE DISEASE

• Fibrous Dysplasia
• localized, benign, progressive replacement of
  bone by a fibrous proliferation intermixed with
  poorly formed, haphazardly arranged trabeculae of
  woven bone,
• Not lined by osteoblasts
• form configurations likened to Chinese figures,

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Fibrous Dysplasia

• Monostotic - 70,
• asymptomatic,
• Polyostotic - 25
• with deformities and fractures, esp. of the
  craniofacial bones,
• the clinical course is unpredictable,
• rarely secondary sarcoma develops (after
  irradiation)
• McCune-Albright syndrome
• polyostotic disease with Endocrinopathies (3 -
  5), irregular skin pigmentation (coast of
  Maine), and precocious sexual development,

93
SKELETAL AND SOFT TISSUE DISEASE

• Fibrosarcoma Malignant fibrous histiocytoma
• Overlapping clinical, radiographic and pathologic
  features,
• Middle age Elderly
• Most arise de novo
• some arise on a background of Paget disease, bone
  infarcts and prior radiation,
• Both present as gray-white infiltrative masses,
  hemorrhagic

94
Fibrosarcoma Malignant fibrous histiocytoma

• Fibrosarcoma
• MF
• fibroblasts in a herringbone pattern
• moderately well differentiated
• No Giant cells Histiocytes
• Better prognosis

• MFH
• MgtF
• fibroblasts in a storiform or starry pattern
• Poorly differentiated
• Bizarre multinucleated giant cells and
  neoplastic-appearing histiocytes
• Bad prognosis

95
SKELETAL AND SOFT TISSUE DISEASE Ewing sarcoma
and Primitive Neuroectodermal Tumor (PNET)

• Closely related malignant small round cells
• identical 1122 chromosomal translocation,
• Neuroectodermal tumor often reveals neural
  differentiation,
• Major difference is - Ewing sarcoma is more
  undifferentiated (other PNETs are
  differentiated)

96
SKELETAL AND SOFT TISSUE DISEASE
Ewing's sarcoma

• This primary bone tumor
• irregular tan to red to brown tumor mass is
  breaking through the cortex.
• Normal fatty marrow is seen at the far right.

97
Ewing's Sarcoma

• MC in children of 10 to 15 yr.,
• 80 are lt 20YR., boysgtgirls,
• Blacks are rarely affected,
• 2nd most common bone sarcoma in childhood (?1st
  MC)
• Arises in the medullary cavity of diaphysis
• Long tubular bones, esp. Femur and Flat bones of
  the pelvis,
• invades cortex penetrates periosteum to produce
  a soft tumor extension

98
Ewing's Sarcoma
Ewing's sarcoma is one of the "small round blue
cell" tumors
Granular cytoplasmic staining by PAS stain
99
Ewing's sarcoma

• Composed of
• sheets of uniform small round cells that
• Homer-Wright pseudo rosettes
• scant cytoplasm, which often contains glycogen,
• little fibrous stroma but prominent necrosis in
  regions remote from vessels,
• metastasize to other bones or elsewhere

100
Ewing's sarcoma

• Clinically
• painful, enlarging mass often tender, warm,
  swollen suggesting infection,
• the periosteal reaction produces layers of
  reactive bone deposited in an onion-skin fashion,
  
• Rx. combined radiation, chemotherapy and surgery,
  there is now a 75 5-year survival rate

101
SKELETAL AND SOFT TISSUE DISEASE

• Giant Cell Tumor of Bone
• (GCT)
• locally aggressive neoplasm
• MC in epiphyseal ends of long bones
• Age- 20 and 55,
• gt50 occur about the knees, but virtually any
  bone can be involved,
• GCT is rare in skeletally immature people
  (Children) and infrequent in the elderly

102
GCT

• Histologically
• uniformly distributed, osteoclast-like,
  multinucleated giant cells in a plump spindle
  cell background in a spatial orientation
• the neoplastic cell is the spindled stromal cell,
  the multinucleated cells are thought to arise
  from fusion of the spindle cells,
• foci of necrosis, hemorrhage, hemosiderin or
  osteoid

