2. Premalignant Lesions of Surface Epithelial Origin Flashcards
1
Q
What is the normal histology of the oral mucosa?
A
parakeratinized, stratified squamous epithelium
2
Q
What part of the oral mucosa isn’t parakeratinized?
A
Palate and Gingiva, which is orthokeratinized
3
Q
Dysplasia involving the entire thickness of the epithelium with: no maturation and no keratin.
A
CIS - highest grade of dysplasia
4
Q
What do all grades of dysplasia except CIS show?
A
Some keratin production on the surface
5
Q
Why are dysplasia and CIS not considered cancer?
A
There is no invasion with access to blood and lymphatics
6
Q
What are the 4 histological architectural changes that occur with dysplasia and CIS?
A
- Bulbous or teardrop-shaped rite ridges
- Loss of polarity
- Keratin or epithelial pearls
- Loss of epithelial cell cohesiveness, but intact bm b/c no invasion
7
Q
What are the 6 histological cytologic changes that occur with dysplasia and CIS?
A
- Enlarged cells, nuclei and nucleoli
- Increased nuclear:cytoplasmic
- Hyperchromatism
- Pleomorphism (cellular and nuclear)
- Increased, altered and displaced mitoses
- Dyskeratosis (premature keratinization of individual cells)
8
Q
Where do up to 50% of oral malignancies occur, that are associated with reverse smoking?
A
Hard palate
This is an unusual location
9
Q
How many years after cessation does it take, before your cancer risk is that of non-smokers?
A
10 years
10
Q
Risk for what is 2-6x greater than of those that quit smoking after their 1st cancer?
A
2nd primary UADT Carcinoma
11
Q
What is the Clinical Appearance of Smokeless Tobacco Keratosis?
A
- A reactive change to placement of the product
- Gray/white, translucent plaque with rippled appearance and blending borders,
- Probably isn’t a true leukoplakia
12
Q
What is the presence of dysplasia seen with Smokeless Tobacco?
A
Infrequently ~3%, compared to 5-25% for Leukoplakia
13
Q
What in Betel Quid or Paan Quid causes euphoria by enhancing the alkaloids released from the areca nut?
A
Slaked lime
14
Q
What is the lifetime risk for developing oral cancer due to betel chew or paan quid use?
A
8%
Even tobacco-free Paan increases risk
15
Q
What is Oral Submucous Fibrosis associated with?
A
Habit of Betel Nut Chewing
16
Q
What is Oral Submucous Fibrosis?
A
- A chronic progressive scarring disease of the oral mucosa
- High-risk Precancerous Condition
17
Q
In the pathogenesis of Oral Submucous Fibrosis, what does the areca nut primarily due?
A
Stimulates Fibrosis
18
Q
In the pathogenesis of Oral Submucous Fibrosis?
A
- Alkaloid from the areca nut –>
- Stimulates fibroblasts to synthesize collagen
19
Q
In the pathogenesis of Oral Submucous Fibrosis, what effect do high levels of copper have?
A
increase collagen cross-linking
20
Q
What is the initial clinical presentation of Oral Submucous Fibrosis?
A
- Vesicles
- Petechiae
- Xerostomia
- Generalized Oral Burning Sensation (Stomatopyrosis) with Intolerance to spicy foods
21
Q
What gradually forms as Oral Submucous Fibrosis progresses? (3)
A
- Formation of fibrous bands with oral pallor and stiffness
- Lose depth of the vestibule due to scaring
- Soft palate has a pale look due to all of the collagen laid down
- Leading to increasing Trismus
- Develop Leukoplakic lesions, with dysplasia that have a tendency to undergo malignant transformation
22
Q
What is the Histology of Oral Submucous Fibrosis?
A
- Hyperkeratosis with epithelial atrophy & atypia is seen
- Pronounced collagen deposition in submucosal CT
23
Q
What may be used to improve mild cases & severe cases of trismus associated with Oral Submucous Fibrosis?
A
- Intalesional corticosteroids
- Surgical splitting of fibrous bands, with skin grafts & mouth props, physiotherapy
24
Q
Does cessation of betel nut habit stop Oral Submucous Fibrosis?
A
No, but the pt should still d/c betel nut habit
This is in contrast to the cessation of smoking tobacco
25
What percent of Oral Submucous Fibrous cases show dysplasia at initial biopsy?
~10%
* **All pts should be biopsied** to confirm dx & assess for dysplasia
* Biopsy even if they don't have a Leukoplakia
26
What percent of Oral Submucous Fibrosis cases undergo malignant transformation to SCCA in a 17 yr period?
