Potentially Malignant Disorders and Oral Cancer Flashcards
What does the term potentially malignant disorders include?
Potentially malignant lesions
Potentially malignant conditions
What is a potentially malignant lesion?
Altered tissue in which cancer is more likely to form
What is a potentially malignant condition?
Generalised state/condition associated with increased cancer risk
What are examples of systemic conditions which are considered potentially malignant?
lichen planus- erosive/ulcerative variants (esp on tongue or gingiva)
Oral Submucous fibrosis- associated with chewing of betel nut
Iron deficiency
Tertiary syphilis
What occurs in Oral Submucous Fibrosis?
Abnormal collagen deposits in connective tissue of submucosa
Makes expansion and movement different
Muscles undergo degradation
Limited mouth opening
What makes iron deficiency a potentially malignant condition?
Associated with thinning of mucosa- easier passage of pathogens and carcinogens into tissue
How can tertiary syphillis present intra-orally?
As a mass of granulation tissue on tongue (can also get leukoplakia like lesions)
What is leukoplakia?
Clinical diagnosis:
White patch- can’t determine underlying cause (can’t be scraped off)
-> Higher risk of malignant transformation than normal mucosa (depends on other patient factors- habits etc)
What is a white patch that can be wiped off likely to be?
Acute pseudomembranous candidiasis (thrush)
What are the clinical predictors for malignant change in leukoplakia lesions?
Older age
Female sex
Idiopathic cause- lack of risk factors, unexplainable lesion
Site- floor of mouth and tongue are high risk
Non-homegenous lesions
Verroucous/Ulcerated erythroleukoplakia
What are histopathology assessment of potentially malignant lesions useful for showing us?
Dysplasia
Atrophy- seen in erythroplakia
Candida infection
Which type of candida infection is associated with malignancy?
Chronic hyperplastic Candidosis (candida leukoplakia)
Purely white or mixed red and white lesion
Associated with smoking
Why may it be useful to look at the DNA content of leukoplakia lesions when assessing malignant potential?
As increased copies of genes present within chromosome can be a hallmark that the cell is carrying signs of malignant change
Which molecular markers are commonly found in oral epithelial dysplasia?
Enzymes- cox1/2
Viruses
Growth factors- VEGF
What is the purpose of p53 protein?
Helps stop cell division when there is genetic damage present
What is the different about the gene that codes for p53 in malignancy?
It is often missing, inactive or mutated
What is unusual about HPV+ pro-pharyngeal cancer?
Better prognosis than HPV-
What is dysplasia?
Disordered growth or maturation of a tissue
What is cellular atypia?
Changes in cells:
Spaces appearing- separation
Poor arrangement- not neat
Strange appearance
-> darker (takes different amount of stain- hyperchromatism)
-> Neomorphism (variety of shapes and sizes in nucleus or cells)
What are the grades of epithelial dysplasia? (done using microscope)
hyperplasia
mild
moderate
severe
carcinoma-in-situ
What are the features of basal hyperplasia?
Increased basal cell numbers- act as stem cells in basal compartment
Architecture:
regular stratification
basal compartment is larger
No cellular atypia
What are the features of mild dysplasia?
mild atypia- not all cells are showing signs
In lower third only
Reactive- infection, trauma, smoking (remove cause- this will likely regress)
What are the features of moderate dysplasia?
Dysplastic change extends into middle third
Moderate atypia- spacing present, pleomorphism, hyperchromatism
More round and bulbous rete ridges
What are features of severe dysplasia?
Extends into upper third
Severe atypia- Widespread dark nuclei (hyperchromatism), loss of polarity
Multiple mitoses- cells undergoing division closer to surface (should occur at basal layer only)
What are the features of carcinoma in situ? (theoretical concept)
Malignant but not invasive- confined to epithelium (contained by BM- no spread to connective tissue)
Affects full thickness of epithelium
Pronounced atypia
-> wide rete pegs
-> Widespread mitotic abnormalities
Inflammation of underlying connective tissue (indicative of immune reponse)
What are the issues with histopathology confirmation of malignancy?
Invasive
Cannot monitor tissue response to treatment effectively
Not suitable for mass screening
Which techniques may be used to monitor dysplastic changes in oral cavity in the future? (and recurrence/treatment effectiveness)
Salivary biomarkers
Next gen sequencing
AI
What are the 2 main factors in carcinogenesis?
Genetic component
Environmental component (carcinogens)
What happens to cells as a result of genes becoming mutated?
Every gene produces a protein which carries out a function
Mutation causes gene product to be inactivated or over/under expressed
Gene expression is altered- target for protein is changed
Alteration in function of the cell
What are the stages in carcinogenesis?
Initiation- mutation occurs in gene (cell can divide carrying that mutation- which may not repair)
Promotion- secondary mutation occurs in genes that code for reparation of DNA
-> this may become malignant now
Transformation- cell then cannot repair DNA damage (genome can become unstable)
Progression- cell becomes malignant and divides/multiplies eventually forming tumour
Which changes can occur in chromosomes that may lead to malignancy?
Aneuploidy- abnormal number
Translocations- part of one chromosome breaks off and attaches to another (can cause unwanted activation of other chromosomes)
-> leukaemia
Amplifications- extra copies of genes
Which changes can occur in genes that may lead to malignancy?
