Neoplasia - lung, CRC, cervical Flashcards
1
Q
define neoplasm
A
formation of new tissue
2
Q
benign nomenclature
A
finish in oma
eg: adenoma
3
Q
malignant nomenclature
A
finshes in sarcoma
eg: fibrosarcoma, osteo sarcoma
4
Q
emsenchymal tissue (fibrous) benign and malignant name
A
fibroma
fibrosarcoma
5
Q
smooth muscle benign and malignant names
A
leiomyoma
leiomyosarcoma
6
Q
bone benign and malignant names
A
osteoma
osteosarcoma
7
Q
epithelial (glandular) benign and malignant names
A
adenoma
carcinoma (adenocarcinoma)
90% of cancers
8
Q
benign neoplasms - characteristics
A
well differentiated
encapsulated
low mitotic rate (slow division)
9
Q
define mitotic rate
A
number of cells dividing (spindles)
10
Q
=malignant neoplasms - characteristics
A
abnormal proliferation (high mitotic rate)
no differentiation (diff to adjacent tissues)
abnormal nuclei (high N:C ratio)
for tumours
undergo metastasis AND angiogenesis
11
Q
metasitasis overview - 2steps
A
- in situ - cancer cells are still above the basement membrane
- invasive - move through BM and degrade ECM to move to adjacent vessels to migrate
12
Q
pathways of metastasis
A
- haematogenous - blood flow usually to liver and lungs
- lymphatic system
- direct (organ to organ)
- perineurally - via neural sheath (head and neck cancer)
13
Q
metastasis definition
A
movement from primary to secondary site
secondary tumour is named after origin
eg: breast cancer metastises to lungs its called metastatic breast cancer
14
Q
define pleomorphism
A
variability in shape and size
15
Q
anaplasia definition
A
lack of differentiation
16
Q
dysplasia
A
disordered growth
pleomorphic
hyperchromatic nuclei
17
Q
metaplasia definition
A
change of cell type
18
Q
progression of cancer sequence
A
normal -> metaplasia -> dysplasia
19
Q
grade classification
A
T tumour size
N nodes involved
M metastasis
20
Q
stage classification
A
more useful when there is metastasis/high grade
uses the stage
21
Q
requirements of malignant cells (8)
A
self sufficient growth signals
insensitive to growth inhibition signals
evade apoptosis
achieve limitless replication potential
sustain angiogenesis
ability to invade and metastasise
reprogram their energy metabolism
avoid detection + destruction by immune cells
22
Q
normal cell division - cell cycle
A
by mitosis to replace damaged/dead cells
RB, P53 (tumour supressor genes) monitors cell cycle and cause repair or apoptosis.
growth factor tyrosine kinase - binds to receptor causing signal transduction, then mvmt into nucleus and proliferation occurs
23
Q
cell types of cell cycle that are dysregulated in cancer + its effects
A
DNA repair genes = no repair
proto oncogenes = overstimulation of proliferation
tumour supressor genes = loss of breaking proliferation
24
Q
roles of RB and p53
A
breaks of proliferation
25
roles of proto oncognese
proliferation
26
accumulated development of cancer
start with normal epithelium
several mutations occur causing dysplasia (low then high grade) = carcinoma in situ
- more mutations cause metastasis past BM = invasive carcinoma
27
carcinogens defintion, examples
cause DNA mutations
chemicals (asbestos, coal, tobacco smoke, sawdust)
UV rays, x rays, cathode rays
ionisation radiation
oncogenic viruses
28
proto-oncogene -> oncogene
proto-oncogene to oncogene ahppens from mutations that cause hyper active gene product, increased trasncription, gene amplification.
translocation of a gene from one chromosome to another = generate a protein
29
BCR - ABL proto-oncogene example
normally: ABL on on echromosome and BCR on another
mutation: after translation, both genes on sam chromosome
causes: production of a functional protein that drives leukemia
30
BRCA1/2
usually a tumour supressor and usually repair.