103
GCT

• X-rays - distinctive (not pathognomonic)
  revealing large, lytic, soap-bubble lesions,
• No stippling basophilic staining of protoplasm
  and calcifications,
• histologically can't tell which will metastasize,
  
• Most are localized Rx. by curettage or
  conservative resections,
• 40 to 60 recur locally,
• 1 to 2 -deceptively benign-looking metastases to
  the lungs, ( the only case where a benign tumor
  metastasized)
• 10 - obviously anaplastic metastases

104
SKELETAL AND SOFT TISSUE DISEASE Metastatic
tumors of Bone

• Adults, gt50 of skeletal metastases originate
  from cancers of the prostate, breast, kidney and
  lung,
• Children, secondary skeletal involvement is MC
  from Neuroblastoma, Wilm's tumor, osteosarcoma
  and Rhabdomyosarcoma,
• Most bony metastases are Lytic,
• tumor cells elaborate prostaglandins,
  interleukins and parathyroid hormone related
  protein that stimulate osteoclastic bone
  resorption,
• Osteosclerotic -most often induced by prostate
  and breast cancer by stimulating osteoblastic
  activity

105
SKELETAL AND SOFT TISSUE DISEASE Osteoarthritis

• Degenerative joint disease (DJD)
• Characterized by
• progressive deterioration and breakdown of
  articular cartilage,
• Mainly weight-bearing joints,
• Leading to subchondral bony thickening and bony
  overgrowths (osteophytes- spurs) about the joint
  margin,
• Heberden nodes- subcutaneous, non-tender bony,
  knobby protrusions at the margins of the distal
  inter phalangeal joints,
• Cause - unknown (likely related to metabolic and
  biochemical alterations)

106
DJD

• Osteoarthritis is a common problem,
• frequency increases with aging.
• One or more joints can be affected.
• Joints subjected to stressful "wear and tear" are
  more prone to damage to hyaline cartilage.
• prominent right first metatarsal-phalangeal joint
  from narrowing and flattening of articular
  surfaces, with reduced range of motion

107
DJD
108
DJD

• Common site for changes of osteoarthritis--the
  knee.
• Narrowing of joint spaces with the osteophytes.
• Mild subluxation partial dislocation of the
  femur on the tibia.

109
DJD

• Primary DJD
• occurs de novo,
• mostly in men in midlife and women a bit later,
• frequency increases with age to about 80 of
  those older than 70 years,
• the prevalence of osteoarthritis increases
  exponentially after the age of 50
• Secondary DJD
• appears at any age in a previously damaged or
  congenitally abnormal joint

110
DJD

• Relationship between age and previous injury
  suggests that wear and tear contributes to the
  genesis of this disease,
• Shoulder and Elbow are often involved in baseball
  players
• knees in basketball players
• knees and hands are more common in women
• Hips in men

111
DJD

• Morphologically
• Oligoarticular,
• Earliest changes
• Loss of proteoglycans and decreased metachromasia
  of the articular cartilage, associated with focal
  loss of chondrocytes alternating with areas of
  chondrocyte proliferation (cloning) and increased
  matrix basophilia,
• Next -fissuring, pitting and flaking of the
  cartilage ? vertical clefts down to the
  subchondral bone, flaking of the cartilage
  exposes underlying bone, which appears ivory-like
  (eburnation)

112
DJD

• With continued joint motion
• polishes the surface,
• subchondral microcysts
• fractures develop,
• Synovium shows a mild chronic inflammatory
  infiltrate (nonspecific synovitis)
• Osteocartilaginous metaplasia,
• Fragments of which create osteocartilaginous
  metaplasia, fragments create Loose bodies

