Neoplasia

Question 1

pre-neoplastic change

Answer 1

reversible change in response to cell injury –> increased risk of neoplasia

Question 2

steps in neoplastic transformation

Answer 2

initiation - irreversible change in genetic make up of cell
promotion - outgrowth of initiated cells in response to promoting agents (benign tumour)
progression - malignant transformation - irreversible change

hallmarks of progression - increasing instability and increased cell heterogenicity

Question 3

mutagens

Answer 3

agents that cause mutations

Question 4

carcinogens

Answer 4

agents that cause cancer

Question 5

complete carcinogens

Answer 5

agent that is both an initiator and a promoter

Question 6

latent period

Answer 6

time before tumour clinically detectible - smallest detectible is around 1cm ( 10^9 cells - 30 rounds of division)

Question 7

neoplastic circumvention of prevention processes

Answer 7

sensescence -
should have permanent arrest at G1 in response to DNA damage, stress and telomere shortening - mediated by p53
neoplastic cells produce telormerases to increase length so can still replicate

apoptosis -
circumvented through inactivation of p53 gene, activation of survival signalling apthways adnd inactivation of death factor signalling pathways

Question 8

p53

Answer 8

central monitor of stress
activated by anoxia, inappropriate signalling by mutated oncoproteins, or DNA damage

DNA damage sensed –> p53 induces apoptosis or senesence

most cancers show loss of function mutations in p53 gene

Question 9

IHC

Answer 9

differentiate between neoplasia (monoclonal) and inflammation (polyclonal)

ascertain histiogenesis of tumour

Question 10

PARR

Answer 10

PCR for antigen receptor rearrangements

differentiate between B and T cells

Question 11

morphology benign tumours

Answer 11

well differentiated - looks like original cells
structure similar to tissue of origin
little to no anaplasia
slow expansion
mitotic figures rare
little necrosis
no local invasion
no metastasis

Question 12

morphology malignant tumours

Answer 12

poorly differentiated - lost function, may have new functions
tissue of origin may be unclear
variable degree of anaplasia
rapid growth
abnormal mitotic figures
necrosis - if poor blood supply
local invasion
metastasis

Question 13

malignancy

Answer 13

potential to metastasise

Question 14

cellular processes of malignancy

Answer 14

loosened intercellular junctions
degradation of basement membrane
adhesion to ECM
migration
intravasation - tumour associated macrophages and angiogenesis
tumour emboli
extravasation - leakage of chemokines

Question 15

lymphatic spread

Answer 15

most carcinomas and sarcomas

pre-existing routes of normal lymphatic drainage
regional lymph nodes may be bypassed - “skip metastasis” - adenocarcinoma of intestine goes to mesenteric lymph node first

Question 16

hematogenous spread

Answer 16

more in sarcomas than carcinomas

more in veins than arteries - thinner walls

veins –> vena cava –> capillary beds of lungs

veins –> portal vein –> liver

Question 17

transcoelomic spread

Answer 17

“seeding”

from tumours on surface of abdominal or thoracic structures
visceral or parietal spread

eg. ovarian or pancreatic adenocarcinomas

usually fatal

Question 18

mast cell tumours

Answer 18

mutation in KIT proto-oncogene

dogs - solitary cutaneous masses
cats - spleen

reddening - due to histamine
ulceration
pruritus
oedema
swelling

paraneoplastic syndrome (rare) - histamine acts on stomach causing sytemic anaphylaxis and/or vomiting

diagnosis -
FNA - quick and cheap and can potentially grade tumours but tends to underestimate high grade
biopsy - histopath, needs GA and more expensive but grading more accurate

cats stains - giemsa and toliudine
dog stain - H&E

Question 19

grading

Answer 19

linked to prognosis

high grade -
>7 mitotic figures per 10 hpf
>3 multinucleated cells per 10 hpf
karyomegaly - nuclear diameter of at least 10% neoplastic cells by at least 2x

Question 20

staging

Answer 20

assessment of whether a tumour has metastasised

T - local tumour
N - regional lymph nodes
M - distant metastases

Question 21

sentinel metastasis

Answer 21

first metastasis - usually to local lymph node

Question 22

paraneoplastic syndromes

Answer 22

clinical signs caused by a neoplasm indirectly and distant from the primary mass or metastases

Question 23

paraneoplastic syndrome - reproductive tumours

Answer 23

sertoli cell -
hyperoestrogenism - feminisation, gynecomastia, bone marrow suppression, squamous metaplasia of prostate

granulosa cell -
horse
inhibin producing - anoestrous
ostrogen producing - nymphomania, continuous oestrous
androgen producing - male behaviour
testosterone - elevated in most cases

Question 24

paraneoplastic syndrome - thymoma

Answer 24

associated with myasthenia gravis, polymyositis, various dermatoses

exfoliative dermatitis in cats

Question 25

paraneoplastic syndrome - hypercalcemia of malignancy

Answer 25

many neoplasms

PUPD most common sign
bradycardia, lethargy, weakness

anal sac carcinomas or adenomas of parathyroid gland - produce parathyroid like hormone

less common - multiple myeloma, squamous cell carcinoma, metastatic bone tumours, lymphoma

Question 26

myeloma

Answer 26

plasma cell neoplasia

3 types -
extramedullary plasmacytomas
solitary bone plasmacytomas
multiple myeloma - involving bone marrow of multiple joints

increased immunoglobulins
multifocal osteolysis on radiography

Question 27

paraneoplastic syndrome - multiple myeloma

Answer 27

multiple

hypercalcemia - bone damage
pancytopenia - marrow damage
haemorrhage - from pancytopenia and platelet dysfunction
hypervicosity syndrome - due to circulating globulins
renal disease - nephrocalcinosis decondary to chronic hypercalcemia

Question 28

amyloidosis

Answer 28

amyloid = pathogenic proteinaceous substance, polypetides arranged in beta pleated sheets

protein folding disorders
biologic function lost

causes -
genetic - kidneys in abyssinian cats and sharpeis, liver in siamese cats
chronic inflammation
plasma cell tumours

nasal amyloidosis in horse