Oral cancer Flashcards
(144 cards)
1
Q
What is the worldwide epidemiology of oral cancer?
A
It is the 6th most common cancer worldwide and the total cases are 263000. The frequency is 2%. The incidence is 3.9/100000. There are 128000 deaths (in 2008) and the death rate is 48%. There are parts of the world where oral cancer is the main type of cancer including Papa New Guinea. In India and Sri Lanka oral cancer is one of the main types of cancer.
2
Q
What are the oral cancer England stats?
A
- Total cases - 6767
- Frequency - 2% of all cancers
- Incidence - males 12/100000 and females 7/100000
- Deaths - 2119
- 5 year survival - 58%, death rate is 31% (most likely an underestimate)
- For men it is the 10th most common cancer and 15th for women in the UK
Deaths from cancer are increasing. There are some regional differences in the UK for head and neck cancer. England has the lowest rate and Scotland has the highest rate.
3
Q
For what people is the incidence of oral cancer increasing?
A
The problems are that it is increasing in incidence, younger people are getting it (age demographic is shifting) and there is little improvement in survival. The mouth cancer data from cancer research UK shows that there is a 32% increase in males over the last 10 years and a 33% increase in women. We are seeing more women with oral cancer and younger people.
4
Q
Why has there only been a modest increase in survival in 50 years in the UK?
A
Patients present late and 70% of patients present with late stage disease. If you get metastasis then you are straight into late stage disease - stage IV and the prognosis halves. We want to diagnose patients early/precancer.
Look at table in notes.
5
Q
Which types of oral cancer have the best and worst survival rates?
A
Cancer of the lip has the best survival rate as it is easiest to see. Oral cavity, tongue, oropharynx and hypopharynx have lower survival rates as they are more difficult to see.
6
Q
What are the biggest risk factors for oral cancer?
A
Smoking and alcohol.
7
Q
What is the aetiology of oral cancer?
A
It is multifactorial and there is no single factor identified. There is genetic predisposition in some but the main causes are environmental. Factors vary in different geographical regions or ethnic groups. There are inherited factors in oral cancer such as polymorphisms in genes involved in the metabolism of carcinogens and these have been linked to individual susceptibility:
- Tobacco - glutathione transferases
- Alcohol - alcohol dehydrogenase (ALDH2)
There are also risk factors associated. Social deprivation has an association.
8
Q
What inherited cancer syndromes are associated with an increased risk of oral cancer?
A
- Li-Fraumeni
- Fanconi anaemia - 60% of these patients get oral cancer
- Xeroderma pigmentosum
9
Q
What are the risk factors for oral cancer?
A
- Tobacco
- Alcohol
- Sunlight
- Infections - viruses, fungi, bacteria
- Diet and nutrition
10
Q
What are the different types of tobacco use?
A
Smoking: - Cigarettes - Pipes - Cigars - Reverse smoking Smokeless: - Betel quid - paan - Snuff - Chewing tobacco
11
Q
When is the risk of oral cancer with smoking greatest?
A
Tobacco has a definite relationship with oral cancer and the risk is greatest in heavy users (>25/day). Risk is greater if accompanied by alcohol use. There is a definite relationship of smokeless tobacco with oral cancer established by epidemiological studies and observation of lesions.
12
Q
What is betel nut/paan?
A
Betel nut/paan is the seed of a palm tree and is used as a stimulant in some parts of the world. It is chopped up and wrapped in the leaves of a vine and coated with lime. It is often mixed with tobacco and spices. It is reportedly chewed by up to 600 million worldwide especially in South and Southeast Asia.
13
Q
What are the effects of betel nut/paan?
A
- Self-reported energy boost, possible adrenaline release stimulated by alkaloids
- Traditional beliefs about health benefits but little clinical evidence
- Addictive
- Stains the teeth
- Linked with oral cancer
- Regular users 28 times more likely to develop oral cancer than others
14
Q
How can alcohol cause oral cancer and what are the recommended alcohol limits?
A
Consumption of alcoholic drinks is a risk factor for oral cancer. Ethanol alone is not carcinogenic – may be how it is metabolised or some of the other additives. The amount of ethanol is more important than the type. The risk is greatest when accompanied by tobacco use. There is increasing importance in young patients. Recommended alcohol limits for men and women is 14 units – 6 pints of beer, 7 glasses of wine or 14 single shots of spirits.
15
Q
How can UV cause oral cancer?
A
UV is an important cause of lip (skin) cancer (BCC, SCC, melanoma). UV light causes solar keratosis and dysplasia of the skin.
16
Q
How can HPV cause oral cancer?
A
There is good evidence for the role of HPV in oropharynx (tonsil and base of tongue) cancer and some evidence of oral lesions. HPV 16 and 18 have been implicated. HPV is associated with about 60% of OPSCC cases in the UK. HPV related oropharyngeal SCC has a younger patient demographic without traditional risk factors. They often present with lymph node metastases. The prognosis is good with chemoradiotherapy but the advantage is lost if also a smoker. There is a vaccination.
17
Q
How can candida cause oral cancer?
A
It has an association with oral cancer development. Candida can produce carcinogens from nicotine and alcohol. It can often infect pre-malignant lesions. Candida leukoplakia (CHC) is often non-homogenous and dysplastic.
18
Q
What genes are associated with oral cancer?
A
- Oncogenes - differing oncogenes activated, geographical variations, no clear relationship with disease
- Tumour suppressor genes - P53 mutation or inactivation, many other genes
- Viral component - HPV
19
Q
What are the stages of development of oral cancer?
A
There is a multistage carcinogenesis in oral cancer. The stages are initiation, induction and progression. You start with a normal cell and there are multiple genetic events (inherited and environmental factors) which lead to precancer. There are further multiple genetic events leading to cancer. The window is longer between normal cell and precancer so this is when we want to act.
20
Q
What is field change?
