neoplasia Flashcards
(25 cards)
What are some other terms for “pre-malignant”
dysplasia (intraepithelial neoplasia)
carcinoma in situ - high end dysplasia, but not yet invasive
difference between benign neoplasm + dysplasia
benign = ordered
dysplasia = disordered, premalignant lesion, mutation
definition of progression from in-situ dysplasia to carcinoma
invasion - malignant cells breach BM to invade underlying stroma
no have access to lymphatic/vascular invasion -> metastatic spread to lymph nodes, distant organs
which are the low-risk types of HPV? and which are high risk
low risk - 6+11
- mild cause of genital warts
- CIN1
high risk - 16+18
- CIN2-3
- squamous cell carcinoma
pathogenesis of Barrett’s oesophagus
risk
chronic reflux oesophagitis -> repetitive mucosal injury by gastric acid + duodenal content (bile, pancreatic enzymes)
=> cellular proliferation
=> likely exposure to carcinogens
=> re-epithelialisation by columnar epithelium
risk: malignant transformation
histo changes in barrett’s oesophagus
- inflammation of epithelium -> proliferative response
=> hyperplasia + expansion of basal cell response - oedematous response in epithelium
- eosinophils + lymphocutes
see transition of squamous epithelium -> glandular epithelium (not gastric but its own epithelium)
describe barrett’s epithelium
glands wtih large number of goblet cells (intestinal-type)
also expresses intestinal type proteins
=> intestinal metaplasia
Barrett’s oesophagus -> neoplasia
what do you see in
- low grade dysplasia
- high grade dysplasia
- intramucosal carcinoma
- deep invasive adenocarcinoma
low grade = enlarged, atypical nuclei, bit more disorganised + hyperchromatic
high grade dysplasia = severe nuclear atypia (not yet invasive)
intramucosal = fusion of glands (has got to lamina propria - bad bc there are lymphatics there)
deep invasive - deeply invade muscle layers
what needs to be breached for progression to invasive carcinoma
cervix oesophagus colon breast prostate
all = access to lymphatics + blood = metastatic potential
cervix = BM oesophagus = BM colon = muscularis mucosae (no lymph in lamina propria) breast = myoepithelial cell layer loss prostate = basal cell layer loss
what is familial adenomatous polyposis?
autosomal dom syndrome
have APC mutation
> 100 adenomatous polyps in large bowel
=> high incidence of early onset colorectal carcinoma
histology of an adenomatous polyp
abnormal crypt architecture (tubular or viliform)
dysplasia
- crowded cells
- enlarged, hyperchromatic, pseudostrat nuclei
- goblet cell depletion
- more mitoses
no invasion beyond musc mucosae
colon - where are the lymphatics?
beyond the musc mucosae - none in lamina propria
Genetic pathways of colorectal cancer
- which are most common in sporadic CRC
chromosomal instability
(change number, copies, translocation)
= FAP
- 75-85% of sporadic`
microsatellite instability
= HNPCC/Lynch
- 15% of sporadic
CpG island methylator phenotype
~15% of sporadic
- common in prox bowel
what are common genetic changes in dysplasia-carcinoma sequence
loss of APC function
- ↓cell adhesion, ↑cell proliferation
- is early event in adenoma formation
chromosomal instability
- increased nuclear DNA content
accumulated mutations
- proto-oncogenes: K-RAS, B-RAF
- tumour suppressor - SMAD4/2, p53
- activation of telomerase
what is lynch syndrome (hereditary non-polyposis colorectal cancer)
most common familial colorectal cancer syndrome
autosomal dom
inherit mutation in DNA mismatch repair gene
early onset colorectal cancer (45yo)
also get extracolonic cancers - endometrium, renal pelvis/ureter, stomach, small bowel, ovary
what is the microsatellite instability pathway? (neoplasia)
example in colorectal
defective DNA mistmatch repair
=> get widespread mutations in DNA microsatellites
microsatellites - mono or di-nucleotide repeats
inc mutations in proto-oncogenes, tumour suppressor genes, DNA repair genes
example: loss of MLH1 protein (tumour suppressor DNA repair gene)
Sessile serrated adenoma/polyp
- where does it typically arise
- features (histo/morph)
- what mutations are comonly seen
- why might they be missed at colonoscopy
- what might they mean
proximal colon
features: mixed hyperplastic + dysplastic
- saw-tooth architecture
- more complex branching than hyperplastic polyp of crypts (prolfieration of cells)
- elongated, vesicular nuclei, prominent nuceloli
- increased atypia with dysplasia
- non invasive
freq: BRAF V600E mutation - precursor for CRC
is sessile -> hard to see on colonoscopy
risk of interval tumours
macroscopic features of colorectal cancer:
- growth patterns
- cut surface
- what do you assess for invasion
prox colon - bulky, polypod, exophytic (bulge in lumen, but doesn’t cause obstruction)
distal colon, rectum - annular, stenosing (apple core), ulcerated
=> bleeding, alternating constipation + diarrhoea
cut surface - firm, white (desmoplasia), necrotic
mucoid in mucinous tumours
invasion: muscularis mucosae, muscularis propria, lymph nodes, adj organs, perforation into peritoneal cavity
Staging of colon cancer - Modified Duke’s (ABCD)
A - invades beyond musc mucosa
B - invades beyond musc propria
C - lymph node metastases
D - distant metastase
staging of colon cancer - TNM
T = depth of tumour invasion Tis - insitu T1 - musc mucosa T2 - musc propria T3 - beyond T4 - other organs/perforates
N = nodes
N0 - none
N1 - in 1-3 LN
N2 - 4+ LN
M - metastases
Mx - can’t be assessed
M0 - none
M1 - distant
common site of colon cancer metastasis
liver -> portal blood
what are some high risk features of colorectal cancer?
If high grade
- tumour predominately solid, rather than gland formin
If T3 with localised perforation, or T4
if has close, indeterminate, positive margins
if lymphovascular invasion (inc likelihood of mets)
if <12 nodes examined (may have understaged)
features of nuclear atypia
irrecular contours variable size, shape mitoses abnormal chromatin increased nuclear:cytoplasmic ratio
what are some targeted therapies for coloncancer, what are they targeting
what mutations render it ineffective
target EGFR - block its signalling - inhibit growth
= cetuximab, panitumumab
K-RAS and B-RAF are activating mutations -> inneffective
MSI can improve outcomes
