Quiz 2 Flashcards
“Textbook” progression of leukoplakias (3 steps)
- Thin LPs
- Thick/homogeneous
- Granular/nodular or verrucous/verruciform
Pts with oral submucous fibrosis are ____x more likely to develop SCC
19x more likely
This is why it is a high risk lesion
What is the 1 cell in the body that shows reverse polarization
Ameloblast
Actinic cheilitis (cheilosis)
PREMALIGNANT lesions on lip due to chronic UV exposure
6 histologic features of Granular, Verruciform Leukoplakia
- Irregular (verruciform) hyperkeratosis
- Bulbous rete pegs
- Lymphocytes (mod #s)
- Mod/severe dysplasia
- Congested vessels
- Candida hyphae (maybe)
Of the 95% of leukoplakias that are NOT malignant at 1st biopsy, about ___% undergo subsequent malignant transformation
5%
In TNM staging, what does TNM stand for?
T = tumor size in cm N = regional lymph node involvement M = distant metastasis
What is the main diagnostic feature (microscopically) of focal epithelial hyperplasia (hecks disease)
Mitosoid bodies
Erythroleukoplakia (speckled leukoplakia)
Leukoplakia with patches of redness
Incidence of proliferative verrucous leukoplakia
4x more in females
Cause of verruciform xanthoma
Unknown
Most likely reactive or immune response to trauma
The risk for oral SCC in smokeless tobacco users is ____ compared to smoking
Less
4 other symptoms associated with smokeless tobacco keratosis
- Gingival recession
- Periodontitis
- Caries
- Tooth wear
Idiopathic leukoplakia incidence
Pts >40 yrs
What role does smoking play in proliferative verrucous leukoplakia
No/minor role
Which HPV subtypes may be causative factors for proliferative verrucous leukoplakia?
HPV 16 + 18
Acanthosis
Diffuse epidermal hyperplasia
Aka thicker epithelium
Betel quid/Guthka
*cause of oral submucous fibrosis
Betel leaf, areca nut, slaked lime, catechu, tobacco? Sweeteners?
4 features of Muir Torre syndrome
- Autosomal dominant
- Cutaneous tumors of sebaceous origin
- Visceral malignant diseases
- Multiple keratoacanthomas
Definition of idiopathic leukoplakia
Clinical white lesion that does not rub off + cannot be characterized clinically as any other disease
Leukoplakia is _______
PREMALIGNANT
Incidence of oral submucous fibrosis
India, South East Asia (where ppl use betel quid)
Young pts
HPV associated oral cancers are different from the others how?
Better prognosis
The single most effective measure to lower the risk for oral cancer is…
Reduce exposure to tobacco + alcohol
Actinic cheilitis (cheilosis) has the same pathology as ______ but in a different location
Actinic keratosis
____% of the dysplasia that present as clinical leukoplakias (thick + granular) will undergo malignant transformation
10-15%
Where do you see sanguinaria associated keratosis
Mx buccal vestibule
Mx alveolar ridge
Names for a raised lesion
Papule
Nodule
3 high risk sites of erythroplakia
- Floor of mouth
- Tongue
- RMP
6 danger signals of malignant transformation
- No cause (risk factors)
- Causative agent carcinogen
- Location (high risk sites)
- Ulceration
- Induration
- Redness (erythroplakia)
10 signs of epithelial dysplasia
- Hyperchromatism (dark nuclei)
- Pleomorphism (abnormal shape nuc)
- Increased nuclear/cytoplasmic ratio
- Dyskeratosis (prematrue keratinization)
- Increased mitotic activity
- Abnormal mitotic figures
- Loss of polarity
- Bulbous rete pegs
- Keratin pearls
- Loss of epithelial cell cohesiveness
7 intrinsic risk factors for oral cancer
- Iron deficiency (plummer vinson syndrome)
- Vitamin A defiency
- Bacteria (tertiary stage syphilis)
- Candida
- HPV 16 + 18
- Immunosuppression (HIV, drugs)
- Oncogenes + tumor suppressor genes
HPV positive tumors have a better prognosis bc…
Respond v well to radiation + chemo
Red lesions are red because
Epithelium is thin = close to blood vessels
What are the 2 clinical forms of focal epithelial hyperplasia (hecks disease) and how many/where are the lesions
Papulonodular
Papillomatous
Multiple lesions on lips, tongue, gingiva, tonsils (typically in anterior)
What cancer can develop from smokeless tobacco keratosis? Risk?