A
Field change is a concept which involves field cancerisation which is the area of abnormal mucosa. If you only treat the lesion you can see you leave behind an area of abnormal mucosa which you cannot see which may lead to additional lesions. All/most of the oral mucosa is abnormal but not necessarily clinically or on histology. Subsequent tumours may develop in the ‘field’ of abnormal mucosa or may be completely different. You can get recurrence by leaving behind some tumour, or from the field or from another field. It is therefore important that oral cancer patients (or precancer) are carefully followed up after treatment.
21
Q
What is a precancerous lesion?
A
A precancerous lesion is a morphologically altered tissue in which cancer is more likely to occur than in its apparently normal counterpart. The preferred term is now potentially malignant. There are two lesions which are leukoplakia and erythroplakia.
22
Q
What is Leukoplakia?
A
The WHO definition of leukoplakia is a white patch that cannot be rubbed off and cannot be characterised clinically or histologically as any other disease and that is not associated with any physical or chemical causative agent except the use of tobacco.
23
Q
What is the epidemiology of Leukoplakia?
A
Epidemiology of leukoplakia: no good registration schemes so no figures. Most precancer studies have looked at leukoplakia. The prevalence ranges from 0.9-26.9% and depends on the size of study and the population studied. The worldwide prevalence is 2.6% from a recent systematic review. A study of over 2000 patients in dental practice in the UK showed a prevalence of 2.8%.
24
Q
What is the difference between homogenous and and non-homogenous leukoplakia?
A
Homogenous leukoplakia is flat and plaque like and uniformly white. Non-homogeneous leukoplakia has variation in colour or texture. It also includes speckled, exophytic, nodular, verruciform.
5% of leukoplakias become malignant in 5 years. Homogenous ones are 1-5% and non-homogenous is 20%. Red areas in the leukoplakia are worrying.
25
What are the indicators of malignant potential?
- Site – lateral border of tongue, ventral tongue, floor of mouth, anterior tonsil to lateral part of soft palate
- Colour – red patches higher risk
- Texture – thicker areas and variations in thickness high risk
- Presence of candida (seen in biopsy)
- Degree of dysplasia (biopsy – histology)
26
What is erythroplakia?
Erythroplakia WHO definition is a red patch on the oral mucosa which cannot be characterised clinically or histologically as due to any other condition. The use of the term erythroplakia varies. The prevalence is unknown but much less common than leukoplakia, but a much larger malignant potential than leukoplakia. It often shows severe dysplasia or CiS. It may be the earliest clinical sign of invasive SCC. Often already cancerous when biopsied – 25%.
27
What can the histology of leukoplakia show?
It can range from:
- Hyperkeratosis with no dysplasia
- Hyperkeratosis with dysplasia (mild, moderate, severe)
- Carcinoma in situ
- Squamous cell carcinoma
28
What is epithelial dysplasia?
Epithelial dysplasia is a collective term used to embrace a number of individual atypical features. It is graded as mild, moderate or severe on extent/degree of atypical features so it is ‘subjective’. It is a pre-malignant state with an increased risk of cancer development. Severe dysplasia involving the full epithelial thickness is called carcinoma in situ.
29
What are the architectural and cytological features of atypia in the epithelium?
Architectural features:
- Irregular epithelial stratification
- Loss of basal cell polarity
- Drop shaped rete processes
Cytological features:
- Increased numbers of mitotic figures
- Cellular and nuclear pleomorphism (variety in shape and size)
- Nuclear hyperchromatism (ploidy) - staining too darkly as too much DNA in cells
- Individual cell keratinisation
- Loss of intercellular adherence - cells break apart
30
What are the differences between mild, moderate and severe dysplasia?
See images in notes.
Mild dysplasia shows all changes in the basal third. It is mostly cytology rather than architecture. In moderate dysplasia there are architecture changes into the middle third. In severe dysplasia there are changes in the upper third and there will be numerous mitoses/mitotic figures through full thickness (white halos). These should only be seen in the basal layer.
31
What is carcinoma in situ?
Carcinoma in situ is malignant but not invasive. There is abnormal architecture in full thickness of viable cell layers. It is pronounced cytological atypia – mitotic abnormalities frequent.
32
What percentage of leukoplakia shows dysplasia on biopsy?
20-50%. It is 20% for homogenous and 50% for non-homogenous.
33
What can happen with a dysplastic lesion?
- Progress to malignancy - 20%
- Regress - 20%
- No change - 40%
- Increase in size - 20%
34
What are the high and low risk areas of the mouth?
```
High risk 80%
- Lateral margins of tongue
- Floor of mouth
- Retromolar, soft palate and fauces
Lower risk:
- Gingiva
- Buccal mucosa
- Labial mucosa
- Hard palate
Look at images in notes.
```
35
What techniques and technology can be used in diagnosis and prediction of oral cancer?
- A thorough and systematic examination
- Mucosal stains e.g. toluidine blue (orascreen), areas that are abnormal have more DNA and stain blue, many conditions will stain blue e.g. lichen planus so not very specific
- Imaging systems e.g. veloscope - blue excitation light shone on oral mucosa, when normal it gives green fluorescence, abnormal will not fluoresce. The main problem is specificity, it will tell you something is wrong but not whether it is serious or not so not that helpful
- Brush biopsy (cytobrush) - a technique for sampling cells of a lesion, painful and requires LA, atypical and malignant cells are found in the basal layer so need to get it to that layer, cytological assessment, lab on a chip - modified brush used to take sample then place a chip and use biomarkers, place in machine and it tells you whether there is dysplasia, DNA image cytometry
36
What are the potentially malignant conditions?
- Chronic hyperplastic candidosis
- Actinic keratosis
- Submucous fibrosis
- Lichen planus
37
What is chronic hyperplastic candidosis?
It is classically present at the angle of the mouth, histologically epithelium is hyperplastic with long rete processes, chronic inflammatory processes underneath, candida hyphae purple lines extending into surface. Treat candida with (fluconazole) and then reassess lesion, further biopsy if concern.
38
What is actinic keratosis?
It is a rough scaly patch from exposure to the sun often seen on the lips.
