potentially malignant lesions Flashcards
potentially malignant lesion
WHO defintion
altered tissue in which cancer is more likely to form
potentially malignant condition
WHO definition
generalised state with increased cancer risk (systemic)
potentially malignant disorder
umbrella term which covers both potentially malignant lesions and conditions
what terms are no longer used and why
premalignant, precancerous, preneoplastic
pre gives defintiive indication
* not every single one will be so potentially is better
use potentially malignant
4 potentially malignant disorders
lichen planus
oral submucous fibrosis
iron deficiency
tertiary syphillis
is lichen planus a potentially malignant disorder
sometimes
can affect skin and mucous membranes - esp if oral cavity
not all types are at risk of developing malignancy
* eroisve and ulcerative on tongue and gingiva are high risk
what is oral submucous fibrosis
Betal nut chewing can lead to dev
Abnormal collagen deposited in epithelium
* Makes tissues of oral cavity hard to expand or move
* Muscles undergo liquidation
* Pt have limited mouth opening
Higher risk of oral cancer
is iron deficiency a potentially malignant disorder
Oral epithelium thinner than normal – issue as important barrier against pathogens and carcinogens
More at risk of infection and carcinogens as result
is tertiary syphillis a potentially malignant disorder
rare now
massive granulation tissue on the tongue, predispose to develop oral cancer
can get white leukoplakia like lesion on tongue as well
lesions that are potentially malignant
4
leukoplakia
erythroplakia
erytholeukoplakia
chronic hyperplastic candidosis
leuko and erythoplakia are
clinical dx
can’t determine underlying cause
form a list of diff dx
* try scraping off
* candida albicans? –> acute pseudomembranous candidiasis (thrush)
if investigations still unclear –> leukoplakia
most carcinomas in the UK arise from
clinically normal mucosa
other areas have a higher incidence from potentially malignant lesions (e.g. India)
leukoplakia is X more likely to progress to cancer than clinically normal mucosa
50-100 times
will all leukoplakias develop into cancer?
no
unable to predict which ones will
pt factors have a role - habits, where they are from etc
clinical factors that play a role on chance of cancer development from leukoplakia
5
- age
- gender
- idiopathic
- site
- clinical appearance
age impact on cancer progression
older the pt more likely
inc incidence with age
gender impact on leukoplakia progression to cancer
more likely in females
idiopathic leukoplakia progression into cancer
more likely if pt has no other risk factors
e.g. no smoking, no tobacco use, no/limited alcohol, good diet but have an unexplained white patch on tongue
sites that have inc progression to cancer from leukoplakia
floor of mouth
tongue
gingiva
sublingual keratosis - extreme high risk
buccal mucosa - low risk
clincial appearance that has inc progression to oral cancer from leukoplakia
non-homogenous
* verrucous, ulcerated leuko-erythroplakia
* warty, knobbly, ulcerated, mix red and white - higher risk
* Biopsy and manage quickly - Some parts may already be malignant
homogenous appearance less - all same colour, consistency
gold standard for assessing malignant potential
histopathology
histopathology preditors of malignant change
4
dysplasia
atrophy - thinner, esp in erythro lesions
candida infection - chronic hyperplastic candiasis or candida leukoplakia
* get mixed colour lesion or pure white
* associated with smoking
* has potential to become malignant
biological markers: DNA content in leukoplakia
* inc DNA due to inc in chromosomes or amplification of genes
* Signs the cells is acquiring characteristics or hallmarks
molecular markers in oral epithelium dysplasia
wide variety
* Signalling pathways - EGFR
* Cell cycle - Ki67; p53; pRB
* Immortalization -Telomerase
* Apoptosis - p53, p21
* Angiogenesis - VEGF
* COX-1&2 enzymes
* Proliferation and differentiation markers
* Viruses: HPV +, HPV-
* Loss of heterozygosity (LOH) 3p, 9p,13q ( retinoblastoma),17p
no markers (single/combination) ID to help determine progression
p53
tumour suppression gene
* makes protein that helps cell division when irreparable genetic damage
Cancer has it deleted, inactivated or mutation - 80% Head and neck cancer
**Strong indicator lesion is on its way to malignancy **
HPV
inc incidence of oropharyngeal cancer
* Different from oral cancer
Tumours positive for HPV have better prognosis than negative HPV tumours
