Exam 2- White and Red Pre-Malignant Lesions Flashcards
A lesion which has a greater than normal risk of transformation to cancer.
Premalignant/precancerous lesion
A disease or habit associated with greater than normal risk to develop a premalignant lesion or cancer in tissues affected.
Premalignant/precancerous condition
T/F Precancerous/premalignant doesn’t mean it will turn into cancer it just means has the possibility to turn into cancer.
True
Oral mucosa- mostly ____________, strat squam epi except for hard palate and gingiva which is __________.
parakeratinized, orthokeratinized
T/F Skin is orthokeratinized strat squam epi.
True
What are the 4 layers of strat squam we talked about?
- Corneum
- Granulosum
- Spinosum (prickle layer)
- Basale
True/False Elderly have more keratin because overtime skin gets more keratinized.
False
*.Bottom of the foot is more keratinized as you age looked keratin.
To say something is histologically premalignant you have to show there is _________ _________.
Epithelial dysplasia
What is “epithelial dysplasia”?
alteration of epithelial maturation (dysmaturation)
What are the two dysplasia changes talked about in class?
- Architectural changes (FAR)
- Cytologic changes (CLOSE UP)
What are the architectural changes? (4 we discussed)
- Bulbous, round, tear drop shaped rete ridges
- Loss of polarity (cells pushing of BM) the cells are crowded and jumbled
- Keratin or epithelial pearls (concentrically layered keratinized cells)
- Loss of epithelial cell cohesiveness
Precancerous/premalignant invade into the underlying tissue.
FALSE- the Basement membrane is intact no invasion
Cytologic changes for premalignant lesions
- Enlarged cells, nuclei and nucleoli
- Increased ___________/____________ ratio (nucleus larger less cytoplasm)
- _______________
- Pleomorphism (cellular and nuclear size changes)
- Increased, altered and displaced ______
- Dyskeratosis - premature keratinization of individual cells
- Enlarged cells, nuclei and nucleoli
- Increased nuclear/cytoplasmic ratio (nucleus larger less cytoplasm)
- Hyperchromatism
- Pleomorphism (cellular and nuclear)
- Increased, altered and displaced mitoses
- Dyskeratosis - premature keratinization of individual cells
Cytologic changes for premalignant lesions
- Enlarged cells, nuclei and nucleoli
- Increased nuclear/cytoplasmic ratio (nucleus larger less cytoplasm)
- _________________
- _________________ (cellular and nuclear)
- Increased, altered and displaced mitoses
- ___________ - premature keratinization of individual cells
- Enlarged cells, nuclei and nucleoli
- Increased nuclear/cytoplasmic ratio (nucleus larger less cytoplasm)
- Hyperchromatism
- Pleomorphism (cellular and nuclear)
- Increased, altered and displaced mitoses
- Dyskeratosis - premature keratinization of individual cells
The thickness of the altered epithelium affected determines the “_______” of dysplasia.
grade
The thickness of the altered epithelium affected determines the “grade” of dysplasia.
Mild dysplasia lower ____
Moderate dysplasia lower _____
Severe dysplasia lowe ______
Carcinoma in Situ (CIS) ________ _________ dysplasia with no maturation (no keratin even being made on the surface, cells at the bottom look like the cells at the top they are not maturing at all)
Mild dysplasia lower 1/3rd
Moderate dysplasia lower 1/2
Severe dysplasia lowe 2/3rd
Carcinoma in Situ (CIS) full thickness dysplasia with no maturation.
T/F Dysplasia and CIS are NOT cancer as there is no invasion with access to blood and lymphatics.
True
Gray Area
Some clinical white lesions don’t show dysplasia but are still microscopically abnormal. They may be diagnosed as:
__________ = thickened keratin layer
Hyperkeratosis + ________ = thickened keratin layer and basal/parabasal cell layers are altered
Epithelial hyperplasia or _________ = _________ layer is thickened
Hyperkeratosis = thickened keratin layer
Hyperkeratosis + atypia = thickened keratin and basal and parabasal cell layers are altered
Epithelial hyperplasia or acanthosis = spinous layer is thickened
Statistics of Smokeless tobacco keratosis.
