Flashcards in SA Oncology Deck (345)
How do you usually assess staging of oral tumours?
FNA or biopsy
Assess local lymph nodes in all cases (can contain tumour even if not enlarged)
Advanced imaging eg CT
How do you carry out distant staging of oral tumours?
Depends on tumour type
Thoracic imaging adequate for some
Abdominal imaging also for melanoma (can migrate to abdomen as well as thorax)
When doing surgical removal of an oral tumour, what margins should you include?
At least 2cm
What would be your first choice for management of an oral tumour?
Surgery (over radiotherapy) where excision is possible
Give some complications of performing oral tumour surgery in cats and dogs
Bleeding, recurrence, infection, altered cosmetic appearance, difficulty prehending food, salivation, mandibular drift after hemi-mandibulectomy
Small number of cases may never eat normally again
Give some clinical signs of oral tumours in small animals
Loose teeth/ proliferative or ulcerative lesions noticed at dentals
Epistaxis (if invading nasal cavity)
How much mammary tissue should you remove with low-risk lesions?
Single mastectomy (single gland)
What excision margins should you use for mobile and fixed mammary tumours?
Mobile: whole gland removal is enough
Fixed: need 2cm margins and removal of affected abdominal fascia/wall
Is it advisable to neuter dogs at the time of mastectomy when removing mammary tumours?
Might reduce the risk of further tumour development, and improve survival of dogs with complex carcinoma
What is Ki-67?
Marker of dividing cells
A FNA taken of a canine inflammatory carcinoma would show what?
Inflammatory cells and tumour cells
What is the prognosis of canine inflammatory carcinomas?
Excision not typically feasible
Recurrence very common
Treatment is palliative
Medical therapy might prolong survival by a few months
Which systemic therapy drugs could you use when treating canine mammary tumours?
5-FU and cyclophosphamide shown to be beneficial in one small study
Pre-operative desmopressin prolongs survival in higher grade tumours
What % of feline mammary tumours are malignant?
How does mammary tumour size affect mean survival time in cats?
> 2 cm: MST= 6 months
< 2 cm: MST= > 3 years
Which lymph nodes should you asses when investigating feline mammary tumours?
Inguinal and axillary bilaterally
Regarding feline mammary tumours, is it better to perform chain mastectomy or regional mastectomy?
Chain in cats, regional in dogs
What is the optimum treatment plan for feline mammary tumours?
Surgery and chemotherapy (doxyrubicin/cyclophospamide)
Why should you radiograph the abdomen as well as the thorax when staging melanoma?
Melanomas may migrate to the abdomen as well as thorax
What treatment would you recommend for a fibrosarcoma or squamous cell carcinoma?
Surgery followed by adjuvant radiotherapy generally gives better results than surgery alone
Why is radiotherapy alone a reasonable treatment option for oral melanoma?
Surgery is associated with high rates of local recurrence
How is diagnosis of melanoma achieved?
Melanin-containing mesenchymal cells on histology
Some tumours don't contain melanin and IHC (immunohistochemistry) is required for diagnosis
How aggressive are oral melanomas?
High metastatic rates (up to 80%)
Describe some anti-metastatic treatments for melanoma
Chemotherapy can cause shrinkage of tumours but does not appear to extend survival
Plasmid vaccine immunotherapy
How aggressive are oral squamous cell carcinomas?
Low metastatic rate
Low recurral rates (eg 10% for mandible)
What is the third most common canine tumour?
What medical therapy can you use to treat oral squamous cell carcinoma?
Piroxicam (NSAID) +/- carboplatin (chemo drug)
Give some clinical signs of a tonsilar squamous cell carcinoma
Enlarged cervical lymph nodes -> abscessation
Enlargement of one or both tonsils
What is the metastatic rate of tonsilar squamous cell carcinoma?
How do you treat tonsilar squamous cell carcinoma?
Local control of tonsilar enlargement: surgery or radiotherapy
Surgery or radiotherapy for lymph node metastasis
Carboplatin or mitoxantrone chemotherapy might be beneficial
Fibrosarcomas mostly affect which types of dogs?
Of which age?
Large breed dogs eg labrador
Middle aged (7.5 years on average)
How aggressive are fibrosarcomas?
Low/moderate metastatic risk (lung and occasionally lymph nodes)
How would you treat a fibrosarcoma?
Surgery, but high recurrence rate (40-60%) (MST=12 months)
Multimodal therapy ofen best (surgery plus radiotherapy) (MST=18-26 months)
Can do radiotherapy alone (MST=7 months)
Smaller tumours= better outcomes
Describe a low histological grade, high biological grade sarcoma of the mouth
Aggressive, rapidly-progressing oral tumour with benign histological appearance even after large biopsy
Very locally invasive
How would you treat a low histological grade, high biological grade sarcoma of the mouth?
Surgery and radiotherapy as very locally invasive
What are epulides?
Benign lesions arisimg from the gingiva
What are the 2 types of epulides?
Acanthomatous: aggressive local behaviour, bone invasion
Peripheral ondontogenic fibroma: slow growing firm masses, usually not invasive
How do you treat an osteosarcoma?
Surgery (radiotherapy does not extend survival)
Complete excision vital
Does a mandibular or maxillary osteosarcoma have a better prognosis?
Mandibular (14-18 months vs 5-10 months)
What is the local recurrence rate of an oral osteosarcoma?
What is the most common feline oral tumour?
Squamous cell carcinoma
What 3 factors increase the risk of a cat developing oral squamous cell carcinoma?
Use of flea collars
Exposure to smoking
Canned foood inc tuna
What is the most common site of a feline oral squamous cell carcinoma?
Base of tongue
How aggressive is a feline oral squamous cell carcinoma?
Low metastatic risk (higher risk in caudal lesions)
Recurrence after surgery is common
Which tumour type can be described as having a 'popcorn' appearance on radiographs?
How does viral papillomatosis appear?
Do you treat it?
Wart-like lesions affecting oral soft tissues
Usually resolve in 4-8 weeks
Which dog breeds are more prone to oral eosinophilic granulomas?
Where are they found?
Husky, cavalier king charles spaniel
Found on the ventral and lateral aspects of the tongue
How do you treat an eosinophilic granuloma?