39
What is submucous fibrosis?
It is predominantly seen in Indians and other Asians. It is associated with areca nut use (paan). The precise mechanism is still uncertain. Once it develops there is no regression and no effective treatment. There is a reported risk of malignant transformation 2.3-7.6%. In the initial stages you get fibrosis of the oral mucosa. When the patient opens the mucosa blanches and they cannot open properly. You will see brown staining, red and white patches. Histologically there is fibrosis in underlying tissue, epithelium is atrophic with atypia (dysplasia) and lots of collagen.
40
What is lichen planus?
There are erosive/atrophic forms e.g. on the lateral surface of the tongue or gingiva there is a significant risk of developing oral cancer. Reticular forms are less likely.
41
What are the signs of oral cancer?
You get keratosis, dysplasia and then carcinoma. The signs are:
- Persistent ulcer
- Persistent white, red or mixed patch
- Exophytic mass
- Fixation of tissue
- Induration
- Sensory/motor deficit
- Tooth movement/mobility
- Lymph node enlargement/fixation
42
What are the symptoms of oral cancer?
- None
- Soreness/irritation
- Paraesthesia/anaesthesia
- Disruption of function
- Dysphagia
- Often advanced when you see symptoms
Patients will often have no symptoms. Diagnosis is through a good incisional biopsy.
43
What are the types of oral cancer?
- Squamous cell carcinoma (mostly)
- Verrucous carcinoma - relatively low grade, rarely metastasises, tobacco/snuff use, exophytic surface, 'pushing' invasive pattern, lots of recurrences, may develop into SCC at some point (image in notes)
- Others (histological subtypes, very aggressive, patients do badly) - basaloid, spindle cell
44
Why are cancers graded?
It gives an indication of prognosis. It helps differentiate tumours that may do well from tumours that may not. Grading is done by the pathologist on biopsies.
45
What are the different grades that can be given to a cancer?
- Well differentiated - resembles cell of origin, expresses keratins (differentiation), low grade
- Moderately differentiated (majority) - still epithelium with a little bit of keratinisation, resembles cell of origin, may produce some keratin, patients don't tend to do well
- Poorly differentiated - no keratin (does not differentiate), may not resemble cell of origin (anaplastic), often there will be central necrosis, high levels of division, aggressive
46
What is TNM used for?
To assess the local extension of the disease. The important features in the primary tumour are:
- Overall tumour size
- Invasion into muscle (tongue etc)
- Involvement of nerves/blood vessels
- Invasion into bone
The surgeon will want to know how deep the lesion is. Once the lesion is greater than 5mm this has a worse prognosis as the risk of lymph node metastasis increases.
47
What is the sign of malignancy histologically?
Invasion of the epithelium into the underlying connective tissue. There will be islands of epithelium in the connective tissue.
48
Where can oral cancer spread to?
It is important to know where the cancer has spread to (muscle, floor of mouth, tongue, superficial spread, submandibular gland). We look at perineural spread so if the tumour is growing around nerves. It may use nerves as a scaffold to help it grow and spread. Extensive spread related to IAN may give recurrence. Tumours in vessels are important – lymphovascular invasion. This allows metastasis so is important. Spread into bone makes a tumour a T4 tumour even if small. If patient is edentulous it can travel through gaps in cortex and if dentate via the periodontal ligament. Patients with this wont do well.
49
What are the effects of previous irradiation on oral cancer?
- There are often multiple points of entry wherever tumour near bone
- Extensive spread within bone
- Most frequent route through alveolar crest
50
What are the signs and symptoms of lymph node metastasis and in what percentage does this occur?
50% of patients will have metastases to regional lymph nodes. The signs and symptoms are:
- Painless enlargement
- Rock hard mass
- Fixation - indicates tumour has spread from node into surrounding tissues
51
How does the tumour invade lymph nodes?
The tumour enters the lymph node by the subcapsular sinus via afferent lymphatics. Then there will be metastasis which will grow in the node.
52
What are the lymph nodes in the head and neck?
- Preauricular
- Submandibular
- Submental
- Upper jugular
- Mid jugular
- Lower jugular
- Upper posterior cervical
- Mid posterior cervical
- Lower posterior cervical
Look at images in notes.
53
What is extranodal extension? (extra-capsular spread)
When there is spread of carcinoma through the fibrous capsule of a lymph node into the surrounding soft tissues. It can be detected clinically due to fixation, tethering, skin invasion, cranial nerve defects (e.g. facial nerve in parotid gland), with radiological confirmation or pathologically. ENE is a new addition to the 8th edition of the TNM manual and confers a poor prognosis in oral cancer. ENE decreases 5 year survival by 50%. Less than 1cm - 23% EC spread, 2-3cm 53% and more than 3cm 74%.
54
What is haematogenous spread?
Haematogenous spread is what gives us M in TNM. It is a late event and is related to advanced disease and poor prognosis. It is most commonly to lungs.
55
What is the prognosis of oral cancer based on?
- Site – further back the worse the prognosis
- Grade – poorly differentiated is worse
- Stage
- Size T
- Spread N and M
- Extracapsular spread
- Multiple primaries (multiple cancers) – 15-20%
- Synchronous or metachronous
56
What is the management of oral cancer?
- Confirm/establish diagnosis by biopsy
- Thorough clinical examination
- Imaging for extent of spread (MRI and then CT scan of chest to check for spread), PET scan to trace where there is tumour around the body
- Review at multidisciplinary team meeting
- Treatment plan formulated
- Surgical excision and/or
- Radiotherapy and/or
- Chemotherapy
- Palliation
57
What is the general role of a radiologist in managing patients with oral cancer?
It falls into 3 distinct areas:
- Diagnosis - does the patient have imaging signs of cancer?
- Staging - how far has the cancer spread?
- Surveillance - has the cancer recurred after treatment?
58
How can radiology be used to diagnose cancer?
