Oncology Flashcards
what is cancer?
diverse range of conditions with a common theme of persistent, pointless proliferation of host cells often to the detriment of the host
what is the spectrum of behaviour that can be displayed by tumors?
truly benign
highly malignant
local characteristics of malignancy but do not metastasise
what are the 6 features necessary for the development of cancer?
evading apoptosis
self-sufficiency in growth signals (not required from the body)
insensitive to anti-growth signals
tissue invasion and metastasis
limitless reproductive potential (continuous growth)
sustained angiogenesis
what is angiogenesis and why is it of benefit to cancer growth?
creating of new blood vessels which can enable further growth of cancer
what is apoptosis?
cell death
why is cancer a genetic disease?
the hallmarks of cancer originate from alterations in genes within the patient themselves rather than being hereditary where the gene alteration would be inherited from the parent
what alterations in genes can lead to cancer?
apoptosis does not occur
loss of tumor suppressor genes - the cell cycle can run on unchecked while abnormal cells are produced
overactive oncogens promote tumor growth
what are oncogens?
tumor promoting genes found secondary to mutation
what is an example of a tumor suppressor gene and the effect if it is altered?
P53 checkpoint gene - halts mitosis if DNA is damaged, if altered cell cycle will not be stopped and altered DNA will continue
define neoplasia
new growth - abnormal
define tumor
a swelling (inferred to be neoplasia)
define benign
neoplasia that forms a solid cohesive tumor and does not metastasise
define malignant
neoplasm with the capacity for local invasion and metastasis
define cancer
malignant tumor
define metastasis
development of secondary tumor remote from the primary tumor
what are the 2 features used to describe tumors?
tissue of origin
status (benign or malignant)
what are the 3 main tissues of origin for tumors?
epithelial cell
mesenchymal cell
round cell
what is a malignant tumor of epithelial tissue known as?
carcinoma
what is a malignant tumor of the mesenchymal tissue known as?
sarcoma
what is malignant cancer of the lymphocytes known as?
lymphoma
what is malignant cancer of the mast cells known as?
mast cell tumor
what is the suffix used in benign tumors?
—oma
what are the important clinical features of a cancer?
effect on the host
response to treatment
what is the response of a cancer to treatment a reflection of?
tumor growth
tumor grade
tumor behaviour
what are the main areas of tumor behaviour assessed?
local behaviour
metastatic potential
paraneoplastic effects
do tumors grow at a steady rate?
no - growth kinetics vary with time
when does most of the tumor growth occur?
before detection
what is the effect of tumor growth occurring mostly when undetected?
tumor can be quite advanced before it is detected
what can a tumor be detected by palpation or radiography?
once 1cm in diameter
0.5-1g in weight
made of ~10^9 cells
what is the growth fraction of a tumor?
the proportion of actively dividing cells within the tumor
what is time for tumor to double in size a reflection of?
growth fraction of the tumor
what happens to tumor doubling time as the tumor grows?
tends to lengthen
what are tumor growth characteristics described in terms of?
tumor doubling time
when is the tumor most susceptible to treatment?
during the exponential growth phase when the tumor is usually undetectable
what happens to the tumors susceptibility to treatment as growth slows and they become detectable?
less susceptible to radiation or chemo than healthy gut and bone marrow
what does the response of a tumor to chemo and radiotherapy depend on?
growth fraction of the tumor as rapidly dividing cells are susceptable
once tumors are detectable what has happened to the growth fraction?
it is reaching plateu
what tumor is the exception when it comes to the relationship between tumor size and growth fraction?
lymphoma - remains susceptible to chemo and radiotherapy as still grows rapidly even when tumor burden is high
what effect will tumor treatment have on the body once tumor is palpable?
proportion of dividing cells in tumor is often less than that in normal, rapidly dividing body tissues such as intestinal epithelium and bone marrow
treatments to tackle rapidly dividing cells are likely to be toxic to the body
are tumors formed of homogenous cells?
no - mass of heterogenous cells some of which are rapidly dividing and others that are slower
do cancer cells remain the same as they grow?
no - modify their properties mainly by small, sequential mutations
what can be used to predict the likely behaviour of a tumor?
