Neoplasia 5 Flashcards
-Define indirect effects of cancer- paraneoplastic syndromes -Be familiar with the most common examples in veterinary medicine- hypercalcaemia, hypoglycaemia, cachexia. -Describe the aetiology of cancer- genetics and cancer, virally induced tumours. -Give examples of virally induced tumours in a range of species -Equine sarcoids- why are they so difficult? (28 cards)
INDIRECT SYSTEMIC EFFECTS ON THE HOST
PARANEOPLASTIC SYNDROMES.
- Indirect/remote effects
- Caused by tumour cell products
- 75% incidence in humans, unknown in veterinary medicine.
PARANEOPLASTIC SYNDROMES
May occur early, allowing early tumour diagnosis- IF THEY ARE TUMOUR SPECIFIC.
The associated metabolic abnormalities must be treated.
Severity reflects tumour burden- tumour response to therapy, recurrence or spread.
CACHEXIA
A paraneoplastic syndrome with complex aetiology:
Anorexia, poor digestion, nutritional demands of tumour tissue, nutrient loss in effusions or exudates, metabolic/endocrine derangements.
-Muscle and fat loss
-Extra calories do NO reverse the catabolic sate
-Cytokines and hormones are implicated- TNF-a, IL-1, IL-6, prostaglandins.
DYSPROPORTIONATE to nutritional demands of animal due to tumour nutritional demands, nutrient loss etc.
CANCER RELATED HYPERCALCAEMIA
Excess circulating calcium.
Clinical signs- Muscle weakness, cardiac arrhythmia, anorexia, vomiting, renal failure.
-Excess parathyroid hormone- major Ca regulator.
-Increased mobilisation of Ca from bones
-Increased absorption of Ca by kidney
-Increased reabsorption of Ca by gut.
Loss of calcium from bones is replaced with much fibrous tissue (collagen) from spindle cells. More is needed to support tissues as it is weaker. FIBROUS OSTEODYSTROPHY.
eg. ‘Big nose’ in horses- nasal bones are affected by hypercalcaemia- fibrous osteodystrophy causes blocking of airways and thus dystrophy.
Clinical signs are nothing to do with tumour! REMOTE EFFECTS
HYPOGLYCAEMIA
Decreased glucose.
DIRECT- eg. insulomas (functioning tumours of pancreatic islet B cells- produce much insulin, decreasing circulating glucose)
or PARANEOPLASTIC- other tumour cell types.
CLINICAL SIGNS:
Nervous system- high glucose requirement, so this will be affected first. Lethargy, incoordination, muscle weakness, seizures.
GASTRIC/DUODENAL ULCERATION AND HAEMORRHAGE
Direct- eg. Pancreatic carcinoma- increases gastrin production, which can ulcerate gut and cause haemorrhage.
Indirect- eg. Visceral Mast cell tumours- increase histamine on to bloodstream, where it binds to receptors on the parietal cells of the stomach and induces increased HCl release.
Peritonitis is seen on ulceration- abdominal pain, vomiting.
FEMINISATION SYNDROME
Seen in dogs with Sertoli cell tumours.
Indirect effect- Sertoli cells produce oestrogen which causes feminisation:
Thinning of skin, pendulous abdomen, gynaecomastia.
Can sometimes be reversible.
CANCER RELATED ANAEMIA
Possible causes:
- Anaemia of chronic disease
- Bone marrow invasion (bone marrow cells replaced by tumour cells- MYELOPHTHISIS)
- Haemolysis
- Blood loss.
Neutrophils depleted first, then platelets, then other cells.
GENETICS AND CANCER
Heritable DNA changes ie. in germline sequences.
- Enhanced/decreased/absent expression of normal proteins
- Increased expression of abnormal proteins (eg. p53 inactivated/not expressed)
- Oncogene encoded proteins overexpressed.
Altering the profile of the tumour cell determines the tumour PHENOTYPE.
GENETICS AND CANCER AETIOLOGY
- Heritable changes in the germline sequences in all cells.
- Somatic changes that accumulate in individual cells and tissues over time.
GERMLINE MUTATIONS AND CANCER SYNDROMES
Human- BRCA1 and BRCA2 genes (breast and ovarian cancers)
Canine- GERMAN SHEPHERD DOGS- Germline mutations can cause hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis.
- Bilateral, multifocal renal tumours
- Uterine leiomyomas (benign smooth muscle tumours)
- Skin nodules (dermatofibrosis)
ACQUIRED SOMATIC MUTATIONS
- INTRINSIC FACTORS- by products of metabolism (eg. ROS)
- EXTRINSIC FACTORS- chemical, radiation (complete carcinogens- cause initiation and promotion), viruses.
ENZOOTIC BOVINE HAEMATURIA
Caused by bracken fern- contains quercetin, a chemical carcinogen.
Affects urinary bladder- Vascular hyperplasia/ectasia, haematuria.
A wide range of mesenchymal and epithelial tumours are seen.