For the typical oral cavity SCC, radiology is not needed for diagnosis as the clinical appearance provides the most insight. However patients can often present with a lump in the neck or salivary glands that may have no distinguishing clinical features. Not all of these patients will have cancer and imaging to separate out the benign from the malignant is readily available in all hospitals. This is usually done with ultrasound as neck lumps are often superficial, and when combined with image guided biopsy can produce a histological diagnosis in 1 visit.
59
What are Warthins tumour and Hodgkin lymphoma?
Warthin's tumour is a benign salivary gland tumour in the tail of the parotid gland seen in smokers. It iscystic and solid.
Hodgkin Lymphoma symptoms are itching and sweating at night, lump under the jaw and armpits, malignant tumour in lymph nodes.
60
What is the purpose of staging a cancer?
The purpose of staging is to accurately define the extent of the primary cancer, including the structures that it invades into as well as those structures that might be included in the resection if surgery is performed. As well as documenting the primary tumour, spread to regional lymph nodes is also evaluated as is distant spread outside normal anatomical bounds. Staging cancers is an important process that helps to select the most appropriate treatment options e.g. whether a curative or palliative route is planned and also whether surgery or chemoradiotherapy or combined treatment is thought to be best. Staging also helps to predict prognosis as larger cancers with extensive lymph node spread have a poorer prognosis than smaller cancers without lymphadenopathy. In cases of advanced disease, staging may spare the patient debilitating surgery that will not have any significant effect on survival.
61
What types of radiograph are used to stage cancers and what are the contraindications?
Magnetic resonance imaging MRI is the mainstay of radiological staging for oral cancer for oral cancer. In some patients MRI is contraindicated and some are unable to tolerate the scanning environment: for these CT (computed tomography) is used instead. Contraindications may be medical e.g. pacemaker or claustrophobia. CT scan isn’t as good. MRI is a small enclosed environment. CT scan is less enclosed.
62
What is metastasis and the system used to stage cancers?
Spread outside the local draining lymph nodes is metastasis or distant metastasis. The almost universal standard for cancer staging is the TNM manual that is published by the union for International cancer control UICC. Version 8 was adopted at the start of 2018.
63
What is the T in the TNM classification?
Look at image in notes.
T is based on the size and depth of invasion (how deep it extends into tissue). T0 is no evidence of primary tumour so you cannot see it. T1 is less or equal to 2cm and DOI less than 5mm. T2 is less than or equal to 2cm and DOI between 5mm-10mm. OR greater than 2cm and less than 4cm and DOI less than 10mm. T3 is greater than 4cm and DOI greater than 10mm. T4 is invading into deep structures e.g. bone and masticatory muscles. Size can be measured in the mouth or on an MRI and DOI is measured histologically.
64
What is the N in the TNM classification?
N0 is no lymph node metastasis. N1 is a single ipsilateral node less than 3cm and no extranodal extension. N2a is a single ipsilateral node between 3-6cm and extranodal extension negative. N2b is multiple ipsilateral nodes less than 6cm and extranodal extension negative. N2c is contralateral/bilateral nodes less than 6cm and extranodal extension negative. N3a is any node greater than 6cm and extranodal extension negative. N3b is any node that is extranodal extension positive.
65
What is the M in the TNM classification?
M0 is no distant metastasis, M1 is distant metastasis present e.g. lung.
66
How can ENE be detected radiographically?
If the node appears smooth in circumference then it has expanded but the cancer has not burst through so it is ENE negative.
67
How is the TNM staged?
- Stage I is T1, N0, M0.
- Stage II is T2, N0, M0
- Stage 3 is T3, N0, M0 or T1/2/3, N1, M0
- Stage IVa is T4, N0, M0, T4, N1, M0, T1/2/3/4, N1/2, M0
- Stage IVb 0s T1/2/3/4, N3, M0
- Stage IVc is T1/2/3/4, N1/2/3, M1
68
What are the recent figures for a 5 year survival from cancer research UK?
With oral cancer 55% live for at least 5 years. The lip has a 90% survival at 5 years, the tongue a 50% survival at 5 years and the oral cavity a 47% survival at 5 years.
69
How is the prognosis affected by lymph node spread?
It is significantly affected and survival falls by half when comparing N0 to N1 and again falls by half for spread to the contralateral neck N2c.
70
Where do metastases usually occur and how can they be detected radiographically?
Although oral cancer does not often metastasize to distant sites, the staging of a patient as M1 indicates that any treatment will be palliative rather than curative. Distant metastases usually occur in the chest, either as spread to mediastinal (between lungs) lymph nodes or as lung metastases. Therefore, all patients usually have some form of chest imaging in their diagnostic work-up. A chest x-ray will exclude large lung masses but a CT scan is more sensitive, and will identify small deposits.
71
Why is detecting recurring cancer after treatment difficult?
Both surgery and radiotherapy alter the appearance of the oral cavity and neck as well as its texture, due to scarring, which makes the detection of cancer recurrence difficult if you rely soley on the clinical examination. Imaging helps to identify recurrent tumour, though distinguishing the effects of treatment from cancer recurrence can be very difficult.
72
What imaging is used to detect recurring cancer?
. Imaging is usually with MRI and repeated imaging using the same modality can be used to monitor suspicious sites and make serial measurements. When both the clinical examination and MRI are uncertain, positron emission tomography PET can be used to measure glucose metabolism – cancer cells are more metabolically active than normal cells which can be useful to identify a site for biopsy.
73
What is the most important role of imaging in oral cancer?
Staging as accurate staging ensures that patients get the treatment that is appropriate for their disease.
74
What are the roles of the pathologist?
- Prior to treatment they establish/confirm the diagnosis and report on prognostic features
- During treatment they use a frozen section from surgery to determine the completeness of excision
- After treatment they determine the completeness of excision, report on factors important in prognosis and planning of further treatment
75
Prior to treatment what does a pathologist look at on an incisional biopsy?
- Depth of invasion - superficial or into underlying structures
- Pattern of invasion - are the tumour islands cohesive (invade all together) or non-cohesive (individual cells spread out - more aggressive so requires more aggressive treatment)
- Degree of differentiation - well, moderately or poorly differentiated
76
What does the pathologist do during treatment (surgery)?
