Oncology Flashcards
What are the characteristics that are allowed to rise due to cancer?
Evading apoptosis
Self-sufficiency in growth signals
Insensitivity to anti-growth signals
Tissue invasion and metastasis
Limitless replicative potential
Sustained angiogenesis
What are the properties of a benign tumour?
- Slower rate of growth
- Expansive and well defined boundaries
- Often minimal effects in adjacent tissues
- Potential curative surgery
- No metastasis
- Often minimal but can be life-threatening if bleeds or in a vital organs
- Possible paraneoplastic effects
What are the properties of malignant tumours?
- Faster rate of growth
- Invasive, poorly defined limits
- Often serious effects on adjacent tissues
- Only curative surgery if complete resection (clear margins and no metastasis)
- Metastasis
- Often life-threatening
- Possible paraneoplastic effects
What is cellular pleomorphism?
Increased variation in the size, shape and texture of cells.
Which cells demonstrate nuclear pleomorphism?
Malignant cells
What are the changes associated with nuclear pleomorphism?
Increased nuclear size
Large nucleoli
Multiple nucleoli
Coarse chromatin
Increased mitotic figures
Abnormal mitotic figures
Why are malignant tumours hard to excise fully?
Grow by local invasion and may extend microscopically into surrounding tissues
What are the physical clues of local invasion?
- Diffuse, indistinct boundaries
- Fixation of the tumour in one or more planes
- Thickening of adjacent tissue
- Spontaneous bleeding or ulceration
What are the routes that metastasis occurs?
Blood
Lymphatics
Transcoelomic/across serous membranes, such as mesentery or pleura
Iatrogenic (during FNA)
What is the most common site for development of haematogenous secondary tumours?
Lungs
What are the other possible sites for haematogenous secondary tumours?
Those with high blood flow – liver, spleen and kidneys.
How do paraneoplastic effects arise?
From the production and release of biologically active substances from cancer from distant organs.
What is haematological paraneoplastic syndrome?
Changes in the counts of red blood cells, white blood cells and platelets. Anaemia and thrombocytopenia are the most common manifestations
Name and describe the different mechanisms of haematological paraneoplastic syndrome.
Myelopthisis - the invasion of bone marrow by neoplastic cells. A non-regenerative anaemia affecting multiple cell lines.
Haemorrhage - typically a regenerative anaemia.
Immune mediated haemolytic anaemia - cross reactivity between cancer cells and red blood cells. Typically acute, severe and strongly regenerative.
Anaemia of chronic disease - generally mild and non-regenerative.
What is hyperviscosity paraneoplastic syndrome?
Blood is made more sludgy:
- Increased blood cell numbers (erythrocytosis or polycythaemia)
- Excessive production gamma-globulins.
What is hyperhistaminaemia paraneoplastic syndrome?
Tumours can release histamine and vasoactive amines, such as mast cell tumours. Causes local signs of oedematous swelling, erythema and pruritis.
What is a very rare possibility of hyperhistaminaemia paraneoplastic syndrome?
Anaphylactic shock is technically possible should there be massive and sudden release of histamine from the tumour but this is rare (so people can be nervous about sampling mast cell tumours but is very rare).
What is immune mediated paraneoplastic syndrome?
Due to cross reactivity between cancer cells and healthy cells. Such as immune mediated haemolytic anaemia, immune mediated thrombocytopenia and myasthenia gravis.
What is endocrine paraneoplastic syndrome?
Endocrine tumours and non-endocrine tumours can produce hormones or hormone-like substances. The clinical signs are dependent upon the hormone
What is pyrexia paraneoplastic syndrome?
Thought to be due to the production of cytokines by the neoplasm. Could also get if cancer grows very quickly and becomes larger than its blood supply can support causing necrosis and pyrexia.
What is the approach to managing pyrexia paraneoplastic syndrome?
Rule out and treat other causes of pyrexia that are commonly encountered in patients with cancer, such as secondary infection
What is cachexia paraneoplastic syndrome?
Loss of fat and muscle in patients with cancer, this weight loss can be despite adequate nutritional intake. The underlying mechanism is unknown but is thought to be due to production of cytokines by neoplastic cells.
What are the aims of investigation with oncology patients?
- Make a histological/cytological diagnosis
- Determine the extent of local and distant spread
- Investigate and treat any tumour-related or concurrent complications
- The patient’s ability to tolerate therapy
- To determine the overall prognosis
What are the steps taken in the approach to cancer?
- History
- Physical examination
- Laboratory testing
- Imaging
- Biomarkers
- Biopsy
In what ways can cytology samples be collected?
Touch/impression preparations
Fine needle aspirates
Cytospins of body fluids/effusions
What do cytological samples indicate about a tumour?
Indication of the nature of the tumour and to help to identify cytological features of malignancy
What are the advantages of establishing a diagnosis via FNA and cytology?
