HISTO: Bone Tumours Flashcards
How common are bone tumours? When are primary malignant bone tumours more common?
- Very rare
- malignant tumours 60x less common than lung cancer
- primary malignant bone tumours most common in children and young adults
Femur metaphysis
What type of site predilection is present in bone tumours?
Occur around the knee most commonly
BUT different tumours have different site and age predilection
What are the clinical features of bone tumours?
- pain
- swelling,
- deformity,
- fracture
Must ask about:
- age, site, duration, ?hx of trauma
- ?multiple lesions, ?associated disease
How do you diagnose bone tumours?
XR:
- Evaluate site, size, margin
- ?solitary or multiple, ?soft tissue extension
- ?associated disease or fracture
Biopsy
- Needle biopsy preferred option
- Performed by radiologist usually with Jamshidi needle
- +/- US or CT guidance
- Open biopsy for sclerotic or inaccessible lesions
- Imprint (cytology) preparations are very useful
- Optimal treatment is early referral to specialist centre
Malignant - trabecular bone is irregular here, there is a mix of cartilagenous tissue which shouldn’t usually be there
Normal bone marrow is shown below
List some bone tumour-like conditions.
- Fibrous dysplasia
- Metaphyseal fibrous cortical defect/non-ossifying fibroma
- Reparative giant cell granuloma
- Ossifying fibroma
- Simple bone cyst
List 5 benign bone tumours.
How common is fibrous dysplasia? Who is most affected?
- F>M
- Up to age 30yrs
- Polyostotic disease can be associated with endocrine problems and rough border café au lait spots on skin (McCune Albright syndrome)
Which genetic mutation may be present in fibrous dysplasia?
Somatic mutation in guanine-nucleotide binding protein (G-protein). (GNAS mutation chr 20 q13)
Which syndrome can fibrous dysplasia be associated with?
McCune Albright syndrome
Polyostotic disease can be associated with endocrine problems and rough border café au lait spots on skin
What % of fibrous dysplasia undergoes malignant transformation?
<1%
What is shown?
Soap bubble osteolysis
Characteristic feature of fibrous dysplasia is that it will always be present in more than 1 bone whereas primary bone scarcoma would not, unless metastasis.
What are the histological features of fibrous dysplasia shown here?
Marrow replaced by fibrous stroma
Rounded and curved trabecular bone - called “Chinese letters”
With benign diagnosis of fibrous dysplasia, what is the treatment?
Resection with narrow margins can be used if cosmetically unacceptable
No aggressive treatment necessary
What deformity is shown here? What is the consequence? (left femur on image)
Fibrous dysplasia causing Shepherd’s crook deformity
Bone is weak and cystic so predisposed to fractures
What are the commonest sites of osteochondromas?
What is a feature of this osteochondroma?
This bone outgrowth has a stalk or stem that sticks out from the normal bone. If the tumor has a stalk, the structure is called pedunculated.
What are the histological features of osteochondromas?
Mimic tubular bone and will have a cartilagenous surface overlying the cortical and trabecular bone
What is an enchondroma? What are the most common sites?
Enchondroma - cartilagenous proliferation within the bone
Majority in the hands, some in feet, less in long bones
What is this sign in enchondroma?
Popcorn calcification
What is shown?
Enchondroma - well circumscribed proliferation so can use a narrow excision (this is a benign condition)
Is this tumour benign or malignant?
Benign - but can be locally aggressive. Features include that it is well demarcated and although it has gone through cortex it is still not leaving surface.
This is an example of a giant cell tumour (borderline malignancy)
What is the site of most giant cell tumours?
Epiphysis with metaphyseal extension
Ends of long bones, knees most affected
Who is most affected by giant cell tumours?
20-40yo
F>M
Are the XR and histological features of giant cell tumours?
XR: lytic
Histo: osteoclasts on background of spindle/ovoid cells, locally aggressive, may recuur and can metastasise
NB: this is borderline malignancy
What are the giant cells in giant cell tumours of bone?
Sheets of osteoclasts
What is the commonest malignant bone tumour?
Metastatic
Which sites would you not expect metastatic malignant bone tumours not to occur?
Below elbow and below knee is not expected
Which tumours in adults commonly metastasise to bone?
- Breast
- Prostate
- Lung
- Kidney
- Thyroid
Which tumours in children commonly metastasise to bone?
- Neuroblastoma
- Wilm’s tumour
- Osteosarcoma
- Ewings
- Rhabdomyosarcoma
Name 3 types of primary malignant bone tumours.
Osteosarcoma - bone forming tumour
Chondrosarcoma - cartilage forming tumour
Ewing’s sarcoma/PNET (primitive peripheral neuroectodermal tumour) - undifferentiated mesenchymal tumour
What are the most common sited of osteosarcomas? What ages are affected and what sex?
Peak in adolescence (75% <20yo)
60% occur in knee
What are the XR and histological features of osteosarcoma?
X-ray: usually metaphyseal, lytic, permeative, elevated periosteum(Codman’s Triangle)
Histo: malignant mesenchymal cells +/- bone and cartilage formation
What is the prognosis for osteosarcomas and why?
Prognosis: poor- 60% 5 year survival.
Treatment is usually chemo and limb salvage surgery but chemo is poor as tumours are poorly vascularised
How are osteosarcomas classified?
1. According to site within bone:- i.e. intramedullary, intracortical, surface
2.Degree of differentiation:- i.e. high, intermediate or low grade
3. Multicentricity:- i.e. synchronous or metachronous
4.Primary or secondary
What sign of osteosarcoma is seen on this XR?
