Bone pathology 2

  1. Osteomyelitis
    Inflammation of bone caused by infection: acute or chronic
  2. Osteomyelitis - Routes
    Hematogenous (most common)

    Extension from adjacent infection

    Traumatic or iatrogenic implantation
  3. Which bacteria most commonly cause pyogenic osteomyelitis?
  4. Fungus is more commonly found to be the cause of osteomylitis
  5. Acute osteomyelitis - pathophysiology
    bone infection --> bacteria proliferate --> inflammation --> sequestrum --> involucrum ---> sinus tract: pus drainage
  6. Acute osteomyelitis - treatment
    antibiotics + surgery
  7. Sequestra
    dead bone, no ostecytes

    empty lacunae on histology slide
  8. involucrum
    new bone formed around sequestra
  9. Osteonecrosis - avascular necrosis - pathology
    disease, trauma or idiopathic --> compromised blood supply to bone --> bone undergoes ischemic necrosis
  10. osteonecrosis - which part of the skeleton is most commonly affected?
    femur head
  11. osteonecrosis - treatment
  12. Bisphosphonates - physiology effect
    Potent inhibitors of osteoclastic activity
  13. Bisphosphonates - classification
    • •Non-N-containing:
    • –The first generation bisphosphonates are
    • readily metabolized by osteoclasts

    • •N-containing: 
    • –aminobisphosphonates. Addition of a nitrogen side chain. 2nd generation, long half life, potent
    • •Most reported cases are caused by
    • intravenously administered aminobisphosphonates
  14. Osteonecrosis of the Jaw - cause
    –Bisphosphonates (Bisphosphonate-Associated Osteonecrosis)

    –Denosumab: anti-RANKL antibody
  15. Osteonecrosis of the Jaw - clinical
    • –Exposed non-vital bone (sequestrum).
    • Similar to radiation-induced osteonecrosis.

    • –The majority occurs after an invasive dental procedure. Spontaneous cases have been
    • reported
  16. ONJ - differential
    osteomyelitis and bisphosphonate
  17. ONJ - pathogenesis
    •Inhibition of bone remodeling by inhibiting osteoclast function
  18. ONJ - can be differentiate using histology and presence of sequestrum
  19. ONJ - radiograph:
    ill-defined radiolucency with patchy radiopacity

    can't be differentate with radio-induced osteonecrosis
  20. ONJ - clinical usage and risk
    • –The risk of developing complications appears to increase with time of use of the
    • medication

    •Postmenopausal osteoporosis:  taken orally, low risk

    •Paget disease of bone: taken orally or intravenously

    • •Tumor bone disease (multiple myeloma, breast and prostate cancer): intravenously, high
    • risk

    –Bone metastases

    –Tumor-induced hypercalcemia
  21. ONJ - tx
    • Prevention is most important/effective
    •  All necessary invasive dental procedures should be performed before starting IV
    • bisphosphonate/Denosumab

    Pain control + antibiotics
  22. Osteoradionecrosis - pathology
    Damages to bone cells, decreased bone metabolism

    Inhibits angiogenesis
  23. OR- clinical
    similar to ONJ

    –Exposed non-vital bone

    • –The majority occurs after an invasive dental procedure. Spontaneous cases have been
    • reported
  24. OR - dx
    radiation history and clinical presentation, confirmed by biopsy
  25. OR - tx
    prevention is the best course of action

    Surgery + antibiotics
  26. Classification of Bone tumors
    •Bone forming

    –Benign: Osteoma, Osteoid osteoma & Osteoblastoma

    –Malignant: Osteosarcoma

    •Cartilage forming

    –Benign: Osteochondroma, Chondroma

    –Malignant: Chondrosarcoma

    •Fibro-osseous: Fibrous dysplasia, Ossifying fibroma, cemento-osseous dysplasia (will discuss in oral pathology course)


    –Giant cell tumor of bone (mostly benign)

    –Ewing sarcoma
  27. central vs peripheral tumor
    • central inside the bone
    • peripheral in the tissue
  28. Osteoma - common site & malignant grade
    Benign lesion of membranous bone

    Head and neck is the most common site

    paranasal sinus
  29. Osteo - radiograph
    a well-defined radiopaque mass
  30. Multiple osteomas are feature of ...
    Gardner’s syndrome
  31. Osteoma - tx
    No treatment necessary unless symptomatic
  32. Osteoid Osteoma & Osteoblastoma - histology
    •Benign tumors that share similar histology

    –Anastomosing trabeculae of osteoid and woven bone lined by plump, active osteoblasts
  33. Osteoid Osteoma & Osteoblastoma - radiograph
    well-circumscribed lesion with patchy calcifications
  34. Osteoid Osteoma vs Osteoblastoma
    •Osteoblastoma: >2cm, pain not localized and not relieved by aspirin.