- Quick
- Cheap
- Easy
- Non-invasive
- Distinguish inflammatory vs neoplastic lesions
- Differentiate mast cell tumours from lipomas
- Easy to send away to pathologist
What are the disadvantages of establishing a diagnosis by FNA and cytology?
- Results are more likely to be inconclusive that with histopathology
- There are some risks to consider in your approach
- Doesn’t allow assessment of tissue architecture and grading
What are the risks of establishing a diagnosis with FNA and cytology?
- Can you remove potentially seeded cells along needle tracts in subsequent surgery?
- Degranulation of MCTs (rare)
- Bleeding with some types of malignancy
What does histological examination allow over cytological examination?
Allow tumour grading as it collects whole pieces of tissue
What is tumour grading?
The microscopic assessment and quantification of parameters that correlate with the clinical aggressiveness of a neoplasm based on the tumours architecture
What is the advantage of incisional biopsy over excisional biopsy?
Know the type and grade of tumour prior to surgery. This allows for better surgical planning
What should be ensured and avoided when conducting an incisional biopsy?
- Avoid superficial ulceration, inflammation or necrosis
- Ensure adequate depth
- Try to include a boundary between tumour-normal tissue
- Do not predispose to local tumour reoccurrence or dissemination
- Do not compromise subsequent therapy
What is the risk of not doing an incisional biopsy?
Going in blind/excisional biopsy has the risk of having dirty margins and having to in again for a secondary surgery, which is much harder and has a much poorer prognosis.
When may an excisional biopsy be appropriate?
If knowledge of tumour type and grade does not change the approach, excisional biopsy may be more appropriate, such as a bleeding splenic tumour.
What is tumour staging?
Extent of neoplastic disease, such as volume and degree of spread. It helps to determine the feasibility of therapy and prognosis. Considers the histological grade, local invasion and metastatic spread.
What is TNM staging and how is it conducted?
Tumour – physical examination of mass, histopathology or from imaging.
Nodes – palpation of lymph node size and texture, imagine and FNA.
Metastasis – history, physical examination, imaging, FNA and bone marrow aspiration
What should be done before any treatment is started?
As a minimum, inflated chest radiographs should be taken to look for metastasis before any treatment is started. Ideally all 4 views: left and right lateral, dorsoventral and ventrodorsal.
What is required for metastasis to be distinguished from end-on pulmonary vessels?
Over 5mm diameter
What are the 3 possible outcomes of cancer treatments?
Cure – all cells that have the capacity for tumour regeneration eradicated
Remission – all clinical evidence of cancer has disappeared, occult cancer cells remain and relapse will occur at some point
Palliation – reduce pain/improve sense of well-being and/or correct physiological malfunction
What are the 3 main methods of cancer treatment in animals?
Surgical excision – only treatment likely to result in a cure
Radiation
Anti-cancer/cytotoxic drugs – chemotherapy
When does failure of surgery occur?
- Regrows at primary site due to incomplete resection
- Has already metastasised
- Is systemic, such as multicentric lymphoma
What are the 2 types of radiotherapy for cancer treatment?
External beam radiation therapy – uses megavoltage x-rays
Brachytherapy – e.g. radioactive iodine therapy for the treatment of hyperthyroidism
How does radiotherapy treat cancer?
Damaging the DNA within cells, impairing their replication and resulting in cellular death
How long is radiotherapy used for?
Multiple doses over 4-6 weeks
Why is general anaesthesia important in radiotherapy?
Radiation is delivered accurately to the neoplastic tissue to avoid injury of healthy tissues so GA needed.
What is the price range for radiotherapy?
£1000-£5000
What types of tumours is radiotherapy useful for?
For local cancers rather than systemic disease. Ideal for primary tumours with no local or distant metastasis.
What are the acute side effects of radiotherapy?
Skin reddening
Local hair loss
Desquamation (scaly skin)
Severe exfoliative dermatitis
What are the chronic side effects of radiotherapy?
Depigmentation
Dermal fibrosis
Osteonecrosis
Neural necrosis
When is chemotherapy indicated as a treatment option?
- Chemo-sensitive tumours
- Primary therapy for haemopoietic malignancies (lymphoma)
- Adjunct with surgery for solid tumours to eradicate/manage metastatic disease
Why do we not use chemotherapy for the treatment of solid tumours?
- Most act upon processes in cell growth and division, such as DNA replication, mitotic spindle
- So rapidly dividing cells are most susceptible and those in their resting phase of the cell cycle (G0) are most resistant
- Cells in G0 can act as a ‘reservoir cells’ that can re-populate unless there is complete surgical excision
When do we ideally use chemotherapy?
When the growth fraction is at its highest, such as early in disease process or after surgical debulking.
What is debulking?
Forced to remove tumour and leave dirty margins, not possible to excise with clear margins.
What 3 things must occur for chemotherapy to work?
- The drug must reach the cancerous cells
- Must exert a cytotoxic effect within the cell
- Resistance must not develop
What will the effectiveness of chemotherapy be determined by?
