Bone Forming Tumors: Osteosarcoma
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Questions and Answers

What is the most common type of osteosarcoma?

  • Low grade conventional osteosarcoma
  • High grade conventional osteosarcoma (correct)
  • Chondroblastic osteosarcoma
  • Fibroblastic osteosarcoma

    • What is the characteristic finding on X-ray for osteosarcoma?

  • Neither lytic nor sclerotic lesion
  • Only lytic lesion
  • Both lytic and sclerotic lesions (correct)
  • Only sclerotic lesion

    • What is the main function of SATB2 immune histochemical staining?

  • To diagnose chondrosarcoma
  • To identify bone differentiation (correct)
  • To identify cartilage differentiation
  • To diagnose osteosarcoma

    • What is the characteristic histological feature of osteosarcoma?

    <p>Severe anaplasia and pleomorphism</p> Signup and view all the answers

    What is the typical location of osteosarcoma?

    <p>At the end of the long bones</p> Signup and view all the answers

    What is the significance of Codman triangle in osteosarcoma?

    <p>It is a radiological feature of osteosarcoma</p> Signup and view all the answers

    What is the primary consequence of losing P53 function?

    <p>Genetic instability</p> Signup and view all the answers

    According to Knudson's two-hit hypothesis, what is required for tumor progression?

    <p>Two-hit mutations in the Rb1 gene</p> Signup and view all the answers

    What is the main reason for poor survival in osteosarcoma patients?

    <p>Chemotherapy resistance</p> Signup and view all the answers

    What is the primary characteristic of retinoblastoma?

    <p>Malignant tumor of the retina</p> Signup and view all the answers

    What is the significance of 90% necrosis in response to neo-adjuvant chemotherapy?

    <p>It is a sign of good response to chemotherapy</p> Signup and view all the answers

    What is the role of Rb in the cell cycle?

    <p>To regulate the cell cycle</p> Signup and view all the answers

    What is the main challenge in studying osteosarcoma?

    <p>Relatively rare occurrence of osteosarcoma</p> Signup and view all the answers

    What is the characteristic of osteosarcomas in the Rb1/Tp53 mouse model?

    <p>They are mostly metastatic</p> Signup and view all the answers

    What is the primary abnormality in Paget's disease of bone?

    <p>Osteoclasts</p> Signup and view all the answers

    What is the role of P53 in osteosarcoma?

    <p>It is a tumor suppressor gene</p> Signup and view all the answers

    What is the characteristic of Li-Fraumeni syndrome?

    <p>Autosomal dominant with high penetrance</p> Signup and view all the answers

    What is the significance of high genetic instability in osteosarcoma?

    <p>It creates neoantigens that can be targeted by immunotherapy</p> Signup and view all the answers

    What is the characteristic of osteosarcomas in Paget's disease of bone?

    <p>They are characterized by giant multinucleated osteoclasts</p> Signup and view all the answers

    What is the main goal of blocking checkpoints in immunotherapy for osteosarcoma?

    <p>To avoid immune destruction</p> Signup and view all the answers

    Study Notes

    Bone Forming Tumors

    • Osteoma, osteoid osteoma, osteoblastoma, and osteosarcoma are types of bone forming tumors
    • Osteosarcoma is a high-grade conventional tumor

    Osteosarcoma

    • Most commonly occurs around the knee, at the end of long bones
    • Characterized by osteoids (non-mineralized bone matrix)
    • Typically presents as a painful mass in the bone, especially at night due to low cortisol levels
    • Most common in long bones of the extremities, especially distal femur and proximal tibia
    • Conventional high-grade is the most common and aggressive type
    • Diagnosis is typically made with an X-ray, which may show both lytic and sclerotic patterns

    Codman Triangle

    • Periost is lifted by the tumor in the bone

    Histology

    • Severe anaplasia and pleomorphism (different formed nuclei)
    • Eosinophilic cytoplasm (more pink)
    • Identification of neoplastic disorganized woven bone with a lace-like pattern
    • Unmineralized matrix > osteoid
    • Subclassification according to matrix (some make cartilage, some bone, and some fibroblastic tissue)
    • No specific immune histochemical staining (SATB2) -> marker for bone differentiation

