General oncology

Question 1

What are the indications for taking aspirates?

Answer 1

All cutaneous masses
Enlarged lymph nodes
Draining lymph nodes local to a tumour
Sampling of abnormalities in organ parenchyma
Scars of incomplete tumour excisions
Bone marrow aspirates

Question 2

What are some of the pitfalls of taking aspirates?

Answer 2

• Small / amorphous tumours surrounded by fat.
• Tumour dissemination.
• None diagnostic or none representative sample

N.B now recommended to do 4 seperate FNA samples of mammary tumours to have a good chance of finding out the type of tumour

Question 3

What are the types of round cell tumour?

Answer 3

Lymphoma
Mast cell tumours
Histiocytoma
Transmissable venereal tumours
(Malignant melanoma)

Question 4

What are the criteria for malignancy?

Answer 4

 Anisocytosis
 Macrocytosis
 Increased cell exfoliation
 Increased mitotic figures
 Abnormal mitosis
 Open chromatin
 Pleomorphism
 Macrokaryosis
 Increased N : C ratio
 Anisokaryosis
 Multinucleation pattern
 Nuclear moulding
 Large nucleoli
 Angular nucleoli
 Anisonucleosis

Question 5

How do you decide if something is malignany?

Answer 5

Normally need at least 3 criteria of malignancy noted repeatedly, however this may not be the case where there is lots of inflammation or in highly active tissue (e.g. liver)

Question 6

How do benign tumours normally appear?

Answer 6

Cells do not vary significantly in size or shape
Small, regular nuclei, low nuclear: cytoplasmic ratio
Fine, smooth nuclear chromatin
Indistinct/absent nucleoli
Normal cytoplasm

Question 7

How do epithelial cells appear?

Answer 7

Polygonal to round
Round to oval nucleus
In groups/ clumps
Exfoliate well

Question 8

How do mesenchymal cells appear?

Answer 8

Few exfoliate
Central nucleus
cytoplasmic tails

Question 9

How do normal lymph nodes appear on cytology?

Answer 9

 Mainly small lymphocytes • 75-95%
 2/3rds size of neutrophil
 Round nuclei
 Scant pale cytoplasm Scant, pale cytoplasm
 Small numbers of lymphoblasts, plasma cells, lymphogranular bodies
• occasional mast cell, neutrophil or macrophage - < 3 %

Question 10

How do reactive cells appear in LNs?

Answer 10

All nodes are reactive to a degree
No clear line between normal and reactive
Mixed population of small and medium sized lymphocytes
Lymphoblasts (up to 15%), plasma cells (up to 10%), macrophages

Question 11

How do cells appear with lymphoma?

Answer 11

Large cells in the majority!
Cytological aberations
Can be difficult in when the population is medium sized
Caution in young cats with multicentric lymph node enlargement - better to biopsy

N.B large cell = >2x size of a neutrophil

Question 12

Excisional biopsy is rarely appropriate - when is it appropraite?

Answer 12

• Canine mammary tumours
• When preoperative histology
 Is impractical
 Unlikely to alter a therapeutic surgery
• Lymph nodes
• Masses removed from body cavities

Question 13

When should you do electrophoresis and what are the considerations?

Answer 13

In cases of hypergammaglobulinaemia
• Blood and / or urine
• Always check travel history

Question 14

Outline thymidine kinase

Answer 14

Enzyme associated with cell proliferation
K is a marker of the volume of replicating cells in the animal and consequently an indirect measure of neoplastic burden.
Those lymphoma patients with the highest TK activities are likely to have the highest neoplastic burden or replication rate and these may have a worse prognosis than those lymphoma patients with lower levels.

Question 15

How may you diagnose chronic myelogenous leukaemia

Answer 15

high neutrophil count, the presence of neutrophils at all stages of differentiation, and basophilia, and can also include lymphocytosis, eosinophilia, and thrombocytosis. However, in cases where there is extreme neutrophilia and other causes are suspected, such as infection and paraneoplastic expansion of neutrophils associated with some cancers, finding the bcr-abl translocation is considered diagnostic for CML, and its absence virtually rules out the disease

Question 16

What is the use of C-kit in MCTs?