- Whether a single/multiple agents are used
- The mechanism of action
- The dose
- The timing of administration
What are the advantages of using single chemotherapeutic agents?
Decreased cost
Decreased risk of toxicity
Decreased time in hospital
What are the disadvantages of single chemotherapeutic agents?
Decreased efficacy
Drug resistance faster to develop
What are the advantages of using multiple chemotherapeutic agents?
Greater efficacy
Drug resistance slower to develop
What are the disadvantages of using multiple chemotherapeutic agents?
Increased cost
Increased risk of toxicity
Increased time in hospital
Name 10 chemotherapeutic drug classes.
Alkylating agents
Platinum compounds
Anti-metabolites
Anti-tumour antibiotics
Tyrosine kinase inhibitors
Enzyme
Plant alkaloids
NSAIDs
Glucocorticoids
Immunotherapy
What is the mechanism of action for alkylating chemotherapeutic agents?
Cross-links DNA, inhibiting replication and transcription
Name 3 examples of alkylating chemotherapeutic agents.
Cyclophosphamide
Lomustine
Chlorambucil
When are alkylating chemotherapeutic agents used?
Lymphoma
Multiple myeloma
What is the mechanism of action of platinum compound chemotherapeutic agents?
Cross-linking and damaging DNA, inhibiting replication and transcription
Name 2 examples of platinum compound chemotherapeutic agents.
Cisplatin
Carboplatin
When are platinum compound chemotherapeutic agents used?
Osteosarcoma
What is the mechanism of action of anti-metabolite chemotherapeutic agents?
Inhibit use of cellular metabolites during growth/division
Name 3 anti-metabolite chemotherapeutic agents.
Cytarabine
Azathioprine
Methotrexate
When are anti-metabolite chemotherapeutic agents used?
Lymphoma
Leukaemia
What is the mechanism of action of anti-tumour antibiotics?
Several, including the promotion of free radicals and the inhibition of enzymes required for DNA replications
Name a anti-tumour antibiotic.
Doxorubicin
When are anti-tumour antibiotics used?
Lymphoma
What is the mechanism of action of tyrosine kinase inhibitors for chemotherapy?
Inhibits tyrosine kinase, which when activated leads to aberrant cell growth Used only to treat tumours expressing c-kit mutation and tumours with poor prognosis that cannot be surgically excised.
Name 2 tyrosine kinase inhibitors.
Mastinib
Toceranib
When are tyrosine kinase inhibitors used as chemotherapeutic agents?
Mast cell tumours
GI stromal tumours
What is the mechanism of enzyme chemotherapeutic agents?
Destroys circulating asparagine which is necessary for protein synthesis
Name an enzyme chemotherapeutic agent.
L-asparaginase
When are enzyme chemotherapeutic agents used?
Lymphoma
What is the mechanism of plant alkaloid chemotherapeutic agents?
Disable the mitotic spindle
Name 2 plant alkaloid chemotherapeutic agents.
Vincristine
Vinblastine
When are plant alkaloid chemotherapeutic agents used?
Lymphoma
Mast cell tumour
What is the mechanism of action of NSAIDs as chemotherapeutic agents?
Induce apoptosis
Name 2 NSAID chemotherapeutic agents.
Piroxicam
Meloxicam
When are NSAIDs used as chemotherapeutic agents?
Transitional cell carcinoma
Colonic adenocarcinoma (common in bladder)
What is the mechanism of glucocorticoids as chemotherapeutic agents?
Cytotoxic to lymphocytes and decreased lymphocyte proliferation
Name a glucocorticoid chemotherapeutic agent.
Prednisolone
When are glucocorticoids used as chemotherapeutic drugs?
Lymphoma – often combined with other agents, poor on its own
What is the mechanism of immunotherapy chemotherapeutic agents?
Causes antibody production that cross react with canine tyrosinase which is essential for melanin synthesis
Name an immunotherapy chemotherapeutic agent.
Melanoma vaccine
When are immunotherapy chemotherapeutic agents used?
Digit and oral melanoma
What is the benefit and consequence of higher doses of chemotherapeutic drugs?
Higher doses of chemotherapeutic drug are likely to kill a greater number of neoplastic cells. But higher doses of chemotherapeutic drugs are likely to cause side effects, due to having cytotoxic effects on rapidly dividing tissue such as bone marrow and gut epithelium.
By which order of kinetics do chemotherapeutics act?
First order kinetics – they kill a fixed percentage of cells opposed to a set number of cells
Why are chemotherapeutic drugs given at regular intervals?
You will not eradicate all the cells after a single dose. The promptness of beginning therapy and the regularity of treatment will impact treatment outcome
Distinguish primary and secondary resistance of chemotherapeutic agents.
Primary - the cancer was resistant to the drug in the first place
Secondary (or acquired) - resistance develops due to mutation and selection of resistant clones
What are 3 mechanisms of chemotherapeutic agent resistance?
- Selected cells acquiring the capability to reduce drug uptake
- Detoxify the drug
- Repair the DNA damage that these drugs cause
What slows the development of chemotherapeutic drug resistance?