Bracken fern also produces immunosuppressants, so immnosurveillance is ineffective.
Action of carcinogens, immunosuppressants, and additional viruses can cause various tumours:
Haemangiomas/polyps- benign.
ras (oncogene) action causes malignancy:
Haemangiosarcomas/transitional cell carcinoma/papillary carcinoma.
VIRUSES AND CANCER
RETROVIRUSES- FeLV, FIV, Jaagsiekte sheep retrovirus, bovine leukosis virus.
HERPESVIRUSES- Marek’s disease virus, Kaposi’s sarcoma virus, Lucke frog virus, Epstein-Barr virus.
PAPILLOMAVIRUSES- Rabbit (Shope) papillomavirus, bovine, canine and caprine papillomavirus.
VIRAL ONCOGENESIS
DOMINANT ONCOGENES- Host or non-host cell origin.
INSERTIONAL MUTAGENESIS- Activates expression of cellular oncogenes.
HIT-AND-RUN MECHANISM- Transient residence on target cells (is present for long enought o cause damage) eg. bovine papilloma.
INDIRECT MECHANISMS- Suppression of host immune system.
-Stimulation of target cell proliferation.
IMPORTANT VIRALLY INDUCED VETERINARY TUMOURS
RETROVIRUS:
- FeLV- leukaemias, lymphomas
- Bovine leukosis virus- leukaemias, lymphomas
- FIV- lymphomas
- Jaagsiekte- pulmonarcy carcinomas
- Avian leukosis virus- leukaemias, lymphomas
HERPESVIRUS:
-Marek’s disease- lymphoproliferative disease in poultry.
MOST COMMON TUMOUR IN DOMESTIC ANIMALS?
LYMPHOMAS/LYMPHOSARCOMAS.
Solid tumours comprised of lymphocytes.
Originate in tissues and can migrate to bone marrow.
Various classification methods.
LYMPHOSARCOMAS
-MULTICENTRIC- Present in multiple lymph nodes.
Bilateral node enlargement. Node is replaced by soft, white tissue.
Liver and splenic white pulp are infiltrated.
-THYMIC- Firm white mass replaces thymus. This can compress the heart and lungs.
-ALIMENTARY- Nodules, plaques or ulcers in the alimentary tract. (can replace normal wall of tract- thickened)
Enlarged mesenteric lymph nodes.
BOVINE LYMPHOSARCOMA
- Enzootic bovine lymphoma- seen in adult cattle due to Bovine Leukaemia Virus (BLV) infection- should NOT be seen in the UK.
Retrovirus, shows horizontal spread. Infected lymphocytes, arthropods, needles. - Sporadic bovine lymphosarcoma- Seen in young cattle, is seen in UK. Multicentric/thymic. Disseminated disease seen at 3-6 months of age.
FELINE LYMPHOSARCOMA
-80-90% of older cats with feline lymphosarcoma are FeLV negative.
Mostly alimentary, B cell tumours.
Thymic, multicentric and renal can also be seen.
-In young/middle aged cats, feline lymphosarcoma IS likely to be a result of FeLV (retrovirus) infection- unvaccinated cats eg. indoor cats.
Many manifestations, usually T cell.
Thymic, multicentric, also renal and alimentary.
CANINE LYMPHOSARCOMA
No obvious cause. (not retroviral or other)
One of the most common tumours seen, middle aged dogs.
MULTICENTRIC most common form, though alimentary, thymic and cutaneous are also seen.
70-80% are B cell tumours, ~20% are T cell, occasionally ‘null cell’.
Hypercalcaemia is seen in ~20% of cases.
JAAGSIEKTE
Driving sickness in sheep.
Ovine pulmonary carcinoma/pulmonary adenomatosis.
Transmissible retrovirus induced pulmonary neoplasia.
High incidence in Scotland, S. Africa and Peru, NOT in Australia/NZ.
Retrovirus infects mature sheep mainly and horizontal transmission is encouraged by the copious nasal discharge seen and by intense husbandry.
Death is seen after several months as there is no specific humoral immune response to the retrovirus.
JAAGSIEKTE- GROSS FINDINGS
EARLY STAGES- Lungs enlarged, heavy, wet, with firm grey, variably sized nodules.
LATER STAGES- Nodules become confluent.
Large sections of both lungs are infiltrated.
Secondary pneumonia can be seen due to affected immune balance.
Cut section- Airways are full of oedematous fluid and mucoid secretion.
JAAGSIEKTE- MICROSCOPIC FINDINGS
BRONCHIOALVEOLAR CARCINOMA- Cuboidal or columnar epithelial cells line airways or alveoli. Form papillary or acinar structures.
POSSIBLE SEQUELAE- Bronchopneumonia, abscesses, fibrous pleural adhesions.
METASTASES- Seen later in disease. Tracheobronchial/mediastinal lymph nodes.
Can also progress to pleura, muscle, liver and kidneys.
