Malignant bone-cartilage tumours Flashcards
What normal cell type does osteosarcoma originate from?
Malignant osteoblasts
What is the most common primary malignant bone tumour, excluding haematopoetic tumours?
Osteosarcoma
In which bone region does an osteosarcoma commonly occur?
Metaphyseal region
At what stage of life does osteosarcoma commonly present?
Adolescence
At what age is first incidence of osteosarcoma most common, and in which bone region and why?
Under age 20 (puberty growth spurt)
Growth plates of bones have fastest growth due to increased proliferation: allows predisposition to osteosarcoma development
Does the 2nd highest peak incidence of osteosarcoma commonly develop as primary or secondary tumours?
Secondary
At which life stage is secondary osteosarcoma most prevalent, and why?
Older age (more men)
Have conditions that cause predisposition to osteosarcoma development
Give 3 examples of pre-existing conditions that cause predisposition to secondary osteosarcomas?
Paget’s disease
Previous radiation
Bone infarcts
What is the correlation between retinoblastoma and osteosarcoma?
Patients with germline/somatic/random mutation of retinoblastoma gene have 1000x risk of developing sporadic (no cause) osteosarcoma
What mutation is caused by Li-Fraumeni syndrome, and how does it affect incidence of osteosarcomas?
Germline TP53 gene mutations leading to elevated incidence of osteosarcoma
What is the correlation between tumour suppressor genes and osteosarcoma incidence?
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)
Which 2 oncogenic cell-cycle regulators are overexpressed by low-grade osteosarcomas, and what are their oncogenic functions?
MDM2 (inhibits p53)
CDK4 (inhibits RB)
Describe the macroscopic appearance of osteosarcomas?
Grey/white, bulky mass with cut surface that shows haemorrhaging, fibrosis, cystic degeneration
Can see Codman triangle
Describe the radiological appearance of the centre of the osteosarcoma mass itself?
Mixed radiolucent/lytic areas and sclerotic areas
Infiltrative/not well-defined border
Describe what is meant by the radiological sunburst/’hair on end’ periosteal reaction, in osteosarcomas?
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
Describe what is meant by the radiological Codman triangle, in osteosarcomas?
Tumour breaks through cortex into periosteum that has insufficient time to completely ossify, so only raised periosteum edge ossifies, forms a triangle shape
Give examples of aggressive bone lesions that commonly have the radiological sunburst sign?
osteosarcoma
Ewing sarcoma
osteoblastic metastases from prostate, lung, breast cancer
Give examples of aggressive bone lesions that commonly have the radiological Codman triangle sign?
osteosarcoma
Ewing sarcoma
metastases
chondrosarcoma
osteomyelitis setting
giant cell tumour
aneurysmal bone cyst
Describe the 2 characteristic microscopic features of osteosarcoma?
Unmineralised (light pink) and mineralised (dark pink) trabeculae in interconnected network
Between trabeculae, malignant osteoblasts secrete osteoid (dark purple)
What normal cell type does chondrosarcoma arise from?
Chondrocytes (cells that produce cartilage)
What substance does a chondrosarcoma produce?
Cartilage
Which bones do chondrosarcomas commonly develop in, and give 3 specific bony structures?
Axial skeleton and proximal extremities
Eg. pelvis, ribs, shoulders
Which age range is commonly affected by chondrosarcomas?
Older adults (over 40 yrs old)
Are chondrosarcomas equally common in men and women?
Twice as common in men
Are chondrosarcomas mostly primary or secondary?
Primary
15% are secondary
Which 2 types of tumours do secondary chondrosarcomas usually arise from?
Enchondroma
Osteochondroma
What 2 forms of chondrosarcomas are more aggressive then its conventional form?
Mesenchymal
Dedifferentiated (transient process by which cells become less specialized and return to an earlier cell state within the same lineage)
What is the main macroscopic feature of chondrosarcomas?
Painful enlarging mass
What are the main 3 radiological features of chondrosarcomas?
Ring and arc patterns/clumped densities
Soft tissue mass
Destroyed bone cortex
What are the 3 main microscopic findings of chondrosarcomas?
Nuclear pleomorphism
Higher nuclear to cytoplasmic ratio
Irregular cells membranes
Do grade 1 chondrosarcomas usually metastasise?
No
How do grade 3 chondrosarcomas usually metastasise, and to where?
Haematogenous spread
Lungs
Which normal cell type does Ewing sarcoma arise from, and where in the bone?
Neuroectodermal cells
Medullary cavity
Malignant cancer
What are the 1st and 2nd most common childhood primary bone tumours?
Osteosarcoma
Ewing sarcoma
Is Ewing sarcoma more common in boys or girls, and what is the typical age range?
Boys
15 years old and younger
Does Ewing sarcoma normally metastasise?
Yes
Does Ewing sarcoma usually respond well to chemotherapy?
Yes
What chromosomal mutation is typically associated with Ewing sarcoma?
Balanced 11;22 translocation: Fuses the EWSR-1 gene on chromosome 22
to the FLI-1 gene on chromosome 11
What is the 2 characteristic microscopic findings of Ewing sarcoma, and what normal cells can these be mistaken for?
Small, round, blue cells with little cytoplasm
Psuedo-rosettes: Cells cluster around pink necrotic area
Which resemble lymphocytes
What are the 4 main radiological findings of Ewing sarcoma?
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
Why does the onion skin periosteal reaction occur in bone?
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
What is Wilms tumour/nephroblastoma?
Rare, malignant kidney cancer that affects children
What is rhabdomyosarcoma, and what 6 body areas does it commonly affect in children?
Most common soft tissue sarcoma in children, that develops from muscle or fibrous tissue
commonly affects head, neck, bladder, testes, womb, or vagina
