Neoplasia Flashcards
pre-neoplastic change
reversible change in response to cell injury –> increased risk of neoplasia
steps in neoplastic transformation
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
mutagens
agents that cause mutations
carcinogens
agents that cause cancer
complete carcinogens
agent that is both an initiator and a promoter
latent period
time before tumour clinically detectible - smallest detectible is around 1cm ( 10^9 cells - 30 rounds of division)
neoplastic circumvention of prevention processes
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
p53
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
IHC
differentiate between neoplasia (monoclonal) and inflammation (polyclonal)
ascertain histiogenesis of tumour
PARR
PCR for antigen receptor rearrangements
differentiate between B and T cells
morphology benign tumours
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
morphology malignant tumours
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
malignancy
potential to metastasise
cellular processes of malignancy
loosened intercellular junctions
degradation of basement membrane
adhesion to ECM
migration
intravasation - tumour associated macrophages and angiogenesis
tumour emboli
extravasation - leakage of chemokines
lymphatic spread
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
hematogenous spread
more in sarcomas than carcinomas
more in veins than arteries - thinner walls
veins –> vena cava –> capillary beds of lungs
veins –> portal vein –> liver
transcoelomic spread
“seeding”
from tumours on surface of abdominal or thoracic structures
visceral or parietal spread
eg. ovarian or pancreatic adenocarcinomas
usually fatal
mast cell tumours
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
grading
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
staging
assessment of whether a tumour has metastasised
T - local tumour
N - regional lymph nodes
M - distant metastases
sentinel metastasis
first metastasis - usually to local lymph node
paraneoplastic syndromes
clinical signs caused by a neoplasm indirectly and distant from the primary mass or metastases
paraneoplastic syndrome - reproductive tumours
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
paraneoplastic syndrome - thymoma
associated with myasthenia gravis, polymyositis, various dermatoses
exfoliative dermatitis in cats
paraneoplastic syndrome - hypercalcemia of malignancy
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
myeloma
plasma cell neoplasia
3 types -
extramedullary plasmacytomas
solitary bone plasmacytomas
multiple myeloma - involving bone marrow of multiple joints
increased immunoglobulins
multifocal osteolysis on radiography
paraneoplastic syndrome - multiple myeloma
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
amyloidosis
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
