Lecture 3: MSK 3 (bone cancer)

Question 1

Types of Bone Cancer

Answer 1

→ primary bone tutors are relatively rare - start w/n the bone → secondary tumors in the skeletal (start w/n the bone) - breast cancer - postate cancer - lung cancer

Question 2

Distant Metastasis

Answer 2

→ spread through vascular + lymphatic pathways → there is a selectivity of cancer + how they spread throughout the body - great cancer to bones → dormancy

Question 3

Common sites of Metastasis (bone cancer)

Answer 3

→ lower extremity (43%) → pelvic bone (70%) → vertebra (74%)

Question 4

Bone Tumors: Fibrosarcoma

Answer 4

• Firm, fibrous mass of collagen, malignant fibroblasts, and osteoclast-like giant cells
• Usually affects metaphyses of the femur or tibia
• Metastasis to the lungs is common

Question 5

Staging of Metastasis

Answer 5

→ stage 1: no metastasis → stage 2: local invasion → stage 3: spread to regional structures → stage 4: distal metastasis - most bone cancers are at stage 4 - only exception = primary tutor w/n bony tissue + originating in the bone itself

Question 6

Symptoms and Complications of Bone Cancer

Answer 6

pain, decreased mobility, pathlogic fractures (complications that arrise

Question 7

Clinical Manifestations (bone cancer)

Answer 7

→ Gi-tract issues → pain → fatigue → anemia → cachexia → leukopenia → thrombocytopenia → hair + skin issues

Question 8

Evaluation of Bone Cancer

Answer 8

• ˜Medical imaging is performed
  
  • Medical imaging is performed + and able to detect how cancer has metasesized to the legion
• ˜Radiographs vs. Bone Scans
  
  • preferred method for assessing bone cancer – have a greater level of specifity or sensitivity – detecting the bone cancer at earlier stages in the progression of cancer

Question 9

TNM System

Answer 9

→ T = Tumor (primary tump size + magnitude of the tumor - 0 to 3 levels) → N = Nodes (involvelemt of nodes - 0 to 2 levels) → M = metastasis (magnitude of the cancer metastasizing - 0-2 levels)

Question 10

Osteoclerostic Bone Metastases

Answer 10

• ˜Excessive bone formation due to osteoblasts and regulatory factors = Disorganized, weakened bone tissue
• Endothelin-1 = stimulant of osteoblast progenitors
• help osteoblast formation + activity
• Direct stimulus of osteoblast progenitors and are linked to a substantial amount of pain
• Bone morphogenetic proteins (BMPs) = ectopic bone formation

• Ectopic – above regular bone surface and regular bone tissue growth

• Secondary to metastatic tumours of the prostate and breast

Question 11

How Do Bone Tumors Form?

Answer 11

Question 12

Histological Characteristics of Bone Tumors

Answer 12

→ malignant bone tutors - increased nuclear/cytoplasmic ratio - irregular borders to tumor cells - excess chromatin - increase in mitotic rate **bony tissue is constantly remodelling***

Question 13

Malignant Tumors

Answer 13

→ grow rapidly → not encapsulated → invasive → poorly differentiated → high mitotic index → can spread distantly (metastasis)

Question 14

Definition of Metastasis

Answer 14

→ direct invasion of contagious cells + organs → metastasis to distant organs (lymphstics + blood) → cell migration + angiogenesis is present - blood vessel can be transported, access to systematic circulation

Question 15

Myelogenic Tumors

Answer 15

• Giant cell tumour
• Causes extensive bone resorption because of the osteoclastic origin (breakdown) and RANKL (lead to osteoclast activity à regulatory factor that promotsebone absorption) overexpression
• Located in the epiphyses of the femur, tibia, radius, or humerus
• Has a slow, relentless growth rate

Question 16

Pattern of Bone Destruction

Answer 16

Question 17

Bone Tumors: Osteosarcoma

Answer 17

• Most common malignant bone-forming tumour
• Predominantly in persons under 20 years; occurs in 50- to 60-year-olds if they have a history of radiation therapy
• Tumours contain osteoid produced by anaplastic stromal cells
• Deposited as thick masses or “streamers”
• Located in the metaphyses of long bones
• 50% occur around the knees

Question 18

Osteogenic Bone Formation

Answer 18

• How cells Migrate from primary tumor through the blood circulation and effect bone tissue

End up at a site distant from where they originate

• Controls bone resorption and formation
• When osteoclast = activity is high – exceeds that of osteoblasts then osteolytic bone tumors tend to form – breakdown of bony tissue
• Osteoblasts = tend to proliferate and exceed that of the osteoclasts – bone formation occurs – isochromatic bone tumor (metastasized)
• There a a very high umber of cytokines and hormones that are regularity factors in controlling the development of tumors – cytokines (introluckins – “il”, TNF alpha osteolotic bone tumors, RANKL system, endothelium 1

Question 19

Treatment of Bone Cancer

Answer 19

˜Treatment is complex with no cure, challenges with prevention)

• Early diagnosis of primary tumour
• Medical management of bone cancer = surgery (amputation if regionalized), radiation therapy

Question 20

RANK/RANKL Inhibitors

Answer 20

• ˜Interaction of RANK/RANKL normally promotes osteoclast formation
• ˜Target osteoclastic bone resorption
• ˜Reduction in tumour development related to inhibition of osteoclastic resorption, may inhibit bone metastases

Question 21

Benign Tumors

Answer 21

→ grow slowly → well defined capsule → not invasive → well differentiated → low biotic index → not metastasized

Question 22

Bone Tumors: Chondrosarcoma

Answer 22

• Cartilage-forming tumour
• Tumour of middle-aged and older adults
• Infiltrates trabeculae in spongy bone; frequent in the metaphyses or diaphysis of long bones
• Tumour expands and enlarges the bone
• Causes erosion of the cortex and can expand into the neighboring soft tissues

Question 23

Derivation of Bone Tumors

Answer 23

→ may originate from bone cells, cartilage, fibrous tissue, marrow or vascular tissue - osteogenic (bone cells) - chondrogenic (cartilage) - collagen (fibrous tissue) → most common - myelogenic (bone marrow/vascular tissue) → most common

Question 24

Osteogenic Bone Metastasis

Answer 24

• ˜Osteoclast > Osteoblast activity = weakened bone integrity
• ˜Secondary to cytokine, hormone imbalance in bone remodeling
• ˜Process of Osteoclasts + tumour cells = osteolytic lesions
• ˜Bone marrow involvement and activation of neurons
• with respect to caner cells are migrating to the site of bone, bone is going to retract (remove itself – weakened, for form more bony tissue
• Osteolytic tissue - osteoclasts are more dominant
• There are cells (stromal cells) present w/n the bone marrow that help to establish and progress the metastases of cancer
• These regions of bone marrow )contain neurons, platelets and endothelial cells) – when indiduals have bone cancer they have a large amount pain in bones + joints – activation fs sympathetic neurons by the cancerous cells that have metastasized to create pain in the region – increase further proliferation

Question 25

How Cancer Spreads

Answer 25

→ primary tumor formation → local invasion (cellular manipulation occurs) → intravastation → survival in the circulation (basement membrane to cells) → arrest at a distant organ site extravasation → micrometasis formation (primary formation of a small number of cancerous cells that have spread to the primary tumor to other parts of the body) → metastasic colonization → clinically detachable macroscopic metastasis