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Flashcards in Neoplasia 5 Deck (28):
1

INDIRECT SYSTEMIC EFFECTS ON THE HOST

PARANEOPLASTIC SYNDROMES.
-Indirect/remote effects
-Caused by tumour cell products
-75% incidence in humans, unknown in veterinary medicine.

2

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.

3

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.

4

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

5

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.

6

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.

7

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.

8

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.

9

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.

10

GENETICS AND CANCER AETIOLOGY

-Heritable changes in the germline sequences in all cells.
-Somatic changes that accumulate in individual cells and tissues over time.

11

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)

12

ACQUIRED SOMATIC MUTATIONS

-INTRINSIC FACTORS- by products of metabolism (eg. ROS)
-EXTRINSIC FACTORS- chemical, radiation (complete carcinogens- cause initiation and promotion), viruses.

13

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.

14

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.

15

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.

16

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.

17

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.

18

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.

19

BOVINE LYMPHOSARCOMA

1. 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.

2. Sporadic bovine lymphosarcoma- Seen in young cattle, is seen in UK. Multicentric/thymic. Disseminated disease seen at 3-6 months of age.

20

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.

21

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.

22

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.

23

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.

24

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.

25

LYMPHOID LEUKOSIS- CHICKENS

Retrovirus.
Genetic selection has eradicated this disease from commercial strains of poultry, but cases are still seen in non selected ornamental strains.
Not an economic problem in today's poultry industry.

26

MAREK'S DISEASE- CHICKENS

MOST COMMON AND IMPORTANT LYMPHOPROLIFERATIVE DISEASE IN CHICKENS.
Cause by Marek's Disease Virus, a herpesvirus.
Causes heavy economic losses.

Natural transmission- Young chicks via horizontal, direct and indirect contact.
Airborne route- infectious viral particles are spread from feather follicles.
Virus particles show high resistance in the environment.

27

MAREK'S DISEASE- CLINICAL SIGNS

Classical, chronic paralytic form- Seen in young adults (reproductive and laying hens).
Incoordination, ataxia, gait abnormalities.
Asymmetric progressive paresis followed by paralysis.
Gross lesions seen as asymmetric hypertrophy and discolouration of BRACHIAL and COELIAC PLEXUSES and LARGE PERIPHERAL NERVES.
Also visceral lymphoid tumours.
Grey eye.
Hepatomegaly with diffuse or multinodular neoplastic infiltration.

28

EQUINE SARCOIDS

Non productive (does not produce any infectious virions) infection of BPV.
Mode of transmission is not establised- Flies could act as vectors.
Locally aggressive, non metastatic fibroblastic tumours of skin.
Make up 30% of all equine skin tumours.
Any breed/age/sex, most common in 3-6 year olds.
Any area of body- head, legs and ventral trunk common.
BIPHASIC TUMOURS have a layer of hyperplastic epithelium over their surface.