~8%
27
How much of an increased risk do Oral Submucous Fibrosis pts have for developing Oral Cancer?
19x
28
What carcinogens does marijuana release at a 50% higher levels than tobacco?
Polycyclic hydrocarbons & Acetaldehyde like tobacco
29
What is a promotor of tobacco, creating a synergistic effect to develop cancer (RR=15)
Alcohol
30
What is the pathogenesis of alcohol?
* Ethanol turns to acetaldehyde (carcinogenic)
* Carcinogenic impurities in alcoholic drinks
31
What is the HPV type that is associated with OPSCC?
mostly HPV 16
32
HPV-associated OPSCC has increased dramatically in what groups of pts? (4)
* ~10 yrs younger
* Higher socioeconomic group
* Increased % in whites (men)
* Strong assoc with sexual behavior
33
What HPV associated ds has a more favorable prognosis (~30%) than those associated with tobacco and alcohol, that don't have HPV in their tumor?
HPV associated OPSCC
34
What is the Gold Standard for determining clinically relevant HPV infection of the Oral Cavity?
Expression of viral oncogenes E6 and E7 mRNA
35
What is the prevalence rate of HPV in oral cancers?
6%
it is not recommended to routinely test for HPV in Oral Cancers, because there is such a small % that have it
36
What does Therapeutic Irradiation increase the risk of?
**NEW primary malignancy**, either sarcoma or carcinoma
37
What is the pathogenesis of therapeutic irradiation?
Decreases immune response, and causes alterations in DNA
38
What conditions cause **mucosal atrophy**, with predisposition to develop cancer? (5)
* Oral Submucous Fibrosis
* Atrophic Lichen Planus/Lichenoid Dysplasia
* Discoid Lupus Erythematosus
* more so if it effects the lips
* Plummer-Vinson Syndrome
* Tertiary Syphilis
39
What population is affected with Plummer-Vinson Syndrome?
Women 30-50 years old with Scandinavian/Northern European background
40
What are the signs and symptoms of Plummer-Vinson Syndrome? (4)
* Iron Deficiency Anemia
* Papillary atrophy of the tongue
* **Esophageal Web** Formation
* **Koilonychia** = spoon-shaped nails
41
What is there an increased risk for with Plummer-Vinson Syndrome?
5-50% increased risk of **UADT Carcinoma**, mostly **esophagus**
42
What is Tertiary Syphilis strongly assocaited with?
**Dorsal Tongue Carcinoma**, before antibiotics when arsenic was used for tx
NOT a Proven RF
43
What are 5 uncommon etiologies of **oral cancer/precancerous lesions**?
* Vitamin A Deficiency
* Cheilitis Glandularis
* Dyskeratosis Congenita
* Mate Drinking
* Sanguinaria
44
What is the pathogeneis of Vitamin A Deficiency?
**Excess mucosal keratinization**, leads to Leukoplakias
45
What is Cheilitis Glandularis?
Rare inflammatory condition of **minor salivary glands**
46
What does Cheilitis Glandularis cause?
* Swelling causes eversion of lower lip, the mucosal side is exposed to sunlight causing Actinic Cheilitis
* 18-35% develop SCC of the lower lip
47
What is the etiology of Dyskeratosis Congenita?
* **Recessive X-linked** (more common in men)
* Mutation in **telomerase**
48
What does the mutation of telomerase in Dyskeratosis Congenita lead to the development of?
Leukoplakia on the **Tongue** and **UADT**
Promotes the cell to continue to divide
49
Why is it important to watch pts with Dyskeratosis Congenita and to biopsy any changes?
* **~1/3 of lesions transform** over 10-30 years
50
What effect does Mate Drinking have on the risk for Oral Cancer?
2x increased risk
51
What is Sanguinaria?
Herbal extract from **blood-root plant**
* possesses anti-microbial/anti-inflammatory properties
* Use to be put into mouthwashes and toothpastes (Viadent)
* **Not a proven risk factor** for oral cancer development
52
What is the clinical characteristic that \> 80% of pts with a history of Sanguinaria use, it is a dead giveaway?
Maxillary Vestibule Leukoplakia
Maxillary Alveolar Mucosal Leukoplakia
*(this is a strange place to have a leukoplakia)*
53
What can Tumor Suppressor Genes exhibit?
* **Loss of Heterozygosity**
* **TP53 Mutation**
* **Hypermethylation** (p16)
* Cyclin dependent kinase inhibitor leads to inactivation and tumor growth
54
In Molecular Carcinogenesis what causes the **cell cycle** to be **uninhibited** causing increased growth?
