Pathology - Tumours Flashcards
What is an Osteochondroma/Exostosis
Bony Outgrowth capped by a cartilage cap, attached to the underlying skeleton by a bony stalk
Where do Exostoses occur?
Metaphyses near the growth plate of long tubular bones near the knee, pelvis, scapula and ribs
What is the ratio of exostoses cases that are solitary outgrowths
85%
When does exostoses occur most commonly?
First 2 decades
If malignant, what does exostoses lead to?
chondrosarcoma
What is the pathophysiology of exostosis?
EXT1 & EXT2 genes mutated which code for enzymes to make heparan sulfate glycosaminoglycans = decrease diffusion of IHH which regulates cartilage growth
State a factor that increases malignant transformation of exostoses
Multiple Outgrowths: Multiple Hereditary Exostoses Syndrome (bones may be bowed or shortened)
What is the morphology of exostoses cases?
Sessile, Pedunculated, 1-20cm, cap made of hyaline cartilage and covered in perichondrium
What is the histologic appearance of Exostoses?
Disorganised growth plate; undergoes Endochondral ossification (newly made bone forms inner portion of head and stalk
What are morphological features of chondromas?
- Well Defined
- No soft tissue invasion
- Calcification - stippled, flocculent
- Bulbous Expansions
- Complications: Fractures, Malignant Degeneration
What are histological features of chondromas?
- Mature Hyaline Cartilage (Gray-blue/translucent)
- No Cytological Atypia
- No permeation of bone trabeculae or marrow
- No Soft Tissue Invasion
What is the morphology of a simple bone cyst?
Cyst-like structure with fibrous wall
Amorphous pink material with a cementum-like appearance
What is the molecular mutation of a Simple Bone Cyst?
FUS or EWSR-1-NFATC2 fusion
What are the clinical features of a simple bone cyst?
- Benign, Fluid Containing Lesion
- Occurs in metaphyses
- 50% present as pathological fracture
Most common occurence of simple bone cysts?
4-10 years old
What is an osteoid osteoma?
Benign bone-forming tumour characterised by extensive reaction and pain disproportionate to size
Clinical features of osteoid osteoma?
- pain becomes unrelenting when untreated
- nidus in bone
Locations of Osteoid Osteoma?
Cortical Diaphyseal (65%-70%)
Femur > Tibia
Intracapsular (esp femoral neck)
Spine (10%, usually posterior elements)
EpiD of osteoid osteoma?
- 10-25 years old
- M:F = 3:1
- 4% of primary tumours
- Rarely malignant change to osteogenic sarcoma
- 20% recurrence
Treatment of Osteoid Osteoma & Osteoblastoma?
OO: Aspirin, NSAIDS, radiofrequency ablation
OB: Curettage followed by bone grafting
Imaging of Osteoid Osteoma?
- Oval Lytic Lesion (loosened lesion) in cortical bone; rounded; sclerosis
- Sclerosis may obscure underlying lytic nidus on radiograph
- Calcified nidus and cortical sclerosis (thickening) on CT
Distinguish between Osteoid Osteoma and Osteoblastoma?
Thick rim of reactive cortical bone
Features of Osteoblastoma?
Anastomosing woven bone trabaculae rimmed by abundant osteoblasts
Loose and vascular intrabacecular spaces
No malignant features (atypia, invasion, maligant osteoid)
What age does osteosarcomas occur?
10-25
How do osteosarcomas present?
Soft Tissue Swelling & Intermittent Pain
Pathological Fracture (15%)
Where and how do osteosarcomas metastasise to?
Lungs, Liver via hematogenous spread
Where are sites of origin of osteosarcomas?
Metaphyses of long bones (distal femur, proximal tibia, proximal humerus)
Arises within the meduallary cavity and extends to cortex
What radiological sign is an indicator of aggresive osteosarcoma
Triangular Shadow between cortex and raised periosteal ends (Codman Triangle)
What is a diagnostic radiological sign of osteosarcoma?
Sunburst periosteal reaction - tumour breaks through the cortex & lifts the periosteum
What type of lesion is osteosarcoma?
Sclerotic, lytic or mixed
What mutations are involved in osteosarcoma?
- R13
- P53
- CDKN2A (encodes tumour suppressors p16 & p14)
- MDM2 & CDK4 overexpressed (function to inhibits p53 and R13)
What are the histological features of osteosarcoma?