a number of cytological and histological features
what does the grade of a tumor depend on?
mitotic rate (speed of division) cellular and nuclear characteristics and how different they are from normal
what is tumor grading important for?
prognosis
what does benign and malignant tumor behaviour differ according to?
rate of growth manner of growth effect on adjacent tissues surgery metastasis effect on host paraneoplastic effects
what is the general behaviour of benign tumors?
slow growth expansive, well defined boundaries minimal effect on adjacent tissues surgery is potentially curative metastasis does not occur effect on the host is often minimal but can be life-threatening if it bleeds or is in vital organ paraneoplastic effects are possible
what is the general behaviour of malignant tumors?
often rapid, perpetual growth
invasive, poorly defined boundaries
invasive, often serious effect on adjacent tissues
surgery only curative if complete resection with 2-3 cm margins and no metastasis
metastasis occurs
effect on the host is often life-threatening
paraneoplastic effects are possible
how do malignant tumors grow?
by local invasion and may extend microscopically into surrounding tissues which cannot be appreciated by eye (lab analysis essential)
what are the physical clues of local tumor invasion?
diffuse, indistinct boundaries
fixation of the tumor in one or more planes
thickening of adjacent tissues due to invasion
spontaneous bleeding due to angiogenesis
what is a feature of malignancy?
the ability to spread to distant tissues
how may metastasis occur?
via the blood producing secondary tumors in any body organ
via lymphatics, first to local and regional lymph nodes
transcoelomic across the pleural or peritoneal space
iatrogenic during FNA
what is the most common site for development of haematogenous secondary tumors?
lungs
where are primary lung tumors seen?
more rarely (seen in cats) but will metastasise to peripheral sites (e.g. digit)
what are other common sites of metastasis?
those with high blood flow e.g. liver, spleen, kidneys, bone and CNS
what is the largest malignant tumor usually?
the primary
what are paraneoplastic syndromes?
signs arising from the indirect effect of tumors production and release of biologically active substances
what may be the first indication of neoplastic disease?
paraneoplastic syndromes
how dangerous can PNS be to the patient?
may be life threatening before the cancer directly kills the patient
what are the main haematologic PNS seen?
anaemia
throbocytopenia
leukopenia
what element of PNS causes anaemia?
reduction in available iron so fewer RBC
what is one of the most common haematologic PNS in dogs and cats?
anaemia
what are the signs of anaemia?
weakness
lethargy
tachypnoea
what are the signs of thrombocytopenia?
bleeding
what are the signs of leukopenia?
susceptibility to infection
what is hyperviscosity syndrome?
increased blood cell numbers leading to sludging blood and poor circulation
what can cause hyperviscosity syndrome?
leukaemia
primary polycythaemia
secretion of excess erythropoetin by certain tumors casing secondary polycythaemia
excess gamma globulins secreted by certain tumors
what provides the effects of hyperviscosity syndrome?
excess protein
excess RBC
what are the clinical signs of hypervisocity syndrome?
lethargy tremors thromboembolism disorientation episodic weakness bleeding ataxia seizures retinal haemorrhage and detachment
what tumors often cause hyperhistaminaemia?
mast cell tumors
in what animals are mast cell tumors common?
dogs
how can hyperhistaminaemia be caused?
mast cell tumors releasing histamine and vasoactive amines especially when handled for FNA or surgery
what effects can be caused by hyperhistaminaemia?
local
systemic
what are the local effects of hyperhistaminaemia?
oedematous swelling with erythema and pruritus
tendancy for localised bleeding due to heparin release
delayed wound healing or dehiscence after surgery due to released proteases which cause breakdown of healthy tissues
what are the systemic effects of hyperhistaminaemia?
anaphylactic shock due to massive sudden release of histamine leading to vasodilation and hypotension
gastroduodenal ulcer due to histamine release
how can anaphylactic shock due to hyperhistaminaemia be prevented during mast cell tumor surgery?
premedication with antihistamine prior to surgical manipulation
how can gastroduodenal ulcer due to hyperhistaminaemia be prevented during mast cell tumor surgery?
treat with H2 antagonist or proton pump inhibitor
what are cancer related immune mediated reactions caused by?
cross reactivity between cancer cells and healthy cells
what are the main immune mediated PNS?