Surgery and corticosteroids
Where are oral eosinophilic granulomas found in cats?
How do you treat them?
Upper lip, mear midline
Steroids/hyperallergenic diets, radiotherapy, surgery
From when is there no risk reduction in neutering of mammary tumours?
No risk reduction after second season
How does obesity lead to increased risk of mammary tumours?
Obesity -> reduced sex hormone-binding globulin -> increased oestrogen levels
What is the mean age of dogs with benign mammary tumours?
What about malignant mammary tumours?
Benign: 7-9 years
Malignant: 9-11 years
What is the mean age of cats who develop mammary tumours?
Which dog breeds are more prone to mammary tumours?
Poodles, chihuahuas, dachshund, maltese, cocker spaniel, yorkshire terrier
Which cat breeds are more prone to mammary tumours?
How can you diagnose mammary tumours?
Can use FNA to exclude other ddx
How can you stage a mammary tumour?
Local staging: assessment of local lymph nodes
Cranial 2 glands drain to axillary lymph node
Caudal 2 glands drain to inguinal lymph node
Middle gland drains either way
Distant staging: thoracic radiographs, abdominal US, consider bone pain as mammary tumours can metastasize to bone
Where do lymphomas arise?
Arise from lymphoreticular cells (T or B cells)
Normally arise from lymphoid tissue but can arise from virtually any tissue
Give 2 dog breeds that are pre-disposed to lymphoma
Give some factors that may predispose a dog to lymphoma
Genetic and molecular factors
Toxins (eg pesticides)
Immunological factors (animals on immunosuppressive tx are more likely to develop lymphoma)
What age of dog is more likely to develop lymphoma?
Middle aged to older
(Although can affect any age)
What are the 5 presentations of lymphoma?
Multicentric (can appear in any location, mainly lymph nodes)
Extra-nodal (CNS, renal, heart, bladder)
What clinical signs would you see in a dog with multicentric lymphoma?
Generalised peripheral lymphadenopathy +/- other clinical signs
Some dogs clinically well
Non-specific signs (weight loss, inappetence/anorexia, lethargy, pyrexia)
Specific signs (diarrhoea, cough, vomiting, ocular signs)
Regional oedema if lymph drainage is impaired
What clinical signs would you see in a dog with cranial mediastinal lymphoma?
Signs of hypercalcaemia (muscle tremors, PUPD, vomiting/diarrhoea, anorexia, weight loss)
Occasionally vena cava syndrome (obstruction of vena cava -> pleural effusion, dyspnoea, ascites, subcutaneous oedema)
Altered PMI of heart on auscultation (heart is caudal to where we expect to find it)
Give some clinical signs of alimentary lymphoma in dogs
Weight loss, anorexia, pan-hypoproteinaemia (hypoalbuminaemia), evidence of malabsorption
Occasionally multicentric lymphadenopathy
Tends to be aggressive in dogs
Wha are the 2 forms of cutaneous lymphoma?
Epitheliotrophic: T cells, solitary or generalised
Non-epitheliotrophic: more frequently B cells, more likely to have lesions elsewhere
Different appearances. Progression to raised, erythematous plaques/nodules. Variable pruritus.
Is cutaneous lymphoma responsive to chemotherapy?
Describe extranodal CNS lesions in dogs
Mass lesion or diffuse
Variable neurological deficits
Commonly ocular involvement
Generally T cell
What is meant by a paraneoplastic syndrome?
A syndrome (set of signs and symptoms) that is a consequence of the tumour but is not due to the presence of tumour cells in that location
What signs of neoplastic syndrome may you see with lymphoma?
Immune-mediated diseases (eg pemphigus, IMHA) (as Neoplastic B cells can release monoclonal immunoglobulins)
How do you diagnose canine lymphoma?
Cytology or histopathology
-PARR (false positives and negatives)
-Flow cytometry (false positives and negatives)
Elements of which virus have been found in tumour tissue in cats with lymphoma?
These cats, however, are FeLV negative
Cats have a 80x increased risk of lymphoma if they have which two viruses?
FeLV and FIV
What is meant by 'extranodal' lymphoma?
Lymphoma originating in non-lymphoid tissue
Cats of what age are affected by multicentric lymphoma?
Do cats with multicentric lymphoma tend to have regional or generalised lymphadenopathy?
Give the clinical signs of multicentric lymphoma in cats?
Non-painful regional lymph node enlargement
What condition do dogs get secondary to lymphoma which cats do not?
Which age of cats is more likely to get cranial mediastinal lymphoma?
Is a certain breed more prone?
Younger (2-3 years old)
Give the clinical signs of cranial mediastinal lymphoma in cats
Regurgitation/distress (mass is compressing oesophagus)
Lethargy, exercise intolerance
Palpable reduction in compressibility of cranial thorax
Deceased lung sounds
May have pleural effusion
What is the most common type of lymphoma in cats?
What age of cats are affected?
Older cats (>10 yrs old)
Give the clinical signs of alimentary lymphoma in cats?
Insidious weight loss
Occasionally vomiting (secondary gastritis)
Give the 3 main categories of extranodal lymphoma in cats and their clinical signs
CNS (signs depend on site)
Nasal/retrobulbar (nasal discharge, epistaxis, obstruction, exopthalmus)
Renal (malaise, anorexia, renomegaly, azotaemia)
Cutaneous lymphoma in cats usually takes which form?
Is cutaneous lymphoma in cats responsive to chemotherapy?
How do you diagnose lymphoma in cats?
Excisional/wedge biopsy of node
Which types of lymphoma in cats are more likely to be high grade?
How do you treat lymphoma in cats?
Multi-drug chemotherapy (high dose COP is best for cats)
What is the mean survival time for cats with lymphoma without therapy?
What about with high dose COP?
COP: 1 yr=49%, 2 yr=40%
Give some side effects of chemotherapy in cats
Myelosuppression (check haem prior to every bolus) (intermittently check urine in case of UTIs)
Hair loss (whiskers)
What must you do in a cat with alimentary lymphoma when surgically excising the mass lesion?
Biopsy lymph nodes (even if they look normal)
What supportive therapy can you give to a cat with alimentary lymphoma?