In US ____% of all people 12 yrs, _____% of of male high schoolers. More common in ______ and _________.
Habit start ______yrs. The younger the pt the more likely and stronger the addictions
In US 3.2% of all people 12 yrs, 13% of of male high schoolers. More common in southeast and midwest.
Habit start 8-14yrs. The younger the pt the more likely and stronger the addiction.
Name the pathology:
Gray/white, translucent plaque with rippled appearance and blending borders. Probably not a true leukoplakia.
Blending border usually - thickened layer of keratin and thickened epi some. Some cases dysplasia. History of smokeless tobacco use.
Smokeless tobacco keratosis
How do you tx Smokeless tobacco keratosis?
Resolution expected within 6 wks (usually 2-3 wks) of changing placement site of product
Biopsy leathery or nodular areas
Name the pathology:
Chronic progressive scarring disease and high-risk precancerous condition associated with betel nut chewing
Oral Submucous Fibrosis
Where are you likely to find Oral Submucous Fibrosis (demographics)?
Southeast asia and India
___% of the world’s population has a betel nut chewing habit
20%
T/F In the US and Europe there is very little evidence for significantly increased risk between smokeless tobacco and oral cancer.
True
Dysplasia is seen infrequently for smokeless tobacco ___%
Compared to ______% for leukoplakia.
3%; 5-25%
T/F In india and southeast asia (betel quid) significant increased risk for leukoplakia and oral cancer.
True!
Betel quid w/ tobacco (odds ratio= 7.46)
Betel quid w/o tobacco (odds ratio = 2.82)
Nut of the areca palm is wrapped in the leaf of a piper betel vine, together with slaked lime (CaOH), tobacco and spices.
What enhances the alkaloids released from the areca nut?
Slaked lime (calcium hydroxide)
What 2 things does the areca nut release?
Alkaloids and Flavenoids
What do alkaloids vs flavonoids do?
Alkaloids - stimulate _______ _______ (making tissue look white and fibrous) and cause _________
Flavonoids- inhibit ____________
Activated inflammatory cells release cytokine/growth factors which promotes _______
_________ is carcinogenic leading to epithelial dysplasia
Alkaloids - stimulate collagen synthesis (making tissue look white and fibrous) and cause euphoria
Flavonoids- inhibit collagenase
Activated inflammatory cells release cytokine/growth factors which promotes fibrosis.
Tobacco is carcinogenic leading to epithelial dysplasia
When talking about betel quid what stimulates collagen synthesis (making tissue look white and fibrous) and cause euphoria?
Alkaloids
When talking about betel quid what inhibits collagenase?
Flavonoids
Signs and symptoms of ______ ________ _________ may occur as soon as 2-3 yrs (commercial paan) with 2-5 quids/day with daily frequency being more important than duration.
Name a few signs and symptoms.
oral submucous fibrosis
Fibrous band with oral pallor leading to increasing trismus.
Oral burning sensation (stomatophyoris).
Vesicles, petechiae, xerostomia
Some pt develop leukoplakia that can become dysplastic or turn into oral cancer
T/F Some pt with oral submucous fibrosisi develop leukoplakia that can become dysplastic or turn into oral cancer
True
T/F Cessation of betel nut stops OSF.
False but pt should still discontinue it
T/F All pt with oral submucous fibrosis should be biopsied to confirm the diagnosis and assess for dysplasia (~10% at initial dx)
True
How do you tx oral submucous fibrosis?
DEF biopsy 10% show dysplasia at initial diagnosis
Approximately _____% of oral submucous fibrosis will undergo malignant transformation to _______.
Approximately 8% of oral submucous fibrosis will undergo malignant transformation to squamous cell carcinoma.