Multi-agent protocols
Why is prednisolone treatment a 1 way street?
May be used as palliative care before a definitive diagnosis is made or as a ‘light touch’ chemotherapeutic option for some cancers (lymphoma). But pre-treatment ‘helps’ drug resistance to develop more swiftly.
Why is safe handling of chemotherapeutic drugs important?
Mutagenic
Abortifacient
Teratogenic
Carcinogenic
Irritants
Vesicants
How are people at potential risk of animals receiving chemotherapeutic agents?
Cytotoxic drugs can be found in the urine, saliva and faeces of patients receiving chemotherapy
What are 8 examples of implementing safe handling of chemotherapeutic drugs?
- Protocols for dealing with spillages and ready prepared spill-kits
- Pregnant people should never handle cytotoxic drugs
- Appropriate PPE – chemospecific gloves and face protection
- All employees and owners must be informed of the risks
- Provision of owner guidance to limiting exposure with saliva, urine, vomit, faeces
- Use of closed systems for drawing up and administering medications
- Never re-capping needles to avoid accidental inoculation
- Purple flagged containers for disposal of cytotoxic agents
What are the possible gastrointestinal side effects of chemotherapeutic agents?
Vomiting
Diarrhoea
Nausea
Stomatitis
Loss of mucosal integrity = increases risk of bacterial translocation to blood = sepsis
How can gastrointestinal side effects be managed?
Nausea causing use of anti-emetics
What are 2 examples of chemotherapeutic agents that cause gastrointestinal side effects?
Doxorubicin and cisplastin can both cause vomiting.
What are some bone marrow side effects of chemotherapeutic agents?
Anaemia
Leukopenia
Secondary infections
Thrombocytopenia
Bleeding disorders
What are 3 examples of chemotherapeutic agents that cause bone marrow side effects?
Doxorubicin
Vinblastine
Cyclophosphamide
Why is routine haematology conducted before a cytotoxic agent is given?
Inform whether the chemotherapy dose is delayed, reduced or if therapy needs to be stopped.
What are the dermatological side effects of chemotherapeutic agents?
Irritants and vesicants - cause tissue inflammation or even necrosis should they be administered inappropriately – for example should the drug extravasate during intravenous administration. Clean stick in each limb, if not, may have to do a different day
Name 3 chemotherapeutic agents with dermatological side effects.
Vincristine, cisplatin and doxorubicin – vincristine in the subcutaneous tissue can result in the patient having a limb amputation
What are the urinary side effects of chemotherapeutic agents?
Stranguria
Dysuria
Pollakiuria
Haematuria
Sometimes these signs are irreversible
Name a chemotherapeutic agent with urinary side effects.
Cyclophosphamide can cause urinary toxicity – otherwise known as ‘sterile haemorrhagic cystitis
How is urinary toxicity managed?
Send owner home with dipsticks and check daily for haematuria, may be a UTI or need to stop chemo immediately
What are the cardiac side effects of chemotherapeutic drugs?
Tachyarrhythmias (acute) and cardiomyopathies which may lead to congestive heart failure (chronic).
Name a chemotherapeutic agent with cardiac side effects.
Doxorubicin - given slowly to help avoid the development of arrythmias. Avoid using in breeds of dogs susceptible to cardiomyopathies
What are the renal side effects of chemotherapeutic agents?
Proximal tubular necrosis leading irreversible loss of renal function - this could lead to the development of acute and/or chronic kidney disease.
Name 3 chemotherapeutic agents with renal side effects.
Cisplatin
Methotrexate
Doxorubicin (do not give to cats)
How are renal side effects of chemotherapeutic agents avoided?
- Administering these drugs alongside IV fluids
- Monitoring urea and creatinine
- Avoiding use in patients with pre-existing renal disease
What are the hepatic side effects of chemotherapeutic agents?
Transient or irreversible loss of liver function
Name a chemotherapeutic agent with hepatic side effects.
Lomustine
How can hepatic side effects of chemotherapeutic agents be avoided?
The regular monitoring of hepatocellular enzymes (e.g. ALT and AST) and concurrent administration of anti-oxidant, such as SAMe (s-adenosyl methionine) can help in avoiding hepatotoxicity
What are the clinical signs of multicentric lymphoma?
(Within lymph nodes) Painless lymphadenopathy, with or without PUPD and non-specific signs.
What is the prevalence of multicentric lymphoma in cats and dogs?
Dogs = 80%
Cats = 20-30%
What are the clinical signs of alimentary lymphomas?
Vomiting, weight loss, diarrhoea, may have palpably thickened intestinal loops or palpable abdominal mass.
What is the prevalence of alimentary lymphoma in cats and dogs?
Dogs = 7%
Cats = 50-70%
What are the clinical signs of cutaneous lymphomas?
A wide variety of non-specific changes. Mya be generalised/solitary, may progress from scaly alopecia to thickened erythematous ulcerative lesions. May or may not be pruritic.