Vitamin B12 (as disease is malabsorptive)
What rescue therapy can you use in cats with lymphoma?
Doxorubicin or Lomustine
What is a rescue therapy?
Drug given when animal develops a drug resistance to chemotherapy drugs and relapses
What is leukaemia?
Neoplastic proliferation of WBCs in bone marrow which then enters systemic circulation
How is leukaemia classified?
By cell type and progression
Acute vs chronic
Lymphoid or myeloid
What is the prognosis like for acute feline leukaemias?
Weeks-months when with chemotherapy
What treatment is available for acute feline leukaemia?
Supportive therapy: blood transfusion, antibiotics, barrier nursing
Multi-drug chemotherapy (addition of cytarabine infusions may improve response)
Chronic leukaemia in cats is more commonly a proliferation of which cell?
How do you treat chronic leukaemia in cats?
What is the survival time?
How do you diagnose leukaemia?
Haematology with manual differential and smear evaluation
Flow cytometry of peripheral blood to determine if lymphoid or myeloid
Staging to evaluate extent of disease (thoracic radiographs, abdominal US, cytology of liver/spleen)
Bone marrow biopsy (cytology plus histology)
What is multiple myeloma?
Systemic neoplastic proliferation of plasma cells
Results in overproduction of antibody (IgA or IgG)
Give some clinical signs of multiple myeloma?
Hyperproteinemia which can lead to hyperviscosity syndrome (neuro symptoms, retinal detachment, congestive heart failure, hypertension, coagulopathy)
Bone marrow involvement can lead to cytopenias
Renal disease in 33-50% of dogs
May see circulating plasma cells on haematology
How do you diagnose multiple myeloma?
Haematology, biochemistry, urinalysis
Serum protein electrophoresis
Cytology: liver, spleen, bone marrow
In order to be diagnosed with multiple myeloma, dogs need to fulfil two of which four criteria?
1. Monoclonal gammopathy (prescence of M protein- produced by plasma cells- in blood)
2. Radiographic evidence of osteolytic bone lesions
3. >5% neoplastic plasma cells or >10-20% plasmacytosis in bone marrow)
4. Bence-Jones proteinuria
What treatment can you use for multiple myeloma?
-Antibiotics if secondary infection
-Therapy for hypercalcaemia
-Chemotherapy (prednisolone plus Melphalan)
Local extramedullary plasma cell disease may be treated surgically if no systemic involvement
What are the 3 immunophenotypes of lymphomas?
Null phenotype (neither T nor B)
What has a better prognosis: B-cell phenotype lymphoma or T-cell phenotype lymphoma?
'B-cell is better, T-cell is terrible'
Give the 5 stages of lymphoma
1: Single lymph node/organ affected
2: Many lymph nodes affected in 1 half of the body
3: Generalised lymph nodes affected
4: Hepatic and/or splenic involvement
5: Bone marrow/blood/CNS involvement
How do you carry out staging of lymphoma?
Haematology (abnormal cells on smear-may see large blast cells instead of normal lymphocytes)
Biochemistry (hypercalcaemia in dogs, look for neutropenia which would indicate myelosuppression and bone marrow involvement)
Aspirate or biopsy of lymph nodes
Thoracic radiographs, abdominal US
Bone marrow biopsy
What is the medial survival time for dogs with lymphoma who don't receive any treatment?
4-6 weeks if asymptomatic
What is the medial survival time for dogs with lymphoma who are on prednisolone alone?
High dose COP is made up of which drugs?
What is the medial survival time for dogs with lymphoma who receive high dose CHOP treatment?
Why may epirubicin be used instead of doxorubicin in COPH treatment for lymphoma?
Doxorubicin can affect heart contractility
Give some side effects of chemotherapy in dogs
GI toxicity: vomiting, diarrhoea, nausea (chemotherapy kills rapidly dividing cells eg cells in gut lining)
Myelosuppression: neutropenia, thrombocytopenia, anaemia
Sterile haemorrhagic cystitis (cyclophospamide)
Surgery for lymphoma in dogs could be considered for which types?
Early stage 1 disease
Rare Hodgkins lymphoma
Possibly extranodal lymph one
What should you consider when treating CNS lymphoma?
Many drugs do not penetrate the BBB
Which drugs can be used to control clinical signs of cutaneous lymphoma?
Retinoids (related to vitamin A, regulate epithelial cell growth)
What rescue protocols can you use in dogs with lymphoma?
DMAC (dexamethosone, Melphalan, actinomycin-D, citarabine
CCNU (Lomustine), L-asparaginase, prednisolone
Single agent anthracyclines (doxorubicin/Epirubicin if not already in COP protocol)
How often should you see patients who are in complete remission and no longer on treatment for lymphoma?
Monthly at least for the first 6 months, then every 2-3 months
When should you restage lymphoma?
When there are no sentinel lymph nodes to follow
When patient is not doing as well as expected/clinical signs don't resolve
At the end of an induction phase
At the end of a discontinuous protocol
Give some GI problems seen with neoplasia
Cancer cachexia/ sarcopenia complex
How does cancer cachexia/sarcopenia and anorexia occur?
1. Cancer cells preferentially use glucose for energy. Poor tumour blood flow leads to anaerobic respiration -> increased lactate production and altered insulin sensitivity
2. Cancer related cytokine production and inflammation can affect metabolism
3. Some patients suffer poor appetite but can see changes even with normal appetite
Give some clinical signs of cancer cachexia/ sarcopenia and anorexia
Weight loss, reduced fat mass, lean muscle loss, poor tolerance of treatment
How can you treat cancer cachexia/sarcopenia and anorexia?
Maintain/increase calorific intake by giving low carbohydrate, high fat diet
Omega 3 PUFA may be beneficial in reducing inflammation related changes
Why do GI tumours often have associated gastric or duodenal ulceration?
Due to poor blood supply and altered wall structure (can rupture or bleed-> anaemia)
Some tumours produce hormones/metabolites -> gastric acid -> ulceration (eg gastronomas)
Dogs with mast cell tumours have elevated what in their blood?