    Classification

    • Conventional osteosarcoma: 80%
    • Telangiectatic osteosarcoma: ~4% -> a lot of blood vessels and blood
    • Small cell osteosarcoma: 1.5% -> less aggressive form, less metastasis
    • Several other rare osteosarcoma subtypes

    Clinical

    • Most prevalent malignant primary bone tumor
    • Occurs mainly in adolescents/young adults
    • Bimodal age distribution (young adults, but also older people due to radiation or Paget's disease)

    Survival

    • Chemotherapy resistance: poor survival in 40% of patients
    • Metastases, especially to the lungs, are the cause of poor survival

    Treatment

    • Surgery, amputation or limb salvage
    • Neo-adjuvant chemotherapy (before surgery, less heavy surgery)
      • Doxorubicin
      • Cisplatin
      • Methotrexate
    • Surgery > resection is studied response to chemotherapy
      • >90% necrosis: considered as good response
      • Associated with good prognosis
    • Post-surgery chemotherapy

    Issues in Osteosarcoma Studies

    • Relatively rare
    • Preoperative chemotherapy destroys tissue for research
    • No specific hereditary syndrome for OS
    • No benign precursor
    • Gross genetic instability, chromothripsis & kataegis (a lot of breaks in the chromosomes)

    Immunotherapy

    • Ongoing research
    • High genetic instability > neoantigens
    • High T-cell infiltrate
    • Need HLA expression
    • Expression of T-cell blocking proteins
    • Blocking checkpoints: avoiding immune destruction, genome instability & mutations

    Pathways

    • Research: two genes inactivated -> RB and P53

    Hereditary Disorders

    • Li-Fraumeni syndrome: P53 gene
    • Related to osteosarcoma

    Li-Fraumeni Syndrome

    • Autosomal dominant with high penetrance (93% before age 50)
    • TP53 gene is mostly mutated, sometimes CHK2
    • Sarcoma is the index diagnosis
      • 25% of LFS tumors are sarcoma
      • Of these, 40% are osteosarcoma
    • Of note: TP53 mutations also occur in dog osteosarcoma

    P53 and Cell Cycle

    • P53 detects molecular changes and stops the cell cycle
    • Loss of P53 leads to genetic instability

    Knudson's Two-Hit Hypothesis

    • For tumor progressor gene inactivation

    Retinoblastoma

    • Malignant tumor of the retina (primary)
    • Birth/childhood
    • Unilateral/bilateral
    • Sporadic/hereditary
    • Second tumor: 60% sarcoma, mainly osteosarcoma

    Rb Mutation Spectrum

    • RB1 is a huge gene
    • Mutations occur on all parts of RB1

    Rb and Cell Cycle

    • Rb is also involved in the cell cycle

    Rb and Osteosarcoma

    • 70% of primary osteosarcomas

    Rb1/TP53 Mouse Model

    • Conditional knockout for Rb1 and Tp53 > only osteoblastic precursor cells have Rb1 and Tp53 loss (Osx-Cre)
    • These mice get osteosarcoma
    • These osteosarcomas are mostly metastatic
    • Apparently, there is synergy between Rb and Tp53, needs to occur both

    Paget's Disease of Bone

    • Increased bone resorption
    • Increased bone formation
    • Pain, fractures, deformities
    • Bone tissue of poor quality
    • Secondary tumors
    • Primary abnormality resides in osteoclasts (osteoclasts are too active)

    Osteosarcoma in Paget's Disease

    • Increased risk to get osteosarcoma (0.15-1%)
    • Age of onset is late
    • Characterized by giant multinucleated osteoclasts

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    Explore the characteristics and features of bone forming tumors, including osteosarcoma, osteoma, osteoid osteoma, and osteoblastoma.

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