* Overexpression of:
* **EGFR**
* **Telomerase**
* **Cyclin D1**
55
What makes oral tissues look white? (5)
* Increased keratinization
* Acanthosis
* Edema
* Thermal or Chemical Injury
* Extrinsic Coatings
* Debris and/or bacterial/fungal organisms (plaque, candida) that adhere but can be rubbed off the oral mucosa
56
What 10 diagnoses must be ruled out before a dx of Leukoplakia can be made?
* Leukoedema
* Cheek Chewing
* Frictional Keratosis
* Nicotine Stomatitis
* Tobacco Pouch Keratosis
* Chemical Burn
* Candidiasis
* Lichen Planus
* White Sponge Nevus
* Cinnamon Reaction
57
Where do 90% of leukoplakias that show dysplasia come from?
* Tongue, Lip Vermilion, and FOM
58
What population do Leukoplakia's have a predilection for?
* Males (70%), usually greater than 40 yrs old
* Increase with age, average age of 60 years
59
What is the clinical appearance of Leukoplakia's?
* Often **sharply demarcated,** **white patch** or **plaque** with **variable surface textures**
* Thick or Thin
* Smooth Granular-Nodular or Verrucous
* Homogenous vs. Non-homogenous
60
If a red component is present in leukoplakia what is it called?
Speckled Leukoplakia or Erythroleukoplakia
61
What are the phases of Leukoplakias?
* Normal Mucosa
* **Thin, smooth leukoplakia** (hyperkeratosis)
* **Thick, fissured leukoplakia** (mild/moderate dysplasia)
* **Granular, verruciform leukoplakia** (moderate/severe dysplasia)
* **Erythroleukoplakia/CIS**
* Becomes _thinner_
* Starts to look _red_, not making keratin
* May _ulcerate_
62
What is the histology of Leukoplakias?
Some degree of Hyperkeratosis or Acanthosis
63
What are the **High Risk Sites** of Leukoplakia?
* Latero-Ventral Tongue
* FOM
* Retromolar Pad/Tonsillar Pillar/Soft Palate area
64
What percent of high risk sites of leukoplakia shows dysplasia?
24-42% show dysplasia
65
What are the **Low Risk Sites** of Leukoplakias?
* Buccal Mucosa
* Hard Palate
* Dorsal Tongue
66
What percent of low risk sites of leukoplakia shows dysplasia?
11-18% show dysplasia
67
What percent of leukoplakias show dysplasia for all sites?
5-25% all of Leukoplakias will show dysplasia
68
How long does it take for transformation of leukoplakias to occur?
2-4 years, but can be variable from months to several years
69
Why do leukoplakias need to be followed closely?
~1/3 of Leukoplakias **recur after excision**
70
What is the tx for leukoplakias with **mild dysplasia** or **hyperkeratosis with atypia**?
* Tx varies
* **D/C carcinogenic habits** (smoking) may lead to resolution
* May **remove** OR **observe** very closely based on size, location, etc.
71
What is the tx for leukoplakias with **Moderate Dysplasia** or **Worse (Severe Dysplasia, CIS)**?
* **Remove** by most convenient means available
* Usually excision
* Large lesions use laser, electrocautery, cryosurgery
72
What is the Malignant Transformation Risk (by clinical appearance) of **thin leukoplakias**?
Sledom transforms without clinical alteration
73
What is the Malignant Transformation Risk (by clinical appearance) of **thick, homogenous leukoplakias**?
1-7%
74
What is the Malignant Transformation Risk (by clinical appearance) of **Granular or Verruciform Leukoplakia**?
4-15%
75
What type of Leukoplakias have the highest Malignant Transformation Risk (by clinical appearance)?
* Non-Homogenous = higher risk
* Erythroleukoplakia = 28%
76
What is the Malignant Transformation Risk for **Severe Dysplasia**?
20-43%
77
What is the Malignant Transformation Risk for all dysplasia combined?
* \<2% per year
* 12% over time
78
What are other risk factors for malignant transformation of Leukoplakias? (6)
* Female
* Older Age
* Nonsmoking Status
* Lesion Persistence
* Large Size
* Ventro-Lateral Tongue/FOM (16-39%)
79
In summary what features increase risk for leukoplakia to progress to cancer?
* High risk sites
* Non-homogenous, red/speckled or ulcerated are higher risk (appearance)
* Presence of dysplasia
* Increased grade of dysplasia
80
What is the follow-up for an excised leukoplakia with dysplasia?