Give some consequences
Can causes GI signs, ulceration and bleeding
Describe protein-losing enteropathy in dogs with cancer
Not specific for cancer but seen particularly with GI lymphoma
Diffuse GI lesions can allow protein loss
Low total protein, globulin and albumin, often with diarrhoea
Low albumin can lead to ascites
Other effects due to loss of proteins that bind hormones, clotting factors etc
How does acute and chronic anaemia occur with neoplasia?
Acute: systemic effect due to haemorrhage from a tumour
Chronic: systemic effect due to low grade haemorrhage from a tumour, or systemic effect secondary to PNS ie excess histamine/gastrin -> ulceration
Give some clinical signs of acute blood loss anaemia associated with neoplasia
Anaemia initially non-regenerative then becomes regenerative
Give some clinical signs of chronic blood loss anaemia associated with neoplasia
Poorly regenerative microcytic hypochromic anaemia due to iron deficiency
What is myelopthisis/myelopthisic anaemia?
Which cytopenias are seen?
How do you diagnose?
Crowding out of stem cells in the bone marrow by tumour cells
Tumours might produce suppressive cytokines
Neutropenia then thrombocytopenia then non-regenerative anaemia (normochromic, normocytic)
Diagnose by bone marrow aspirate
What is a common cause of non-regenerative anaemia?
Chronic inflammatory disease
Anaemia is due to disordered iron storage, and shortened RBC life span
Cancer is a cause
Give some clinical signs of hyperoestrogenism caused by testicular tumours
Initially neutrophilia then bone marrow hypoplasia
Neutropenia, thrombocytopenia, non-regenerative anaemia
Feminisation signs, symmetrical alopecia, pendulous prepuce, hyperpigmentation, penile atrophy, gynecomastia, prostatic metaplasia
What clinical sign is typical of immune-mediated disease?
Give a tumour type that can cause microangiopathic anaemia
How does microangiopathic anaemia occur?
Fragmentation and shearing of RBCs caused by fibrin networks
Schistocytosis is a key indicator
Eosinophilia is most commonly associated with which neoplasia types?
Mast cell tumour, T cell lymphoma
What is a monoclonal gammopathy?
Excess production of a single immunoglobulin (antibody) by tumour cells (eg multiple myeloma)
How would you recognise a case of monoclonal gammopathy?
Elevated serum globulins on biochemistry
Clinical signs due to hyperviscosity (neuro signs including seizures and coma, cardiac signs), reduced immune function, renal failure, coagulopathies, ocular disorders
Gammopathies detected by electrophoresis of serum and urine (Bence Jones proteins)
How do you treat monoclonal gammopathies?
Plasmapheresis and tumour-directed treatment
What coagulation problems can occur with neoplasia?
Altered platelet function
Disseminated intravascular coagulation
Which tumour types commonly cause hypercalcaemia?
Lymphoma, anal sac adrenocarcinoma, hyperparathyroidism
Give some clinical signs of hypercalcaemia
GI signs (inappetence, vomiting)
Calcification of soft tissues (esp kidneys)
How would you manage a severe case of hypercalcaemia?
Initially rehydrate with NaCl 0.9% (3-4 x maintenance)
Then continue fluids
Consider bisphosphonates (toxic to osteoclasts -> slows Ca release from bone)
Consider salmon calcitonin
How would you do a hypercalcaemia work up?
Asses tCa, if high asses ionized calcium, also consider phosphate
Rectal exam for anal gland carcinomas
Aspirate lymph nodes
Check history for diet/toxin exposure
Imaging of thorax and abdomen, US neck esp if high calcium and low phosphate
Bone marrow biopsy
Consider ACTH stimulation test if other signs are consistent with hypoadrenocorticism
Hypoglycaemia is most commonly seen with which tumour type?
Give some clinical signs of hypoglycaemia
Weakness, disorientation, seizures, coma, death
How would you manage hypoglycaemia?
Emergency: IV glucose, CRI glucose if necessary
Medical management: prednisolone, diazoxide, octreotide
Remove inciting tumour
Ectopic ACTH syndrome is associated with which tumours located where?
How do you diagnose ectopic ACTH syndrome?
Positive for hyperadrenocorticism tests + localisable tumour
No signs of adrenal-associared hyperadrenocorticism
How can a tumour cause myasthenia gravis?
Tumour produces ACHr antibodies -> cross-react with acetyl choline receptors
Myasthenia gravis is most commonly seen with which tumour type?
Give some clinical signs of myasthenia gravis
Megaoesophagus and regurgitation
Feline paraneoplastic alopecia (FPA) is seen in cats of which age?
Older cats (7-16 years)
Give some clinical signs of feline paraneoplastic alopecia
Alopecia (non-pruritic, symmetrical, initially affects ventral abdomen and limbs)
Footpad lesions (scale, crusting, painful fissures)
Malassezia dermatitis (eyes, nose, claw beds, may be pruritic)
What is superficial necrolytic dermatitis?
Dermatitis associated with hepatic disease and pancreatic neoplasia
Associated amino acid deficiency -> keratinocyte degeneration and skin necrosis
Secondary to increased hepatic metabolism of amino acids
Footpad hyperkeratosis and crusting dermatitis
Lethargy, inappetance, sometime diabetes mellitus
What is panniculitis?
Inflammation of subcutaneous fat
What would you see on a slide with pancreatic panniculitis?
Inflammation and hydrolysis of adipose tissue
What causes pancreatic panniculitis?
Pancreatic enzymes released into bloodstream -> hydrolysis of fat in tissues -> inflammation
Associated with pancreatitis, pancreatic carcinoma, adenocarcinoma
Which tumour types are associated with paraneoplastic pemphigus?
Lymphoma, thymoma, splenic sarcoma, metastatic thymic mass
How would you recognise paraneoplastic pemphigus?
Vesicles which rapidly rupture
Severe ulceration of oral cavity and mucocutaneous junctions
Lesions often bilaterally symmetrical
Clawbeds and pressure points may be affected
How would you diagnose paraneoplastic pemphigus?
Impression smear cytology
Typical lesion distribution and histopathological changes
Haematology, biochem, urinalysis
Thoracic and abdominal radiography
FNA cytology and/or biopsy of primary tumour
How would you manage paraneoplsatic pemphigus?
Surgical/medical management of primary neoplasm
Immunosuppressive therapy rarely effective for cutaneous lesions
What is FTAED?
