Premalignant White/Red Lesions Flashcards
Premalignant/Precancer lesion
A lesion which has a greater than normal risk of transformation to cancer
Premalignant/Precancerous condition
A disease or habit associated with greater than normal risk to develop a premalignant lesion or cancer in tissues affected
Describe normal oral mucosa histoloy
Mostly parakeratinized, stratified squamous epithelium except for gingiva and palate which is orthokeratinized
Describe normal skin histology
Orthokeratinized, stratified squamous epithelium
To be histologically premalignant, a lesion must show….
“epithelial dysplasia” = alteration of epithelial maturation (dysmaturation)
Epithelial Dysplasia
The thickness of the altered epithelium affected determines the “grade”
-Mild dysplasia (lower 1/3)
-Moderate dysplasia (lower 1/2)
-Severe dysplasia (lower 2/3)
-Carcinoma in situ (CIS) - full thickness dysplasia with no maturation (no keratin, cells at bottom = cells at top)
**Note: dysplasia and CIS are NOT cancer as there is no invasion with access to blood and lymphatics
What are the architectural changes (overall, low-power appearance) seen histologically with dysplasis/CIS?
-Bulbous, tear-drop shaped rete ridges
-Loss of polarity (maturation to the surface)-cells are crowded and jumbled
-Keratin or epithelial pearls (concentrically layered keratinized cells)
-Loss of epithelial cell cohesiveness (but intact basement membrane - lack of invasion)
What are the cytologic changes (how single cells are altered) seen histologically with dysplasis/CIS?
-Enlarged cells, nuclei and nucleoli
-Increased nuclear/cytoplasmic ration
-Hyperchromatism
-Pleomorphism (cellular and nuclear)
-Increased, altered and displaced mitoses
-Dyskeratosis - premature keratinization of individual cells
Describe the histologic gray area
Some clinical white lesions don’t show dysplasia but are still microscopically abnormal. They may be diagnosed as:
1. “hyperkeratosis” - thickened keratin layer
2. “hyperkeratosis and atypia” - thickened keratin and basal and parabasal cell layers are altered
3. “epithelial hyperplasia” or “acanthosis” - spinous layer is thickened
**Based on the clinical presentation, some may have premalignant potential, and require follow up.
Smokeless tobacco keratosis
-Gray/white, translucent plaque with rippled appearance and blending borders
-Probably not a true leukoplakia - small increased risk for oral cancer for moist snuff, chewing tobacco
-Resolution expected within 6weeks (usually 2-3wks) of changing placement site of product
-Biopsy leathery or nodular areas
Oral Submucous Fibrosis (OSF)
Chronic progressive scarring disease and high-risk precancerous condition associated with betel nut chewing
OSF clinical
Signs/symptoms may occur as soon as 2-3yrs (commercial paan) with 2-5 quids/day with daily frequency being more important that duration.
-Vesicles, petechiae, xerostomia and generalized oral burning sensation (stomatopyrosis) with intolerance to spicy foods
-Gradual collagen deposition causes fibrous bands with oral pallor and stiffness leading to increasing trismus
-Some patients also develop leukoplakia that can become dysplastic or turn into oral cancer
OSF management
-Patients should discontinue the betel nut habit. Cessation doesn’t stop OSF though
-Cancer risk:
1. All patients with oral submucous fibrosis should be biopsied to confirm the diagnosis and assess for dysplasia (approx. 8% undergo malignant transformation to SCC)
-If there is trismus:
1. Intralesional corticosteroids may improve mild cases
2. Severe cases may require surgical splitting of fibrous bands, with skin grafts and mouth props, physiotherapy
Leukoplakia definition
Leuko=white; plakia=patch
-WHO original definition: “a white patch or plaque that cannot be characterized clinically or pathologically as any other disease”
-Clinical term only. Should be used after exclusion of known entities that produce white patches/plques
-When defined this way (i.e. other clinical entities are excluded), leukoplakia can be considered a premalignant lesion
-Male predilection, usually >40yrs
Diagnoses that must be excluded: NOT leukoplakia
-Leukoedema
-Cheek chewing
-Frictional keratosis
-Nicotine stomatitis
-Smokeless tobacco keratosis
-Chemical burn
-Candidiasis
-Lichen planus
-Contact reaction
What is the most common oral premalignant lesion?
