Malignant bone-cartilage tumours

Question 1

What normal cell type does osteosarcoma originate from?

Answer 1

Malignant osteoblasts

Question 2

What is the most common primary malignant bone tumour, excluding haematopoetic tumours?

Answer 2

Osteosarcoma

Question 3

In which bone region does an osteosarcoma commonly occur?

Answer 3

Metaphyseal region

Question 4

At what stage of life does osteosarcoma commonly present?

Answer 4

Adolescence

Question 5

At what age is first incidence of osteosarcoma most common, and in which bone region and why?

Answer 5

Under age 20 (puberty growth spurt)

Growth plates of bones have fastest growth due to increased proliferation: allows predisposition to osteosarcoma development

Question 6

Does the 2nd highest peak incidence of osteosarcoma commonly develop as primary or secondary tumours?

Answer 6

Secondary

Question 7

At which life stage is secondary osteosarcoma most prevalent, and why?

Answer 7

Older age (more men)

Have conditions that cause predisposition to osteosarcoma development

Question 8

Give 3 examples of pre-existing conditions that cause predisposition to secondary osteosarcomas?

Answer 8

Paget’s disease

Previous radiation

Bone infarcts

Question 9

What is the correlation between retinoblastoma and osteosarcoma?

Answer 9

Patients with germline/somatic/random mutation of retinoblastoma gene have 1000x risk of developing sporadic (no cause) osteosarcoma

Question 10

What mutation is caused by Li-Fraumeni syndrome, and how does it affect incidence of osteosarcomas?

Answer 10

Germline TP53 gene mutations leading to elevated incidence of osteosarcoma

Question 11

What is the correlation between tumour suppressor genes and osteosarcoma incidence?

Answer 11

70% osteosarcomas occur due to acquired genetic abnormalities in tumour suppressor genes

eg.RB, p53, CDKN2A (gene encodes two tumour suppressors, p16 (a negative regulator of cyclin-dependent kinases) and p14 (which augments p53 function)

Question 12

Which 2 oncogenic cell-cycle regulators are overexpressed by low-grade osteosarcomas, and what are their oncogenic functions?

Answer 12

MDM2 (inhibits p53)

CDK4 (inhibits RB)

Question 13

Describe the macroscopic appearance of osteosarcomas?

Answer 13

Grey/white, bulky mass with cut surface that shows haemorrhaging, fibrosis, cystic degeneration

Can see Codman triangle

Question 14

Describe the radiological appearance of the centre of the osteosarcoma mass itself?

Answer 14

Mixed radiolucent/lytic areas and sclerotic areas

Infiltrative/not well-defined border

Question 15

Describe what is meant by the radiological sunburst/’hair on end’ periosteal reaction, in osteosarcomas?

Answer 15

Lesion grows so fast that periosteum has insufficient time to lay down another bone layer, instead sharpey’s fibres stretch perpendicular to bone surface

Occurs in other aggressive bone lesions too

Question 16

Describe what is meant by the radiological Codman triangle, in osteosarcomas?

Answer 16

Tumour breaks through cortex into periosteum that has insufficient time to completely ossify, so only raised periosteum edge ossifies, forms a triangle shape

Question 17

Give examples of aggressive bone lesions that commonly have the radiological sunburst sign?

Answer 17

osteosarcoma

Ewing sarcoma

osteoblastic metastases from prostate, lung, breast cancer

Question 18

Give examples of aggressive bone lesions that commonly have the radiological Codman triangle sign?

Answer 18

osteosarcoma

Ewing sarcoma

metastases

chondrosarcoma

osteomyelitis setting

giant cell tumour

aneurysmal bone cyst

Question 19

Describe the 2 characteristic microscopic features of osteosarcoma?

Answer 19

Unmineralised (light pink) and mineralised (dark pink) trabeculae in interconnected network

Between trabeculae, malignant osteoblasts secrete osteoid (dark purple)

Question 20

What normal cell type does chondrosarcoma arise from?

Answer 20

Chondrocytes (cells that produce cartilage)

Question 21

What substance does a chondrosarcoma produce?

Answer 21

Cartilage

Question 22

Which bones do chondrosarcomas commonly develop in, and give 3 specific bony structures?

Answer 22

Axial skeleton and proximal extremities

Eg. pelvis, ribs, shoulders

Question 23

Which age range is commonly affected by chondrosarcomas?

Answer 23

Older adults (over 40 yrs old)

Question 24

Are chondrosarcomas equally common in men and women?

Answer 24

Twice as common in men

Question 25

Are chondrosarcomas mostly primary or secondary?

Answer 25

Primary 15% are secondary

Question 26

Which 2 types of tumours do secondary chondrosarcomas usually arise from?

Answer 26

Enchondroma Osteochondroma

Question 27

What 2 forms of chondrosarcomas are more aggressive then its conventional form?

Answer 27

Mesenchymal Dedifferentiated (transient process by which cells become less specialized and return to an earlier cell state within the same lineage)

Question 28

What is the main macroscopic feature of chondrosarcomas?

Answer 28

Painful enlarging mass

Question 29

What are the main 3 radiological features of chondrosarcomas?

Answer 29

Ring and arc patterns/clumped densities Soft tissue mass Destroyed bone cortex

Question 30

What are the 3 main microscopic findings of chondrosarcomas?

Answer 30

Nuclear pleomorphism Higher nuclear to cytoplasmic ratio Irregular cells membranes

Question 31

Do grade 1 chondrosarcomas usually metastasise?

Answer 31

No

Question 32

How do grade 3 chondrosarcomas usually metastasise, and to where?

Answer 32

Haematogenous spread Lungs

Question 33

Which normal cell type does Ewing sarcoma arise from, and where in the bone?

Answer 33

Neuroectodermal cells Medullary cavity Malignant cancer

Question 34

What are the 1st and 2nd most common childhood primary bone tumours?

Answer 34

Osteosarcoma Ewing sarcoma

Question 35

Is Ewing sarcoma more common in boys or girls, and what is the typical age range?

Answer 35

Boys 15 years old and younger

Question 36

Does Ewing sarcoma normally metastasise?

Answer 36

Yes

Question 37

Does Ewing sarcoma usually respond well to chemotherapy?

Answer 37

Yes

Question 38

What chromosomal mutation is typically associated with Ewing sarcoma?

Answer 38

Balanced 11;22 translocation: Fuses the EWSR-1 gene on chromosome 22 to the FLI-1 gene on chromosome 11

Question 39

What is the 2 characteristic microscopic findings of Ewing sarcoma, and what normal cells can these be mistaken for?

Answer 39

Small, round, blue cells with little cytoplasm Psuedo-rosettes: Cells cluster around pink necrotic area Which resemble lymphocytes

Question 40

What are the 4 main radiological findings of Ewing sarcoma?

Answer 40

Permeative 'moth-eaten' radiolucent areas of bone diaphysis Large soft-tissue mass with no osteoid Lamellated/onion skin periosteal reaction: Bony concentric cells Sunburst/’hair on end’ periosteal reaction

Question 41

Why does the onion skin periosteal reaction occur in bone?

Answer 41

Lesion grows unevenly in fits so periosteum has time to lay down a bone layer until lesion grows again, causing pattern of concentric bony shells

Question 42

What is Wilms tumour/nephroblastoma?

Answer 42

Rare, malignant kidney cancer that affects children

Question 43

What is rhabdomyosarcoma, and what 6 body areas does it commonly affect in children?

Answer 43

Most common soft tissue sarcoma in children, that develops from muscle or fibrous tissue commonly affects head, neck, bladder, testes, womb, or vagina