When treating oral submucous fibrosis how would you treat mild cases of trismus vs severe cases?
intralesional corticosteroids may improve mild cases
severe cases may require surgical splitting of fibrous bands, with skin grafts and mouth props, physiotherapy
Name the pathology:
WHO defines it as “a white patch of plaque that cannot be characterized clinically or pathologically as any other disease”
Leukoplakia
What is the most common oral premalignant lesion?
Leukoplakia
Demographics of oral leukoplakia.
Men over age 40
1.5-4.3% prevalence worldwide
Description of a leukoplakia:
Often sharply demarcated white ______ or _______
Variable surface texture
thin or thick
Smooth or rough
granular/nodular or verrucous
homogeneous vs non-homogeneous
If red component is present, called “________ leukoplakia” or “_______________”
Patch or plaque
“speckled leukoplakia” or “erythroleukoplakia”
Normal Mucosa→ ______ _______ leukoplakia → _______ _________ leukoplakia → Granular, __________ leukoplakia (moderate/severe dysplasia with inflammation) → Erythroleukoplakia (becomes thinner and loses ______ production because cells are now so abnormal, _________ , red areas, ulceration, severe dysplasia or carcinoma in situ)
Normal Mucosa→ Thin smooth leukoplakia → Thick fissured leukoplakia → Granular, verruciform leukoplakia (moderate/severe dysplasia with inflammation) → Erythroleukoplakia (becomes thinner and loses keratin production because cells are now so abnormal, atrophy, severe dysplasia or carcinoma in situ)
Almost all leukoplakias have some degree of __________ (wet keratin appears white) and/or __________ (thickening of the spinous/epithelial cell layer).
Almost all leukoplakias have some degree of hyperkeratosis (wet keratin appears white) an/or acanthosis (thickening of the spinous/epithelial cell layer).
What proves a lesion is premalignant?
Demonstration of epithelial dysplasia histologically
T/F If dysplasia is not seen you dont have to worry about the lesion being premalignant.
False
No dysplasia does NOT mean a lesion doesn’t have premalignant potential.
clinical correlation is needed
How do you tx a leukoplakia with moderate or worse dysplasia?
Remove by the most convenient means available (excision, laser, electrocautery, or cryosurgery, etc.)
How do you tx a leukoplakia with Mild dysplasia or hyperkeratosis with atypia?
Tx varies
Discontinue carcinogen habits (smoking) may lead to resolution
Mild dysplasia may be removed or observed very closely based on size, location etc.
Malignant transformation risk of leukoplakia by clinical appearance:
Thin leukoplakia-seldom transform without clinical alteration
Thick homogenous leukoplakia ___%
Granular or verruciform ____%
Non-homogeneous higher risk
Erythroleukoplakia _____%
Thin leukoplakia-seldom transform without clinical alteration, likely not to progress
Thick homogenous leukoplakia 1-7%
Granular or verruciform 4-15%
Non homogeneous higher risk
Erythroleukoplakia 28%
Malignant transformation risk of leukoplakia by site:
What are the high risk sites?
- Lateroventral tongue
- floor of mouth
- soft palate/tonsillar pillar
- lip vermillion
Malignant transformation risk of leukoplakia by site:
What are the intermediate risk sites?
Gingiva
Malignant transformation risk of leukoplakia by site:
What are the low risk sites?
- Buccal mucosa
- hard palate
- dorsal tongue
*note buccal mucosa is a high risk site when pt is using betel quid
Malignant transformation risk of leukoplakia by dysplasia :
Non-dysplastic leukoplakia ______%
Mild _____%
Moderate ______%
Severe _______%
All dysplasia combined <___% per year and ____% over time
Non-dysplastic leukoplakia 0.85-2%
Mild 4%
Moderate 4-11%
Severe 20-43%
All dysplasia combined <2% per year and 12% over time
Other risk factors of leukoplakias.
Though leukoplakia occurs more often in men, women who are older age with no risk factors have more risk for them to turn into cancer when they develop. Note: females dont develop leukoplakias as much as men
What percent of leukoplakias recur even after excision?