Surgeons take biopsies around the specimen that they have removed and send to pathology to check they have removed all of the tumour. The section is frozen and placed in a tissue cutting machine. The section is stained with HNE and the pathologist determines whether the surgeon has completely excised the tumour. If not the surgeon may remove more tissue.
77
Why is a frozen section during surgery controversial?
- Prolongs operation
- Expensive and time consuming
- May not increase patient survival/prognosis
- Difficult to know where the section was taken from - margin may be large
- Frozen sample difficult to analyse under microscope as lots of blood as it has just been removed
78
What does a pathologist look at after treatment?
They need to look at the margins where the surgeon has cut to check they are clear of cancer. They need to look at extent of spread and completeness of excision. Look at:
- Surface diameter
- Depth of invasion
- Pattern of invasion - cohesive or non-cohesive
- Distance of tumour from mucosal and deep margins
- >5mm is a clear margin
- <5mm is a close margin
- <1mm or at margin is an involved margin
- Need to determine whether there is vascular or neural invasion as patients are likely to have recurrent disease if there is vascular or neural invasion as it can travel to another part of the body and recur there
- Establish whether tumour has spread to nodes
79
What does the histology show when there has been invasion of lymph nodes and ENE?
Dark cells are lymphocytes which you expect to see in lymph nodes. There will be epithelial cells but if there is no ENE they are enclosed in a capsule. If there is ENE the capsule will be obliterated and cancer has burst out of node.
80
What will be in the final report of a pathologist?
Primary tumour:
- Diameter of tumour
- Depth and pattern of invasion
- Grade of tumour (not grade of dysplasia), clearance from deep and mucosal incision margins
- Invasion into bone
- Clearance of bone margins
- Lymphatic, vascular or peri-neural invasion
Neck dissection:
- Number of nodes at each level
- Number of containing metastasis at each level
- pTNM stage
81
What stain is used for HPV?
p16 staining looks for HPV associated SCC.
82
What are the different locations of head and neck cancer?
- Larynx
- Oral cavity (floor of mouth, anterior 2/3 of tongue, alveolus, retromolar trigone, hard palate)
- Oropharynx
- Hypopharynx
- Nasopharynx
- Major salivary gland
- Nose and sinuses
- Bones of the jaw
- They have many common features but also important differences in biological behaviour.
83
What is a multidisciplinary approach?
A multidisciplinary approach involves drawing appropriately from multiple disciplines to explore problems outside of normal boundaries and reach solutions based on a new understanding of complex situations. It is person centred coordinated care.
84
Who is in the head and neck MDT team?
- Anaesthetist with a special interest in head and neck cancer
- Gastroenterologists, radiologist, surgeon, other health professionals with expertise in gastrostomy creation, feeding tube placement and support for patients who require tube feeding
- Ophthalmologist
- Pain management specialist
- Therapeutic radiographer
- Maxillofacial/dental technician
- Dental therapist/hygienist
- Benefits adviser
- Clinical psychologist
- Physiotherapist
- Occupational therapist
- Neurosurgeon (for skull base)
- Neuro-otologist (for skull base)
- Palliative care specialist (doctor or nurse)
- GMP
- GDP
85
What is stated in the oral rehabilitation 2013 contract?
There should be appropriate assessment of patient's oral rehabilitative needs across the pathway and the provider must ensure that specialist oral rehabilitation is provided.
Many patients face complex oral rehabilitation and dental health issues during and after oncology treatment so it is important to include a consultant in RD/oral rehabilitation in the MDT.
86
What do the SIGN guidelines say?
- 90% of patients presenting with head and neck cancer have dental disease but dental management is regarded by many patients as low priority in their treatment
- Oral/dental rehabilitation should be carried out by specialist practitioners with a working knowledge of the principles of radiotherapy and surgery
- Patients with head and neck cancer, especially those planned for resection or whose teeth are to be included in radiotherapy field should have the opportunity for a pre-treatment assessment by an appropriately trained experienced dental practitioner
87
What are the aims of a pre-treatment assessment?
- Avoidance of unscheduled interruptions to primary treatment as a result of dental problems
- Pre-prosthetic planning/treatment e.g. planning for primary implants/impressions for obturator
- Planning for extraction of teeth with doubtful prognosis or are at risk of dental disease in the future and are in an area where there would be a risk of osteoradionecrosis
- Extractions be carried out as early as possible in the patient journey but as a minimum at least 10 days prior to radiotherapy
- Planning for restoration of remaining teeth as required
- Preventive advice and treatment
- Assess potential for post treatment access difficulties e.g. trismus, microstomia
88
What are the short term side effects of treatment?
- Mucositis – inflammation and ulceration of the mucosal lining of the oral cavity
- Infection – chemotherapy induced neutropenia makes the patient susceptible to bacteria, viral and fungal infections. Oral candida infections are extremely common following chemo or radiotherapy
- Xerostomia – dry mouth resulting from a decrease in the production of saliva as a result of radiotherapy
89
What are the long term effects of treatment?
- Altered anatomy – surgical ablation and reconstruction can cause permanent changes in oral anatomy making prosthetic rehabilitation difficult
- Rampant dental cares – radiogenic dental caries is thought to be the result of reduced salivary flow as well as possible direct radiogenic damage to the amelodentinal junction by radiotherapy
- Trismus – may be caused by surgical scarring or by radiotherapy induced fibrosis of the masticatory muscles
- Mastication difficulties – if a significant number of opposing pairs of teeth are lost
- Osteoradionecrosis – hypovascularity and necrosis of bone followed by trauma induced or spontaneous mucosal breakdown leading to a non-healing wound
- Xerostomia – Challacombe
- IMRT reduces the risk of xerostomia and may also do for osteoradionecrosis after treatment
90
What preventative management can be done by a dentist?