What is the prevalence of cutaneous lymphomas in dogs and cats?
Dogs = 6%
Cats = 0.2-3%
What are the clinical signs of mediastinal lymphoma?
Dyspnoea, tachypnoea (from space occupying effect and/or pleural effusion), pre-caval syndrome, with/without PUPD.
What is the prevalence of mediastinal lymphoma in dogs and cats?
Dogs = 3%
Cats = 10-20%
What are the clinical signs of extra-nodal lymphomas?
Site dependent - such as bone, heart, CNS
What is the prevalence of extra-nodal lymphoma in dogs and cats?
Dogs = 3%
Cats = 1-10%
How is lymphoma diagnosed?
- FNA of enlarged lymph nodes of affected organs for cytology
- Submandibular LNs drain the mouth and periodontal disease is common in these patients so avoid
- Biopsy if FNA are non-diagnostic
How do we determine the prognosis of lymphoma?
- Haematology
- Biochemistry
- Thoracic radiographs: mediastinal mass negative prognostic factor
- Abdominal ultrasonography – stage III and IV, same outcome
- Fine needle aspirates with/without tissue biopsy
- Immunophenotyping (immunocyto/histochemistry)
- Bone marrow aspirate if haematological abnormalities
What are the 3 steps of the WHO staging system for lymphoma?
- Anatomical site
- Stage
- Substage
How is anatomical site used to stage lymphoma?
Multicentric
Alimentary
Thymic
Skin
Leukaemia
Extra-nodal
Distinguish the 5 stages of lymphoma.
I – involving single node or lymphoid tissue in single organ
II – involvement of multiple lymph nodes in a region
III – generalised lymphadenopathy
IV – III with lover/spleen involvement
V – blood/bone marrow involvement
How is lymphoma classified by substage?
Substage a – clinically well without systemic signs
Substage b – clinically unwell with systemic signs
What are the properties of a worse lymphoma prognosis?
- T cell
- Large cell type
- Higher stages
- Substage b
- Being male
- Presence of hypercalcaemia
- Forms that are not multicentric
- Pre-treatment with steroids
What is the effect of pre-treatment with steroids?
Increases chances of patient developing multidrug resistance
What are the properties of a better lymphoma prognosis?
- B cell
- Small cell type
- Lower stages
- Substage a
- Being female
- Absence of hypercalcaemia
- Multicentric form
- Avoidance of steroid pre-treatment
What is the mean survival time of lymphoma with no treatment?
4-6 weeks
Name 4 treatments of lymphoma.
Single agent prednisolone
Single agent doxorubicin every 3 weeks
CHOP = cyclophosphamide, hydroxydaunorubicin, oncovin, prednisolone
COP = cyclophosphamide, oncovin, prednisolone
What are the mean survival times of lymphoma with each treatment option?
Prednisolone = 2-3 months
Doxorubicin = 6-9 months
COP = 6-9 months
CHOP = 12 months
Name an advantage of each lymphoma treatment.
Prednisolone = least expensive, prednisolone is cheap
Doxorubicin = less expensive, less frequent
COP = 70-8-% remission
CHOP = 75-80% remission, 25% alive at 2 years
What is LOP?
Lomustine instead of cyclophosphamide preferred for T cell.
Why is lymphoma trickier in cats to treat?
- More likely to be substage b
- Chemotherapy challenging due to their small size
- Cats do not tolerate doxorubicin well
- Generally respond less well to treatment
What is the outcome of feline lymphoma treatment?
MST 8 months with COP protocol, remission rates only 50-70%
How does resistance to chemotherapeutic agents develop?
- Insufficient dosing
- Failure to achieve therapeutic concentration at sanctuary sites, such as CNS
- Multi-drug resistance (MDR-1 gene expression) – expression of P-glycoprotein transmembrane drug efflux pump, induced by pre-treatment with steroids
What is leukaemia?
A neoplastic proliferation of haemopoietic cells originating from within the bone marrow. Can be lymphoid, such as proliferating from lineages of lymphocytic cells or non-lymphoid/myeloid, originating from neutrophil, basophil, eosinophil, monocyte, megakaryocyte and erythrocyte cell lineages.
How are leukaemias differentiated?
Well differentiated – chronic leukaemia, generally insidious diseases
Poorly differentiated – acute leukaemia, generally a rapid disease course
Which cells form myeloid leukaemia?
Common myeloid progenitor cells
Megakaryocytes
Thrombocytes
Erythrocytes
Mast cell
Myeloblast
Basophil
Neutrophil
Eosinophil
Monocyte
Macrophage
Which cells form lymphoid leukaemia?
Common lymphoid progenitor
Natural killer cell
B cells
T cells
Plasma cell
What causes penias in leukaemia?
The infiltration of neoplastic cells into the bone marrow impedes production of normal haemopoietic cells
Why is lymphocytosis commonly seen in leukaemia?