1/3rd
After a leukoplakia has been discovered when is the timeframe till transformation to occur?
2-4 years but can be variable so need to follow closely
What is the typical follow up plan for an excised leukoplakia with dysplasia vs one without dysplasia?
Every 3 months for an excised leukoplakia with dysplasia
every 6 months for leukoplakia without dysplasia (but if other risk factors then follow up every 3 months)
Name the pathology:
A red patch/plaque that cannot be clinically or pathologically diagnosed as any other condition
Erythroplakia
Name the pathology:
Velvety red, well-demarcated patch, usually affecting the lateral tongue, floor of the mouth or soft palate
Erythroplakia
T/F Generally Erythroplakia are painless.
True
What is the Red appearance in erythroplakia due to?
lack of surface keratin production and epithelial atrophy
T/F Erythroplakia has a greater risk for transformation than a leukoplakia.
False
Erythroplakia has the same risk factor as leukoplakia but generally more advanced when detected.
Microscopically ____% of these erythroplakia lesions have severe epithelial dysplasia or worse at the time of biopsy.
90%
How do you tx an erythroplakia?
Similar to that of leukoplakia having similar degree of epithelial dysplasia - surgical excision often preferred to rule out cancer
T/F Leukoplakia and erythroplakia are pretty well demarcated.
True
Name the pathology :
Multiple leukoplakias, often extensive, that spread and thicken over time
Proliferative Verrucous Leukoplakia (PVL
T/F Proliferative Verrucous Leukoplakia is associated with HPV.
False no assoicaiton with HPV
What is the common site to find Proliferative Verrucous Leukoplakia?
Gingiva but other sites can be affected as well
T/F Proliferative Verrucous Leukoplakia is uncommon but has a high risk presentation.
True
Demographic Proliferative Verrucous Leukoplakia.
Female predilection (4:1), mean age 65 yrs, only 1/3rd have traditional risk factors (NO smoking or alcohol history usually)
Only _____ of those diagnosed with Proliferative Verrucous Leukoplakia have traditional risk factors (NO smoking or alcohol hx usually).
1/3rd
Name the pathology:
Early lesions does not usually show dysplasia. Most of these lesions have Hyperkeratosis/hyperplasia with variable dysplasia, maybe atypia, often verrucous surface.
Proliferative Verrucous Leukoplakia
In a study done about _____% of pt diagnosed with Proliferative Verrucous Leukoplakia develop ______. About _____% actually died from cancer.
64% ; SCCa within a mean follow up of 7.4 years; 40%
How do you tx Proliferative Verrucous Leukoplakia (PVL)?
Optimal tx remains to be determined
Surgical or ablative therapy, but recurrence common
(cherry pick the worst areas)!!!
Malignant transformation is a frequent complication, even in lesions without previous biopsy evidence of dysplasia
T/F Malignant transformation is a frequent complication with Proliferative Verrucous Leukoplakia, even in lesions without previous biopsy evidence of dysplasia.
True
Red or white lesions that persist for more than 2-3 wks that cannot be ascribed to any known causes must get a…
BIOPSY!
What is the etiology of actinic cheilitis?
chronic sun exposure
Name the pathology:
* Term for actinic keratosis (precancerous skin conditions) involving the vermillion zone of the lower lip
Actinic Cheilitis
T/F Actinic Cheilitis has a strong female predilection.
False - male predilection
What is the clinical progression of actinic cheilitis?
- Atrophy (blotchy pale) dryness, fissures
- scaly/crusty and thickening
- leukoplakia
- ulceration
How do you tx Actinic Cheilitis (Cheilitis)?
Typically excision (scalpel or laser) - incisional biopsy
Long term follow up is recommended for actinic cheilitis as ____x increased risk for cancer of the lip.
