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Questions and Answers
What is the most common type of osteosarcoma?
What is the most common type of osteosarcoma?
What is the characteristic finding on X-ray for osteosarcoma?
What is the characteristic finding on X-ray for osteosarcoma?
What is the main function of SATB2 immune histochemical staining?
What is the main function of SATB2 immune histochemical staining?
What is the characteristic histological feature of osteosarcoma?
What is the characteristic histological feature of osteosarcoma?
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What is the typical location of osteosarcoma?
What is the typical location of osteosarcoma?
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What is the significance of Codman triangle in osteosarcoma?
What is the significance of Codman triangle in osteosarcoma?
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What is the primary consequence of losing P53 function?
What is the primary consequence of losing P53 function?
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According to Knudson's two-hit hypothesis, what is required for tumor progression?
According to Knudson's two-hit hypothesis, what is required for tumor progression?
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What is the main reason for poor survival in osteosarcoma patients?
What is the main reason for poor survival in osteosarcoma patients?
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What is the primary characteristic of retinoblastoma?
What is the primary characteristic of retinoblastoma?
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What is the significance of 90% necrosis in response to neo-adjuvant chemotherapy?
What is the significance of 90% necrosis in response to neo-adjuvant chemotherapy?
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What is the role of Rb in the cell cycle?
What is the role of Rb in the cell cycle?
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What is the main challenge in studying osteosarcoma?
What is the main challenge in studying osteosarcoma?
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What is the characteristic of osteosarcomas in the Rb1/Tp53 mouse model?
What is the characteristic of osteosarcomas in the Rb1/Tp53 mouse model?
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What is the primary abnormality in Paget's disease of bone?
What is the primary abnormality in Paget's disease of bone?
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What is the role of P53 in osteosarcoma?
What is the role of P53 in osteosarcoma?
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What is the characteristic of Li-Fraumeni syndrome?
What is the characteristic of Li-Fraumeni syndrome?
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What is the significance of high genetic instability in osteosarcoma?
What is the significance of high genetic instability in osteosarcoma?
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What is the characteristic of osteosarcomas in Paget's disease of bone?
What is the characteristic of osteosarcomas in Paget's disease of bone?
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What is the main goal of blocking checkpoints in immunotherapy for osteosarcoma?
What is the main goal of blocking checkpoints in immunotherapy for osteosarcoma?
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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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Description
Explore the characteristics and features of bone forming tumors, including osteosarcoma, osteoma, osteoid osteoma, and osteoblastoma.