Feline thymoma-associated exfoliative dermatitis
Generalised exfoliative dermatitis, mostly associated with thymoma
Keratosebaceous accumulations, crusting and ulceration
What is cutaneous flushing?
Periodic release of vasoactive substances by tumours resulting in skin colour changes
Mainly in dogs with mast cell tumours
What is nodular dermatofibrosis?
Well-differentiated, collagenous nodules mainly on limbs but also heads and trunk
Seen in middle aged GSDs with bilateral renal cysts or cyst adenocarcinoma
What is hypertrophic osteopathy?
Palisading periosteal proliferation along the shafts of long bones
Associated with pulmonary tumours, cause unknown
Give some clinical signs of hypertrophic osteopathy
Limbs feel warm and uncomfortable to touch
How do you diagnose hypertrophic osteopathy?
Radiography of long bones and pelvis
How do you treat hypertrophic osteopathy?
Remove inciting cause (tumour)
Why might you get pyrexia with a tumour?
Expression of inflammatory cytokines by or in response to the tumour
Which tumours are more likely to have an associated pyrexia?
Lymphoma, renal cancers, hepatic tumours
Hypercalcaemia occurs secondary to which tumour type?
Anal sac adenocarcinoma
What is the differene between grading and staging of tumours?
Staging= how far it has spread (extent of disease)
Grading= histopathological features
What are the stages of oral tumours?
T= primary tumour
N= metastatic disease in local and regional lymph nodes
M= distant metastatic disease
Does ulceration usually imply a tumour is malignant or benign?
Give some risks of performing a bipsy when investigating neoplasia
-Seeding of tumour cells
-Compromise of future surgery
-Damage to adjacent structures
Describe a needle core biopsy
-Cylinder of tissue is removed from the lesion by a specialised needle (eg Trucut, Cook's- semi automated)
Give some advantages of needle core biopsies
-Larger sample size than aspirate (some evaluation of architecture)
-Inaccessible tissues can be accessed percutaneously
-Multiple samples can be taken
-Superficial lesions can be biopsied under sedation and LA
Give some disadvantages of needle core biopsies
-Smaller sample size than other biopsy methods
-Greater risk of complications than aspirate (esp for intracavitatory biopsies)
-Noot good for lymph nodes
Which tool would you use to take a bone core biopsy?
What is the most common type of incisional biopsy?
Give some advantages of taking an incisional biopsy
-Good evaluation of architecture
-Can do histopathological grading
Give some disadvantages of taking an incisional biopsy
-GA normally required
What should you make sure you don't do when taking an incisional wedge biopsy?
-Disrupt the tumour bed, as you'll make it larger
-Should avoid major structures, and necrotic, damaged or infected areas
What are surface pinch and grab biopsies used for?
-Accesible surfaces (resp tract, GI tract, urogenital tract)
-Very small biopsies so always take multiple biopsies
What are punch biopsies used for?
-Cutaneous and other superficial lesions only
-NOT lymph nodes
What is an excisional biopsy?
-Entire abnormal area is removed
-Only used when knowledge of tumour type will not affect treatment
What are the only 3 cases where an excisional biopsy can be performed without first diagnosing the tumour type?
-Haemorrhagic splenic mass
-Must still stage first!
Are most skin tumours in cats and dogs benign or malignant?
Give some contraindications for excisional biopsy of skin lesions
-Rapidly growing mass
-Ill-defined or poorly demarcated lesion
-Peritumoural oedema or erythema
-Injection site masses in cats
-FNA suspiscious of mast cell tumour or soft tissue sarcoma
What % of mineral contect of bone must be lost for lysis to be apparent on a radiograph?
-Lack of obvious lysis does not mean there is no bony involvement
How can you investigate whether or not a tumour has metastasized to lymph nodes?
-Palpation (esp increased firmness, enlargement)
-Imaging (radiography, US)
-Biopsy (wedge biopsy)
Where do thyroid carcinomas tend to metastasize to?
Retropharyngeal lymph nodes
Where do tumours of the distal forelimb metastasize to?
Prescapular lymph nodes
Where do tumours of the proximal forelimb metastasize to?
Axillary lymph node
Give some common sites for neoplasia metastasis
-Parenchymatous organs (liver, spleen, kidney)
How would you differentiate lung metastases from pleural osteomas?
Osteomas are denser, have jagged edges
Give the basic steps of tumour metastasis
-Vacularisation of tumour
-Invasion of tumour cells into vasculature
-Dissemination (evasion of host immunity)
-Arrest (adhesion to normal cells)
What are the 2 ways that tumours can metastasise?
-In the circulatory system
-In the lymphatic system
Give some examples of tumours which spread via the circulatory system
Give some examples of tumours which spread via the lymphatic system
-Mast cell tumours
Give the stages of primary tumours
Tis: pre-invasive carcinoma
T0: no evidence of tumour
T1: tumour <2cm diameter
T2: tumour 2-4cm diameter
T3: tumour >4cm diameter
T_a: no bone invasion
T_b: bone invasion
Give some tumour types that are highly metastatic
-Oral/mucosal malignant melanoma
-Visceral and subcutaneous haemangiosarcoma
-Long bone osteosarcoma
-High-grade mast cell tumours
-Most mammary carcinomas in cats
Which tumour types don't metastasise?
-Oral basal cell carcinoma
Where do mast cell tumours tend to metastasize to?
Liver and spleen
Where would the contents of the abdomen be pushed by a renal mass?
What are the main differentials for a maxillary mass in a cat?
-Squamous cell carcinoma (most common in cats)
What are the main differentials for a firm mass on the distal tibia in a large dog?
What are the main differentials for a history of L sided mucoid nasal discharge, occasionally stained with blood?
-Nasal adenocarcinoma (most common in a dog)
Spindle cells indicate the presence of what?
What is chemotherapy?
The use of systemic treatments to destroy or control the growth of neoplastic cells
Give some indications for chemotherapy
-Risk of metastatic disease eg haemoangiosarcoma
-Delay/prevent local tumour recurrence
What are the 3 classes of chemotherapy?
Adjunctive chemotherapy (used with either surgery or radiation, chemo usually done last)
Neoadjunctive chemotherapy (chemo before surgery eg to reduce size of tumour)
How do chemotherapy drugs affect cells?