- Maintenance of good OH by effective tooth brushing: flossing daily
- Dietary advice with regard to caries prevention
- Daily topical fluoride application (2800 or 5000ppm fluoride toothpaste) in custom made trays or brush on. Daily fluoride mouthrinse.
- Daily use of GC tooth mousse TM containing free calcium
- Saliva replacement therapy/use of frequent saline rinses
- Jaw exercises to reduce trismus (therabite)
91
What are the soft tissue and mandibular rehabilitation options?
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Soft tissue reconstruction:
- Radial forearm flap RFT
- Anterolateral thigh flat ALT
- Latissimus dorsi
- Rectus abdominus
- Flaps based on scapular/para-scapular axis
Mandibular reconstruction:
- Fibula flap
- Deep circumflex iliac artery flap DCIA
- Scapula flap
- RFF
Look at image in notes.
```
92
When should surgery or prosthodontics be used?
Prosthetic options reduce the morbidity of treatment and can give excellent results but reconstructive options should be considered as the defect becomes larger and more complex. The choice between reconstruction or prosthetics requires discussion between the ablative, reconstructive team and the prosthodontist, maxillofacial technician and the patient. There are clear advantages in simplifying the surgery and using prosthetic options but this choice becomes more difficult to deliver and for the patient to cope as the defect becomes larger and more complex. Obturators are used when there is a defect resulting in a communication between nose and mouth. Impressions can be difficult and patients may not be able to open mouth properly.
93
When are primary implants used?
- Where there is continuity of mandible
- In patients who require the prosthetic obturation of significant maxillary defects
- Where retention of the obturator is likely to be compromised
- In patients undergoing rhinectomy or orbital exenteration
94
What are the types of oral cancer?
- SCC 90%
- Adenocarcinoma
- Small cell carcinoma
- Sarcoma
- Lymphoma
- Skin - SCC, BCC, malignant melanoma, merkel cell tumour
When seeing a patient need to know types of cancer, stage, fitness of patient and patient wishes.
95
What investigations are needed?
- Clinical examination
- Blood tests
- Examination under anaesthesia
- Biopsy
- Imaging
- Of primary - MRI, CT
- Potential sites of metastatic disease (GDG-PET scan, CT scan thorax/CXR)
96
How can cancer be classified?
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Type of cancer cell:
- Glandular - adenocarcinoma
- Skin/mucosa - SCC
- Connective tissues - sarcoma
- Small cell - small cell carcinoma
Grade:
- Degree of differentiation usually G1-3
- TNM staging ( T size of tumour, N spread to lymph nodes and M spread to distal organs)
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97
What is HPV and who is it seen in?
Human papilloma virus is a DNA virus with orogenital transmission. It causes cervical and oropharyngeal SCC. It is considered a distinct disease entity. It is seen in younger patients <50 years of age and non-smokers and reduced alcohol exposure. It has an improved response to chemoradiation with a 28% reduced risk of dying and 49% reduced risk of local recurrence.
98
What are the disease stages?
Early is stage I-II and has a single modality approach. It has a favourable prognosis except in the nasopharynx. Late is stage III-IV, M0. This is the majority of the workload, it requires an MD approach. It is potentially curable and has significant sequelae - acute and late. In the oral cavity it usually means combined treatment - surgery, chemotherapy, radiotherapy.
99
What is the history of radiotherapy?
Radiotherapy has been used as a cancer treatment for 100 + years. Speciality grew in early 1900s due to work of Marie-Curie – polonium and radium. Radium used until the mid-1900s. Linear accelerators in 1940s.
100
What is radiotherapy?
Radiotherapy is the use of x-rays (ionising radiation) to treat cancer. Energy is higher in a therapeutic setting as opposed to diagnostic setting. Diagnostic x-rays are up to 150kv and therapeutic photons are 80kv-20Mv. The amount of radiation absorbed by the tissues is called the radiation dose or dosage and the unit of radiation is a gray (Gy). It is given in up to 50% of cancer patients. Ionising radiation interacts with water molecules to produce free radicals. Free radicals cause DNA damage. Malignant and normal cells are damaged. Damage to normal cells leads to side effects. Normal cells can repair if tolerance is not exceeded. It is oxygen dependent. The treatment machine is called a linear accelerator.
101
What are the considerations prior to radiotherapy?
- Nutritional requirements - feeding tube
- Dental assessment and treatment
- Speech and swallowing assessment - mouth and jaw exercises
102
How is radiotherapy delivered?
An immobilisation device is made which is a perspex head shell. This is to minimise involvement during radiotherapy and ensure accurate reproducibility in the treatment set up. It has reference marks. Need to keep patient very still and reproduce same position every day.
There needs to be localisation of tumour volume by clinical exam, radiology, knowledge of possible routes of spread, CT scan or x-ray fluoroscopy.
Then there needs to be defining target volume and critical structures. This includes tumour volume plus a margin of normal tissue. Critical structures include spinal cord, brain stem, eyes etc.
CT planning scan.
Define RT fields and treatment plan (dosimetrists and physicists). Prescribe dose and fractionation schedule which depends on site and intent of treatment. There needs to be verification during treatment to ensure fields are accurate and if any adjustments needed. Review of patient during treatment (nutrition - weekly dietetic review, commencing PEG nutrition, side effects). look at image.
103
What is the difference between early and late side effects for radiotherapy?
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Early (acute):
- Develop during or shortly after RT
- Very common
- Nearly always resolve
Late (chronic):
- Develop months to years (>40 years) after RT
- Very rare
- Irreversible and often severe
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104
What are the early effects of RT?
- General – nausea, lethargy, oedema
- Skin – redness, blistering/moist desquamation
- Mucosal surfaces – mucositis, ulceration, reduced taste, dysphagia
- Salivary function – sticky, dry
- Hair – loss in treated area
- Oesophagus – sore swallowing
- Lungs – pneumonitis (dry cough, breathlessness)
- Bowel – diarrhoea, abdominal pain, nausea
- Bladder – frequency, cystitis type symptoms
- Bone marrow – decrease in blood counts
- Neurological – Lhermitte’s syndrome
105
What are the late effects of RT?