High numbers of circulating neoplastic cells are usually seen, such as lymphocytosis, due to circulating neoplastic lymphoblasts.
What is common in leukaemia?
Infiltration of liver and spleen is generally common
How is a lymphoid leukaemia different to lymphoma?
- Leukaemia cells found in bone marrow and blood, lymphoma cells are in lymph nodes and lymph system.
- Stage V lymphoma can look similar to lymphoid leukaemia but lymphoid leukaemia does not have lymphadenomegaly.
- Acute lymphoid leukaemia tends to effect younger patients, has no worse prognosis and is less responsive to chemotherapy
How is leukaemia diagnosed?
Haematology
Blood smear examination
Bone marrow aspirates or bone marrow biopsy
How can leukaemia be treated?
Chemotherapy
Although for chronic leukaemia treatment may not be warranted – may have no clinical signs and impact upon patient welfare and may live like this for many years.
What is the prognosis of leukaemia?
Even with treatment is generally poor, although those with chronic forms will live longer than those with acute forms.
Which characteristics of a lump are most important to not on clinical records?
- Location
- Size (callipers) and shape
- Boundaries
- Mobile or fixed
- Texture, flaccidity and turgor – character
- Discharge or inflammation
- Tissue affected
- Patient response to lump
How much approximately do you think it costs in total for consult fee, to perform an FNA from 1 lump and send it for cytological diagnosis before VAT?
£151-200+
What information should you include on your lab report/cytology submission form?
- Anatomical location
- Cytological results of FMA
- Photos
- Dimensions
- Time frame
- Active and inactive changes
- Meds patient is on
What must be taken into consideration when surgically removing a tumour?
- Incision shape
- Incision orientation – based on skin tension lines
- Extent of lateral margins
- Extent of the deep margin – want deep fascial layer
- Subcutaneous sutures
- The use of drains - avoid is possible
- Cutaneous sutures
- Give antihistamines post operatively
What should you do to a tumour before sending it to a lab for cytology?
Ink tumour to make sure lab can tell you whether you can a clear or dirty margin.
What are the grades of soft tissue sarcomas?
Grades I, II and III
What is the prognosis of soft tissue sarcomas?
Prognosis depends on the grade and to some degree the completeness of surgical excision
What are the characteristics of soft tissue sarcomas?
- Locally invasive
- Highly aggressive locally but does not spread
- Overall low metastatic rate of 10-25%
- Lymph metastasis is uncommon
- Poor exfoliative
- Difficult to differentiate from inflammation
- Can recur so is malignant but not going to cause death
What is the challenge of diagnosing soft tissue sarcomas?
Notoriously difficult to diagnose from FNA – may come back as soft tissue inflammation but use clinical reasoning to decide whether you think it is actually an STS.
What is the best way to maximise chances of making a diagnosis for soft tissue sarcomas from an FNA?
It is pointless doing a FNA, do a biopsy. Use the re-positioning technique, use the suction and aspiration technique or use both techniques.
What is en bloc?
Remove all at the same time
Distinguish macroscopic and microscopic tumours.
Macroscopic tumour = visible to the naked eye
Microscopic tumour = invisible to the naked eye
What is surgical morbidity?
Temporary or permanent disability caused by the surgery
Define palliation.
Easing the severity of the underlying condition without removing the cause
What is sentinel/draining lymph node?
Lymph node draining a specific part of the body
What is an undifferentiated tumour?
A tumour where the cells aren’t classifiable, which is a measure of malignancy
What is wide excision?
Removal of a tumour using wide margins decided by evidence for that tumour type at that site.
List possible benign epithelial tumours.
Adenoma
Basal cell tumour
Benign epithelial cysts/polyps
Epithelioma
Hamartomas
Papillomas (warts)
Pilomatricoma
Trichoblastoma/trichoepithelioma
List the possible malignant epithelial tumours.
Adenocarcinoma
Basal cell carcinoma
Carcinoma
Squamous cell carcinoma
List the possible benign mesenchymal tumours.
- Benign nerve sheath tumours – neuroma, schwannoma, neurofibroma
- Fibroma
- Haemangioma
- Haemangiopericytoma
- Leiomyoma
- Lipoma
- Osteoma
List the possible malignant mesenchymal tumours.
Fibrosarcoma
Haemangiosarcoma
Infiltrative lipoma/liposarcoma
Leiomyosarcoma
Malignant nerve sheath tumours – neurofibrosarcoma
Osteosarcoma
Soft tissue sarcoma
List the possible benign round cell tumours.
Histiocytoma
Plasmacytoma
Melanocytoma
List the possible malignant round cell tumours.
Mast cell tumour
Lymphosarcoma
Melanoma
Multiple myeloma
Malignant histiocytosis
Which organs can and can’t be removed with aggressive margins?
Skin and liver = no
Spleen = yes
What are the main 3 equine external tumous?
Sarcoids
Squamous cell carcinoma
Melanoma
Less common: mast cell, fibrosarcoma, lymphoma/lymphosarcoma
What are equine sarcoids?
