Sarcomas Flashcards
What is a sarcoma?
A malignant cancer that arises from transformed cells of mesenchymal origin
Cells that lack polarity and are surrounded by significant stroma
Name the subtypes of sarcomas based on their origin:
- Bone
- Connective tissue
- Blood vessels
- Muscle
- Fat
- Cartilage
- Bone = osteosarcoma
- Connective tissue = soft tissue sarcoma, fibrosarcoma
- Blood vessels = haemangiosarcoma
- Muscle = rhabdomyosarcoma (striated muscle), leiomyosarcoma (smooth muscle)
- Fat = liposarcoma
- Cartilage = chondrosarcoma
Describe the general behaviour of sarcomas
Locally invasive
Metastatic risk varies with tumour type
The metastatic risk of sarcomas is highest in which tumour types?
Osteosarcoma
Haemangiosarcoma
Histiocytic sarcoma
For soft tissue sarcomas, fibrosarcomas and peripheral nerve sheath tumours metastatic potential is affected by?
Grade
Define the stage of a tumour
Extent: how far has it got?
Clinical assessment of current disease burden
Does the disease burden limit outcome ?
Define the grade of a tumour
Histological features
Activity, Vascularity, Invasion,
Necrosis, Differentiation
What is the likely behaviour ?
How can sarcomas be diagnosed?
Fine needle aspiration and cytology
Biopsy and histology +/- IHC
How can you stage sarcomas?
Is there evidence of metastasis ?
- Aspiration of local lymph nodes, even if palpably normal
- Imaging dependent upon tumour type
- Sample other abnormalities identified on examination
Describe the uses of FNA for sarcomas
Cheap, quick can be done without sedation or GA
Higher chance of non-representative sample
No grade
Describe the uses of a Tru-cut biopsy for sarcomas
Small samples
Chance of non-representative sample – diagnosis or grade
May be possible to do under sedation
Describe the uses of a biopsy and histology for sarcomas
Larger samples therefore better chance of diagnosis and accurate grade
Requires GA, more morbidity and cost
Describe radiography of primary sarcomas
- Radiographs relatively insensitive
- more than 60% of mineral content of bone must be lost for lysis to become apparent
- All soft tissues except fat look the same
Describe the use of CT for imaging primary sarcomas
Better appreciation of osteolysis or new bone production
Many more shades of grey (different tissues)
Surgical planning
Radiation planning
Describe the use of MRI for imaging primary sarcomas
Excellent for surgical planning esp trunk/body wall
Most sarcomas metastasise via which route?
Haematogenous
In which cases of sarcomas would you want to FNA local and regional LNs?
FNA if node palpably abnormal and in all cases where LN metastases more likely:
- Higher grade tumours
- Suspected histiocytic tumours
- Tumours around joints
Describe distant metastasis of sarcomas, and how to diagnose this
Depends on tumour type
All sarcoma’s have a predilection for lung metastasis:
- Inflated (i.e. under GA) 3 view thoracic radiographs
- CT is more sensitive if available
Describe the limitations of imaging for sarcomas
- Limitations of x-ray
- Increased sensitivity of CT for bone involvement and pulmonary nodules
What are the lesions? - Lung lesions often cannot be sampled
- Not all nodules are metastatic
- Larger and/or more numerous tend to be metastases
Soft tissue sarcomas are most commonly seen in which patients?
- Middle to large breeds may be predisposed
- Median age 8 -11 years
- Some breed predilections e.g. fibrosarcomas in Retrievers
- Younger animals in predisposed breeds
Describe the treatment algorithm for soft tissue sarcomas
- Biopsy confirmed soft tissue sarcoma
- Wide surgical margin excision
- If margins are histologically complete, grade tumour
- If margins are histologically incomplete, wide surgical resection of scar or adjunctive radiation therapy
How should patients with grade 1 and 2 soft tissue sarcomas be managed following removal?
Routine follow up at 1, 3, 6, 9, 12 and 18 months
How should patients with a grade 3 soft tissue sarcomas be managed following removal?
Routine follow up at 1, 3, 6, 9, 12 and 18 months
Consider adjunctive chemotherapy with doxorubicin based protocol
What should be done if a soft tissue sarcoma has a pseudocapsule?
Do not try to shell the tumour out of this - remove it all
Describe the ideal surgical margins for a soft tissue sarcoma
- 3 cm lateral and 1 fascial plane beyond the extent of tumour
- ‘Tumour’ includes FNA tracts and biopsy scars
- Not always possible, limited by anatomy
How are margins of excision assessed?