- Skin - telangiectasia, fibrosis, necrosis
- Scalp – permanent hair loss with high dose
- Eyes – cataracts, reduced vision
- Lung – fibrosis, breathlessness
- Oesophagus, bowel – strictures/narrowing
- Kidneys – hypertension, renal failure
- Brachial plexus, spinal cord – sensory and motor impairment of limbs – swelling
- Endocrine – hypothyroidism, growth hormone deficiency, premature menopause
- Gonads – infertility, impotence
- Bone – impaired growth in children, necrosis
- Second malignancies
106
What is post-operative radiotherapy for?
It is adjuvant radiotherapy following surgery and for patients considered high risk of locoregional recurrence?
107
Who is at high risk of locoregional recurrence?
```
Primary disease:
- Involved or close margins
- Advanced T stage
- Lymphovascular invasion
- Perineural invasion
LN disease:
- Extracapsular spread LN
- LN >3cm in size
- More than 1 LN involved
- More than 2 LN involved
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108
What is palliation?
Palliation can be with chemotherapy or radiotherapy and this is when tumour is too advanced so cannot be cured. For chemotherapy you require a reasonable PS (WHO 0-2). It is useful in palliation of symptoms such as pain, difficulty in speech/swallow, halitosis due to tumour, ulceration tumour/nodal mass. Palliative radiotherapy is used to improve the quality of life in patients with recurrent, locally advanced or metastatic disease. It is used for bone and brain metastases, where cure is not possible, where patient is not fit to receive radical RT and if there is compression of vital structures e.g. spinal cord, SVCO. The intent is to relieve symptoms and minimise effects from treatment. It may prolong survival.
109
How can palliative treatment prolong life?
It prolongs life by 10 weeks to BSC. Untreated median survival is 4 months.
110
How are side effects minimised for palliative radiotherapy?
Small number of total fractions (sessions) using relatively low doses (some times large fraction size).
Radiotherapy is very useful for fungation, bleeding and pain. Re-treatment. Dose: few fraction 5-15, palliative dose (reduced toxicity).
111
How is radiotherapy technology developing?
It is developing rapidly to provide more accurate delivery, dose escalation, less toxicity, greater monitoring during treatment. New types:
- Conformal 3D radiotherapy
- IMRT
- Rotational treatment - rapid arc
- Robotic mounted treatment machines - cyberknife
112
What is anaplastology?
It is the restoration of absent parts of the body through artificial means. It is mostly to do with patient well being – may not want lots of surgery to reconstruct.
113
What are the odontogenic tissues?
```
Epithelium:
- Oral epithelium
- Dental lamina
- Enamel organ
- Reduced enamel epithelium
- Rests of malassez
Mesenchyme:
- Dental papilla
- Dental follicle
- Periodontal ligament
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114
What can remnants of odontogenic epithelium develop into?
- Hertwigs root sheath - radicular cysts
- Reduced enamel epithelium - dentigerous cysts
- Dental lamina - ameloblastoma, ameloblastic fibroma, CEOT, keratocyst, gingival cysts
115
What does the follicle contain?
The follicle contains odontogenic epithelium even though tooth formation is complete. These can proliferate and give islands of odontogenic epithelium. Lots of stem cell markers are in the dental lamina which allows it to grow and divide and some of these remain active.
116
What is the most common presentation and location of odontogenic tumours?
Most odontogenic tumours present as radiolucent lesions. Some may contain calcifications. Most are often at the angle of the mandible.
117
What is the classification of odontogenic tumours?
```
Benign (most common):
- Odontogenic epithelium alone
- Odontogenic epithelium and odontogenic mesenchyme +/- dental hard tissues
- Odontogenic mesenchyme alone
Malignant:
- Carcinomas and sarcomas
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118
What is the epidemiology of odontogenic tumours?
- Odontogenic neoplasms are rare
- Less than 1% of all oral tumours
- Ameloblastoma is the most common neoplasm 15%, then myxoma, then calcifying odontogenic cyst, then adenomatoid odontogenic tumour, then ameloblastic fibroma
- Odontomes are not neoplasms and are more common
119
What are the types in group 1: odontogenic epithelium alone?
- Ameloblastoma
- Adenomatoid odontogenic tumour AOT
- Calcifying epithelial odontogenic tumour CEOT
- Squamous odontogenic tumour SOT
120
What is an ameloblastoma?
It is benign but locally destructive. It occurs in age 30-50 and 80% in the mandible, mostly at the angle. Clinically it is often asymptomatic. There will be buccolingual expansion (not seen with keratocysts). There may be root resorption or displacement. Radiographically there will be a uni or multi-locular radiolucency. The bone on the lingual side of the mandible is thinner so if it comes through the bone it will most likely happen on the lingual side. This may cause a problem due to the medial pterygoid being on the lingual side of the mandible. So although the tumours are benign, they are destructive and will extend into tissue planes. Occasionally they can be fatal due to the way they expand and grow. They can be seen in the maxilla also.
121
What are the two components of ameloblastoma?
They often have two components – solid component (proliferation of epithelium) and cystic component. Once ameloblastomas become large they will be predominantly be cystic. If it is solid and large it is most likely malignant.
122
What are the subtypes of ameloblastoma?
```
Conventional type: intra-osseous 85%:
- Follicular
- Plexiform
- Many tumours contain both patterns
Unicystic: intraosseous 14%:
- Single cyst not multilocular
- Less common
- Controversial
Peripheral: extraosseous 1%:
- Not arising within jaw bone, arise in gingiva
- Dental lamina remnants can be in gingiva, not just in bone
Look at histology images in notes.
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123
What does the histology of ameloblastoma show?
In the follicular pattern there are columnar ameloblast like cells at the periphery and stellate like area in the centre. The epithelium resembles the enamel organ. Cysts form in stellate reticulum like areas.
In the plexiform pattern columnar ameloblast like cells form cords and there is little or no reticulum like areas. Cysts form in stroma.