- Proliferation of fibroblasts
- Genetic susceptibility and infection with bovine papilloma virus
- Virus present in normal skin but transforms in sarcoids
- Flies may be involved in spread
Where can sarcoids form on horses?
Eyelids
Prepuce
Between hindlegs
Any are where there has been trauma/wound
What are occult sarcoids?
Likely earliest form of the disease but some remain stable for years without any problem
What are verrucose sarcoids?
Grey, scaly, flaky. Can mistake for rubs or other skin diseases on horses
What are nodular sarcoids?
- Discrete, firm, defined nodules under the skin
- Involvement under the skin too, so can’t just treat the outside bit
- Eyelid, axilla, inner thigh and groin
What are fibroblastic sarcoids?
- Fleshy and aggressive
- Like sites of trauma
- Can grow very rapidly
- Can have involvement under the skin too so can’t just treat the outside
What are malignant sarcoids?
- Rare
- Most aggressive type
- Spread extensively through the skin with cords of tumour tissue interspersed with nodules and ulcerating fibroblastic lesions
- Often some overlying verrucous and occult change in the skin
Why should eyelid sarcoids in horses not be treated topically with creams?
Do not use creams on eyes as they will be irritated and rub it into eye and cause blindness
Name 3 newer treatments used to treat equine sarcoids?
Aldara topical cream
Cisplatin beads
Radiotherapy
How is aldara topical cream used to treat sarcoids?
- Chemotherapeutic agent effective against virally induced tumours
- Repeated topical application
- Effective antiviral and antitumor activity by inducing inflammatory response
- Good for fibroblastic, occult or verrucose sarcoids
What are the side effects of aldara topical cream?
- Can get swelling and pain after application. If so, wipe clean after a few hours, phenylbutazone day of application, cold hosing day after application.
- Side effects include small amount of scarring and white hairs
How to cisplatin beads treat equine sarcoids?
- Cisplatin impregnated beads, incision into sarcoid then close. About 1 bead per 1-2cm square
- Slowly release cisplatin into surrounding tissues
How does radiotherapy treat equine sarcoids?
- Brachytherapy or external beam
- No pain during or after treatment
- Very mild crusting of lesion – no severe inflammation
- White hair is most significant side effect
- External beam radiation can be used where surgery or significant inflammation could be harmful (eye)
Where do equine squamous cell carcinomas commonly form?
Most common tumour of the eye/adnexal structures and genitalia
What is the aetiology of equine squamous cell carcinomas?
- Areas lacking in pigment indicating UV radiation as instigating cause
- Also some evidence for equine papilloma virus as initiating cause
- Likes eyelids/3rd eyelid in horses with pink skin around the eye
How may penile squamous cell carcinomas present in horses?
- Bleeding at start of urination
- Smell or occasional discomfort (kicking at belly)
Name 8 treatment options of equine squamous cell carcinomas.
- Surgical excision
- Injectable or topical 5-flourouracil
- Aldara cream
- Radiation therapy
- Oral piroxicam
- Topical Mitomycin ocular drops
- Laser/cryotherapy
- Cisplatin beads
What are the risks of surgical excision of equine squamous cell carcinomas?
May have to have major surgery like a perineal urethrostomy (severe surgery)
Lose a lot of blood
Have to learn how to urinate again
Get bad sores
Very expensive so do in a younger horse
How does oral piroxicam treat equine squamous cell carcinomas?
- Anti-inflammatory
- Prevent angiogenesis
- Prevent metastasis
Side effect: diarrhoea
What is the most successful treatment of equine penile squamous cell carcinomas?
Total penile amputation and perineal urethrostomy
May choose to just amputate distal part of locally treat. Followed by piroxicam 2 months
What are equine melanomas?
Dark melanotic tumours in older grey horses. On the skin or under the skin as nodules. Eyelids, parotid salivary gland, under tail, around anus and penis
What are the 3 ways equine melanomas can be treated?
- Cisplatin beads
- Radiation
- Melanoma vaccine
Describe mast cell tumours in horses. How are these treated?
Close to joints, synovial structures, often feel gritty on biopsy (mineralized)
Surgical excision, radiation, oral steroids
Describe fibrosarcomas in horses. How are these treated?
Difficult to differentiate from sarcoids
Surgical excision, radiation, oral steroids
How are cutaneous lymphomas treated in horses?
Oral steroids, chemotherapy, surgical excision
Long term prognosis guarded so consult with specialist
What are the differential diganoses and clinical signs of each for nasal discharges in older horses?
Tooth Root Abscess – nasal discharge, epiphora, quidding, foul-smelling
Fungal Rhinitis – nasal discharge, epiphora, foul-smelling
Mass – nasal discharge, facial deformity, reduced airflow, weight loss. Necrotic smell but not horrible
Primary bacterial sinusitis
How do equine ovarian granulosa cell tumours present?
Anoestrus
Stallion-like behaviour
Nymphomania
Normal to enlarged ovary with inactive opposite ovary
How do equine mammary tumours present?
