Sarcomas

Question 1

What is a sarcoma?
Subtypes?

Answer 1

• a malignant cancer that arises from transformed cells of mesenchymal origin
• Mesenchyme – cells of connective / structural tissues

Subtypes vary by cell of origin
* Bone - osteosarcoma
* Connective tissue - soft tissue sarcoma, fibrosarcoma, myxosarcoma
* Peripheral nerves - peripheral nerve sheath tumour
* Blood vessels - haemangiosarcoma
* Muscle – rhabdomyosarcoma (striated muscle rare), leiomyosarcoma (smooth muscle - uncommon)
* Fat – infiltrative lipoma, liposarcoma
* Cartilage - chondrosarcoma, synovial cell sarcoma
* (Lymphatic and haematopoetic cells – many of these tumours are considered separately – based on behaviour)

Question 2

What is general behaviour of sarcomas?

Answer 2

• Locally invasive
  *Metastatic risk varies with tumour type (osteosarc, haemangiosarc = v high) + Grade

Question 3

How would you assess sarcomas?

Answer 3

• Clinical examination
• Diagnosis = FNA + cytology, Biopsy and histology, +/- IHC
• Staging - is there evidence of metastasis ?
• Aspiration of local lymph nodes
• Imaging dependent upon tumour type
• Sample other abnormalities identified on examination
• Co-morbidities

Question 4

How would you perform primary tumour imaging?

Answer 4

• Radiographs are relatively insensitive
  – >60% of mineral content of bone must be lost for lysis to become apparent
  – All soft tissues except fat look the same
• CT better
  – Better appreciation of osteolysis or new bone production
  – Many more shades of grey
  – Surgical planning
  – Radiation planning
• MRI – Excellent for surgical planning esp trunk/body wall

Question 5

What is most likely location of mets for sarcoma?

Answer 5

• Lungs

Question 6

What are soft tissue sarcomas?

Answer 6

• Tumours of mesenchymal origin
• Account for 9 -15% of all canine tumours
• Middle to large breeds may be predisposed
• Median age 8 -11 years
• Some breed predilections – Fibrosarcomas in Retrievers
• Younger animals in predisposed breeds

Question 7

What is surgical Tx?

Answer 7

• Tumours = grow along path of least resistance, often have a pseudocapsule (do not try to ‘shell out’)
• Complete excision important to outcome
• Ideal surgical margins = 3 cm lateral and 1 fascial plane
  beyond the extent of tumour

Question 8

How are margins of excision assessed?

Answer 8

• Most common = CARDINAL = 3 cross sections
• Bread loafing (cut like you would a loaf)
• Shaved margins - expensive

Question 9

What is incomplete excision?

Answer 9

• Residual tumour tissue still in animal = tumour likely to recur
• Tumour cells within <3mm of tissue edge
• Probability of recurrence depend on tumour type + grade

Question 10

What can be done if incomplete excision + microscopic residual disease?

Answer 10

• Further wide surgical excision
• Adjuvant radiation therapy
• Active monitoring - high risk (only considered when chance of recurrence is low)

Question 11

What are prognostic factors for post tumour removal?

Answer 11

• Successful surgery = MST >4years

Progonstic factors =
* Tumour grade and mitotic rate
* Tumour size
* Tumour location
* Achieving local control of the tumour

Question 12

What should be done with non-resectable tumours?

Answer 12

• Refer to specialist?
• Reduce tumour to microscopic disease - followed by RT / chemotherapy
• Primary RT = less effective
• Anti-metastatic treatment - for high grade soft tissue sarcomas

Question 13

What are feline injection site sarcomas?

Answer 13

• Tumours develop at sites where cats typically get injections
• Research has shown location of tumours change with vaccine practices
• Development associated with certain vaccines (Rabies / FeLV) but can be seen in cats who have never had these
• Histologically =
• Malignant fibroblasts
• Inflammation – often high lymphocyte component
• Macrophages taking up foreign material thought to be adjuvant / carrier

Question 14

How would you assess a feline injection site sarcoma?

Answer 14

• Examination – Usually firm cutaneous or subcutaneous mass
• 3-2-1 rule for investigation = USE FOR DIAGNOSIS
  – 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
• incisional Biopsy
• Advanced imaging - assess size + margins (highly invasive)

Question 15

Why would you not perform excisional biopsy?

Answer 15

• Almost guarantee treatment failure

Question 16

How would you treat FISS?

Answer 16

• Surgery - 5cm + lateral surgical margins + 2 fascial planes deep
  – This can involve removal of spinous processes of vertebrae
  – Recurrence rates = 47% with dirty margins, 19 % with complete excision
• First surgery is best chance of a good outcome

Question 17

What is adjuvant Tx, When would you use it?