Mutations
Deletions
Amplifications- over-expressed factors
Which epigenetic changes can occur that could lead to malignancy?
methylation of DNA (silences gene)
Histone modification (cannot regulate genes in normal way)
What is an oncogene?
Gene responsible for producing normal growth factors
What are tumour suppressor genes?
Genes that prevent growth of cells
-> Tp53 is most important- often becomes deleted, mutated or inactivated in cancer
What are the oncogenic types of HPV and what do they produce?
HPV 16/18
-> produce E6 which degrades p53 (nothing to stop mutated cells dividing)
What is the Knudsons 2 hit hypothesis?
Within pairs of chromosomes
There are a pair of tumour suppressor genes (one in each chromosome)- both of these must be mutated or lost to cause malignancy
If oncogenes becomes mutated it only requires one for malignancy to occur
Which genes are commonly affected in oral cancer?
Oncogenes
Tumour supressor genes
Genes involved in apoptosis (natural cell death)
-> without this cells would continue to divide
DNA repair genes
MiRNA- strands of RNA associated with neoplastic change
What are the hallmarks of cancer and the type of drug used to combat it?
Sustaining proliferative signalling= EGFR inhibitors
Evading growth suppressors= Cyclin-dependent kinase inhibitor
Avoiding immune destruction= Immune activating anti-CTLA4 mAb
Enabling replicative immortality= Telomerase inhibitors
Tumour promoting inflammation= selective anti-inflammatories
Activating invasion and metastasis= Inhibitors of HGF/c-met
Inducing angiogenesis= Inhibitors of VEGF signalling
Hallmarks and drugs continued:
Genome instability and mutation= PARP inhibitors
Resisting cell death= Proaptotic BH3 mimetic
Deregulating cellular Energetics= Aerobic glycolysis inhibitors
What is the significance of polymorphic microbiomes against oral cancer?
The micro-organisms within the oral cavity may have protective effect against oral cancer
What does the field change theory dictate?
That areas around malignancy are more likely to become malignant (as the whole area could be subjected to the changes which cancer site)
-> if oral cancer- higher risk of pharynx, larynx, respiratory tract malignancy
What are synchronous tumours?
New tumour that develops within 6 months of the primary tumour
What are metachronous tumours?
New tumour that develops within a few years of primary tumour
How is oral squamous cell carcinoma diagnosed? (most common in oral cavity)
Grade (based on differentiation seen on microscope)- well, moderate*, poorly, anaplastic
Pattern of invasive front
-> non-cohesive suggests LN spread
Local extension of disease
What are the features of a cohesive front in oral squamous cell carcinoma?
All cells advance at same rate (like a wave)
-> less likely to spread to LNs
Where does oral cancer tend to spread to?
1.Local extension of disease (varies according to site)
-> mucosal extension
-> muscle (tongue etc)
-> bone
-> nerve
2. Lymphatic spread
3. Haematogenous spread
What are the mechanisms in which oral cancer spreads to bone?
Via gaps in cortex
Via PDL (in dentate patients )
-> presents as unexplained mobility in patients with good OH (requires investigation as tumour may be causing bone disruption)
What part of nerves can tumours spread along? What is the significance of this?
Myelin sheath (of small nerves at advancing edge)
-> correlates to LN spread
-> difficult to erradicate
-> indicator that recurrence is likely
How does spread of cancer to LNs occur?
Permeation- cancerous cells grow within lymphatic vessels
Embolism- parts of the malignancy area break off and travel within lymphatic vessels to node
Extracapsular- malignant cells can grow outside the node and spread to surrounding area
What is a sentinel node biopsy?
Principle draining LN of the malignancy is identified and taken out and studied
-> helps identify micro-metastases (clumps of malignant cells)
How are tumours staged clinically?
T- width, size
N- LN involvement
M- Metastases (distant)
What does metastases by blood in carcinoma indicate?
Late stage disease
-> can spread to lungs and spine
How does haematogenous spread of cancer occur?
Formation of malignant emboli which can be transported in blood
Growth of tumour in vein itself
What are some examples of rarer forms of oral squamous cell carcinoma?
Verrucous (outward growing, thick, warty)
Slow progressing
Rarely metastasis
Better prognosis
Basaloid (appear like basal cells)- associated with HPV
Spindle cell (cells appear like fibroblasts)- aggressive
TMN system:
T – tumour:
§ Tx – no available info on primary tumour
§ To – no evidence of primary tumour
§ TIS – only carcinoma in situ on primary sites
§ T1 - <2cm
§ T2 – 2-4cm
§ T3 - >4cm
§ T4 - >4cm, involvement of antrum, pterygoid muscles, base of tongue or skin
N – node:
§ Nx – cannot be assessed
§ N0 – no clinical positive nodes
§ N1 – single, ipsilateral <3cm
§ N2a – single, ipsilateral 3-6cm
§ N2b – multiple, ipsilateral <6cm
§ N3a – single/multiple, ipsilateral node, one more than 6cm
§ N3b – bilateral
§ N3c – contralateral
M – metastasis:
§ Mx – not assessed
§ M0 – no evidence
§ M1 – distant metastasis present