113
DJD

• Pathogenesis - unknown (but clearly related to
  aging and injury)
• Cause - multifactorial,
• age related changes include
• the capacity of chondrocytes to maintain
  cartilaginous matrix slows,
• alterations in the proteoglycans and collagen
  within articular cartilage, which decrease
  resilience and increase vulnerability to injury,
• chondrocytes elaborate IL-1, which initiates
  matrix breakdown, secondary mediators, such as
  tumor necrosis factor-a (TNF-a), and TGF-b
  enhance release of lytic enzymes

114
DJD

• Although asymptomatic, most experience morning
  stiffness in affected joints,
• No local inflammation,
• Affected joints show restricted range of motion,
  small effusions and crepitus,
• Progressive reduction in mobility and increased
  painfulness with joint motion
• No progressive bony ankylosis abnormal
  immobility and fixation of a joint
• x-rays -bone spurs and joint narrowing
• No known way of preventing or arresting DJD

115
SKELETAL AND SOFT TISSUE DISEASERheumatoid
Arthritis

• Severe form of chronic synovitis that can lead to
  destruction and ankylosis/ abnormal immobility
  and fixation of a joint
• of affected joints,
• blood vessels, skin, heart, lungs, nerves and
  eyes may also be affected,
• 1 of the world population suffers from RA
• FM 31
• peak age- 20's and 30's,
• familial association (HLA-DR4 or DR1 or both)

116
Rheumatoid Arthritis
117
Rheumatoid Arthritis
118
Rheumatoid Arthritis

• Generally affects small, proximal joints of the
  hands and feet
• but then may involve, usually symmetrically the
  wrists, elbows, ankles and knees,
• well-developed lesions show villous hypertrophy
  of the synovium, synoviocytic hyperplasia, and an
  intense lymphoplasmacytic and histiocytic (
  tissue macrophage) synovial infiltrate,
• Exuberant synovium is known as a pannus, fills
  the joint space encroaching articular surfaces

119
Rheumatoid Arthritis

• Release of destructive enzymes (proteases and
  collagenases) and cytokines (particularly IL-1
  and TNF-a), and pannus formation destroy
  cartilage,
• leading to changes reminiscent of DJD but with
  fibrosis and bony ankylosis,
• Neutrophils (RA cells) can be present in the
  synovial fluid,
• Other features
• Rheumatoid nodules in subcutaneous tissues (areas
  of necrosis surrounded by palisade of fibroblasts
  and white cells at pressure joints such as
  elbows),
• acute vasculitis
• nonspecific fibrosing inflammatory lesions of the
  lungs, pleura, pericardium, myocardium,
  peripheral nerves and eyes

120
Rheumatoid Arthritis

• Pathogenesis
• seems to be initiated by an arthritogenic
  microbial agent in an
• immunogenetically susceptible host, after initial
  injury a continuing autoimmune reaction ensues,
• T-cells (CD4) release cytokines and inflammatory
  mediators that ultimately destroy the joint

121
Rheumatoid Arthritis

• genetic susceptibility - linkage to HLA-DR4
• microbial trigger is unknown, but EBV is a prime
  suspect, other agents such as retroviruses,
  mycobacteria, Borrelia and Mycoplasma are also
  suspected,
• once inflammatory synovitis is initiated, an
  autoimmune reaction ensues,
• CD4 cells are activated with release of many
  cytokines, particularly IL-1 and TNF-a,
• these cells within joints mediate lysis of
  articular cartilage and initiate the inflammatory
  synovitis,

122
Rheumatoid Arthritis

• Auto Ab are produced, some against autologous
  immunoglobulin G (IgG),
• Auto Ab against the Fc portion of autologous IgG
  is called Rheumatoid factor (is usually IgM but
  sometimes IgG, IgA or IgE),
• Rheumatoid factor does not contribute to the
  pathogenesis (because about 20 RA factor ve)
• but it may contribute to
• Arthus-like reaction in blood vessels (acute
  vasculitis)
• production of subcutaneous rheumatoid nodules
• Extraarticular lesions

