Osteosarcoma (carcinoma of the bone)-1.pptx

Osteosarcoma

1. OSTEOSARCOMA BAKO DANIEL

2. OUTLINE INTRODUCTION EPIDEMIOLOGY AETIOLOGY CLASSIFICATION PATHOGENESIS MORPHOLOGY CLINICAL FEATURES DIAGNOSIS TREATMENT CONCLUSION

3. INTRODUCTION Osteosarcoma is a rare and aggressive form of malignancy that affects the bones (primarily the long bones). It is the second most common primary malignant bone tumor after multiple myeloma Osteosarcoma is defined as a highly malignant primary bone tumor arising from osteoblasts and characterized by deposition of a malignant osteoid

4. EPIDEMIOLOGY Osteosarcoma has an overall incidence of 5 cases per million persons per year It occurs more frequently in males than in females (1.6:1) Commoner among the black race than in other races It can occur in all ages but has a bimodal age distribution First peak occurs in adolescents. 75% of osteosarcomas occur in persons younger than 20 years Second smaller peak occurs in much older adults It is the 8th highest childhood cancer (2.4%)

5. It commonly occurs in the long bones of the extremities near the metaphyseal growth plates. The most common sites are: Femur - 42% (75% in the distal femur) Tibia - 19% (80% in the proximal tibia) Humerus - 10% (90% in the proximal humerus)

6. AETIOLOGY Like most malignancies, the aetiology is complex and not well understood but risk factors include: Age Sex Rapid bone growth Genetic factors e.g. Li Fraumeni syndrome Hereditary retinoblastoma Rothmund Thompson syndrome Environmental factors

7. CLASSIFICATION Osteosarcoma can be classified as follows: Based on the pathogenetic mechanism Primary Osteosarcoma: This is the commonest type and it arises spontaneously without a known pre-existing condition. This type is commoner in adolescents and young adults Secondary Osteosarcoma: This develops as a result of a pre-existing condition or predisposing factor. E.g. Paget’s disease Chronic osteomyelitis Post irradiation

8. CLASSIFICATION 2. Based on the predominant type of matrix Osteoblastic osteosarcoma: This is the commonest subtype and is characterized by the production of osteoid and the presence of malignant osteoblasts Chondroblastic osteosarcoma: It contains chondroblasts in addition to osteoid Fibroblastic osteosarcoma: This is the least commonest subtype. Fibroblasts are the predominant cell type and osteoid production may be limited

9. PATHOGENESIS About 70% of osteosarcomas have acquired genetic abnormalities such as complex structural and numerical chromosomal aberrations. Molecular studies have shown that these tumors usually have mutations in well-known tumor suppressors and oncogenes RB Individuals with germline mutations in RB have a 1000-fold increased risk of osteosarcoma Somatic RB mutations are present in up to 70% of sporadic osteosarcomas

10. 2. TP53 Individuals with Li Fraumeni syndrome, who have germline TP53 mutations, have a greatly elevated incidence of osteosarcoma Abnormalities that interfere with p53 function are common in sporadic tumors 3. CDKN2A It encodes two tumor suppressors, p16 (a negative regulator of cyclin-dependent kinases) and p14 (augments p53 function) It is inactivated in many osteosarcomas

11. 4. MDM2 A cell cycle regulator It inhibits p53 function It is overexpressed in many osteosarcomas 5. CDK4 A cell cycle regulator It inhibits RB function It is overexpressed in many osteosarcomas

12. MORPHOLOGY GROSS Osteosarcomas are large and bulky destructive tumors They are gritty and gray white They frequently destroy the surrounding cortices and produce soft tissue masses by infiltrating the surrounding soft tissue They also spread through the medullary canal, infiltrating and replacing the marrow Osteosarcomas contain areas of hemorrhage and necrotic degeneration

13. HISTOLOGY The characteristic feature of osteosarcoma is the formation of osteoid matrix or mineralized bone by the malignant tumor cells These tumor cells are surrounded by the osteoid matrix in a lace like pattern The tumor cells are very pleomorphic, have hyperchromatic nuclei and prominent nucleoli Within the tumor, numerous atypical mitoses are also present MORPHOLOGY

14. MORPHOLOGY RADIOLOGY There are two characteristic features seen in osteosarcomas radiographically Codman’s triangle: This is formed as a result of expansion of the tumor and resultant elevation of the periosteum Sunburst appearance: This is formed by presence of highly irregular radiating spicules of newly formed bone These two features depict the aggressive pattern of the tumour

15. CLINICAL FEATURES Osteosarcom as present as painful progressively enlarging masses A pathological fracture may sometimes be the initial manifestation Limited range of movement in the affected joint/limb Cough/dyspnea (metastatic symptoms)

16. DIAGNOSIS Imaging (X-ray, CT scan and MRI) Biopsy Histological examination

17. TREATMENT Surgery Chemotherapy Radiotherapy

18. CONCLUSION Osteosarcoma is a rare and aggressive tumor more often diagnosed among young patients and the elderly. Its destructive and aggressive nature cannot be overemphasized Understanding this tumor is of great importance therefore in making an early diagnosis to aid early treatment.

19. REFERENCES Robbins and Cotran pathologic basis of disease 11th edition Lecture slide by Dr Akpa Phillip

20. THANKS FOR LISTENING QUESTIONS ??