cancer Flashcards
most common cancer
male: colorectal, lung, prostate
female: breast, colorectal
neoplasia
abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissue and persists in the same excessive manner after cessation of the stimuli that evoked the change
types of neoplasm
uncontrolled cell growth -> high rate of cell growth exceed cell death -> aggressive cancer
decreased rate of cell death -> indolent cancer
dysplasia
abnormal change in size, shape and/or organisation of cells
metaplasia
change in cell type
in situ cancer
neoplasm is malignant but has no invaded pass the basement membrane
invasive cancer
spread beyond basement membrane -> invasive and metastatic
relationship between dysplasia and malignant neoplasia
dysplasia -> malignant neoplasia (cancer)
dysplasia is precursor to cancer but not cancer
in dysplasia, once tumour suppressor genes and proto-oncogenes are affected, can lose regulation of cell cycle and become malignant
benign neoplasia
dysregulated growth
- cells highly resemble original cell type and is well circumscribed
- does not become malignant neoplasia
benign vs malignant neoplasia
gross features
- circumscription
B: well-circumscribed mass
M: poorly-circumscribed mass - necrosis/haemorrhage
B: no
M: yes
microscopic features
- mitotic figures
B: no/few mitotic figures
M: mitotic figures present
- N/C ratio
B: normal N/C ratio
M: high N/C ratio
infiltration
B: no infiltration
M: infiltrative (into surrounding tissue)
genetic features
- DNA content
B: normal
M: increased DNA content (additional chromosomes)
- karotype
B: normal
M: anueploidy, polyploidy
histological appearance of cancer cells
- hyperchromasia
- pleomorphism (diff shapes and sizes of cancer cells)
- high mitotic index
- high nuclear: cytoplasmic ratio
- clumped chromatin irregularly distributed
- enlarged/abnormally shaped/ multiple nucleoli
- infiltrative growth (irregular outline)
- metastasis
- anaplasia (dont resemble tissue of orgin)
- poorly formed/leaky blood vessels
Hello peter’s mom nancy can Nicole impress me again lol
“All oma’s are _______ other than ___(3)___”
“Sarcoma” ?
“Carcinoma”?
“Adenoma”?
“Adenocarcinoma”?
“Teratoma”?
“All oma’s are benign other than LYMPHOMA, MELANOMA, GLIOMA ”
“Sarcoma” - arise from connective tissue (mesenchymal)
“Carcinoma” - arise from epithelial tissue/ endothelial lining of organs (ectoderm/endoderm)
“Adenoma”- glandular origin Glandular (what tells you it’s an adenoma, 1)
“Adenocarcinoma” Glandular AND epithelial origins
“Teratoma”- totipotent germ cells
identifying features of carcinoma
carcinoma: keratinisation, keratin pearls, bridging, cell shape
adenoma: intracellular mucin
leiomyo-
papillo-
rhabdomyo-
blastomas
Leiomyo- smooth muscle (ie esopahgus, uterus)
Papillo- papillary appearance
Rhabdomyo- striated muscle (skeletal or cardiac)
Blastomas- “blast” cells (progenitor cells)
mutations causing cancer
for cancer, need to have mutation in both TSG and PO
- tumour suppressor gene -> loss of function mutation
- act recessively (need both alleles to be mutated)
eg FAP, Li Fraumeni Syndrome, BRCA 1/2 - proto-oncogene -> gain in function mutation
- act dominantly
eg MYC (Burkitt’s Lyphoma), Philadelphia Chromosome, HHV8 - mismatch repair genes
- mutation in MMR genes result in inability to repair mutations in TSG and PO
eg HNPCC
FAP
familial adenomatous polyposis
- loss of function mutation in both alleles of tumour suppressor gene (autosomal dominant)
- 100% risk of colon cancer before 50 years old
- cause polyps in colon with varying degrees of dysplasia
- some will develop into cancer since dysplasia -> malignant neoplasia
Li Fraumeni Syndrome
germline mutation of 1 allele of p53 tumour suppressor gene in all cells
- only need 1 more mutation in the other allele of the p53 gene in any cell to cause cancer
(predisposition to all cancers)
BRCA 1/2
breast cancer 1/2
- mutation in this tumour suppressor gene increases likelihood of getting breast, ovarian or other types of cancer
MYC
MYC is the main transcription factor that promotes growth (proto-oncogene)
- gain in function mutation of MYC causes Burkitt’s lymphoma with a starry sky appearance (B cell cancer)
- many B cells with a lot of cell debris that are consumed by macrophages so B cells punctuated by macrophages look like a starry sky
Philadelphia Chromosome
translocation between chromosome 9 and 22 to form BCR/ABL gene on chromosome 22
- BCR/ABL gene codes for constitutively active receptor tyrosine kinase which upregulates growth and mitosis (even in absence of growth factor)
- cause Chronic Myeloid Leukemia
HHV8 (Kaposi’s sarcoma associated virus)
proto-oncogene associated with Kaposi’s sarcoma
- herpes virus contains gene that codes for oncoprotein so when transcribed and translated by host cell, it forms more oncoproteins which stimulate the cell to divide uncontrollably