Oral squamous cell carcinoma (verrucous)
4x more risk vs. non users (but NOT as high as smoking)
3 microscopic features of focal epithelial hyperplasia (hecks disease)
- Nodular broad based mass of oral mucosa
- Numerous mitosoid bodies
- Viral like cytopathic change
4 histologic features of verruciform xanthoma
- Papillary acanthotic epithelium
- Hyperparakeratosis
- Clefts + crypts noted
- Xanthoma (foam) cells in CT papilla
Metastasis from the posterior mouth occurs through…
Superior jugular nodes
Digastric nodes
HPV positive tumors are diagnosed…(6) (compared to HPV negative tumors)
- Dx @ younger age
- Low prevalence of amoking/alch use
- Dx @ more advanced TNM stage
- Dx @ smaller tumor size
- With lumph node positivity
- Presence of metastases
Name for a lesion with an irregular surface
Papillary
Does every cancer have a precancerous lesion?
No
Which 2 conditions increase the risk for development of actinic cheilitis (cheilosis)
Xeroderma pigmentation
Albinism
3 histologic features of Thin, Smooth Leukoplakia
- Hyperkeratosis
- Acanthosis (thick epi)
- Lymphocytes (sometimes)
Which parts of the tongue are high risk for oral cancer
Lateral border
Ventral
What are the 3 theories that explain why HPV positive oropharyngeal cancers respond better to chemo?
- Low rates of genomic damage
- Absence of field cancerization
- Presence of immune responses to HPV antigens
8 premalignant + related lesions of the oral mucosa
- Leukoplakia
- Proliferative verrucous leukoplakia
- Erythroplakia
- Smokeless tobacco keratosis
- Oral submucous fibrosis
- Nicotine stomatitis
- Actinic cheilitis/keratosis
- Keratoacanthoma
Nicotine stomatitis clincal presentation
Diffuse grey/white mucosa with red punctate papules (= inflamed minor salivary glands + their ductal orifices) on PALATE
Incidence of nicotine stomatitis
Men >45 yrs
Pipe + cigar smokers
Hyperchromatism
Dark staining nuclei
*sign of epithelial dysplasia
Plummer vinson syndrome
Iron deficiency
Risk factor for oral cancer
HPV positive tumors are ____ differentiated
Poorly differentaited
What are molluscum bodies
Histo feature of molluscum contagiosum
Large intranuclear inclusions inside bloated keratinocytes
How does transmission of molluscum contagiosum vary in different populations
Teens/adults = sexual
Kids = nonsexual contact
Immunocompetent pts = warm + humid environments
Are smokeless tobacco keratosis lesions reversible?
Yes
Explain the theory that HPV+ tumors respond better to chemo bc of the presence of immune responses to HPV antigens
Immune responses to E6 + E7 oncoproteins help in improved tx responses + px
Where do Keratoacanthomas originate from in the skin? Oral mucosa?
Skin = pilosebaceous apparatus
Oral mucosa = ectopic sebaceous glands? (FG)
Explain the theory that HPV+ tumors are more responsive to chemo because they have an absence of field cancerization
HPV believed to arise from limited foci of infection = less 2nd malignancies
3 high risk sites for oral cancer
- Floor of mouth
- Tongue (lateral border + ventral)
- Soft palate
What is the most common malignancy in the mouth
Squamous cell carcinoma
4 histologic features of Thick, Fissured Leukoplakia
- Hyperkeratosis
- Acanthosis (thick epi)
- Lymphocytes (sometimes)
- Mild/mod dysplasia
Why are white lesions white?
Because the epithelium is thickened = further away from blood vessels
Types of HPV assoc with Focal Epithelial Hyperplasia (Heck’s disease)
HPV 13 + 32
90% of leukoplakias show dysplasia or carcinoma in these 3 locations
- Tongue
- Lip vermillion
- Floor of mouth
2 Tx’s for focal epithelial hyperplasia (hecks disease)
Spontaneous regression
Conservative excision
Why must all erythroplakias be biopsied?
Can’t distinguish clinically
ALMOST ALWAYS squamous cell carcinoma or in situ carcinoma
3 reasons why proliferative verrucous leukoplakia is a high risk oral lesion
- No absolutely predictive histologic pattern
- No tests to prove likely progression
- Must be re-evel v often + totally removed in recurs
How does metastasis of oral squamous cell carcinoma occur?
Through the lymphatics to the ipsilateral cervical lymph nodes
Cases of molluscum contagiosum are _____ in HIV pts (5-18%)
Florid
Clinical differential diagnoses of verruciform xanthoma (3)
Papilloma
Condyloma
Early carcinoma
Multiple keratoacanthomas are a feature of what syndrome?