Answer 17

• Doxorubicin based chemotherapy +/or radiation therapy
• For non-resectable tumours - pre-op RT +/or chemotherapy
• For incomplete resections / marginal resections

Question 18

How can you prevent FISS?

Answer 18

• 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

Question 19

What are bone tumours? What animals are predisposed?

Answer 19

• 85 % of skeletal tumours are osteosarcoma
• Middle age and older dogs
• Small peak in younger dogs
• Typically large breeds =
• Appendicular skeleton – metaphysis of long bones
• Front limbs 2:1 hind limbs
• Small breeds <15 kg contribute only 5 %
• 60% OSA in axial skeleton

Question 20

What are clinical signs + Dx of bone tumours?

Answer 20

• Pain and lameness = Sudden or progressive onset, Localisable to a single bone
• Swelling
• Radiographic changes – 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
• Cytology or histology required to confirm diagnosis

Question 21

What are Ddx for bone tumours?

Answer 21

• Beyond OSA - other differentials include:
• Chondrosarcoma - low metastatic risk
• Histiocytic sarcoma - metastatic risk depends upon location
• Other primaries include fibrosarcoma, haemangiosarcoma
• Other differentials =
• Myeloma / lymphoma (round cell tumour)
• Fungal osteomyelitis
• Metastatic tumours (carcinoma)
• Benign tumours / cysts

Question 22

How are bone tumours treated?

Answer 22

*Aims = Prevention of pain, Delaying development of metastases and extending life

*Amputation =
- Most dogs tolerate amputation very well - Even large dogs and those with mild to moderate orthopaedic problems
- Patients pain free around 1 week after amputation
- Complete ambulatory adaptation takes around 1 month

Question 23

How can you reduce pain with bone tumours?

Answer 23

• AMPUTATION should eliminate pain
• Analgesics - Use layered, multi-modal approach
• Opoids, NSAIDS, paracetamol, amantidine
• Slow bone destruction - Bisphosphonates e.g. pamidronate q 4 weeks
• Reduce sensation - Radiation therapy
• Ongoing and increasing risk of pathological fracture
• Bone stabilisation and fixation by limb sparing surgery
• Aim is to retain limb function
• High rate of infection and implant failure

** PATIENT UNLIKELY TO BE PAIN FREE **

Question 24

What are osteosarcoma prognostic factors?

Answer 24

• Location =
• appendicular - humerus, rib, vertebral + pelvis (poorer prognosis)
• axial - skull OSA = lower metastatic rate, maxilla/ calvarium (worse px)
• Presence of metastatic disease
• Total alkaline phosphatase

Question 25

What should be done for Feline osteosarcoma?

Answer 25

* AMPUTATION * Much lower metastatic potential * Amp may cure!

Question 26

What are haemangiosarcomas?

Answer 26

* Tumours of blood vessel walls - most common in spleen - highly invasive + metastatic

Question 27

CS + Dx of haemangiosarc?

Answer 27

* 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 * 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 * Diagnosis usually requires histology * Staging = imaging / cytology

Question 28

What are poor prognostic factors for haemangiosarcomas?

Answer 28

* 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

Question 29

How are primary lesions of haemagiosarc treated?

Answer 29

* Surgery = - Splenectomy - Beware of ventricular arrythmias after 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 - Useful for muscular or dermal tumours

Question 30

How is metastatic disease treated?

Answer 30

* Survival with metastasis typically 4 – 6 weeks for splenic - Chemotherapy more useful if no gross metastasis * Systemic chemotherapy with anthracycline based protocol - 4 – 6 treatments at 3 weekly intervals - For splenic HSA if no metastasis on staging sx alone MST ~ 2-4 mths; sx + Doxorubicin MST ~ 4 - 6 mths * Metronomic chemotherapy possible option

Question 31

What is thew outcomes of haemangiosarcomas?

Answer 31

* Splenic, intramuscular/subcutaneous and right atrial appendage HSA have a poor px = MST less than 6 months in most studies * Intramuscular HSA in cats can be less aggressive * Dermal HSA can have an excellent outcome = MST of around 1000 days

Question 32

What is histiocytic sarcomas? Where does it affect?

Answer 32

* Highly metastatic sarcoma * Arising from histiocytes – professional antigen presenting cells of the immune system * Can affect lung, spleen, liver, bone, brain and joint

Question 33

Tx of histiocytic sarcomas?

Answer 33

* Best outcomes are achieved with multi-modal 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 * Dogs with solitary periarticular histiocytic sarcoma - No metastasis or disseminated disease at staging can have very prolonged survival