mutation = increased risk of breast, ovarian, prostate, pancreatic and colon cancer
31
P53 normal function VS mutation
normally: tumour supressor gene, repair and apoptosis
mutation = damaged cells proliferate instead of apoptosis
32
P53 normal function VS mutation
normally: tumour supressor gene, repair and apoptosis
mutation = damaged cells proliferate instead of apoptosis
33
paraneoplastic syndromes
accumulation of symptoms that can occur with tumours but arent directly associated with cancer mass effect/invasion
rare disorders triggered by abnormal immune response to cancerous tumour
T cells attack normal cells in the nervous system by mistake = neuro symptoms
middle aged -> older ppl
in with lung, ovarian, lymphatic, breast cancers
eg: cushings syndrome from ACTH mutation
34
normal skin - basal cells
some basal cells are progenitor cells that will divide into 1 progenitor and one daughter cells that ill migrate up and differentiate.
basal cell become keratinocytes to make keratin
Melanocytes are on BM and produce melanin
35
squamous cell carcinoma
UV light exposure
cells on top - terminally differentiated
older ppl
just proliferation problem (not a big issue)
36
basal cell carcinoma
UV light causes transformation on basal cells
more aggressive because they are progenitor cells so will replicate much faster
can cause harm/mortality
37
melanocytes -> melanoma
melanocytes arise on BM
melanin protects from light effects
UV light causes damage to DNA
damage to melanocytes = dysplastic neavi development
some are harmless but others are associated with the development of melanoma
38
melanocytic tumour genetic predisposition
ppl can be born with p16 gene mutation (p16 regulates cell cycle)
autosomal dominant mutation
39
UV damage to proto-oncogenes + tumour supressors
BRAF
p53
NRAS
40
define proto-oncogene
a mutated growth factor which drives cellular proliferation
41
melanoma - radial growth phase (RGP)
first stages
in situ
no potential to for tumour and metastasis
horizontal growth only - contained in BM
can take it out if early recognition
42
mole and melanoma ABCDE
asymmetry
border irregularity
colour variation
diameter (>6mm)
evolution/elevation - vertical growth
43
multistage carcinogenesis of melanocytes - sequence
melanocyte gets mutated = increased proliferation to form a nevus
nevus gets mutated = dysplastic nevus
more mutation = RGP melanoma
more mutation = VGP melanoma (invasive)
44
oncogenic viruses - method, examples, causes
they integrate their DNA into our genome
can reain latent there for year
HPV = cervical cancer
can live in us and not cause anything until we get some immunosuppression
45
normal cervical epithelium
progenitor cells also sit on BM and divide into 1 cell that differentiates and migrates up
46
Cervical cancer - dysplasia cause and features
virus gets in and down to the progenitor cells and into their nucleus to insert its genome.
high N:C ratio, increases with CIN levels
progression = cervical intraepithelial neoplasia (CIN), 1, 2, 3
all still within epithelial layer - hasn't metastasis hence = in situ (can be in situ for many years or very fast)
47
koilocytes
squamous epithelial cells with a different appearance from HPV infection
2-3x larger nucleus
hyperchromatic
halo around nucleus
48
HPV - human papilloma virus, process
diff strands:
HPV-16, 18 most common
viral genes:
- E6 binds our p53 (no apoptosis)
- E7 interferes with p53 transcription + binds to RB (no limiting cell growth) + inactivates p21
49
gardasil
vaccine targets HPV
not live virus
elicits B and T cell response : develops antibodies against HP 6, 11, 16, 18
50
SIL
cytology version of CIN
= squamous intraepithelial lesion
low grade of high grade SIL
51
colorectal cancer - risk factors
age
obesity
T2DM
smoking
alcohol
dietlack of PA
poyposis syndrome
Ulcerative colitis or Crohns disease
family hx
52
colorectal cancer - signs and symptoms
intial:
- iron deficiency aneamia (Rsided)
- changes in bowel habit, bleeding, abnominal discomfort (L sided)
later
- abdomnial pain
- weight loss
- abdomnial mass
53
growth patterns of cancer in hollow organ
exophytic, ulcerative and difusely infiltrative
54
colorectal cancer - pathogenesis
adenoma-carcinoma sequence
start with a polyp (adenoma), accumulation of mutations = carcinoma
in hereditary cases, genetic changes are there at birth
55
adenoma def
benign neoplasm
56
polyp def
adenoma
can be sessile and serrated OR pedunculated (on a stork)
57
colorectal cancer - aberrant crypt formation (ACF)
clusters of abnormal tube-like glands in colon and rectum lining
forms pre polyps - earlier changes of cancer that cna be seen
apoptosis resistant
58
mismatch repair
can have a mutation of genes that usually repair mismatches and insertions or deletions.
