Potentially malignant disorders and oral cancer Flashcards
What is the WHO definition of Potentially malignant lesions?
- Altered tissue in which cancer is more likely to form
What is the WHO definition of potentially malignant condition?
- Generalised state with increased cancer risk
What are some potentially malignant conditions (systemic conditions)?
- Lichen planus (erosive or ulcerative on gingiva and tongue increased)
- Oral submucous fibrosis
- Iron deficiency
- Tertiary syphilis
Why does a person with iron deficiency at higher risk of developing cancer?
- Iron deficiency leaves oral epithelium thinner
- Oral epithelium vital part of proetcting against pathogens and carcinogens
- When barrier is decreased - increased risk of infections of carcinogens
What are some potentially malignant lesions?
- Leukoplakia
- Erythroplakia
- Chornic hyperplastic candidiasis
What mucosa do most carcinoma in the UK arise from?
- Clinically normal mucosa
Where in the world does most cancer arise from potentially malignant lesions?
- High incidence arease
- e.g. India
How many more time is leukoplakia likely to progress to cancer than clinically normal mucosa?
- 50 to 100 times
What is the most common type of white patch that can be scraped off?
- Acute pseudomembranous candidosis
- aka thrush
What is leukoplakia?
- White patch which cannot be attributed to any other diagnosis
What is erythoplakia?
- Red patch that cannot be attributed to any other diagnosis
What are the predictors of malignancy in leukoplakia?
- Age (incidence increases with age)
- Females more likely
- Idiopathic (no risk factors ass with oral cancer more likely to become malignant)
- Floor or mouth , tongue and gingivae have high risk
- buccal mucosa has low risk
- Non homogenous e.g. verrucous, ulcerated leuko-erythroplakia have higher risk than homogenous
What is it called when there is a white patch on the floor of mouth?
- Sublingual keratosis
- Extremely high risk of developing into oral cancer
What is the gold standard for assessing malignant change in a lesion? What are we assessing?
- Histopathology
- Dysplasia
- Atrophy (thinner)
- Candida infection (presence of candida hyphae - chronic hyperplastic candidiasis or aka candidal leukoplakia )
There is a new way being researched to assess malignant change by histopathology, what is it termed and what are we assessing?
- Biological markers
- DNA content in leukoplakia showing hallmarks for future maligancy
What gene whether it has been mutated or other can be a strong indicator that the lesion is on its way to becoming malignant?
- p53
What is a risk factor of oropharyngeal cancer? What prognosis does this give?
- HPV
- Presence of HPV gives better prognosis
What is dysplasia?
- Disordered maturation (growth) in a tissue
What is atypia?
- Changes in cells
- Different to dysplasia
What are the two categories of criteria for diagnosis of epithelial dysplasia from histopatholgy?
- Assess Architectural changes first (abnormal maturation and stratification)
- Then assess Cytological changes (cellular atypia)
What is the WHO 2005 grading of epithelial dysplasia?
- Done via microscope !
- Hyperplasia
- Mild
- Moderate
- Severe
- Carcinoma-in-situ
What is basal hyperplasia in terms of histopathology?
- Increased basal cell numbers
- Architecture has regular stratification and basal compartment is larger
- No cellular atypia
*arrow shows basal compartment being larger
What is mild dysplasia in regard to histopathology?
- Architectural changes in lower third
- Cytological changes of mild atypia
- Mild atypia such as pleomorphism, hyperchromatism
What is pleomorphism ?
- Variety of shapes and sizes
- Can be from nucleus or cell or both together
What is hyperchromatism?
- Increased in DNA content therefore taking up more staining so appears darker purple on histopathologucal analysis
What are some factors that can contribute to mild dysplasia and what is likely to happen if these factors are removed?
- Trauma
- Infection
- Smoking
- Removal of these factors likely to cease the mild dysplasia
What is moderate dysplasia in terms of histopathology?
- Architectural change extends into middle third of epithelium
- Cytology : moderate atypia (plemorphism or hyperchromatism)
What is severe dysplasia in terms of histopathology?
- Architectural changes extend to upper third epithelium
- Cytology: Severe atypia and numerous mitoses , abnormally high up in epithelium, loss of polarity, pleomorphism and hyperchromatism
Where does mitoses usually happen?
- At basal cell layer
What is carcinoma-in-situ?
- Theoretical concept
- Malignant but not invasive (still contained within basement membrane of epithelium)
- Abnormal architecture (full thickness of viable cell layers)
- Pronounced cytological atypia with mitotic abnormalities frequent
- Needs full removal if found in a pt
What is present in the underlying connective tissue if a pt has a malignancy?