Muir Torre syndrome
7 histologic features of Erythroleukoplakia (speckled LP)
- Irregular hyperkeratosis
- Bulbous + crowded rete pegs
- Epithelial atrophy
- Lymphocytes (mod-numerous)
- Severe dysplasia
- Carcinoma in situ?
- Congested vessels
What is different about nicotine stomatitis caused by ‘reverse smoking’
Severe keratosis
PREMALIGNANT (otherwise isn’t)
Is nicotine stomatitis premalignant?
By itself = not premalignant
If caused by ‘reverse smoking’ it IS premalignant
Speckled erythroplakia is ALMOST ALWAYS…
Carcinoma in situ or squamous cell carcinoma
Almost all of oropharyhngeal carcinomas are related to…
HPV
Traumatic (frictional) hyperkeratosis
Hyperplastic response (similar to callus) to chronic mechanical irritation
Reversible after stopping trauma
3 histologic features of nicotine stomatitis
- Hyperkeratosis
- Chronic inflammation
- Salivary duct metaplasia
Pleomorphism
Abnormal shaped nuclei
*sign of epithelial dysplasia
Cause of nicotine stomatitis
Develops in response to HEAT (from pipe/cigars)
Symptoms of oral submucous fibrosis
Trismus (can’t open) + burning followed by v stiff + blotchy mucosa
Tongue can be stiff + immobile
Leukoplakic lesions can develop
What are the 2 things that the MDH says about oral cancer?
- Most cases are preventable
2. The single most effective measure to lower the risk is to reduce exposure to tobacco and alcohol
3 different histologic presentations of erythroplakia (in order from most common to least)
- 50% Squamous cell carcinoma
- 40% severe dysplasia or in situ carcinoma
- 10% mild/mod dysplasia
Verruciform xanthoma presents in ____ much more than any other site as small lesions <2 cm
Gingiva
Erythroplakia is usually seen in which pts
50-70 yrs
Metastasis from the lower lip + floor of mouth happens through…
Submental nodes
How does molluscum contagiosum present clinically
Little papules on skin of face, neck, trunk + genetalia
Less often on mucous membranes
__% of leukoplakias are malignant at 1st biopsy
5%
There are wide ranges of risk of transformation from 1 anatomic site to another. How is the floor of the mouth an example of this?
In the floor of the mouth, the transformation rates are HIGH but show only minimal dysplasia
Sanguinaria associated keratosis
TRUE leukoplakia caused by sanguinaria (herb used in certain toothpaste + mouth rinses)
Persist for years even after stopping use
2 features of the histology of molluscum contagiosum
- Lobular proliferation of epithelium
2. Bloated keratinocytes containing large intranuclear inclusions (molluscum bodies)
3 histologic features of actinic cheilitis (cheilosis)
- Epithelium might show dysplasia
- CT shows solar elastosis (sun damage)
- Chronic inflammation
Describe keratoacanthoma lesions
1(+)
Always raised with central depression (cup shaped symmetry)
Verruciform surface
Describe Smokeless tobacco keratosis lesion
Characteristic white/grey lesion
Velvety feel
Blends w surrounding tissues
Rippled mucosa
Molluscum contagiosum can be mistaken for a more localized version of _______
Fordyce granules
But FG usually more generalized
Clinical presentation of early leukoplakia lesions
Thin leukoplakias
Flat/slightly elevated
Greyish white plaque
In the US, the majority of oral idiopathic leukoplakias are…
Benign + probably will never become malignant
Proliferative verrucous leukoplakia is what kind of lesion
High risk oral white lesion
Does traumatic (frictional) hyperkeratosis, cheek chewing (morsiciatio), or toothbrush trauma of gingiva transform to malignancy?
No
Verruciform xanthoma is a primarily ____ disease
Oral
Dyskeratosis
Premature keratinization of individual cells (keratin being made before they go up to the cell surface)
*sign of epithelial dysplasia
70% of idiopathic leukoplakias happen where? (3)
- Lower lip vermillion
- Buccal mucosa
- Gingiva
Location of keratoacanthoma
Sun exposed skin
Less commonly on mucocutaneous jxn
Rarely intraoral mucosa
Keratoacanthoma is a ____ process
Squamoproliferative process
Erythroleukoplakia (speckled leukoplakia) has a ______ change of dysplasia
MUCH higher
Clinical term for erythroplakia
Idiopathic mucosal red patch
What are the 7 high risk sites for malignant transformation (in order)
- Floor of mouth
- Tongue
- Lip
- Palate
- Buccal
- Vestibule
- Retromolar
2% of cases of oral SCC distantly metastasize. What are the 3 common locations?