123
Rheumatoid Arthritis

• Clinically it is variable,
• most patients experience a prodrome of malaise,
  fever, fatigue and musculoskeletal pain before
  joint mobility is reduced,
• the lucky patient experiences mild transient
  disease without sequelae,
• but most have fluctuating disease with the
  greatest progression during the initial 4 to 5
  years,
• in a minority the onset is acute, with rapidly
  progressive limitation of motion and development
  of joint deformities,
• characteristic deformities are
• radial deviation of the wrist with ulnar
  deviation of the fingers,
• extra-articular manifestations

124
Rheumatoid Arthritis

• Extra-articular manifestations
• Rarely the presenting features of the disease
• In patients with high RA factor titers (due to
  deposition of circulating immune complexes)
• of the total morbidity of rheumatoid arthritis
  is caused by
• GI bleeding from long-term aspirin therapy,
• Infections from steroid use,
• Amyloidosis in long-term severe disease,

125
Rheumatoid Arthritis

• RA variants include
• Juvenile-onset rheumatoid arthritis (Stills)
• Felty syndrome (features rheumatoid arthritis,
  splenomegaly and Neutropenia),
• Associated with ulcerative colitis
• Arthritis associated with Sjogren's syndrome

126
Spondyloarthropathies
127
SKELETAL AND SOFT TISSUE DISEASE

• Seronegative Spondyloarthropathies
• all lack rheumatoid factor (seronegative),
• Many are associated with HLA-B27
• 1. Ankylosing spondyloarthritis
• (Marie-Strumpell disease)
• Chronic inflammatory joint disease of vertebrae
  and sacroiliac joints
• Males,
• Begins in adolescence after an infection
• Suspected to be of immunogenetic origin, with
  AutoAb directed at joint elements,
• Follows a chronic progressive course with
  extension to hips, knees and shoulders
• 1/3rd of patients uveitis, aortitis and
  amyloidosis

128
SKELETAL AND SOFT TISSUE DISEASE

• 2. Reiter syndrome
• Triad of Arthritis, nongonococcal urethritis or
  cervicitis and conjunctivitis,
• Most often- Men in 20s and 30s
• Most are - HLA-B27 positive,
• Autoimmune reaction initiated by prior infection,
  
• Ankles, knees and feet may be affected (spine in
  chronic disease) indistinguishable from
  Ankylosing spondylitis,
• Extra-articular involvements include skin, eyes,
  heart, tendons and muscles

129
SKELETAL AND SOFT TISSUE DISEASE

• 3. Psoriatic arthritis
• 5 of patients with the skin disease,
• Small joints arthritis (hands and feet)
• Also extend to ankles, knees, hips and wrists,
  spinal disease (in 1/4 of patients)
• Not as severe as rheumatoid arthritis (less
  joint destruction)
• 4. Enteropathic arthritis
• 10 to 20 of patients with IBD
• migratory oligoarthritis of the large joints and
  spine (resemble Ankylosing spondylitis but is
  less severe
• remits spontaneously in a year or so

130
Suppurative Arthritis
131
SKELETAL AND SOFT TISSUE DISEASE

• Infectious arthritis
• uncommon,
• rapidly destroy a joint to produce permanent loss
  of motion,
• MC- microorganisms can seed the joint
  hematogenously (like osteomyelitis)
• Rarely- direct inoculation or spread from a
  nearby focus of infection

132
SKELETAL AND SOFT TISSUE DISEASE

• Suppurative arthritis
• Most commonly - gonococcus, Staphylococcus,
  Streptococcus, Haemophilus influenzae and gram
  negative coliforms,
• sickle cell disease - Salmonella,
• H. influenzae - in children lt 2yr.,
• S. aureus-in older children and adults,
• Gonococcus- in late adolescence and young adult
  life,
• Most instances-single joint is infected,
• knee, gt hipgtshouldergt elbowgt wrist gt
  sternoclavicular joint,
• Gonococcal arthritis
• mostly oligoarticular
• associated with a skin rash
• genetic deficiency of C5, C6 or C7 (complements)