first thing to look for histopathologicaly
epithelial dysplasia
dysplasia definition
disordered maturation (growth) in a tissue
types: fibrous, osseous, renal, epithelial (oral)
atypia definition
changes in cells
dysplaisa - tissue
describe this
Cellular atypia
Cells normal, well stratified in top 2/3
White spaces between them, not so well arranged, separated from each other, irregular shape - cells showing signs of atypia – bottom 1/3
potentially malignant lesions - criteria for diagnosis
2 groups
assess arichitectural changes then cytology
boundaries between categories not well defined
How much involved in changes
* layers – stratified (arranged in normal manner) or not
* individual cell changes
architectural changes
abnormal maturation and stratification
cytological abnormalities
cellular atypia
grading of epithelial dysplasia by
microscope (NOT clinical)
WHO grading of epithelial dysplasia 2005
6
- dysplasia
- hyperplasia
- mild
- moderate
- severe
- carcinoma-in-situ
basal hyperplasia
inc basal cell numbers
architecture
* regular statification
* basal compartment is larger
no cellular atypia
basal hyperplasia
inc basal cell numbers
architecture
* regular statification
* basal compartment is larger
no cellular atypia
basal cells
divide at membrane then progress through layers of epithelium
describe this
basal cell hyperplasia
increased basal cell numbers
no cellular atypia
architecture
* regular stratification
* basal compartment is larger
mild epithelial dysplasia
architecture
changes in lower third
cytology
mild atypia - generally only show a few signs of cellular atypia (not all the signs)
* pleomorphism
* hyperchromatism
* basal cell hyperplasia
possible cause of mild epithelial dysplasia
can be reactive - smoker, infection, inflammation, trauma
remove cause and likely regress
pleomorphism
variety in shape and size of nuclei/cell or both
hyperchromatism
darker stained nuclei due to inc DNA content
describe this
mild epithelial dysplasia
architecture: changes in lower third
cytology: mild atypia
* generally only show a few signs of cellular atypia (not all the signs)
here - pleomorphism, hyperchromatism, basal cell hyperplasia
moderate dysplasia
architecture
* change extends to middle third (2/3 changed)
cytology
* rete pegs rounder and more bulbous
* separation and increased cell motility
describe this
moderate dysplasia
architecture: change extends into middle third (2/3 changed)
cytology: moderate atypia
* Rete pegs rounder and more bulbous
* Separation and increased cell motility
describe this
moderate dysplasia
architecture: change extends into middle third (2/3 changed)
cytology: moderate atypia
* Rete pegs rounder and more bulbous
* Separation and increased cell motility
severe dysplasia
architecture
* changes extend to upper third (most layers affected)
cytology
* severe atypia and numerous mitoses, abnormally high
mitotic figures not at basal cell layer (white circles - 5 here)
* location and number abnormal - stong malignant indicator
describe this
severe dysplasia
architecture
* changes extend to upper third (most layers affected)
cytology
* severe atypia and numerous mitoses, abnormally high
mitotic figures not at basal cell layer (white circles - 5 here)
* location and number abnormal - stong malignant indicator
see loss of polarity, hyperchromatism, pleomorphism
describe this
carcinoma in situ
theoretic concept
malignant but not invasive
abnormal architecture
* full thickness (or almost full) of viable cell layers
* confined to basal epithelium, no invasion to underlying connective tissue
pronounced cytological atypia
* mitotic abnormalities frequent
* hyperchromatism – dark spots
* pleomorphism – wide and look like pushing down
carcinoma-in-situ
theoretic concept
malignant but not invasive
abnormal architecture
* full thickness (or almost full) of viable cell layers
* confined to basal epithelium, no invasion to underlying connective tissue
pronounced cytological atypia
* mitotic abnormalities frequent
* hyperchromatism – dark spots
* pleomorphism – wide and look like pushing down
management of carcinoma-in-situ
lesion needs immediate removal
malignancy always has X associated with in
inflammation
Indication of good immune response - lacking indicates the immunocompromised
More severe dysplasia - more inflammation in underlying CT
at present detection of potentially malignant lesion by
confirmation by
detection by oral visual examination
confirmation by histopathology