Most common method: cardinal
- 3 sections
- Relies on mass being spheroid
- Not always true
- Sarcomas (and other) tumours invade along tissue planes
Name two other methods of sample preparation for margin assessment
Bread loafing
Shaved margins
Margins of excision are assessed and the results can be one of 3 categories, what are they?
Complete excision
Incomplete excision
Excision with narrow margins (1 - 3 mm between tumour and sample edge)
Describe the features of incomplete tumour excision
- Residual tumour tissue
- Tumour cells within < 3 mm of tissue edge
- Probability of recurrence dependent upon tumour type and grade
If there is microscopic residue of a tumour following removal, what are the further treatment options?
- Further wide surgical excision
- Ideally treat the scar as a tumour and aim for wide surgical excision - Adjuvant radiation therapy
- Ideally delivered as a fractionated protocol i.e 12 or more rather than 4 fractions
- Highly effective tumour control
Describe metronomic chemotherapy as a treatment option for microscopic residual disease
- Continuous, low dose therapy
- Usually low dose cyclophosphamide with piroxicam or meloxicam
- Main target is angiogenesis: immunomodulatory effects
Describe active monitoring as a treatment option for microscopic residual disease
- Generally a terrible idea as most recur and acting before this happens will give better outcome
- Only when chance of recurrence is considered low e.g. low grade STS
- When a complete excision was expected
- When there are questionable margins in one small area
- Check by vet monthly for at least a year
Describe the prognosis in patients with resectable tumours without metastatic disease
Successful surgery +/- RT associated with very good survival MST > 4 years
List 4 prognostic factors for sarcomas
Tumour grade and mitotic rate
Tumour size
Tumour location
Achieving local control of the tumour
Anti-metastatic treatment is used for which tumours?
For high (and possibly intermediate grade) STS.
Also occasionally used palliatively for non-resectable disease and no other options
Name the tumour that develops at at sites where cats typically get injections
Feline injection site sarcoma
Describe the histological appearance of feline injection site sarcomas
Malignant fibroblasts
Inflammation – often high lymphocyte component
Macrophages taking up foreign material thought to be adjuvant / carrier
Describe the 3-2-1 rule for feline injection site sarcomas
Any mass present for 3 months or longer
Any mass greater than 2cm diameter
Any mass that continues to increase in size 1 month after injection
Which biopsy type can be used for feline injection site sarcomas?
Incisional biopsy
- Excisional biopsy almost guarantees treatment failure
Describe diagnosis and staging of feline injection site sarcomas
- Advanced imaging
- Local staging: assessing size, margins as highly invasive
- Distant staging: variable metastatic rate, haematogenous route
Describe the margins needed for feline injection site sarcoma excision
(3 –) 5+ cm lateral surgical margins and 2 fascial planes deep
This can involve removal of spinous processes of vertebrae
Describe treatment for non-resectable feline injection site sarcomas
Pre-operative radiation therapy and / or chemotherapy can be useful
Describe treatment for incomplete resections or marginally resected feline injection site sarcomas
Use of adjuvant radiation therapy associated with the best outcomes.
After Sx and definitive RT:
- 1 year survival – 86%
- 2 year survival 44 – 71 %
- 3 year survival 28 – 68 %
Describe Doxorubicin based chemotherapy for treating feline injection site sarcomas
Possibly longer disease free interval in cats treated with surgery, radiation therapy and then chemotherapy
Risk of nephrotoxicity
Describe the recommendations for preventing feline injection site sarcomas
- Injections to be given in sites amenable to wide surgical excision e.g. limb or tail
- Reduce inflammatory reactions at injection sites – avoiding irritating substances where possible
- Do not over-vaccinate
85% of bone tumours are …?
Osteosarcomas
Describe the predispositions for osteosarcomas
Middle age and older dogs
Typically large breeds
- Appendicular skeleton: metaphysis of long bones
- Front limbs 2:1 hind limbs
- ‘Near the knee away from elbow’
Describe the clinical signs of bone tumours
Pain and lameness
- Sudden or progressive onset
- Localisable to a single bone
Swelling
Describe the radiographic changes of bone tumours
Do not differentiate tumour type
- Bone lysis
- Soft tissue swelling
- New bone: palisades perpendicular to bone – sunburst
- Periosteal elevation: Codman’s triangle
- Long zone of transition
- Does not cross joint
How can bone tumour diagnosis be confirmed?