-Affect DNA synthesis, RNA synthesis, protein synthesis, cell cycle progression
-Drugs may be cell stage specific or active at all stages (less so G0, meaning cells in this stage may be resistant to chemo)
What is meant by the 'growth fraction' of a tumour?
The fraction of cells actively dividing at any given time
What is meant by the 'mitotic index' of a tumour?
% or number of mitoses per high power field on light microscopy
What is meant by the 'mass doubling time' of a tumour?
Time taken for the tumour to double in size
Give some factors which affect chemotherapy success
-Growth fraction and mass doubling time
-Inherent tumour sensitivity
-Tumour cell heterogeneity
-Inherent tumour cell resistance/acquired drug resistance
-Interval between treatments
-Tumour blood supply/oxygenation
Which stage of tumour growth will chemotherapy be most effective in and why?
Early stages, as there will be rapid growth (high growth fraction, low mass doubling time) so more cells will be i the chemotherapy-resistant phases of the cell cycle
Give an example of a tumour which is relatively chemo-sensitive, and one which is poorly chemo-sensitive
Quite chemo-sensitive: lymphoma
Poorly chemo-sensitive: melanoma
What is P-glycoprotein 1?
Pumps drugs out of cells, can lead to drug resistance (eg of cancer cells to chemo)
Why do we want a tumour to have a good blood supply when we are using chemotherapy?
-Better drug delivery
-Higher growth fraction (more cells are in chemo-sensitive stages of cell cycle)
-If there isn't a good blood supply, there will be areas of anoxia (low ph, build up of toxic metabolites)
Why are larger tumorus harder to treat medically?
Tend to outgrow their blood supply -> inadequate drug delivery
Give a typical chemotherapy protocol
COP: cyclophosphamide + vincristine + prednisolone
CHOP: + doxorubicin/epirubicin
What are doxorubicin and epirubicin?
-Chemo drugs (antracyclines)
-Antitumour antibiotics, affect DNA replication
What are cyclophosphamide and lomustine?
-Alkylating agents, affect DNA replication
What is vincristine?
Chemo drug that interferes with mitosis
What are cisplatin and carboplatin?
Chemo drugs (platinum compounds) that affect DNA replication
Which chemotherapy drugs affect purine and pyrimidine synthesis?
Antimetabolites eg 5-fluorouracil, cytosine arabinoside
What is the difference between drug density and intensity?
-Drug density= how often the drug is administered
-Drug intensity= drug dose delivered per time unit (mg/m2/week)
Why do we have an interval between delivery of chemotherapy drugs?
To allow normal tissues to recover
Give some possible immediate toxicity reactions to chemotherapy drugs
Occurs <24 hrs after treatment
-Anaphylaxis/hypersensitivity/erythema (L-asparaginase, cisplatin, antracyclines, cytosin)
-Cardiac arrhythmias (doxorubicin, epirubicin)
-Emesis (platinum compounds, antracyclines)
Give some possible toxicity reactions to chemotherapy drugs that occur 1-5 days after treatment
-GI toxicity (most agents)
-Perivascular reactions (antracyclines, platinums, vinka alkaloids)
-Pancreatitis (corticosteroids, asparaginase, azathioprine, platinum compounds)
What clinical signs would you see if an animal experienced GI toxicity from chemotherapy drugs?
-Direct damage to enterocytes
-Anorexia, vomiting, nausea, diarrhoea
How would you treat GI toxicity from chemotherapy drugs?
-Treat more aggressively than non-chemo patient as if they also develop bone marrow toxicity, sepsis could occur (disrupted mucosal barrier + neutropenia)
-Symptomatic tx: anti-emetics, anti-diarrhoeals, ABs, IVFT, gastroprotectants, appetite stimulants
Give some possible toxicity reactions to chemotherapy drugs that occur 7-10 days after treatment
-Myelosuppression (most drugs)
-Damage to haematopoietic stem cells
How would you treat a patient on chemotherapy medication that develops pyrexia and neutropenia?
-May be septic!
-Translocation of bacteria from patient's own GI flora
-Stop all cytotoxics
-Bactericidal ABs (aerob/anaerob, continue for 3-7 days after recovery)
How would you treat a patient on chemotherapy medication that develops neutropenia without pyrexia?
-Give ABs snf discontinue drugs if neutrophil count is <1x10^9/L
-Otherwise may require drug postponement
Give some other toxicities that can occur after 10 dyas of starting chemotherapy
-Cumulative cardiotoxicity (DCM)
-Sterile haemorrhagic cystitis
-Peripheral neuropathy with vincristine
What should you not give cisplatin to?
Cats (can cause fatal non-cardiogenic pulmonary oedema)
How can 5-fluorouracil negatively affect cats?
Can cause fatal CNS signs
Which chemotherapy drugs are perivascular irritants?
-Vincristine and vinblastine
-Doxorubicin, epirubicin, actinomycin
How would you treat extravastion (leakage) of doxorubicin/epirubicin/actinomycin D?
-Apply cold packs
-Consider immediate surgical debridement (as they are perivascular irritants)
How would you treat extravastion (leakage) of vincristine/vinblastine?
-Apply warm compress
What is metronomic chemotherapy?
-Continuous low-dose chemotherapy
-Main target is tumour blood supply
-Stimulation of immune response
-Direct action on tumour cells
-Inhibition of circulating endothelial cells (CECs)
Which chemotherapy drugs are usually used for metronomic chemotherapy?
Low dose cyclophosphamide with piroxicam (or other NSAIDs) (SID or EOD)
Why may tyrosine kinase inhibitors be used in chemotherapy?
Inhibit the activation of specific signalling pathways involved in some cases of mast cell tumours in dogs
If a dog had a red-orange ulcerative tumour on its lip, what is it likely to be?
Spaying a bitch before its 1st season reduces its likelihood of mammary tumours by how much?
Which neoplasia does castration prevent?
Testicular (not prostatic)
Which neoplasias does spaying prevent?
Ovarian, uterine, mammary (if done before 1st season)
When tumours metastasize to the lungs, is there usually 1 metastasis or many small ones?
What can we use to treat this?
-Many small ones
-Chemo is good at reducing no of small metastases
Why is tumour removal not often done in the mouth?