IMHA and or thrombocytopenia immune mediated nephropathy myasthenia gravis feline paraneoplastic alopecia pemphigus foliaceous
what can immune mediated neuropathies be caused by?
insulinoma
what is myasthenia gravis seen secondary to?
thymoma
when is feline paraneoplastic alopecia, ‘shiny skin disease’, seen?
secondary to pancreatic and biliary carcinoma
what is pemphigus foliaceous (skin disease) secondary to?
thymoma
what tumor types can release hormones or hormone-like substances that have PNS effects?
non-endocrine as well as endocrine
what are the 2 main endocrine related PNS?
hypercalcaemia
hypoglycaemia
what is the most common endocrine related PNS in dogs?
hypercalcaemia
is hypercalcaemia as PNS seen often in cats?
no
how is hypercalcaemia caused as a paraneoplastic syndrome?
tumors release a parathormone-like substance called parathyroid hormone related peptide (PTHrp) which increases total and ionised calcium concentrations
what cancer is hypercalcaemia as a PNS most commonly seen with?
lymphoma
(also anal sac adenocarcinoma, multiple myloma and carcinoma/sarcoma with metastasis
what are the clinical signs of hypercalcaemia?
PUPD anorexia vomiting lethargy depression muscular weakness bradycardia
how does hypocalcaemia lead to PUPD?
antagonises ADH and renal damage
how does hypocalcaemia lead to anorexia?
nausea
how does hypocalcaemia lead to vomiting?
GI effects
how does hypocalcaemia lead to lethargy and depression?
neurological depression
how does hypocalcaemia lead to muscular weakness?
neuromuscular depression
how does hypocalcaemia lead to bradycardia?
cardiovascular effects
what effects of hypercalcaemia are the most importance?
renal
what do the renal effects of hypercalcaemia cause?
dehydration which is worsened by vomiting
renal failure
how is hypoglycaemia caused as a PNS?
pancreatic insulinoma produces insulin
tumors that excessively consume glucose
release of insulin like factor which has the same effect as insulin and causes hypoglycaemia
what tumors lead to excessive consumption of glucose?
hepatoma
hepatocellular carcinoma
large intra-abdominal mass
chronic lymphocytic leukaemia
what are the main tumors which produce insulin like factor?
leiomyoma
GI stromal tumor
(arise from smooth muscle)
what is cancer cachexia?
weight loss
muscle loss
fat loss
what is cancer cachexia caused by?
abnormal metabolism leading to enhanced catabolism
lots of energy used
reduced food intake due to inappetance
how is fever seen as a PNS?
pyrogens cytokines (e.g. IL-1 and IL-6) are produced by the tumor
what is critical in cancer management?
evaluation of type or spread of tumor
what must be done before any cancer treatment is given?
accurate diagnosis of tumor type and grade
what are the aims of cancer investigations?
make a histological / cytological analysis of type and grade
determine the extent of the disease (stage)
investigate and treat any tumor related or concurrent complications
what is the investigation and treatment of tumor related and concurrent complications an assessment of?
the patients ability to tolerate therapy
overall prognosis
what is involved in obtaining a diagnosis?
history physical exam lab tests (biochem and haem) imaging of suspected area biopsy
when can an accurate diagnosis of caner only be made?
microscopic examination of representative tissues or cells
what should be done with all excised masse?
submitted for histology
or
fixed and stored in case the owners change their mind or the patient deteriorates
what does cytology analyse?
the cells
what are the possible methods of gaining samples for cytology?
touch / impression preparations
FNA
analysis of body fluids / effusions
is prep needed for an FNA?
no
what tube is used to store body fluid or effusions?
EDTA
what indications about the tumor can be made by cytology?
nature of tumor
cytological features
what are the disadvantages to assessing a tumor with cytology?
may not provide a definitive diagnosis
false negatives may occur
difficult to differentiate inflammation from neoplasia
when is it especially difficult to differentiate tumor from neoplasia?
if tumor outgrows blood supply or is necrotic
how can histological examination of the tumor be made?
surgical
needle (Tru-Cut)
punch biopsy
what is the most accurate method of tumor diagnosis?
large biopsy sample