- Lung
- Liver
- Bones
Metastasis from the oropharyngeal region occurs through…
Jugulodigastric nodes
Retropharyngeal nodes
Actinic cheilitis (cheilosis) lesions that show _____ are suspicious for SCC
Ulceration
Oral cancer is the __ most common cancer in men + ___ most common in women
11th most common in men
16th most common in women
Progression of proliferative verrucous leukoplakia (5 steps)
*different stages can be present in different sites within the same lesion
- Clinical leukoplakia
- Verrucous hyperplasia
- Verrucous carcinoma
- Papillary squamous cell carcinoma
- Less differentiated squamous carcinoma
3 locations for oropharyngeal carcinoma
- Lateral soft palate
- Tonsillar region
- Base of tongue
6 extrinsic risk factors for oral cancer
- Smoking
- Smokeless tobacco
- Betal quid
- Alcohol
- Occupational exposures (heavy metals)
- UV exposure (lip)
What 5 diseases must be excluded before you dx leukoplakia
- Hyperkeratosis (incl frictional)
- Candidiasis
- Lichen planus
- Tobacco pouch keratosis
- Hairy leukoplakia
Does molluscum contagiosum have malignant transformation?
No
Thick (homogenous) leukoplakia clinical presentation
Progression of thin leukoplakias
Leather like white lesion with distinct borders
⅓ regress
Progression of actinic cheilitis (cheilosis) - 4 stages
- Blotchy, smooth
- Dryness + fissures
- Blurring of vermillion border
- Later stages = scaling, leukoplakic areas, redness, ulceration
What organism causes molluscum contagiosum
Molluscum contagiosum virus (DNA pox virus)
Name for a flat lesion
Macule
Definition of dysplasia
Defect in cell maturation pattern
Actinic cheilitis (cheilosis) incidence
Men 10x more
UV light exposure
More risk with Xeroderma pigmentation + albinism
Sanguinaria associated keratosis is a TRUE leukoplakia, which means it is ____ (although questionable)
Premalignant
May show dysplasia
Proliferative verrucous leukoplakia is usually multifocal (multiple sites), but the most likely location is…
Gingiva
Management of oral submucous fibrosis
Mild = steroids Mod/severe = surgical splitting/excision of fibrous bands
Relapse common
Malignant transformation risk of idiopathic LP varies from study to study because…
Differences in the underlying pathology
Differences in the use of putative carcinogens (e.g. tobacco)
8 anatomic sites for oral cancer (3 HIGH RISK)
- Lip
- Buccal mucosa
- Retromolar trigone
- FLOOR OF MOUTH
- Hard palate
- TONGUE (LATERAL BORDER + VENTRAL)
- SOFT PALATE
Symptoms associated with oropharyngeal carcinoma (3)
- Dysphagia
- Odynophagia (pain during swallowing)
- Otalgia (ear pain)
Leukoplakia may become _________________ WITHOUT change in clinical appearance
Dysplastic or even malignant
How can you tell if a lymph node is metastatic?
Firm
Feel “fixed”
Erythroplakia
Red lesions (thinned epithelium, atrophic)
Cause of erythroplakia
Unknown
Some related to tobacco
Induration
Localized hardening of soft tissue
Feels thick, firm, like something is underneath in the CT
*danger signal for malignant transformation
How does the incidence of oral cancer compare in white men vs. black men >65? Mortality rates? Why?
Oral cancer is more common in white men >65 (bc more HPV assoc cases)
Black men >65 have a higher mortality rate (bc of access, socioeconomic)
Is verruciform xanthoma malignant?
No
5 risk factors for idiopathic leukoplakia
- Tobacco
- Alcohol
- UV light
- HPV
- Unknown
Incidence of verruciform xanthoma
40-70 years
Mostly whites
Slight male predeliction
Heck’s disease is also called
Focal epithelial hyperplasia
Oral cancer is more common in men or women?
Men
Oral submucous fibrosis
High risk premalignant condition caused by betel quid
Explanation behind the theory that HPV+ tumors respond better to chemo because of low rates of genomic damage
Low frequency of TP53 mutations
Low rates of LOH + microsatellite instability
= intact apoptotic responses (= better response to chemo)
Incidence of Focal epithelial hyperplasia (heck’s disease)
Children
Immuncompromised
Native americans (high prevalence)
Multiple members of same family (genetic +or infectious)