133
SKELETAL AND SOFT TISSUE DISEASE

• Tuberculous arthritis
• insidious chronic arthritis
• hematogenous spread or nearby Tuberculous
  osteomyelitis, the
• MC site is the spine (Pott disease) gt hipgtkneegt
  elbowgt wristgt ankle gt sacroiliac joints
• more destructive process than suppurative
  arthritis
• Lyme arthritis
• follows several days or weeks after the initial
  skin infection
• arthritis is remitting and migratory,
• primarily involves large joints (knees,
  shoulders, elbows and ankles)
• morphologically resembles rheumatoid arthritis
• In most cases it clears spontaneously or with
  therapy
• ( 10-permanent deformities)

134
SKELETAL AND SOFT TISSUE DISEASE Gout- arthritis

• Group of conditions that share in common
• Hyperuricemia
• attacks of acute arthritis triggered by
  crystallization of urates in joints ( sodium
  monourate crystals) ve birefringent
• asymptomatic intervals
• eventual development of chronic tophaceous gout
  and arthritis
• Hyperuricemia is necessary for gout,
• but only a small fraction of hyperuricemic
  individuals develop gout,
• Most cases occur in men gt20yr. (women are almost
  never affected till after menopause)

135
Gout- arthritis

• Primary gout
• 90 of all cases,
• 95- idiopathic,
• multifactorial inheritance
• associated with the overproduction of uric acid
• Normal or increased production or under-excretion
  of uric acid
• Predisposing factors
• alcohol use and obesity,
• small of primary cases - specific enzyme
  defects (ex. X-linked, partial deficiency of
  HGPRT - hypoxanthine-guanine phosphoribosyltransfe
  rase)

136
Gout- arthritis

• Secondary gout - 10 of cases
• Most with increased nucleic acid turnover,
• Chronic hemolysis, polycythemia, leukemia and
  lymphoma,
• Less commonly
• drugs (esp. diuretics, aspirin, nicotinic acid
  and ethanol) or
• chronic renal disease leads to symptomatic
  hyperuricemia,
• lead intoxication may induce saturnine gout,
• Rarely the specific enzyme defects
• von Gierke (glycogen storage disease type I)
• Lesch-Nyhan syndrome -only in men and associated
  with neurologic deficits)

137
Gout- arthritis

• Acute arthritis - acute monoarticular or ( 1 to 5
  joints) oligoarticular inflammatory synovitis
• initiated by urate crystal formation within
  joints,
• needle shaped crystals are birefringent with
  polarized light,
• crystals activate Hageman factor with the
  production of chemoattractants (ex. C3a and 5a)
  and inflammatory mediators,
• neutrophils and macrophages accumulate in joints
  and phagocytose crystals,
• release of lysosomal enzymes, toxic free
  radicals, IL-1, IL-6, IL-8, TNF-a, prostaglandins
  and leukotrienes,
• Chronic arthritis evolves from the progressive
  precipitation of urates into the synovial linings
  of joints after recurrent attacks of acute
  arthritis

138
Gout- arthritis

• Tophus - pathognomonic of gout,
• a mass of urates (crystalline or amorphous)
• surrounded by an intense inflammatory reaction,
• macrophages, lymphocytes, fibroblasts and foreign
  body giant cells,
• Sites Ear, Olecranon and Patellar bursae and in
  Periarticular ligaments and connective tissue,
• 3 types of Renal disease develop
• a) acute uric acid nephropathy (intratubular
  urate deposition),
• b) Nephrolithiasis and
• c) chronic urate nephropathy (interstitial urate
  deposition
• ( ethylene glycol causes calcium oxalate
  deposition in renal tubules) formed in alkaline
  urine
• Phosphate stones are formed in the background of
  UTI with protius alkaline urine . To dissolve
  acidify)