cons of histopathology
3
- invasive - biopsy
- cannot monitor tissue response to tx effectively (invasive, load on NHS)
- not suitable for mass screening
possible future options for detection of potentially malignant lesions
3
Salivary biomarkers
* easy, cheap, can be used to monitor and can help indicate recurrence of tumour before clinical detection possible
Next generation sequencing
* Detect disease in people or people at risk of disease
Artificial intelligence AI
* Esp for mass screening in rural areas
2 main factors for carcinogenesis
genetic
environmental (carcinogens)
molecular basis of cancer
3 stages
damage
* inactivated, useless or over/under express
alterd gene expression
* Gene responsible for protein which has a function
altered cell function
* if gene expression is changed and target for protein (function) is changed causes alteration in cell function
molecular basis of cancer
3 stages
damage
* inactivated, useless or over/under express
alterd gene expression
* Gene responsible for protein which has a function
altered cell function
* if gene expression is changed and target for protein (function) is changed causes alteration in cell function
carcinogenesis
Multi step
Initiation
* Mutation to gene
* Cell continues to divide with genetic mutation that wasn’t repaired
* Not enough to form malignant cell
Promotion
* Another mutation in genes that are responsible for repairing DNA
* Cell harbours more genetic mutation due to def DNA repair system
* Whole genome unstable
* Cell becomes malignant
Can be years between initiation and malignant presentation
REVISE BDS1
possible changes to chromosomes
3
aneuploidy
translocations
amplifications
aneuploidy to chromosomes
increase/decrease in number of chromosomes
translocations to chromosomes
break off and add to another part,
can cause certain leukaemias
amplifications to chromosomes
extra copy of genes
so make extra factors
can cause malignancy* (esp if growth factors)*
3 possible changes to genes
which can cause malignancy
mutations
deletions
amplifications
epigenetic changes
which can cause maliganancy
chemical changes in DNA, such as
- methylation - methyl silence genes, stop from functions
- modification of the histones that package DNA - small molecules attach to histones, also regulate gene expression
classes of changes to DNA that can occur in initiaion/promotion during carcinogenesis
changes to chromosomes
* aneuploidy
* translocations
* amplifications
changes to genes
* mutations
* deletions
* amplifications
epigenetic changes
* chemical changes to DNA e.g. methlyation, modificaiton to histones
growth in the body is an equilibrium between
oncogenes and tumoursupressor genes
oncogenes
have normal roles within the cells (produce normal growth factors), differeing oncogenes can be activated
tumour suppressor genes
supres the growth of cells
most imp is Tp53
Knudson’s “two-hit” hypothesis of carconogenesis
Have a pair of tumour suppressor genes – one on each chromosome
* So lose 1 have the other to still function
* But lose both -> two hit hypotheses, cell becomes malignant
Oncogenes (that produce growth factors),
* One becomes mutated - enough for cell to require malignant characterises - not 2 hit
Onco - 1 word 1 knocked needs to work
Tumour suppressor - 2 words need both knocked out
oral cancer genetics possible pathways
5
equilibrium between oncogenes and tumour suppressor genes
genes that regulate apoptosis
* if stopped continue to divide forever, no natural programmed cell death
genes involved in DNA repoar
miRNA - strands of RNA that can play a part in neoplastic transformation
* don’t code to produce protein, regulate things
* target of many drugs
viral component - HPV
HPV and cancer
HPV 16 and 18 are carcinogenic
have E6 protein which degrades p53 - so nothing to stop them passing on this inactivation of tumour suppressor genes
6 hallmarks of cancer
evading apoptosis
self-sufficient in growth signals
insensitivity to anti-growth signals
sustained angiogenesis
limitless replication potential
tissue invasion and metastasis
update to hallmarks of cancer that is key for oral cancer
2011
polymorphic microbiomes
* bacteria have protective function against oral cancer
Connective tissue has effect on cells capacity and needs for malignant growth
drugs developed to target 6 hallmarks (outer circle)
variation in process of carcinogenesis
- “multistep” - initiation, promotion, progression
- sum of genetic changes, not order, important
- how many changes needed?