when they are mutated, repair cant occur
59
benign to malignant - APC beta pathway
mostly in L sided CRC
60
benign to malignant - mismatch repair pathway
mostly in R sided CRC
61
colorectal cancer metastasis
heamatogenously - portal vein to liver
lymphatic system
direct contact
called secondary metastatic colon cancer
62
lung epithelia
changes:
bronchus - ciliated Pseudostratified columnar
bronchioles - cilliated simple cuboidal
alveolus - squamous
63
lung cancer - risk factors
heavy smoking, recent stopped smoking
females
second hand smoke
industrial exposures
scarring from other disease
radiations
64
lung cancer def + patterns of growth
invasive malignant neoplasm arriving from epithelia of lungs ( bronchi, bronchioles, alveoli)
exophytic, ulcerative and infiltrative
65
bronchogenic carcinomas
make up most of 1˚lung cancers
adenocarcinoma and squamous cell carcinoma, large cell carcinoma (together = non small cell lung carcinoma)
small cell carcinoma
66
adenocarcinoma
malignant epithelial tumour with glandular differentiation or mucin production
can be preceeded by precursor lesion: atypical adenomatous hyperplasia.
67
atypical adenomatous hyperplasia
precursor for adenocarcinoma
proliferative lung lesion from alveolar epithelium associated with invasive adenocarcinoma
68
squamous cell carcinoma
proceeded by changes in airways from smoking (cillia, mucous cells..)
starts at the epithelial cells lining the bronchi that has undergone squamous metaplasia from carcinogen. squamous metaplasia progresses to malignant epithelial tumour with keratinisation
69
lung cancer sequence
normal -> (carcinogen) -> metaplasia -> dysplasia
70
invasive squamous cell carcinoma (SCC) fts
forms keratin pearls + intercellular bridges between keratin layers
eosinophilic cytoplasm (very pink)
pleomorphic nuclei
hyper chromatic nuclei
tumour necrosis
71
small cell carcinoma (oat cell) - fts, causes, effects
hyper-chromatic nuclei
pleomorphic nuclein
hgih N:C ratio
high mitotic rate
small undifferentiated cells
cell of origin = neuroendocrine progenitor cell of bronchial epithelium (not epithelial cell) = fast spread along bronhi
mutations: p53, RB
narrowing of airways
72
molecular pathogenesis
common mutations in oncogenesis lung cancer: KRAS, c-MET, EGFR, c=KIT
common mutation in tumour suppressor genes: p53, RB1, p16
73
lung cancer - clinical presentations
cough - w blood sometimes
SOB
post obstructive pneumonia
pain from pleural/chest wall invasion by tumours
weight loss
tracheal/oesophageal obstruction
Hoarseness
74
secondary lung cancer
goes to :
liver, adrenals, bone, skin
will have lung tissue markers
75
metastatic cancers to lungs
melanoma, prostate, carcinoma (kidney, breast, bowel), sarcoma
76
malignant pleural mesothelioma (MPM)
exposure to asbestos where fibres cause an incurable cancer
77
asbestos exposure - consequences, where from
contributes to lung cancer
asbestosis
mesothelioma
mining, construction, demolition, boiler makers
exposure and smoking increases risk of lung cancer more than individual risk factors together