    •Osteoid osteoma: <2cm. Localized pain relieved by aspirin
  35. Osteoid Osteoma & Osteoblastoma - tx
  36. Osteosarcoma - malignancy
    Most common primary malignant tumor of bone

    *Metastatic tumors are the most common malignant tumor of bone
  37. Osteosarcoma - Bimodal age distribution
    occur either at old or young pt

    • –10-20 y/o:  greatest bone growth: primary
    • osteosarcoma
    • •Knee area is the most common site

    –> 50 y/o: usually have underlying condition such as Paget disease or prior irradiation: 2nd osteosarcoma
  38. Osteosarcoma - genetic mutation
    Tumor suppressor genes RB  (retinoblastoma) is mutated 

    Patients with germ-line mutations in the RB gene have a thousand-fold greater risk
  39. Osteosarcoma - histology
    Malignant cell - size variation, mitotic figure 

    The lesion is characterized by production of bone matrix by malignant osteoblasts
  40. Osteosarcoma - clinical
    •Usually present as a painful enlarging, destructive  mass

    –Pathological fracture common
  41. OSteosarcoma - behavior
    –10-20% of patients have pulmonary metastasis at the time of diagnosis

    –Typically spread hematogenously
  42. OSteosarcoma 0 tx
    •chemotherapy + surgery

    –Primary osteosarcoma: current long-term survival rate 60-70%

    –2nd osteosarcoma: prognosis poor
  43. Osteosarcoma - radigraph
    Radiography showed lytic or mixed lesion and indistinct infiltrating border

    • Periosteal rxn 
    • –Codman triangle:
    • •Only the edges of the raised periosteum
    • is ossified

    –Sunburst/sunray spicules/hair-on-end

    •New bone lay down perpendicularly to cortex

    • •–Codman
    • triangle:

    • •Only
    • the
    • edges of the raised periosteum
    • is ossified

    • –Sunburst/sunray spicules/hair-on-end
    • •New bone lay down perpendicularly to cortex
  44. Exostosis
    bony protuberance on the surface of a bone

    •In oral cavity, exostosis only contains bone and is not considered a tumor (no cartilage element)

    •In endochondral bones, exostosis is called osteochondroma
  45. Exotosis - oral cavity vs endochondral
    cartilage or not
  46. Osteochondroma
    •Solitary or multiple (syndrome related)

    •The most common benign bone tumor

    •Only in bones of endochondral origin

    •Arising at the metaphysis near growth plate

    •Tends to stop growing once the growth of skeleton is complete
  47. Osteochondroma - dx and tx
    Dx by radiograph

    No treatment necessary unless symptomatic or suspect malignant transformation

  48. Chondroma - pathology & common site
    • A benign tumor of hyaline cartilage
    • –Enchondroma: arise in medulla

    –Juxtacortical chondroma: on the bone surface

    Usually solitary and present in the metaphyseal region of tubular bones

    Most common site: the short tubular bones of the hands and feet
  49. Chondroma - dx and tx
    Primarily by radiograph.

  50. Chondrosarcoma - characteristic
    Characterized by malignant chondrocytes producing chondroid matrix

    Not as common as osteosarcoma

    Extremely rare in jaws

    More common in the pelvis, shoulder and ribs
  51. Chondrosarcoma - radiograph
    shows an ill-defined osteolytic lesion with/without calcifications
  52. Chondrosarcoma - prognosis
    depends on the grade

    • –Most conventional chondrosarcomas
    • are low grade, 5 year survival rate 80-90%

    • Metastasize hematogenously, lung is the
    • major site
  53. Chondrosarcoma - tx
    depend on the tumor grade

    –Surgery  for low grade, surgery plus chemo and radiation therapies are required in high grade cases.
  54. Fibrous Dysplasia

    A developmental tumor-like condition

    Normal bone is replaced by proliferation of cellular fibrous stroma containing irregular bony trabeculae
  55. Fibrous dysplasia - cause
    • •Caused by somatic mutation of GNAS1 gene (guanine nucleotide-binding protein,
    • poly a-stimulating activity polypeptide 1)

    –depends on the timing/cell type when mutation occurs
  56. Fibrous dysplasia - classification
    –Monostotic: single bone, majority cases, tends to stabilize

    –Polyostotic: multiple bones, craniofacial areas common

    –Polyostotic with other abnormalities:

    • McCune-Albright Syndrome: Cafe au lait
    • pigmentation, multiple endocrinopathies:
    • sexual precocity (early puberty - easier detection in female)
  57. Fibrous dysplasia - manifestation
    • bone enlargement, length discrepancy, bone
    • deformity, pathologic fracture
  58. Fibrous dysplasia - radiograph - hallmark?
    “Ground glass”, early lesions are more lucent