139
Gout- arthritis Tophus
140
Gout- arthritis Crystals
tophus
141
Gout- arthritis

• 50 of the initial attacks of acute gouty
  arthritis
• great toe, or less frequently, the instep, ankle
  or heal,
• physical or emotional fatigue, an alcoholic spree
  or dietary overindulgence precedes and attack,
• attack subsides spontaneously or with therapy,
• recurring within several months to a few years,
• other joints become involved,
• multiple recurrences lead to chronic gouty
  arthritis, about
• 90 of patients with chronic arthritis develop
  some renal impairment,
• Rx. Uricosuric therapy

142
SKELETAL AND SOFT TISSUE DISEASE

• Calcium pyrophosphate crystal deposition disease
  (CPPC)
• chondrocalcinosis or pseudogout
• acute or chronic arthritis secondary to
  deposition of calcium pyrophosphate
• clinicopathologic features of this disease are
  similar to those of gout
• hereditary, sporadic or associated with trauma or
  surgery,
• crystals are frequently present in joint
  specimens from patients with DJD and in
  intervertebral disc material removed from
  patients with herniated discs ( knees)

143
CPPC- deposition disease

• Basophilic-staining rhomboid crystals,
• whether these are causing the joint disease or
  are a secondary phenomenon is unclear,
• knee is the most frequently affected,
• Joint involvement is transient, (in
  50-significant joint damage)

144
SKELETAL AND SOFT TISSUE DISEASE

• Ganglion and synovial cyst
• small, 1 to 1.5 cm, multiloculated, cavitated
  lesion
• found in connective tissues of joint capsules or
  tendon sheaths,
• arises from a focus of myxoid degeneration and
  softening of connective tissues,
• cavities are lined by epithelium and they do not
  communicate with joint cavities,
• favored location - small joints of the wrist,
  where ganglions are palpated as a firm but
  yielding, pea-sized subcutaneous nodule,
• treatable by surgical removal,
• occasionally they may erode the underlying bone

145
Ganglion cyst

• Ganglion cyst
• "bump" on the dorsum of the hand. mainly
• arises in the connective tissue of a joint
  capsule or tendon sheath.
• MC sites - extensor surfaces of the hands and
  feet (wrist).
• following trauma from focal myxoid degeneration
  of connective tissue to produce a cystic space.
• If they are painful, they can be excised.

146
Ganglion and synovial cyst

• herniations of a joint space may occur,
  particularly into the popliteal space from the
  knee joint when there is a marked increase of
  intra-articular fluid or exudate, as in
  rheumatoid or suppurative arthritis, the
  herniations of the knee joints are known as
  synovial or Baker cysts, the autonomic changes
  are those of the underlying articular disease

147
SKELETAL AND SOFT TISSUE DISEASE

• Villonodular synovitis
• group of closely related lesions involving
  synovial membranes and tendons,
• peripheral joints,
• synovial lesions - of fibroblasts, histiocytoid
  cells, fibrohistiocytoid cells, often admixed
  with multinucleated, osteoclast-like cells,
  xanthoma cells and pigmented macrophages,
• localized, - nodular Tenosynovitis (or giant cell
  tumor of tendons), GCT of tendon
• Diffuse- involves the intra-articular synovial
  membrane (often with hemosiderin pigment) -
  pigmented Villonodular synovitis

148
Villonodular synovitis
149
SKELETAL AND SOFT TISSUE DISEASE

• ? These are neoplasms (variants of benign fibrous
  histiocytoma) or reactive, inflammatory
  conditions (synovitis)
• recur, especially the poorly localized forms
• destruction of underlying bone

150
SKELETAL AND SOFT TISSUE DISEASE

• Soft tissue tumors
• - these are mesenchymal proliferations that arise
  in the extraskeletal nonepithelial tissue of the
  body, exclusive of the viscera, coverings of the
  brain and lymphoreticular system, tumors may
  arise in any location, although about 40 occur
  in the lower extremity, especially thighs, 20 in
  the upper extremity, 10 in the head and neck and
  30 in the trunk and retroperitoneum, the larger
  the poorer the outlook, the more superficial the
  better the prognosis, can also classify I to III
  histologically and stage
• NB are usually deep