2x
Tobacco Smoking Stats:
___% males smoked in 1940s
___% of adults smoked today
___% in kentucky
Dose dependent __x more likely to develop cancer 2pk/day
___x more likely 4pks/day
65% males smoked in 1940s
15% of adults smoked today
26% in kentucky
Dose dependent 5x more likely to develop cancer 2pk/day
17x more likely 4pks/day
___% of those with oral cancer are smokers
80%
T/F Pipe and cigar have greater oral cancer risk than cigarettes
True
Value in smoking cessation
Leukoplakias with no or mild dysplasia can shrink
____ yrs after cessation, cancer risk approximates that of non-smokers
Risk for 2nd primary upper aerodigestive tract carcinoma = _____x greater in those that continue to smoke compared to that that quit after first cancer
Leukoplakias with no or mild dysplasia can shrink
10 yrs after cessation, cancer risk approximates that of non-smokers
Risk for 2nd primary upper aerodigestive tract carcinoma = 2-6x greater in those that continue to smoke compared to that that quit after first cancer
T/F 10 yrs after cessation, cancer risk approximates that of non-smokers
True
Generally cancer of the hard palate is very rare, what is one risk factor for oral cancer of the hard palate?
Reverse smoking (in south america and india)
Up to 50% of oral malignancies in these population occur on the hard palate
What is the oral cancer risk associated with marijuana?
Meta analysis can’t confirm or refute an association between head and neck cancer and marijuana use, however a recent cohort study shows an association still need more data
T/F There is an increase risk of oral cancer with heavy alcohol use.
True
Heavy alcohol (4+ beverages a day) 2-14x increase risk this yr said 30 fold increase risk
T/F Tobacco and alcohol have a synergistic effect to develop cancer.
True RR=15
How does alcohol lead to cancer development?
Ethanol -> acetaldehyde (carcinogenic)
Carcinogenic impurities in alcoholic drink
Drys tissues out, thought to increase permeability of epithelium and solubility of carcinogens
HPV-associated (mostly HPV-16) oropharyngeal squamous cell carcinoma (OPSCC) has increased dramatically:
Pt tend to be ____ yr younger
Increased in _____
_______ socioeconomic group
Strong association with _________ __________
Conflicting data on tobacco/alcohol association
Pt tend to be 10 yr younger
Increased in whites
Higher socioeconomic group
Strong association with sexual behavior
Conflicting data on tobacco/alcohol association
T/F There is a more favorable prognosis for HPV oropharyngeal cancer (~30%) compared to those that dont have HPV in them.
True
Old studies used _____ to test for the presence of HPV getting around 20-40% but the presence of the virus didn’t actually tell you if it was leading to cancer.
Now and days the expression of viral oncogenes ____ and ___ mRNA are the gold standard for determining clinically relevant HPV infections (directly in the genome). When tested this way the prevalence drops to around ____%. ___% in the largest study.
HPV___ is the predominant type.
Old studies used PCR to test for the presence of HPV getting around 20-40% but the presence of the virus didn’t actually tell you if it was leading to cancer.
Now and days the expression of viral oncogenes E6 and E7 mRNA are the gold standard for determining clinically relevant HPV infections (directly in the genome). When tested this way the prevalence drops to around 0-9%. 6% in the largest study. This is for people who have ORAL cancer.
HPV16 is the predominant type.
T/F Oropharynx has a stronger association with HPV associated cancer than HPV oral associated cancer.
True
T/F. Oral SCC 20-40% transcriptionally active HPV. Where as OPSCC, 56% have transcriptionally active HPV
False
Oral SCC transcriptionally active HPV 6%
OPSCC transcriptionally active HPV 56%
T/F Given diff tx and better survival, all OPSCC or cervical lymph node metastasis of unknown primary should be tested for high risk HPV.
True!
T/F It is NOT recommended to routinely test for HPV in oral cancers.
True!
T/F UV irradiation (sunlight exposure)
Chronic exposure is main cause of actinic cheilitis → lip cancer.