    Most lesions are poorly defined,  gradually blending into adjacent normal bone
  59. Fibrous dysplasia - dx
    only occur during development --> clinical history

    radiograph, histology and surgical findings
  60. Fibrous dysplasia - tx
    surgical contouring (perform after lesion stabilizes)
  61. Ossifying fibroma
    • A true tumor that  has similar histology
    • with fibrous dysplasia
  62. Ossifying fibroma - radiograph and dx
    • “Ground glass”, starts with a radiolucent lesion
    • Most lesions have well-defined borders (differential)

    Dx: clinical history, radiograph, histology and surgical findings
  63. Giant Cell Tumor of Bone - characteristic
    • characterized by collections of multinucleated
    • osteoclast-type giant cells

    Mostly are benign but some have a malignant behavior: Similar lesion in the jaws is almost always benign
  64. Giant Cell Tumor of Bone - radiograph
    osteolytic lesion, may destroy the cortex
  65. Giant Cell Tumor of Bone - dx
  66. Giant Cell Tumor of Bone - tx
    Surgery, tends to recur
  67. 2 pathology that show multinucleated
    osteoclast-type giant cells
    • hyperparathyroidism and Giant
    • Cell Tumor of Bone
  68. Ewing Sarcoma and Primitive Neuroendocrine
    Share same chromosome translocation

    Fusion between the EWS gene with a member of the ETS family of transcription factor. Need to demonstrate this for the diagnosis

    Constitutively active fusion transcription factor that stimulates cell proliferation
  69. Ewing Sarcoma and Primitive Neuroendocrine Tumor: dx
    •Small round cell tumor

    –Immunohistochemistry stain

    –Chromosome translocation
  70. Ewing Sarcoma and PNET- •Degree
    of  differentiations
    –Ewing sarcoma: un-differentiated, mostly bone tumor

    –PNET: neural differentiation, mostly soft tissue tumor
  71. Ewing Sarcoma and PNET - radiograph
    •destructive lytic lesion with infiltrative margins

    • –Often has a periosteal reaction: onionskin fashion (not in jaw bone) (not a specific
    • finding)
  72. Ewing Sarcoma and PNET - prognosis
    surgery + chemotherapy

    –40-80% 5 year survival rate
  73. Synovial joint - bursa:
    •small fluid-filled sac lined by synovial membrane.

    •It provides a cushion between bones and tendons and/or muscles around a joint
  74. Osteoarthritis
    • Degenerative arthritis, the most common
    • form of arthritis
  75. Osteoarthritis - risk factory
    –Age: >65 y/o


    –any form of joint trauma
  76. Osteoarthritis - distribution
    •can affect any joints

    • –Weight bearing joint,  knee most common
    • •RA: small joints

    • –Usually affects one or a few joints
    • •RA: multiple joints
  77. Osteoarthritis - feature and hallmark
    • Degeneration of the articular cartilage
    • –with only episodic synovitis

    subchondral bone changes: 

    inflammation is secondary 

    Weak muscle/ligament

    Osteophytes (bony outgrowth)

    Fibrillated/destroyed cartilage(primary)
  78. Osteoarthritis - clinical course
    •Slowly developing degenerative breakdown of cartilage

    •Pain exacerbated by use

    •Morning stiffness

    •Limited range of movement
  79. Osteoarthritis - tx
    Lack of structure modifying drugs

    •Weight loss, exercise

    •Pharmacological agent

    • »Analgesics, non-steroidal anti-inflammatory agents, intra-articular administration of
    • steroids or hyaluronic acid

    •Joint replacement surgery (the ultimate measure)
  80. Rheumatoid Arthritis - pathophysiology
    inflammatory cells --> inflammatory cytokine (which makes a vicous cycle through TNF -a) 

    --> synovial cell hyperplasia --> pannus: invasive grannulation tissue --> bone and cartilage destruction
  81. Rheumatoid Arthritis - what kind of disease and characteristic
    Autoimmune disease:

    • systemic chronic inflammatory disease
    • osteoarthritis: not autoimmune disease

    • affects primarily small joints
    • osteoarthritis: primarily affect weight-bearing joints

    Relatively common, female preponderance
  82. Rheumatoid Arthritis - dx and tx
    Diagnosis: imaging (X-ray, MRI), blood test of rheumatoid factor (not very specific)

    • Treatment: anti-inflammatory agent (eg.
    • anti-TNF-a)
  83. Gout - primary risk factor for gout
    hyperuricemia --> tophus (Aggregates of monosodium urate crystals)
  84. Gout - pathogenesis
    Asymptomatic hyperuricemia --> acute gouty arthritis --> "intercritical" gout --> chronic tophaceous gout

    • 1st attack is usually monoarticular
    • Gradually become polyarticular
    • and the attacks recur at shorter intervals
    • Bone erosion caused by the crystal deposit
    • Loss of joint space
    • 20% of patients with chronic gout die of renal failure
  85. Gout - tx
    Medication can abort attack and mobilize tophaceous deposits
Card Set
Bone pathology 2
Bone and cartilage pathology