Leukoplakia
Describe how Leukoplakia looks
-Often sharply demarcated white patch or plaque
-Variable surface texture:
1. thin or thick
2. smooth or rough
3. granular/nodular or verrucous
4. homogeneous vs. non-homogeneous
-If red component is present, called “speckled leukoplakia” or “erythroleukoplakia”
Describe the Leukoplakia phases
- Normal mucosa
- Thin, smooth leukoplakia –> hyperkeratosis, acanthosis, lymphocytes
- Thick, fissured leukoplakia –> hyperkeratosis, acanthosis, lymphocytes, dysplasia (mild/moderate)
- Granular, verruciform leukoplakia –> irregular hyperkeratosis, bulbous rete pegs, lymphocytes, moderate/severe dysplasia, congested vessels, candida hyphae
- Erythroleukoplakia (speckled leukoplakia) –> irregular hyperkeratosis, bulbous and crowded rete pegs, epithelial atrophy, lymphocytes, severe dysplasia, carcinoma in situ, congested vessels
Leukoplakia Histology
-Some degree of hyperkeratosis (wet keratin appears white) and/or thickening of the spinous cell layer (acanthosis)
-Demonstration of epithelial dysplasia histologically proves lesion is premalignant
-….but if dysplasia is not seen does NOT mean that it doesn’t have premalignant potential (clinical correlation needed)
Leukoplakia Tx
-Moderate dysplasia or worse: remove by the most convenient means available (excision, laser, elctrocautery, cryosurgery, etc.)
-Mild dysplasia or hyperkeratosis with atypia - tx varies:
1. D/C carcinogenic habits (smoking) may lead to resolution
2. Mild dysplasia may remove or observe very closely based on size, location, etc.
Leukoplakia malignant transformation risk
The higher grade you go, the higher the cancer risk (think of the phases photo)
White (leukoplakia) or red (erythroplakia) patches/plaques show variable risk to show dysplaisa or SCC based on the location where they occur.
List the high risk sites, intermediate risk sites, and low risk sites.
High Risk:
-lateroventral tongue
-floor of mouth
-soft palate/tonsillar pillar
-lip vermilion
Intermediate Risk:
-gingiva
Low Risk:
-buccal mucosa
-hard palate
-dorsal tongue
List the features that increase the risk that leukoplakia will progress to cancer
-The site (high-risk sites more than low-risk sites)
-The appearance (non-homogenous, red/speckled or ulcerated lesions are higher risk)
-Presence of dysplasia
-Increasing dysplasia grade
Erythroplakia
Erythro=red, plakia=patch/plaque
-A red patch/plaque that cannot be clinically or pathologically diagnosed as any other condition
-Prevalence = <1.0%
-Velvety red, well-demarcated patch, usually affecting the lateral tongue, floor of the mouth or soft palate
-Red appearance is due to the lack of surface keratin production and epithelial atrophy
List the risk factors, histologic appearance, tx and prognosis for Erythroplakia
Risk Factors:
-same risk factors as leukoplakia, but generally more advanced when detected
Histologic Appearance:
-Microscopically, 90% of these lesions are severe epithelial dysplasia or worse at the time of biopsy
Tx and Prognosis:
-Similar for that of leukoplakia having a similar degree of epithelial dysplasia
-Surgical excision often preferred to rule out cancer
Proliferative Verrucous Leukoplakia (PVL)
-Uncommon, high-risk presentation of leukoplakia
-NOT associated with HPV
-Multiple leukoplakias, often extensive, that spread and thicken over time
-Often involve the gingiva. Other sites may be affected as well
-Female predilection, mean age 65yrs
-Hyperkeratosis/hyperplasia with variable dysplasia, often verrucous surface
Proliferative Verrucous Leukoplakia Tx
-Optimal tx remains to be determined
-Surgical or ablative therapy, but recurrence common
-Malignant transformation is a frequent complication, even in lesions without previous biopsy evidence of dysplasia
Red or white lesions that persist for more than 2-3wks that cannot be ascribed to any known causes must get a….