Cytology or histology required to confirm diagnosis
What are the main DDx of bone tumours?
Osteosarcoma
Chondrosarcoma
Histiocytic sarcoma
Fibrosarcoma
Haemangiosarcoma
Myeloma / lymphoma (round cell tumour)
Fungal osteomyelitis
Metastatic tumours (carcinoma)
Benign tumours/cysts
What are the aims of treating bone tumours?
Prevention of pain
Delaying development of metastases and extending life
Describe amputation as a treatment method for bone tumours
Most dogs tolerate amputation very well
- Even large dogs and those with mild to moderate orthopaedic problems
- If it walked in on 3 legs it can walk out on 3 legs
Patients pain free around 1 week after amputation
Complete ambulatory adaptation takes around 1 month
How can you reduce pain in patients with bone tumours?
- Amputation will eliminate pain
- Analgesics: multimodal approach - opioids, NSAIDs, paracetamol
Which drug can be used to slow bone destruction
Bisphosphonates e.g. pamidronate q 4 weeks
How can sensation of bones be reduced?
Radiation therapy
1 fraction yields pain relief in 60 – 90 % for 1 – 3 months
What % of osteosarcomas have metastasis at diagnosis?
95%
How does the location of osteosarcomas influence prognosis?
Appendicular:
- Humerus poorer prognosis than other
- Rib, vertebral and pelvis OSA all have poorer px
Axial:
- Skull OSA has lower metastatic rate
- Local invasion bigger problem
- Maxilla or calvarium worse px
Describe the main features of feline osteosarcomas
Much lower metastatic potential
Amputation may cure
What are haemangiosarcomas?
Tumours of blood vessel walls
- Can affect any tissue
Which tissues are most commonly affected by haemangiosarcomas?
Most commonly spleen (around a third of splenic tumours, half of malignant)
Also liver, right auricular appendage, muscle, skin
Describe the behaviour of haemangiosarcomas
Highly invasive and metastatic
Describe the clinical signs of haemangiosarcomas
Clinical signs usually associated with bleeding
- Shock, collapse, haemoabdomen or pericardial effusion
- Intramuscular: bruising in the dependent part of the limb
- Pericardial effusion if right auricular appendage
Describe the clinical pathology changes seen with haemangiosarcomas
Clinical pathology changes reflect bleeding and altered coagulation:
- Anaemia and sometimes schistocytosis
- In early stages of bleeding - effusion and reduced TP precede measurable anaemia
- Low platelet count
- Prolonged coagulation tests and DIC
Prior to a splenectomy due to a haemangiosarcoma, what needs to be done?
Staging of the tumour
How can haemangiosarcomas be staged?
Thoracic and abdominal +/- cardiac imaging
In older dogs hyperplastic liver nodules cannot be differentiated from metastasis on appearance alone - requires cytology /histology
Describe the poor prognostic factors for haemangiosarcomas
Tumour rupture and bleeding into the abdomen
- but diagnosis often not known at this point
- Other types of splenic tumour will also rupture
Invasive tumours in other sites
How can primary haemangiosarcomas be treated?
Surgery
- Splenectomy
- Compartmental or wide excision in other sites
Survival after splenectomy depends on stage - short if gross metastases already
In non-visceral sites, moderately responsive to radiation
What must you be aware of, that may develop, following a splenectomy
Ventricular arrythmias
Describe treatment for metastatic haemangiosarcomas
- Survival with metastasis typically 4 – 6 weeks for splenic
- Chemotherapy more useful if no gross metastasis
- For splenic HSA if no metastasis on staging sx alone MST ~ 2-4 mths; sx + Doxorubicin MST ~ 4 - 6 mths
What is a histiocytic sarcoma
Highly metastatic sarcoma
Arising from histiocytes – professional antigen presenting cells of the immune system
Which breeds are predisposed to histiocytic sarcomas?
Flat coated retriever, Bernese mountain dogs
Which organs/tissues can be affected by histiocytic sarcomas?
lung, spleen, liver, bone, brain and joint
How are the best outcomes of histiocytic sarcoma treatments achieved?
Multimodal therapy
- Surgery, radiation and lomustine/anthracycline chemotherapy
- Dogs with gross metastasis have quite short survival: MST circa 4 – 5 months
- Dogs with complete response to therapy or no metastasis at diagnosis who have chemotherapy live much longer: MST circa 500 days