Answer 16

only about 10% of all mast cell tumors have ITD, but the presence of these mutations correlates strongly and inversely with outcome, both in cases treated with surgery alone, and cases treated with surgery plus chemotherapy. C-kit ITDs were never found in grade I mast cell tumors, but in both grade II and III MCT.

Question 17

What is clonality assay?

Answer 17

Any diagnostic test that demonstrates that a group of cells is derived from a single clone can be considered a clonality assay. The term is usually used to refer to detection of the unique genes found in each individual B- or T-cell: Ig genes in B-cells and T-cell receptor genes in T-cells. The portion of these genes that encodes the antigen-binding region is the portion that varies between cells, both in size and sequence. Once a B- or T-cell is mature and divides in response to antigenic stimulation, the Ig and T-cell receptor genes are passed on to the daughter cells

Question 18

What is the theory behind clonality assays detecting neoplasia?

Answer 18

In the course of a normal immune response to a pathogen, B- and T-cells are activated, undergo clonal expansion, and eventually die, leaving behind only a small number of residual memory cells. On the other hand, when a cell becomes neoplastic, it is no longer subjected to growth controls, and can expand significantly more than the cells during an immune response. Therefore, if one can establish that the majority of cells in a particular collection of lymphocytes have the same Ig or T-cell receptor gene, it is most likely that these cells are neoplastic rather than reactiv

Question 19

What clonality assays are used for lymphoma?

Answer 19

PCR for antigen receptor rearrangements (PARR) assay

Question 20

When is PARR used?

Answer 20

PARR assay is most commonly used to aid in distinguishing reactive (polyclonal) from neoplastic (monoclonal) lymphocytes when these distinctions are difficult to make with other means.

Question 21

What can cause a false +ve with PARR

Answer 21

erlichia

Question 22

What are some of the considered benefits of metronomic therapy

Answer 22

Reduced angiogenesis, preventing tumour growth
Constant exposure of tumour cells to drugs
endothelial cell selectivity
Reduces t-reg cells (these are the cells that prevent destruction of self cells)

Question 23

What is the mechanism of action of thalidomide?

Answer 23

uncertain but includes inhibition of vascular endothelial growth factor, which is involved in tumour blood vessel formation, and inhibition of multiple tumour‐promoting and inflammatory cytokines, including interleukin (IL)‐1b, IL‐12 and IL‐6, which are associated with myeloma cell survival

Question 24

Who are candidates for C-Kit?

Answer 24

▪ Gross tumours;
▪ Non‐resectable grade II or III tumours (including patients with large numbers of MCTs)
▪ Recurrent tumours where re‐excision and radiotherapy are declined/inappropriate;

Question 25

What are the response rates to C-kit use in MCTs?

Answer 25

40-50%

Lasts normally for around 4-5 months, but can be years

Question 26

What are the pros and cons or tumour vaccinantion?

Answer 26

▪ It has only minor adverse effects;
▪ It can result in immune memory, potentially protecting the patient from disease progression.
However, tumour vaccination has some drawbacks. It takes a long time to develop an antitumour immune response and even more time for a clinical response. Rapid progression of some aggressive canine oral melanomas can mean that patients die before the benefits from vaccination are realised. In addition, cancer can become resistant to immunotherapy via various mechanisms, such as a loss of major histocompatibility complex molecules or tumour antigens, the production of soluble immunosuppressive factors, and the accumulation of suppressive cells such as T‐regs and myeloid‐derived suppressor cells.

Question 27

What is oncept?

Answer 27

Oncept (Merial), a therapeutic tumour vaccine, is a DNA vaccine encoding the human tyrosinase gene. It has been licensed for the treatment of oral mucosal melanoma in dogs in the USA but is still unlicensed in the UK.
In the UK, it can only be administered by oncology specialists and a special treatment certificate must be obtained from the Veterinary Medicines Directorate on a named patient basis (acquired by the treating oncologist).

Question 28

What is Oncept IL-2

Answer 28

Oncept IL‐2 (Merial) contains feline IL‐2 recombinant canarypox virus. It is used to treat cats with fibrosarcoma in combination with surgery and radiotherapy to reduce the risk of/delay the tumour recurring locally. It is recommended for use when the size of the tumour is 2 to 5 cm in diameter and there is no evidence of metastatic disease