BIOPSY
Actinic Cheilosis (Cheilitis)
-Term for actinic keratosis involving the vermillion zone of the lower lip
-Strong male predilection
-Clinical progression: atrophy (blotchy pale), dryness, fissures –> scaly/crusty and thickening –> leukoplakia –> ulceration
-Tx: typically excision (scalpel or laser)
-Prognosis: long term f/up recommended as 2x increased risk for cancer of the lip
Hairy Leukoplakia
-Epstein-Barr Virus (EBV) induced lesion often with superimposed candidiasis
-Usually HIV-infected or other immune compromise. Rare in healthy pts.
-Non-removable white plaque(s) of the lateral tongue
-Faint vertical strands to thick furrowing with shaggy keratotic surface
-Tx: usually resolves with control of HIV infection
Histopathology of Hairy Leukoplakia
-Thick, irregular parakeratin
-Candida infection
-Hyperplastic (thicker) epitherlium with “balloon cells” that show EBV by in situ hybridization
-No dysplasia
-Minimal inflammation
List the etiology of oral cancer and oral precancerous lesions
-Tobacco (smoked/smokeless)
-Alcohol
-HPV
-Radiation (UV or therapeutic)
-Immunosuppression
-Uncommon causes - won’t discuss
What is the value in smoking cessation?
-Leukoplakias with no or mild dysplasia may 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 those that quit after first cancer
Reverse Smoking
-Placing burning end inside mouth
-Up to 50% of oral malignancies in these populations occur on the hard palate
Marijuana association
Recent research can’t confirm or refute association between head and neck cancer and marijuana use
Alcohol association
-Heavy alcohol use (4+ beverages/day) = 2-14 fold increase risk
-With tobacco there is a synergistic effect to develop cancer, RR = 15
-Pathogenesis:
1. ethanol –> acetaldehyde (carcinogenic)
2. carcinogenic impurities in alcoholic drinks
3. may increase permeability to epithelium and solubility of carcinogens
HPV - oral cavity
-Role in oral cavity carcinogenesis is uncertain
-Expression of viral oncogenes E6 and E7 mRNA is not the gold standard for determining clinically relevant HPV infection. HPV16 is the predominant type
HPV testing
-All OPSCC or cervical lymph node metastases of unknown primary should be tested for high-risk HPV
-It is NOT recommended to routinely test for HPV in oral cancers
Radiation
-UV radiation (sun exposure) - chronic exposure is main cause of actinic cheilitis –> lip cancer
-X-irradiation:
1. decreases immune response and causes alterations in DNA
2. increased risk of new primary malignancy (either carcinoma or sarcoma)
Immunosuppresion
Increased risk for oral SCC and other H&N malignancies for patients
-with AIDS
-on immunosuppressive tx for malignancy
-having received an organ transplant
Sanguinaria
-Antimicrobial/anti-inflammatory herbal extract added to OH products
-Strong association with maxillary vestibule or Mx alveolar mucosal leukoplakia
-Unknown if increases risk of cancer development (not proven)
List things that are NOT a cause of premalignancy or oral cancer
-Oral sepsis - bad OH
-Broken teeth
-Dentures
-Galvanism
-Mouthwashes
-Routine dental radiography
How does other bacteria play a role?
-Not a proven risk factor
-Oral bacteria may interact with tobacco and alcohol increasing acetaldehyde
-Periodontal bacteria association with oral cancer not confirmed
How does Candida play a role?
-Not a proven risk factor
-Can overlay leukoplakias but not causing them
-Link to oral cancer not shown
Molecular Carcinogenesis
-Tumor suppressor genes can exhibit loss of heterozygosity, mutation or hypermethylation which can lead to inactivation and tumor growth
-EGFR, telomerase, and Cyclin D1 overexpression lead to increased growth
-Increasing polysomy
Leukoplakia and Dysplasia Tx consideration
-1/3 of leukoplakias recur after excision
-Transformation usually occurs within 2-4yrs but can be variable so follow closely
-Typical follow-up plan (3-6mo):
1. Every 3mo for an excised leukoplakia with dysplasia
2. Every 6mo for leukoplakia w/o dysplasia
List the Diagnostic Techniques (oral premalignant and malignant lesions)
-Scalpel biopsy: gold standard - adjunct to clinical evaluation/biopsy
-Cytology: limited application on red lesions
-Toluidine Blue: most useful in red lesions
-Vizilite: may help visualize subtle leukoplakia, but limited application
-Velscope: some application in margin delineation but insufficient evidence as a screening device
-Brush Biopsy: not recommended as indications for use would also require scalpel biopsy