Not always possible to get 3cm margins
How would you manage an insulinoma?
-Medical and dietary management
-Chemo/radiotherapy not effective
Why is the first surgery the best chance of cure when performing oncological surgery?
-Untreated tumours have more normal surrounding anatomy
-Inappropriate surgery -> tumour seeding
-Most active parts of tumour are at the edges
-If tumour recurs, there is less normal tissue for closure
What surgical margins should you use when removing tumours?
What is the maximum number of ribs you can surgically remove?
When might you use antibiotic prophylaxis when surgically removing a tumour?
-If debilitated patient
-If clean-contaminated/contaminated/dirty surgery
-If surgery >90 mins long
When removing a tumour, how could you allow tumour manipulation without the risk of tumour seeding?
Place 'stay' sutures in normal surrounding tissue
What should you do during surgery after removing a tumour?
Saline lavage (won't wash out any remaining tumour cells but allows removal of blood clots, necrotic tissue, and possible unattached tumour fragments)
How can you reduce tumour cell contamination/seeding during surgical removal?
-Change drapes, gloves, and instruments after removing tumour
Which types of tumours are more likely to be exfoliative?
Tumours of ectodermal origin eg squamous cell carcinoma, mast cell tumour
Why might you remove a lymph node when treating neoplasia?
-If it is histologically proven to contain tumour cells
-Appears grossly abnormal at surgery
-If surgical margins dictate you remove it
Should you provide pain relief during oncological surgery?
-Yes as procedure can cause severe post-operative pain
-Give pre-, intra- and postoperative analgesia
What are the main differentials for a maxillary mass in a dog?
-Squamous cell carcinoma
-Basal cell carcinoma
Which radiographic view would you use if you wanted to view the accessory lung lobe?
What is the mean survival time of a dog with a fibrosarcoma?
Why does radiotherapy not kill all cancer cells at once?
Only targets cells that are rapidly dividing
What is brachytherapy?
-Advanced cancer treatment
-Radioactive sources are placed in/near tumour, giving a high radiation dose to tumour while reducing radiation exposure in the surrounding healthy tissue
-Can be direct (strontium 90) or implantation (iridium wires) or systemic (iodine 131 in cats)
What is teletherapy?
-External beam radiotherapy
-Most common form of radiotherapy (cobalt 60)
How does high energy electromagnetic radiation work in killing cancer cells?
-Radiation is unlikely to hit DNA (as it's so small)
-Instead, damage is caused by ionisation of surrounding water molecules -> free radicals are generated -> free radicals damage DNA
-> Apoptosis, permanent cell cycle arrest, mitotic catastrophe
Is it easier to kill a hypoxic or euoxic cell with radiation therapy?
-In hypoxic cells, DNA damage is rapidly repaired, so 2.5-3 times as much radiation is required to kill hypoxic cells
-Oxygen inhibits the repair of free radical induced damage
Electrons are used in radiotherapy for which types of tumours?
-Superficial (useful when you want to target skin but not underlying organs) as they lose energy as they pass through tissue
What is fractionation?
The practice of giving multiple small doses of radiation instead of one big one
Why is it better to give a single bigger dose of radiation than give two smaller doses at separate times?
Cells can repair themselves between treatments (esp with malignant melanoma)
What is the standard fractionation protocol for radiation?
-M-W-F (Monday, Wednesday, Friday)
-Once weekly if palliative
Give some limitations of fractionation for animals
Why may slower-dividing tissues be more radio-resistant?
Fewer cells are rapidly dividing therefore fewer cells are in the sensitive phases
Are larger or smaller tumours more sensitive to radiation?
-More rapidly dividing, higher growth fraction, more cells in sensitive phases
-Less likely to contain large numbers of hypoxic cells (O2 prevents repair of cell damage)
-Easy to dose accurately and evenly
Are carcinomas or sarcomas more sensitive to radiation?
Give some tumour types which are highly sensitive to radiation
-Transmissable venereal tumour
-Gingival basal cell carcinoma (acanthoma)
How soon after radiation therapy do side effects usually show?
-Can be months or years in slowly dividing tissues (eh bone, neural tissue)
Give some acute side effects of radiation therapy
Which cells do they affect?
-Affect rapidly dividing cells (eg mm, skin)
-Erythema/desquamation (skin peeling)
-Develop soon/after tx
-Resolve within a few weeks of cessation of therapy
Give some late side effects of radiation therapy
Which cells do they affect?
-Affect slowly dividing cells (eg bone, neural tissue)
-Alopecia, skin fibrosis, reduced healing capacity, ischaemic necrosis of brain or bone tissue
For which tumour types may you perform radiotherapy and then removal surgery?
Osteosarcoma and soft tissue sarcomas
Why may you perform radiotheraphy before surgical tumour removal?
-Reduces tumour burden
-Eliminates small number of tumour cells at the periphery of the lesion
Give a negative effect of doing radiotherapy before surgical tumour removal
Can have a negatve impact on wound healing
What is the most commonly diagnosed skin tumour in the dog?
Mast cell tumour
Which dog breeds are more prone to mast cell tumours?
Boxers (low-grade), boston terrier, Shar peis (high-grade)
Where do mast cell tumours usually metastasize to?
Local lymph nodes
Describe the clinical presentation of a mast cell tumour in dogs
-Cutaneous mass of variable external appearance
-Anywhere in the body
-May have local effects: erythema, oedema, pruritus, haemorrhage
-May have systemic signs: vomiting, melaena, rarely collapse and acute death
What do mast cells look like?
Large, round cells with intracytoplasmic granules containing histamine, heparin and proteases
How do you diagnose mast cell tumours?
FNA: round cells with characteristic purple granules
What should you do when staging mast cell tumours?
-FNA of local lymph nodes
-Abdominal US (liver, spleen, LNs)
-Thoracic radiography (rarley metastasize to lungs, but check sternal LNs)
Why is buffy coat examination not an accurate method for staging mast cell tumours?
-Increased no of mast cells in buffy coat does not indicate metastasis as any inflammatory condition can increase systemic mast cells
What is the best system for grading mast cell tumours?