- Present as enlargement, occasional discharge
- Often misdiagnosed as mastitis
How do equine uterine tumours present?
Weight loss
Vaginal discharge
How do equine testicular tumours present?
Present as one sided swelling and discomfort
How are testicular tumours in horses treated?
Surgical hemicastration prior to crossing median raphe
How do equine abdominal tumours present?
Hemangiosarcoma – intra-abdominal bleeding, splenic mass. Colic, weight loss
Lymphoma – intestinal or disseminated. Colic, weight loss
What are the morbidity risks of removing tumours?
High tension = high risk of breakdown
Function post-operatively
What is debulking macroscopically vs microscopically?
Often we remove the macroscopic tumour in the knowledge that there is local and/or distant microscopic tumour tissue
What is debulking for palliation?
- Large masses affecting ability to walk due to pressure on joints or muscles
- Long bone osteosarcoma = amputation reduces cancer associated pain
- Anal sac adenocarcinoma with paraneoplastic syndrome of hypercalcaemia and local lymph node spread
How do we prognosticate for tumours?
- Tissue of origin
- Behaviour – local invasion, chance of spread
- Location
Describe intracapsular/debulking as a surgical resection option.
- Conscious decision to not aim to cure
- Incision is made over and then through the tumour which is then removed in chunks
- Leaves macroscopic tumour behind
Describe marginal excision/excisional biopsy as a surgical resection option.
Removal just outside or through the periphery of a tumour – shelling out, 1 downside if often tumours have a pseudocapsule and marginal excision cuts through this, often leaves microscopic disease behind
What are marginal excision/excisional biopsies appropriate for?
Lymph node
Small cutaneous nodules with plentiful skin
Mammary gland tumours in the dog
CNS tumours for decompression
Exploratory surgery that finds a mass where a repeat surgery is less likely
Describe wide excision as a surgical resection option.
This is the most common technique used where a margin of normal tissue is removed. The surgical plane does not go near the actual tumour. Assumes that the tumour will not invade the underlying fascial plane.
Describe radical ‘en bloc’ excision as a surgical resection option.
Inappropriate for most skin tumours, except for skin on pinna
What are the 4 types of radical excision?
Radical excision = compartmental
Head and neck surgeries – enucleation, maxillectomy, mandibulectomy
Limb and body surgeries – amputation, chest wall, body wall resection
Abdomen – splenectomy or nephrectomy
What are the factors affecting healing following a oncological surgery?
- Site/tension or movement, such as a mass on lower leg, or over a joint
- Tumour known to heal poorly, such as mast cell tumour
- Patient factors such as immunosuppressed like exogenous or endogenous steroid (Cushings)
- Patient factors, such as young and lively versus calm and sedate
What are the generalised riles for surgical margin planning according to tumour type?
Carcinoma = over 1cm
Sarcoma = over 3 cm
Round cells = over 1-3cm
When should histopathology be used in surgical oncological cases?
Always
What can be done if histopathology comes back with incomplete margins?
- Second surgery
- Adjunctive therapy – radiation, chemotherapy
Why are surgical drains avoided in surgical oncological cases?
Due to increased risk of infection, better to close with sutures, if reoperate then must also include the drain exit point in the second surgery due to the risk of tumour spread at first surgery
When are linear and elliptical incisions used in surgical oncological cases?
Linear – no skin to be removes
Elliptical – skin to be removed
What should the incisions length be in surgical oncological cases?
1:3 width:length ratio
What is electrosurgery?
Helps haemostasis and should ideally not be used until the tumour has been excised to avoid making it more difficult to assess histological margins
Name the tension relieving techniques used in surgical oncology cases.
Undermining
Close in multiple layers
Tension-relieving sutures
Releasing incisions
Non-linear closure
What is undermining?
Releases the elasticity of the skin immediately around the surgical site so skin can be advanced into place and avoid tension during closure. Must not disrupt the subdermal blood supply.
How does closing in layers relieve tension?
Spreads the tension from deep to shallow so that the level of the skin is tension free, care with closing down tissue planes that normally move across each other during motion
Does a subdermal plexus flap have its own arterial supply?
No, but an axial pattern flap does
What is the signalment of mast cell tumours in small animals?
- More in dogs than cats
- Labradors, brachycephalics, boxers, Bostons, bulldogs
- Usually singular rather than multiple
What can release of histamine from mast cell tumours cause?
Locally released: Darier’s sign - erythema following handling of mass, oedema
Systemically: hives, pruritis, anaphylaxis (very rare), GI ulceration
How are mast cell tumours diagnosed and staged?
FNA cytology
Histopathology for grading
Metastasis - local spread to lymph nodes. Even if normal size. Difficult to assess cytologically so send off for histopathology. Distant = liver, spleen
How are mast cell tumours surgically treated?
- Minimum 2cm lateral margin
- 1 deep fascial plane
- Larger and deeper margins for higher grade