Codman’s triangle (periosteal)
Sclerotic and lytic lesions are seen. There is invasion of the soft tissue which has pushed the periosteum off.
What are these red cytoplasm osteosarcoma cells seen to be positive for?
Cytology imprint of osteosarcoma cells positive for alkaline phosphatase (red cytoplasm).
What does this slide of osteosarcoma show?
H&E stained section of osteosarcoma
showing mixed histological pattern malignant bone (purple)
in background of less cellular chondroid areas and cellular mesenchymal tumour.
What is a chondrosarcoma?
Malignant cartilage producing tumour
Prognosis: 70% 5y survival (depends on grade & size)
What ages are most affected by chondrosarcoma? Where do they usually occur?
Age: 40y and over
Site: pelvis, axial skeleton, prox femur, prox tibia
What are the XR and histological features of chondrosarcomas?
X-ray: lytic with fluffy calcification
Histo: malignant chondrocytes +/- chondroid matrix may dedifferentiate to high grade sarcoma
How are chondrosarcomas classified?
- According to site - intramedullary, juxtacortical
- Histologically - conventional (myxoid or hyaline), clear cell, dedifferentiated, mesenchymal
Is this the arm or leg?
Arm
Is this benign or malignant?
Chondrosarcoma so malignant
What is Ewing’s sarcoma/PPNET? What is the prognosis?
Highly malignant small round cell tumour
Prognosis : - 75% 5y survival 50% longterm
What ages are most affected by Ewing’s? What sites are most affected?
Age: usually < 20y (80%)
Site: diaphysis/metaphysis of long bones, pelvis
What are the XR and histological features of Ewing’s sarcoma?
X-ray: onion skinning of periosteum, lytic +/- sclerosis (shown below to be affecting the fibula and soft tissue)
Histo: sheets of small round cells
What is a molecular feature of Ewing’s sarcoma which is useful in diagnosis?
Specific chromosome translocation 11:22 (EWS/Fli1)
Immunostaining can be used to exclude other diagnoses and to confirm Ewing’s sarcoma.
NG: ES will be positive for neuroendocrine markers (S100 and synaptophysin) and CD99 but nothing else.
What fusion protein is present in Ewing’s sarcoma?
EWSR1-FL11 fusion protein
rearrangement t(22;22)(q24;q12)
This can be therapeutically exploited
Define soft tissue tumours.
Defined as mesenchymal proliferations which occur in the extraskeletal, non-epithelial tissues of the body - excluding meninges and lymphoreticular system
What sites do soft tissue tumours occur in?
Anywhere. Majority occur in large muscles of extremities, chest wall, mediastinum, retroperitoneum
Does age/sex and ethnicity affect soft tissue tumour incidence?
Age:
- Any age. Majority older patients
- 15% < 15yrs
- 50% > 55yrs
Sex:
- M>F overall, but sex and age varies between histological types
Ethnicity:
- No proven variation
- Ewing’s and clear cell sarcoma rare in Afrocaribbean population
What is the aetiology of soft tissue tumours? What are the risk factors?
Aetiology unknown
RF:
- Genetic Predisposition
- Chemical carcinogens
- Physical ( asbestos, foreign body )
- Viruses
- Immunodeficiency
What are the types of soft tissue tumours?
Liposarcoma/myxoid
Pleiomorphic
Spindle cell tumour
What type of soft tissue tumour is this?
Liposarcoma/myxoid
What are the diffrentials for liposarcoma/myxoid soft tissue tumour?
- Myxoid DFSP
- Embryonal ( Botryoid ) Rhabdo
- Myxoid Chondrosarcoma
- Chordoma
- Signet Ring Lymphoma
- “Balloon Cell” Melanoma
- Mucinous Adenocarcinoma
What type of soft tissue tumour is shown?
Spindle cell sarcoma
What are the differentials for a spindle cell sarcoma soft tissue tumour?
- Fibrosarcoma
- MPNST
- Monophasic Synovial Sarcoma
- MFH
- Leiomyosarcoma
- GIST
- Spindle cell forms of rhabdo, liposarcoma,
- malignant melanoma, Carcinoma
What type of soft tissue tumour is shown?
Pleomorphic tumour
What are the differentials for pleomorphic sarcomas?
- MFH
- Rhabdomyosarcoma
- Leiomyosarcoma
- Liposarcoma
- Malignant Melanoma
Why is this called a “biphasic tumour”?
Synovial sarcomas have epithelial and spindle cell areas.
List some special diagnostic tests that canbe used to help diagnose soft tissue tumours, if histology alone does not suffice.
- Immunohistochemistry
- EM
- Cytogenetics (conventional & interphase)
- FISH
- M-FISH
- SKY
- CGH
- PCR
- RT-PCR
What are the good and bad prognostic factors for a soft tissue tumour?
Good:
- <5cm
- Superficial to deep fascia
- Low histological grade
- Clear excision margin
- Vascular invasion absent
- Diploid
- Low proliferation index
- Present tumour suppressor gene/absent tumour promoter gene
Bad:
- >5cm
- Deep to deep fascia
- High histological grade
- Involved excision margin
- Vascular invasion
- Aneuploid/hyperploid
- High proliferation index
- Absent tumour suppressor gene/present tumour promoter gene
Summarise soft tissue sarcoma staging.
Staging based on prognostic factors and metastasis.
- 0 = 3 good prognostic signs
- 1 = 2 good 1 bad
- 2 = 1 good 2+ bad
- 3 = 3+ bad
- 4 = metastases, regional or distant