True
T/F X-irradiation (radiotherapy to H&N region)
Decreases immune response and causes alteration in DNA. Increase risk of new primary malignancy either carcinoma or sarcoma
True!
What forms of immunosuppression increase risk for oral SCC and other Head and Neck malignancies?
Pt with AIDS
Pt being tx for malignancy with immunosuppression
Pt who had organ transplant
What Anti-microbial/anti-inflammatory herbal extract (blood-root plant) added to oral hygiene products in the 90s had a strong association for development of oral cancer?
Sanguinaria
What Anti-microbial/anti-inflammatory herbal extract was associated with the development of leukoplakia in unusual sites ( maxillary vestibule or alveolar mucosal)?
Sanguinaria
T/F Sanguinaria: unknown if increases risk of cancer development (not proven) but pt should stop use if this is seen
True
What are some historical theories of oral cancer etiologies?
Oral sepsis - bad oral hygiene
Broken teeth
Dentures
Galvanism (two dissimilar metals - electrical zapping)
Mouthwashes (alcohol containing or not)
Routine dental radiography
Other bacteria (not a proven risk factor)
Oral bacteria may interact with tobacco and alcohol increasing acetaldehyde
Perio bacteria - association with oral cancer not confirmed due to variable results
Candida (not a proven risk factor) Can overlay leukoplakia but not causing them
Some strains may metab ethanol to acetyladlehyde or produce nitrosamines but link to oral cancer NOT shown
T/F Candida is not a proven risk factor for oral cancer. But can overlay leukoplakia but not causing them
Some strains may metab ethanol to acetyladlehyde or produce nitrosamines but link to oral cancer NOT shown.
True
Molecular carcinogenesis:
Tumor suppressor genes can exhibit what three things?
- Loss of heterozygosity (LOH)
- Hypermethylation (P16 and RAR-B2)
- Mutation in TP53
This leads to inactivation and tumor growth.
Molecular carcinogenesis:
What are 3 things Dr. Shumay mentioned that are often overexpressed in cancers?
- EGFR
- Telomerase
- Cyclin D1
Leads to increased cell growth.
T/F In molecular carcinogenesis there is usually increasing polysomy (extrachromosomal copies)
True!
Oral Intra epithelium dysplasia cycle:
Initial genetic insult -> ______ -> ______ and _______ methylation –> _____ mutation
Mucosal damage -> ______, ___________ activation -> COX2 upregulation -> _________ overexpression -> increased proliferation / mutations
Initial genetic insult -> LOH -> RAR-B and P16 methylation –> P53 mutation
Mucosal damage -> EGFR, telomerase activation -> COX2 upregulation -> Cyclin D1 overexpression -> increased proliferation / mutations
What is the gold standard oral cancer diagnostic technique?
Scalpel biopsy
What are the 5 adjunct to clinical evaluation/biopsy?
- Cytology
- Toluidine Blue
- Vizilite
- Velscope
- Brush biopsy
Name the adjunct to clinical evaluation/biopsy:
Helpful maybe for lesions like PVL
Not recommended as indication for use would also require scalpel biopsy, but good for widespread lesions because you dont want to cut everywhere.
Brush biopsy
Name the adjunct to clinical evaluation/biopsy:
Stain used to identify lesiona area—- red lesions most useful, does not work for white lesions because dye does not get absorbed
Toulidine blue
T/F Toluidine blue is great to identify white lesions.
False red lesions doesn’t stain white lesions
Name the adjunct to clinical evaluation/biopsy:
acetic acid wash to help make tissue whiter wave a wand on it to help it stand out, may help visualize subtle leukoplakia but limited application. Dr. Shumway says not to get
Vizilite
Name the adjunct to clinical evaluation/biopsy:
margin delineation but insufficient evidence for us as a screening device
Most utility out of all adjuncts
Note a lot of false + though
Velscope
Name the adjunct to clinical evaluation/biopsy:
scrape with spatula limited application of red lesions, send off to lab
same as brush biopsy
Cytology
