Oncology

• The incidence of cancer in dogs in 1 in 3-4. There may be some breed associations. The most common neoplasias are lymphomas, mast cell tumour, soft tissue sarcoma, mammary cancer, osteosarcoma and melanoma.

   

  Incidence of cancer in cats is 1 in 5-6 (so less than dogs). Feline cancer is dominated by FeLV infection, causing lymphoma and leukaemia. Other common cancers are squamous cell carcinoma of the head and neck, mammary cancer and Hodgkin’s lymphoma type disease.
• The clinical consequences of cancer include the primary tumour (it’s compression, invasion, loss of function etc.), paraneoplastic disease (the consequences of cancer e.g. producing PTH like hormone causing hypercalcaemia). Finally, secondary cancer (metastasis, causing debilitation and further organ failure)
• Treatment modality options for cancers vary by type:

  For the primary disease, surgery and/or radiation are the main options

  For disseminated disease, systemic therapy is more appropriate – chemotherapy / targeted therapy / immunotherapy

  Key clinical questions for decision making are what the cancer is and how far has it got.
• In the stochastic model, cancer formation is the phenotypic result of changes over time. There is an initiating step by a cancer forming agent, affecting the genetic material of the cell. If it doesn’t repair this damage, multiple progressing factors push -> malignancy. Progression may be slow as it requires multiple steps. Each stage of multi-step carcinogenesis reflects genetic changes in the cell with a selection advantage -> a highly malignant cell. The age-dependent incidence of cancer suggests a requirement for between 4-7 rate limiting, stochastic events -> malignant phenotype.
• A proto-oncogene describes cellular oncogenes that do not have transforming potential to form tumours in their native state but can be altered to lead to malignancy. Genes which normally controls cell growth and proliferation e.g. growth factors, growth factor receptor, protein kinases, signal transducers nuclear proteins, transcription factors.

  Somatic events, mutation or damage may cause conversion of a proto-oncogene.

  An oncogene is a mutated form of a proto-oncogene.
• mechanisms of oncogene activation:

  1.      Chromosome translocation

  2.      Gene amplification

  3.      Point mutations

  4.      Viral insertion
• Tumour suppressor genes in normal cells act like checkpoints in the cell cycle. If these genes are damaged or removed, then their inhibitory function, leading to uncontrolled cellular replication.
• Acquired capabilities of carcinogenesis:

  • Self sufficiency in growth
  • Insensitivity to anti-growth signals
  • Evade programmed cell death (apoptosis)
  • Limitless replicative potential (reactivation of telomerase)
  • Sustained angiogenesis
  • Ability to invade and metastasise
  • Ability to evade host immunity
• Natural history refers to the progression and development of cancer. Evaluation begins with the principle clinical problem – local disease, invasion, treatment plan. Then we evaluate the primary and secondary disease for the effect on the wider body – we may also evaluate progression. We must consider the overall condition and QOL of the animal.

  We can then consider treatment modalities:

  • Surgery or radiation of the primary disease
  • Systemic therapy e.g. chemotherapy, immunotherapy; for disseminated disease.
• Cancer staging describes the severity of a patient’s cancer based and the size and extent of the primary tumour, and whether the cancer has spread in the body.

  Cancer staging helps to plan appropriate treatment, determine prognosis and exchange information for research.
• Solitary neoplasms are singular and have not metastasised.

  Multicentric neoplasms have multiple sites.

  Disseminated neoplasms have spread through the body
• Most staging systems consider:

  • Site of the primary tumour and cell type
  • Tumour size and extent
  • Lymph node involvement
  • Presence of metastasis
  • Tumour grade where available
• Assessment of a primary tumour should include location, size, shape, consistency (imaging if not visible), cytological or histological diagnosis or classification. All tumours should be measured with callipers for comparison and accurate assessment between visits. A biopsy may be required.
• Assessment of primary tumour:

  Tx: the primary tumour cannot be evaluated e.g. in a cavity

  T0: there is no evidence of the primary tumour

  Tis: A carcinoma in situ (pre invasive : above the basement membrane)

   

  T numbers describe size and extent of the primary tumour (1-4)
• Assessment of regional lymph nodes:

  Nx: cannot be evaluated

  N0: no regional lymph node involvement

  N1, N2, N3: increasing degrees of regional lymph node involvement

   

  Physical examination of a lymph node includes the size, mobility, texture and consistency, presence of any ulceration and relationship with associated anatomical structures.
• A stage 0 cancer is a carcinoma in situ

  A stage 1, 2 or 3 cancer is a larger tumour size and/or spread beyond the organ of origin to the lymph nodes or adjacent organs

  A stage 4 cancer has spread to distant tissues or organs
• Cancer screening in veterinary oncology mainly consists of physical screens (routine exams at annual vaccinations, education of clients to check for lumps and consideration of at-risk patients e.g. unspayed bitches and intact males) and genetic screens (e.g. canine genome project, at-risk populations). Chemical screens are not yet really used in vet med
• Evaluation of metastatic disease occurs in three steps:

  • Physical exam and history – can give clues to metastasis e.g. weight loss, coughing lameness
  • Diagnostic imaging – type depends on the tumour type and its biological behaviour. Particular attention should be paid to the lungs, liver and bones
  • Biopsy – to confirm any masses are metastatic disease vs nodular hyperplasia etc.
• Patient presents with mass -> history with assessment for tumour related complications -> clinical examination of general health, evidence of paraneoplastic disease. Obtain blood and urine -> assessment of primary tumour which may include imaging and FNA or biopsy -> assessment of draining lymph nodes -> assessment for metastatic disease -> treatment options and prognosis
• Biopsy allows for the most appropriate treatment selection to be made per tumour. Biopsies do not negatively influence survival, and allow for histopathological or cytological diagnosis to be established. A bacterial sample for culture and sensitivity may also be indicated. Contradictions are rare but cases where haemorrhage is a risk should avoid biopsy.
• Post-surgical biopsy is essential to make sure surgical margins were adequate, to double-check the histological type and grade, to check if follow-up therapy is required and to inform prognosis
• Before taking a biopsy, considerations must be made for the amount of tissue needed to recover, the position within the tumour you are taking from (e.g. central in a lymph node, margins of an excised mass), type of tissue being biopsied and the anatomic location of the tumour
• Round cell tumours appear like spotty fried eggs of cytology due to the histamine and heparin granules
• Practical types of biopsy include

  • FNA
  • Tru-cut
  • Punch biopsy
  • Excisional / incisional
  • Bone marrow
• Cytology is the examination of individual cells or small growups of cells which have been recovered from tumour masses or neoplastic effusions. It can help identify neoplastic disease however cytological smears rarely look like their original arrangement within the tumour.

  Cytology specimens are easy to recover with little equipment or tumour disruption. Multiple sites within the tumour can be sampled in one biopsy and processing is quick and easy.
• Choice of modality for cancer imaging must consider structure, what equipment etc is available, cost and ability to interpret.

  Radiography is a good initial screen for mets in the lungs, but multiple views are needed.
• Ultrasound allows evaluation of the abdominal organs and lymph nodes and can aid deep biopsy. Can also evaluate tumour invasion.

  Nuclear scintigraphy involves administration of radiopharmaceuticals which localise to areas of tumour or inflammation – most commonly used to detect bony metastasis e.g. osteosarcoma. Sensitive for disease lesions but non-specific for disease aetiology.
• CT imaging is mostly used in treatment planning for radiotherapy, but also for imaging lesions of the skull. Can be combined with contrast to asses extent of invasion. Care must be taken with radiation around the eyes (blindness)

  MRI imaging is primarily used to evaluate CNS as it has good evaluation of soft tissue structures.

  PET (positron emission topography) can show function of a tumour, uses tracers to show sites of rapid cell division
• Excisional biopsiese entirely remove a tumour with margins to be sent for evaluation. These are usually smaller, easy to access masses. They have potential to be curative. They are used when a pre-surgical biopsy will not change the therapy or a biopsy is as dangerous as the excisional surgery.

  Incisional biopsies take a section out of a tumour. Used when a lesions is too large or too difficult to excise easily. Its results will often alter treatment. Samples however may not be representative and may complicate future surgery. Also risk seeding of cancerous cells.
• Needle biopsies are used to remove small cores of tumour tissue from solid lesions (14-22g needles). These are more useful than an aspirate as they recover more tissue so tumour type and architecture can be established. They can reach comparatively inaccessible sites and multiple samples may be removed through a single approach.

  However, needle biopsies see higher incidence of post biopsy complications e.g. haemorrhage, than FNA. For this reason they shouldn’t be used in particularly vascular tumours in inaccessible locations.
• Skin punch biopsies are useful for skin and superficial soft tissue tumours. They recover much more tissue than needle aspirates , with recovered tissue maintaining architecture.
• A bone marrow biopsy is indicated in diagnosis of conditions affecting lymphoid and myeloid systems. Indications may include

  • Non-regenerative anaemia of undetermined cause
  • Secondary immune mediated haemolytic anaemia
  • Staging or diagnosis of haematopoietic tumours
• A bone marrow biopsy can be taken from the humerus, femur or iliac crest.

  The patient is anasthetised, placed in sternal recumbency and the site is clipped and scrubbed. A stab incision is made to the skin over the biopsy site. A bone marrow needle is put into the bone in a cork screw movement. The stylet is removed and a 10ml syringe attached to the needle. Bone marrow is aspirated, needle and syringe removed and marrow placed on slides QUICKLY (clots quickly). Smears are made like blood smears.
• margins of biopsies are marked:

  • With ink or dyes
  • With a suture
• Mast cell tumours are stained with toluidine blue
• For round cell tumours remember LYMPH:

  Lymphoma, TVT, Mast cell, Plasma cell, Histiocyte
• A tumour which reacts positively with CD3 stain is a T cell lymphoma. If CD18 and MHCII are also positive, the tumour may be of histiocytic origin.

  If CD18 is positive but MHCII negative, the tumour may be a mast cell tumour.
• Paraneoplastic syndrome is defined as one or more clinical signs induced by a tumour (distant from the primary site),  usually due to inappropriate secretion of hormones or hormone-like substances, cytokines, enzymes or peptides.

  Factors which cause PNS can be secreted topically e.g. PTH from primary hyperparathyroidism or ectopically e.g. PTHrP from an apocrine anal gland carcinoma. Several organs can be affected by one secreted substance, and the immune system may become dysregulated.
• Recognising paraneoplastic disease (as apposed to normal old-age comorbidities or incidental findings) can help make a tumour diagnosis or narrow down differentials. An effective tumour treatment usually resolves PNS and can then be used as a marker of remission.
• As many cancer patients are older pets, they often have comorbitities and incidental illnesses. Many older animals will have anaemia of chronic disease, stress haemogram and raised liver enzymes. Cancer cachexia however is uncommon in small animals.

  Cancer cachexia is weight loss despite adequate calorific intake.