Differs between malignancy
field change theory
**all the area may be susceptible to developing oral cancer
* Not just the potentially malignant lesion **
genetic instability increasing the possibility of developing cancer
* clinically may appear normal
* difficult to estimate extent of field
* includes pharynx, larynx and respiratory tract.
multiple primaries - 15 to 20%
Can develop a whole new tumour (not a recurrence)
* synchronous – 6 months to 1 year after primary tumour
* metachronous - several years after primary tumour
synchronous tumour
new malignancy 6 months to 1 year after primary tumour
field of change theory
metachronous tumour
new malignancy several years after primary tumour
field of change theory
oral cancer pathology report points
biosy report
4 points
Dx
differentiation and grading
pattern of invasive front
local extension of disease
Dx of oral cancer from pathology report
most are squamous cell carcinomas
squamous cell carcinomas
gradings/differentiations
done by micrscope
4
- well
- moderate (most are)
- poly
- anaplastic
anaplastic SCC
so de differentiated, impossible to know where it came from
pattern of invasive front is
related to nodal spread
help predict if lymph nodes involved
cohesive front
wave like
non cohesive front
advancing in strands, possible correlation with lymph node involvement despite no clinical changes detected
spread of oral cancer
biopsy report
Local extension of disease
varies according to site
* mucosal extension
* muscle (tongue etc)
* bone
* nerve
* salivary gland
Lymphatic spread
Haematogenous spread
signs malignancy spread to bone
Can cause destruction
In pt with good standard OH but have unexplained mobility - needs further investigation, malignancy underlying in bone
perineural spread of malignancy
how
management
Along myelin sheath of nerves
* possible correlation with lymph nodes spread
* Difficult to manage
* Recurrence high
*Perineural spread involving small nerves at advancing edge predicts nodal spread
Extensive spread related to inferior alveolar nerve, may give recurrence*
3 modes of lymphatic spread of malignancy
Permeation – grow inside lymph nodes
Break of emboli - circulate and attach and grow to lymph nodes
Extracapsular spread – grow outside the lymph node, can spread easily
sentinel node biopsy
Principle draining lymph node of area of malignancy is taken out and examined to ID any small malignant lesions (micrometasis), that wouldn’t cause lymph node enlargement but are malignant
lymph permeation of malignancy
grow inside lymph node
maligannt emboli spread to lymph
circulate and attach and grow to lymph nodes
extracapsular spread of malignancy to lymph node
grow outside the lymph node, can spread easily
staging of oral cancer
clincal procedure by examination
TNM
TNM staging
Tumour - width,
Node - lymph node involvement, number and symmetry
Metastases - distal spread
haematogenous spread of malignancy
late feature
enter veins in neck
* Emboli or grow in neck
Metastasis to lungs, and spine
* ? other sites
OSCC subtypes
3
rare types
Verrucous - better prognosis, warty, knobble, slow invasion, rare metastases
Basaloid - assoc with HPV
Spindle cell - aggressive, cells like fibroblasts, hard to ID, poor prognosis