124
How is a unicystic ameloblastoma managed?
A single cystic ameloblastoma with ameloblastomatous epithelium lining a cyst or with a little bit proliferating into the lumen (intraluminal type) can be called true unicystic ameloblastomas. These can be treated like any other cyst by enucleating. The literature supporting this is very poor. The variants of conventional ameloblastoma (mural and multicystic types) cause the problems and should be excised with a margin.
125
What is the management of ameloblastomas?
For conventional ameloblastomas they require excision with margins, reconstruction and the maxilla can be very challenging. The recurrence is 10% for radical treatment.
True unicystic types can be enucleated with careful follow up but these are very rare.
126
What mutations can be seen in ameloblastoma?
Mutations in genes SMO and BRAF which are involved in growth and development of tissues. Mutations in BRAF are seen in ameloblastoma in the mandible and SMO in the maxilla. Fibroblast growth factor receptor can also be mutated among many others.
127
What is an adenomatoid odontogenic tumour and the treatment?
Adenomatoid odontogenic tumour is benign and does not recur, probably a hamartoma. It is seen in age 10-20 and females more than males and most often in the maxilla. It is adenomatoid as it has some features that look like glands or ducts. There is a radiolucency often around a tooth crown which may have calcifications. The differential diagnosis will be dentigerous cyst. Enucleation is sufficient to cure as it is a hamartoma.
128
What is the histology of adenomatoid odontogenic tumour?
- Epithelial cells forming sheets and duct like structures
| - Calcification is common
129
What is a calcifying epithelial odontogenic tumour and the treatment?
Calcifying epithelial odontogenic tumour (Pindborg tumour) is benign but locally destructive. It occurs aged 10-60 and 2/3 are seen in the mandible, molar region +/- unerupted tooth. There will be a radiolucency with speckled calcifications. Treatment is the same as ameloblastoma - excision with a margin.
130
What is the histology for a calcifying epithelial odontogenic tumour?
It is composed of pleomorphic epithelium with calcifications, dentinoid and myloid. Enamel matrix material which may calcify and cuboidal cells with 'prickles'.
131
Is an odontogenic keratocyst a tumour?
The clinical evidence is the pattern of recurrence and the links to Gorlin Goltz. The genetic evidence is PTCH mutations (9q22-31) but these are also seen in dentigerous cysts. In 2005 the WHO changed the name to keratocystic odontogenic tumour KCOT but this was reversed in the 2017 classification.
132
What are the types in group 2: odontogenic epithelium and odontogenic mesenchyme +/- dental hard tissue?
- Ameloblastic fibroma
- Dentinogenic ghost cell tumour
- Odontomes
133
What is an ameloblastic fibroma and the treatment?
Ameloblastic fibroma is benign and occurs in age less than 20 and often in the mandible. It is a well defined radiolucency and 80% is associated with an unerupted tooth. Treatment is enucleation and they will not recur. Some of these tumours will develop dental hard tissue in them so may be developing into odontomes.
134
What is the histology of ameloblastic fibromas?
- Branching cords and islands of epithelium resembling the enamel organ or dental lamina
- Characteristic fine cellular stroma
135
What are dentinogenic ghost cell tumours?
They are benign, very rare and occur mostly in age 40-60 in males more than females and mandible or maxilla. There is a radiolucency which may have calcifications.
Treatment is resection
136
What is the histology of dentinogenic ghost cell tumours?
- Epithelium resembling ameloblastoma
- Ghost cells and dentine
- Overlap with calcifying odontogenic cyst
- Cells expand, differentiate and the nucleus has been dissolved and removed - ghost cells
137
What are odontomes and the types?
Odontomes are hamartomas: benign malformations (not neoplasms – they are developmental disorders). They occur aged up to 20 (developing dentition). It may be mandible or maxilla. There will be a radiolucency containing tooth like structures. The types are compound or complex. These lesions are enucleated and do not recur.
138
What are compound odontomes?
A compound odontoma is twice as common as a complex odontoma. It is more common in maxilla than mandible and seen in the incisor/canine regions. They are small and non-aggressive. A collection of denticles (mini teeth).
139
What are complex odontomes?
Complex odontomes are seen more in the mandible than the maxilla in the premolar/molar regions. They are seen in ages 10-25. There is often a missing tooth in the arch. They are a fused mass of haphazardly arranged tooth tissues but normal morphogenetic relations are preserved.
140
What are the types in group 3: odontogenic mesenchyme alone?
- Myxoma/myxo-fibroma (most common)
- Odontogenic fibroma
- Cementoblastoma
141
What is myxoma and myxo-fibroma, the histology and treatment?
Myxoma and fibromyxoma are benign but locally destructive. They are seen in 10-30 years mostly in the mandible. Clinically there is a slow growing painless swelling. It can be a uni or multi-locular radiolucency with a soap bubble appearance and root displacement or resorption. Histologically there are triangular/stellate cells in loose myxoid stroma, loose connective tissue. Treatment is the same as ameloblastoma.
142
What is odontogenic fibroma and the histology?
Odontogenic fibroma has a wide age range and males more than females. The mandible and maxilla have equal prevalence. There are central and peripheral types. It is most often a unilocular radiolucency. Histologically there is mature fibrous tissue and variable amounts of inactive odontogenic epithelium.
143
What is cementoblastoma and the histology?
Cementoblastoma is benign, occurs in age 10-40 and is usually in the mandible, affecting molar teeth. It is a radiopaque lesion attached to tooth root. Histologically there are sheets of cementum and osteoid in a mosaic pattern and many plump cementoblasts. It resembles osteoblastoma.
144
What are the malignant odontogenic tumours?
```
They are very rare. There are odontogenic carcinomas:
- Ameloblastic carcinoma
- Primary intra-osseous carcinoma
- Sclerosing odontogenic carcinoma
- Clear cell odontogenic carcinoma
- Ghost cell odontogenic carcinoma
- Odontogenic carcinosarcoma
- Malignant variants of other tumours/cysts
There are also odontogenic sarcomas.
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