tumour pathology Flashcards
what is a tumour (neoplasm)?
abnormal growing mass of tissue, the growth of which is uncoordinated with normal tissue
what will happen to the tumour growth if any stimulus which may have caused the tumour to form is removed?
it will continue
is tumour growth irreversible?
true
what two types of tumour are there?
benign
malignant
what separates malignant (cancer) tumours from benign ones?
malignant tumours have the ability to invade adjacent tissue and to metastasise to other sites within the body
what are the 3 most common cancers for males?
prostate
lung
colon
what are the 3 most common cancers for females?
breast
lung
colon
what are the 3 most common overall cancers?
breast
lung
colon
how are tumours classified?
based on tissue of origin
benign vs malignant
what are the names for benign and malignant glandular tumours?
benign: adenoma
malignant: adenocarcinoma
what are the names for benign and malignant tumours of squamous epithelium?
benign: squamous papilloma
malignant: squamous carcinoma
what are the names for benign and malignant tumours of the bone?
benign: osteoma
malignant: osteosarcoma
what are the names for benign and malignant tumours affecting fat tissue?
benign: lipoma
malignant: lipo-sarcoma
what are the names for benign and malignant tumours affecting fibrous tissue?
benign: fibroma
malignant: fibro-sarcoma
what is the name given to malignant cancer of the blood?
leukaemia
what is the name given to malignant cancer of the lymphoid tissue?
lymphoma
what are the names of tumours of the central and peripheral nervous system
CNS: astrocytoma
PNS: schwannoma
what is the difference between ovarian and testicular teratomas? (germ cell tumours)
ovarian usually benign, testicular usually malignant
what are the features of benign tumours?
non invasive growth pattern usually encapsulated no evidence of invasion no metastases cells similar to normal cells cells function similarly to normal tissues well differentiated
what are the features of malignant tumours?
invasive growth pattern no capsule or capsule breached by tumour cells cells are abnormal poor differentiation loss of normal function evidence of spread of cancer
what are some properties of cancer cells?
altered genetics
altered cellular function
abnormal morphology
cells are capable of independent growth
what are some examples of the altered genetics of cancer cells?
loss of tumour suppressor genes
increased function of oncogenes
what are the examples of altered cellular function of cancer cells?
production of tumour related proteins
loss of cell-cell adhesion
altered cell-matrix adhesion
what are some biomarkers indicative of cancer cells?
onco-fetal proteins
oncogene products
growth factors and receptors
what is alpha-fetoprotein indicative of?
teratoma of testis
hepatocellular carcinoma
what is carcino-embryonic antigen (CEA) indicative of?
colon cancer
what is oestrogen receptor indicative of?
breast cancer
what is her2 indicative of?
breast cancer
what is prostate specific antigen indicative of?
prostate cancer
what is the histological appearance of cancer cells?
cellular and nuclear pleomorphism (marked variation in size and shape)
mitoses are present and often abnormal
what are the two processes relating to cell growth and cell death that occur in tumour growth?
angiogenesis
apoptosis
what is the pathology of tumour angiogenesis?
new blood vessel formation by tumours
required to sustain tumour growth
new blood vessels provide a route for release of tumour cells into circulation
the higher the number of blood vessels in a tumour the poorer the prognosis
what is apoptosis and what is its role in tumour pathology?
programmed single cell death
regulates tumour growth
involved in the reponse to chemo/radiotherapy
what is the major clinical problem associated with cancer?
formation of metastatic tumours
what are some modes of cancer spreading?
local spread
lymphatic spread
blood spread
trans-coelomic spread
how would a tumour manage to spread into the blood/lymphatic system?
invasion into the connective tissue is followed by invasion into the lymphatic system/bloodstream
describe the process of tumour metastasis via lymphatics
tumour cells adhere to lymph vessels
tumours invade lymphatic system and then invade lymph nodes
formation of metastasis in lymph node
clinical evidence of metastasis
describe the process of tumour metastasis via blood?
adherence of tumour cells to blood vessels, followed by invasion into blood vessels
invasion of tumour cells into tissue
formation of metastasis
clinical evidence of metastasis
what happens in trans-coelomic spread?
spread of tumour cells across body cavities
what are some example of tumours that show trans-coelomic spread?
lung
stomach
colon
ovary
what are some common sites of metastasis?
liver lung brain bone (axial skeleton) adrenal gland
what are some uncommon sites of metastasis?
spleen
kidney
skeletal muscle
heart
where do tumours of breast tissue commonly metastasis do?
bone and lung
where do tumours of the prostate commonly metastasis to?
bone
where do tumours of the colon commonly metastasise to?
liver
what are some local effects of benign tumours?
pressure and obstruction
what are some local effects of malignant tumours?
pressure obstruction tissue destruction bleeding (anaemia, haemorrhage) pain adverse effects of treatment
why can malignant tumours cause pain?