- Inflammation
- Shows pts has a immune response
- If dysplasia present but no inflammation then pt is immunocompromised
Histopathology is the gold standard for malignancy prediction. What are some negatives hitsopathology?
- Invasive
- Can’t monitor tissue response to txt effectively as can’t repeatedly take tissue samples to test response to txt
- Not suitable for mass screening
What future technique are available for predicting malignancy?
- Salivary biomarkers
- Next generation sequencing
- Artificial intelligence
What are the two main factors of carcinogenesis?
- Genetics
- Environmental damage
What is the very basic molecular basis of cancer?
- Damage to cells
- Lead to altered gene expression
- Lead to altered cell function
What are the 4 stages of carcinogenesis?
- Initiation where there is a change to gene such as carcinogen
- Promotion of the cell via cell multiplication
- Transformation of the cell via genetic change (mutation) into a malignant cell
- Progression of the malignant cell via genetic change into malignant tumour
What are some examples of changes to genes that can occur?
- Change to chromosomes
- Change to genes
- Epigenetic changes
Give examples of changes to chromosomes
- Aneuploidy (extra or missing chromosome)
- Translocations (rearrangement of chromosome)
- Amplification
Give examples of changes to genes that can occur
- Mutations
- Deletions
- Amplifications
Give examples of epigenetic changes
- Chemical changes in DNA
like methylation and modification of histone that package DNA
What types of HPV have oncological ability?
HPV 16 and HPV 18
Give the oral cancer genetic broad overview
- Oncogenes which produce normal growth factors
- Tumour suppressor genes which suppress the growth of cells
- growth of cells in body is in equilibrium between oncogenes and tumour supressor genes
- Most active tumour suppresor gene is Tp53 either mutated or inactivated (in about 50-80% of head and neck cancer pt)
- Genes that regulate apoptosis (cell death) if not done then cell continues lifespan
- Genes involved in DNA repair
- MiRNA (can play a role in neoplastic transformation) - chemo targets these
What is Knudson’s two-hit hypothesis of carcinogenesis?
- Need both Tp53 tumour suppressor genes on the chromosome (pair) mutated or inactivated in order for carcinogenesis to occur
Do you need both of the oncogenes on a chromsome to be mutated or inactivated for malignant progression to occur?
- No oncogenes only need one to be mutated or inactivated for malignancy to occur
- Tumour suppressor Tp53 requires both!
What are the 6 hallmarks of cancer? *KNOW
- Evading apoptosis
- Self sufficiency in growth signals
- Insensitivity to anti-growth signals
- Tissue invasion and metastasis
- Limitless replicative potential
- Sustained angiogenesis
What is the filed change theory (field cancerisation)?
- If the area that the cancer was present has been removed this does not reduced the risk of oral cancer devloping in another area
- there is genetic instability increasing the poss of devloping cancer
- Clincally may appear normal and it is diff to estimate the extend of field
- But multiple primaries of 15-20%
- Can be synchronous or metachronous
What does synchronous mean?
- Primary malignancy that arise within 6 months of first maligancy
What does metachronous mean?
- Primary malignancy that arise more than 6 months apart
What are the important points that come back when oral cancer pathology report is performed?
- Diagnosis of squamous cell carcinoma
- Differentiation and grading
- Pattern of invasive front related to nodal spread
- Local extension of disease
This image shows a cohesive front of dysplasia. What is meant by the term cohesive front?
- Cells advancing at the same rate and same time (sim to a wave)
What is meant by the term non-cohesive front?
- Cells advancing in clumps or strains at different rates
- Positive correlation with lymph node involvement
How is the spread of oral cancer described?
- Local extension of disease
- Varies according to site i.e. mucosal extension, muscle (tongue), bone or nerve - Lymphatic spread
- Haematogenous spread
How can tumour spread into bone?
- If pt is edentulous then via gaps in the cortex
- If pt is dentate via periodontal ligament - bone destruction and increased mobility
What is meant by the term perineural spread?
- Involving small nerved at advancing edge predicts nodal spread
- Extensive spread related to IAN may give recurrence
What are 3 ways lymphatic spread of oral cancer can occur?
- Via embolism
- Via permeation
- Via tumour involved node with extracapsular spread
Require sentinal node biopsy
What is the clinical staging of oral cancer?
TNM
What are some rare types of OSCC?
- Verrucous carcinoma
- Basaloid squamous (common in HPV)
- Spindle cell (aggresive)