- Malignant Tumour Cells - Pleomorphic, Atypia, Hyperchromatic Nuclei, Abundant Mitoses
- Maligant Osteoid Pattern (lace-like pattern of osteoid: tumour cells produce unmineralised osteoid that becomes mineralised bone)
- Invasive Growth Pattern - intravascular patten
- Tumour necrosis, hemorrhage, cystic degeneration
Fun Facts about Osteosarcoma
- Bulky gray white tumours
- Tumour cells can also form broad sheets or primitive trabeculae
- Neoplastic cells can also produce cartilage; if abundant = chondroblastic osteosarcoma
- Tumour destroys surrounding cortices to produce soft tissue masses that spread extensively in the medullary cavity & replace marrow
- May penetrate epiphyseal plate or enter joint - grow along tendoligamentous structure or through attachment site of joint capsule
When do chondrosarcomas occur?
4th to 6th decade
Where does chondrosarcomas occur?
Long bones, pelvis, ribs, spine (<10%)
What are features of chondrosarcomas
- Metaphyseal
- Lucent, Expanded
- Ill-defined margins
- Calcium, amorphous, Calcification
- Cortical Destruction
What is a chondrosarcoma?
A Malignant bone tumour that produces cartilage (but not osteoid)
What are the macroscopic features of chondrosarcoma?
- Large lobulated tumour with pearly white or light blue, often with focal calcification
- Locally aggressive tumour that invades surrounding bone and soft tissue
What are histological features of chondrosarcomas?
- Malignant tumour that produces cartilaginous matrix
- Cytological atypia
- Permeation of bone trabaculae
- Soft tissue and marrow invasion
How do chondrosarcomas present?
Presents as painful, progressively enlarging mass
Radiographic features of chondrosarcoma?
- Ill-defined bone destruction
- Adjacent some tissue swelling
- Calcification
- Foci of flocculent densities
What are the two types of chondrosarcomas and their features?
- Slow growing, low grade: Reactive cortical thickening
- Aggresive, High grade: Destroy cortex, form soft tissue masses
EpiD of chondrosarcoma
15% are secondary - arise from enchondromas or osteochondromas
- EXT, IDH1/2, CDKN2A gene silenccing by DNA methylation
Grading of Chondrosarcomas?
Based on cellularity & nuclear changes in chondrocytes
- well to poorly differentiated correspond to grades 1-3: high grade = locally aggressive + mets to lungs
Spread of chondrosarcomas?
Hematogenously
Treatment of chondrosarcomas?
Surgical excision, (for severe use adjuvant chemotherapy)
Age of Ewing’s Sarcoma?
5-20 years old
Male Female Ratio of Ewing’s Sarcoma?
61M-39F
Sites of Ewing’s Sarcoma?
Femur, Tibia, Fibula, Humerus, Ribs, Clavicle, Pelvis
Symptoms of Ewing’s Sarcoma?
Pain, enlarging mass, tender, warm, swollen
Pathophysiology of Ewing’s Sarcoma?
Translocation t(11,22)
Diagnostic tests for Ewing’s Sarcoma?
FISH or RT-PCR
Radiological Features of Ewing’s Sarcoma?
- Destructive lytic tumour with permeative, moth eaten margins extending into soft tissue
- ‘Onion skin’ periosteal reaction
- Ill-defined destruction of bone that is diaphyseal in location
Histological features of Ewing’s Sarcoma?
- Small, rounded cells with scant clear cytoplasm
- Homer-wright rosettes (central fibrillary space)
- Positive IHC stains: CD99
- Glycogen material
DDx of Ewing’s Sarcoma?
- Osteomyelitis
- Lymphoma
- rhabdosarcoma
- neuroblastoma
- small cell carcinoma
What imaging modalities are used for bone tumours/mets?
- MRI
- Bone Scan - may show lesions throughout
- Plain film - useful for pt with known mets that may present w bone pain or suspected pathological fracture
Method of spread of mets to bone?
- Direct extension
- Lymphatic/hematogenous
- Intraspinal seeding (Batson plexus of veins)
Common location of mets to bone?
axial skeleton (vertebral column, pelvis, ribs, skull, sternum) in which marrow has a rich capillary network
Focality of mets to bone
Multifocal; kidney and thyroid are solitary
EpiD of Mets to bone
75% from prostate, breast, kidney lung
In children, neuroblastima, Wilm’s tumour, osteosarcoma, Ewing’s Sarcoma, Rhabdosarcoma
Effects of Mets
- Lytic - kidney, lung, GI, malignant melanoma
- Blastic - prostatic adenocarcinoma
Changes in bone matrix in mets
- Tumour cells: PGs, cytokines, PTHrP = upregulate RANKL in osteoblasts and stromal cells = increase osteoclastic activity
- Tumour cells: release matrix bound growth factors (TGF- beta, IGF-1, FGF) = support tumour cell growth
- Sclerotic mets: due to tumour cells secreting WNT proteins that stimulate osteoblastic bone formation
Treatment for mets
- Symptomatic relief
- Systemic, chemo, immunotherapy, localised radiation & bisphosphonates
- Surgery to stabilise fractures (esp in spinal mets)