pressure on nerves
perineural infiltration
bone pain from pathological fractures
what are systemic effects of malignant tumours?
secretion of hormones ( can be normal or abnormal)
weight loss- cachexia
paraneoplastic syndromes
effects of treatments
what are paraneoplastic syndromes?
a syndrome that is the consequence of cancer in the body but is not due to the local presence of cancer cells (such as inappropriate hormone secretion)
what is “normal” hormone production from tumours?
when hormones are produced by tumours of endocrine organs (however there is abnormal control of hormone production/secretion)
what is abnormal/inappropriate hormone production from tumours?
when hormones are produced by tumours of an organ that does not normally produce hormones (such as ACTH being produced in lung cancer)
what is dysplasia?
pre malignant change which is the earliest stage that the process of malignancy can be visualised
what are some features of dysplasia?
it is identified in the epithelium
no invasion
can progress to cancer
disorganisation of cells
what would you see at a cellular level in dysplasia?
increased nuclear size
increased mitotic activity
abnormal mitoses
what is the cell cycle?
time interval between mitotic divisions
what are some external factors that control the cell cycle?
hormones, growth factors, cytokines, stroma
what are some intrinsic factors that control the cell cycle?
critical checkpoints- restriction point (R)
what is the significance of the restriction point?
prior to the restriction point progress through G1 depends on external stimuli
after the restriction point the cell cycle progresses autonomously
what are the phases of the cell cycle?
quiescent - G0
interphase - G1, S, G2
cell division - mitosis (M)
when would the cell cycle be arrested in G1?
if the cell size is inadequate
if the nutrient supply is inadequate
if an essential external stimulus is lacking
if DNA damage is detected
when would the cell cycle be arrested in G2?
if the cell size is inadequate
if DNA damage is detected
when would the cell cycle be arrested in S?
if the DNA is not replicated
when would the cell cycle be arrested in M phase?
chromosome mis-alignment
what are the checkpoints in the cell cycle composed of?
system of cyclically active and inactive enzymes
catalytic sub unit activated by a regulatory sub unit
what are catalytic subunits of checkpoints called?
cyclin dependent kinases
what are the regulatory units of checkpoints called?
cyclins
what is the name given to the active enzyme complex at a cell cycle checkpoint?
CDK/cyclin complex
what do active CDK/cyclin complexes do?
phosphorylate target proteins
what effect does phosphorylation of target proteins by CDK/cyclin complexes have?
activates/inactivates the substrate, substrates regulate events in the next cycle phase
what form are CDKs expressed in?
inactive form
what other group of compounds regulates CDK activity apart from cyclins?
CDK inhibitors
what family of CKIs bind to CDK 4 and 6?
INK4A
what is carcinogenesis caused by?
mutation of genetic material that upsets the normal balance between proliferation and apoptosis
mutations of what can cause a cell to lose control of proliferation?
cell division, apoptosis and DNA repair
formation of what causes cancer at chromosome sites?
adducts
what is a DNA aduct?
covalently bound product formed from when chemical carcinogens or their active metabolites react with DNA
what is the primary defect in cancer?
uncontrolled cell proliferation via cell cycle dysregulation
what are the two regulatory pathways that are frequently disrupted to cause cancer?
cyclin D-pRb-E2F pathway
p53 pathway
what is the function of the retinoblastoma gene (pRb)
to activate or inactivate the E2F transcription factor
what is the function of E2F?
potent stimulator of cell cycle entry
what is the effect of absent or inactive pRb?
releases the “brake” on the cell cycle
where are virtually all cancers dysregulated?
G1-S
what are the 4 genes that mutate to cause cancer dysregulation at G1-S?
Rb, CDK4, cyclin D p16
what is the function of p53?
maintains genomic integrity:
what is the effect of increased p53 in damaged cells?
induces cell cycle arrest at G1
facilitates DNA repair
in severe damage - p53 induced apoptosis
what is the effect of mutated p53?
no G1 arrest and no repair of damaged DNA - leads to the proliferation of genetically damaged cells and the formation of malignant neoplasms
what do Rb gene mutations favour?
cell proliferation
what mutations can mimic the effect of pRb loss?
mutational activation of cyclin D or CDK4
mutational inactivation of CDKIs
what are some genetic inherited characteristics of inherited retinoblastoma?
one defective copy inherited
somatic point mutation of the other copy
what are some genetic characteristics of sporadic retinoblastoma?
both hits occur in a single cell
what are some examples of inherited cancer syndromes?
familial retinoblastoma
familial adenomatous polyposis of colon
multiple endocrine neoplasia
what are some characteristics of familial cancers?
family clustering of cancers but individual presdisposition unclear
multifactorial inheritance
early age of onset
multiple/bilateral tumours
what are some examples of familial cancers?
some breast and ovarian cancers