-Patnaik grading system
-3 grades (1=low-grade, well differentiated, 3=high-grade, poorly differentiated)
How do you treat mast cell tumours in dogs?
Often multimodal approach is required: surgery, radiotherapy (after surgery if incompletely excised), chemotherapy (before surgery to shrink tumour)
Which margins should you use when surgically removing a mast cell tumour?
3cm plus 1 fascial plane
Which chemotherapy protocol would you use for mast cell tumours in dogs?
-Vinblastine with prednisolone
-TKIs (tyrosine kinase inhibitors)
What are the 2 forms of mast cell tumour in cats?
-Cutaneous form (cutaneous raised hairless masses, multiple tumours)
-Visceral forms: splenic or intestinal (palpable abdominal mass)
How do you treat cutaneous mast cell tumours in cats?
Surgical excision usually curative
How do you diagnose cutaneous mast cell tumours in cats?
How do you treat splenic mast cell tumour in cats?
Transitional cell carcinomas typically affect which part of the bladder?
Do transitional cell carcinomas have a low or high metastatic rate?
High to medial iliac lymph nodes and other organs (eg liver, spleen, bones)
Which dog breed is more prone to transitional cell carcinomas?
Give the clinical signs of transitional cell carcinomas
-Lower urinary tract signs (stranguria, pollakyuria, haematuria)
-Occasionally signs related to bone metastasis (lameness) or renal dysfunction
How do you diagnose transitional cell carcinomas?
-Histopathologial diagnosis although cytology can sometimes be very suggestive
-Risk of seeding with FNA
How do you treat transitional cell carcinomas?
-Can use NSAIDs alone or NSAIDs with mitoxantrone (chemo drug)
What is the prognosis like for transitional cell carcinomas?
-Poor long term prognosis, but quality of life can be maintained for several months (MST=6-8 months)
What is a sarcoma?
A malignant cancer of mesenchymal origin
Which 2 sarcomas are highly likely to metastasize?
All sarcomas have a predilection to metastasize where?
What surgical margins would you use when surgically removing a soft tissue sarcoma?
3cm plus 1 fascial plane
How can you predict the success of a tumour removal?
-Ask pathologist for margin analysis (aim is for complete excision ie no tumour cells on edge of margin)
-If there are tumour cells within <3mm of tissue edge, possibility of residual tumour tissue left in patient
What treatmnt options do you have if there is miscroscopic disease remaining or narrow excision margins after tumour removal surgery?
-Further wide surgical excision
-Adjuvant radiation therapy (highly effective)
-Metronomic chemotherapy (usually cyclophosphamide and an NSAID)
-Active monitoring (monthly for at least a year)
What should you look out for when using chemotherapy (cyclophosphamide and NSAID)?
-Risk of sterile haemorrhagic cystitis-monitor urine
-Stop if haemturia and no UTI
What is the prognosis like for soft tissue sarcoma?
-If no metastatic disease: >4 years with successful surgery +/- radiotherapy
What would you see histologically in a feline injection site sarcoma?
-Often high lymphocyte numbers (inflammation)
When should you be suspiscious of a feline injection site sarcoma?
-Persists longer than 3 months after an injection
-Increases in size after 1 month after an injection
How do you treat feline injection site sarcomas?
-Surgical removal with 3-5cm margins (can involve removal of spinous processes of vertebrae)
-Best of performed by a specialist
What other treatment should you carry out if you can only perform an incomplete resection/marginal resection of a feline injection site sarcoma?
-Radiotherapy plus chemotherapy (anthracycline-based chemo eg doxorubicin)
Give a risk associated with anthracycline-based chemotherapy (ie doxorubicin/epirubicin)
Risk of nephrotoxicity
What is a haemangiosarcoma?
Give some properties
-Tumour of blood vessel walls
-Can affect any tissue but most commonly spleen
-Highly invasive and metastatic
Give some clinical signs of a haemangiosarcoma
Most commonly associated with bleeding:
-Shock, collapse, haemoabdomen, pericardial effusion (if right auricular appendage affected)
-Intramuscular- bruising in the dependent part of limb
Give some clinical pathology changes seen with haemangiosarcoma
-Anaemia and sometimes schistocytes (sheared RBCs)
-In early stages, effusion and reduced TP precedes anaemia
-Low platelet count
-Prolonged coagulation tests and DIC
What % of splenic tumours are haemangiosarcomas?
How do you treat splenic haemangiosarcomas?
-Surgical excision of spleen or mass
-Tumours are responsive to radiation
What is the prognosis like for haemangiosarcomas?
Poor: even with chemo and surgery, MST=4-6 months
Give some sarcomas of the bone
Do osteosarcomas have a high or low metastatic risk in dogs and cats?
Cats: lower metastatic risk
Osteosarcomas typically affectwhich dogs?
-Middle aged and older dogs
-Typically large breeds (eg Rottweiler)
-Usually FL, near knee
Give some clinical signs of an osteosarcoma
Sudden and progressive pain and lameness
Give some radiographic changes seen with osteosarcoma
-Soft tissue swelling
-New bone- palisades perpendicular to bone
-Zone of transition
How do you diagnose osteosarcoma?
-Cytology or histology
What are the treatments options for osteosarcoma?
-Amputation (feel pain-free after 1 weel)
-Analgesics (multi-modal approach)
-Bisphosphonates to slow bone destruction
-Radiation therapy to reduce sensation
-Bone stabilisation and fixation (patient will never be pain-free, high rate of joint infections)
-Chemotherapy (if no gross metastases; carboplatin or anthracyclines)
How can you investigate whether or not there are metastases after amputaion due to osteosarcoma?
-Measure total alkaline phosphatase (indirect measure of bone isoenzyme ALKP)
-If stays high after amputation -> risk of metastases
-If high but decreases after amputation -> good prognosis
What is a histiocytic sarcoma?
-Highly metastatic sarcoma arising from histiocytes (antigen-presenting cell)
-Can affect liver, lung, spleen, bone, brain, joints
How do you treat a histiocytic sarcoma?
-Best results with multi-modal therapy (surgery, radiation and chemo)
Give some tumour types that are poorly sensitive to radiotherapy
Rhinrial SCC (dogs)
What is the gold standard treatment for canine lymphoma?
Multidrug chemotherapy (high dose COP)