HNPCC
hereditary non-polyposis colorectal cancer
- caused by germline mutation of 1 MMR gene (recessive allele)
FAP vs HNPCC
FAP
- mutation in both copies of APC tumour suppressor gene -> have many adenomatous polyps in colon -> 100% risk of cancer
- cancer can arise from anywhere in colon
HNPCC
- 1 mutated allele of MMR gene passed down so need mutation in other allele of MMR gene to increase susceptibility to mutations in TSG and protooncogene causing cancer
- do not have polyps that could turn cancerous
- cancer arises from colon wall spontaneously and directly
- more commonly associated with rught sided colorectal cancer and high possibility of developing other colon cancers
epithelial-mesenchymal transition
mostly for carcinomas (sarcoma go through analogous process)
1. inactivation of E-cadherin causes loss of contact inhibition and tumour cells gain mobility without undergoing apoptosis
2. basement membrane breached
3. tumour cells transverse the interstitial connective tissue by secreting proteolytic enzymes like matrix metalloproteinases
4. gain access to circulation by penetrating the vascular basement membrane
5. transit through vasculature
6. extravasate from vessel
7. angiogenesis
metastasis
spread of primary cancers to distal sites
primary and secondary lesions
primary lesion: at site of origin, may or may not have metastasised (cannot tell by just look at primary lesion)
secondary lesion: at distal site, indicate metastasis and may be singular or multiple
(if tumour cells do not resemble neighbouring cells, likely to have come from distal site indicating metastasis
metastasis: patterns of spread
- hematogenous spread
- carcinomas
- spread through veins (thinner and more penetrable walls) - lymphatic spread
- sarcomas
- for sarcomas in ECM, tumour cells that lose contact inhibition can be carried by interstitial fluid in connective tissue and drained into lymphatic vessels and lymph nodes
- interstitial fluid -> lymphatic vessels > lymph nodes -> venous system - spread through body cavities
- common in ovarian or GIT cancer
ovarian: cancer cells enter through space between ovary and fallopian tube
GIT: tumour cells in GIT can burst through walls of organs and enter peritoneal cavity
- tumour can seed across large space and gain access to more body components (bad prognosis)
why are some organs more prone to metastasis than others
- lymph nodes
- tunour cells from both lympathic spread and hematogenous spread will pass through lymph nodes - lungs, liver and bone
lungs: metastasis via caval venous system
- metastases will lodge in first organ it reaches with narrow capillaries
- in lungs, walls are thinner and narrower so easier for cancer cells to get lodged and squeeze out of capillaries
liver: metastasis by portal venous system
- cancer of organs in GIT (+spleen and pancreas likely to metastise liver first
bone: highly vascularised and tumour cells can spread through blood and bone have favourable microenvironment with a lot of growth factors and nutrients
- vertebral column
- cancers near vertebral column embolise through paravertebral plexus (tight group of blood vessels near spine) and have vertebra metastasis
2 cancers most likely to spread to vertebral column -> thyroid, prostatic
paraneoplastic syndrome
system complexes not attributable
- local or distant spread of tumour
- hormonal effects indigenous to tissue of origin
eg cushing’s syndrome in small cell lung carcinoma
hypercalcemia in squamous cell lung carcinoma
myasthenia gravis in thymoma (cancer of thymus)
why is grading and staging useful?
determines prognosis and therapy options
grading
how differentiated? (how much the cancer cell resembles the original tissue)
- well differentiated/ moderately differentiated/poorly differentiated (refers to degree of malignancy)
- based on arrangement of cell and cellular features like the
staging
How widespread?
TNM criteria: tumour, node, metastasis
tumour -> extent of invasion at primary site
node -> number of lymph nodes involved
metastasis -> present of metastasis at distant sites (M0: no metastasis and M1: presence of metastasis
tumour markers
used as a screening methods for the detection of cancer and monitoring the amount of of residual tumour or tumour recurrence post therapy
eg
hormone -> Human chorionic gonadotropin
oncofetal antigens -> alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA)
specific protein -> prostate specific antigen (PSA)
glycoproteins-> CA-125 for ovarian cancer
local effects of tumour
palpable mass
pain
haemorrhage and ulceration
obstruction
neuropathies
describe the gross appearance of a malignant tumour
Is POORLY CIRCUMSCRIBED,
NONENCAPSULATED
With a POORLY DEFINED CLEAVAGE PLANE
With SUBSTANTIAL INFILTRATION