Every 3 months
81
What is the follow-up for leukoplakia without dysplasia?
Every 6 months
UNLESS other risk factors are present, then see every 3 months
82
What are the sites usually affected in Erythroleukoplakia?
* Lateral Tongue
* FOM
* Soft Palate
## Footnote
*These are high risk sites for Leukoplakia*
83
What is the red appearance of Erythroleukoplakia due to?
* Lack of surface keratin production
* Epithelial atrophy
84
What are the differences of Erythroleukoplakia and Leukoplakia? (2)
Erythroleukoplakias...
* More advanced when detected
* 90% show Severe Epithelial Dysplasia or worse (CIS) at the time of biopsy
85
What is Proliferative Verrucous Leukoplakia?
* **Multiple leukoplakias**, often extensive, that _spread and thicken over time_
86
What is the most common site affected in PVL?
**Gingiva**, other sites may be affected as well
87
What is the population affected by PVL?
* Female predilection (4:1), only 1/3 have traditional RFs
* Mean female age = 65 yrs
* Mean male age = 49 yrs
88
What is the Histology of PVL?
Hyperkeratosis/Hyperplasia with **variable dysplasia**, often verrucous surface
89
What is the tx for PVL?
* Optimal tx remains to be determined
* Surgical or Ablative Therapy, but **recurrence is common**
90
What is the malignant transformation of PVL?
**64%** of pts develop SCCA, with a mean follow-up of **7.4 yrs**
* *Traditional Leukoplakias, transform much faster, usually within 2-4 yrs*
* *Highest Risk Leukoplakia for malignant transformation, 40% died from cancer*
91
Which adjunct to clinical evaluation/biopsy is not recommended as indications for use would also require scalpel biopsy?
Brush Biopsy
92
Which adjunct to clinical evaluation/biopsy has limited application on red lesions?
Cytology
93
Which adjunct to clinical evaluation/biopsy is **most useful in red lesions**?
Toluidine Blue
94
Which adjunct to clinical evaluation/biopsy may help visulize **subtle leukoplakias**, but has limited application?
Vizilite
95
Which adjunct to clinical evaluation/biopsy has some application in **margin delineation** but insufficient evidence for use as a screening device?
Velscope
96
What is Actinic Keratosis (AK)?
Premalignant sun-induced skin lesion caused by UV light exposure - precursor to SCCA
97
Where are common locations for Actinic Keratosis?
* **Facial skin** and **vermilion zone** (AC) of the lips of fair-skinned persons, **over 40 years old**
98
What is the clinical appearance of Actinic Keratosis?
* Red base with white scaly plaque with sandpaper texture
99
What is the Histology of Actinic Keratosis?
* Hyperkeratosis, usually parakeratin
* Some degree of **epithelial dysplasia** or even **superficially invasive SCC**
* **_Solar Elastosis_** - degeneration of CT from UV damage with increased elastic fibers (stains blue)
100
What is the average time to progression of Actinic Keratosis?
2 years
101
What is the prognosis for Actinic Keratosis if sun exposure is reduced?
25% may regress
102
What population has a strong predilection for developing Actinic Cheilosis (Cheilitis)?
* Male
103
What is the Clinical Progression of Actinic Cheilosis?
* Atrophy (blotchy pale), dryness, fissures
* Scaly/crusty and thickening
* Leukoplakia
* Ulceration (when cancer forms)
104
After tx of Actinic Cheilosis via vermilionectomy what is now a potential problem?
Developement of Cheilitis Glandularis, due to exposed lip mucosa
105
Why is long term follow up of Actinic Cheliosis recommended?
* 2x increased risk for lip cancer
* **Transforms at \>2x the rate that occurs with Actinic Keratosis**
* Good news: takes a long time to transform, mets late, and typically well-differentiated, slower growing lesion
106
What is Bowen Disease?
* Skin equivalent of CIS
* Not always related to sun exposure
107
What is the clinical appearance of Bowen Disease?
Erythematous and scaly, well-defined, irregular plaque on keratinized skin
108
What is Erythroplasia of Queyrat?
A clinical variant of CIS of the penis
109
What is the clinical appearance of Erythroplasia of Queyrat?
Velvety red plaques on penile mucosa
110
What occurs in a pt years after exposure to arsenic, in pts with Arsenical Keratosis?
* **Keratosis of palms and soles**
* palms look pigmented and have scaly plaques
* Skin pigmentation
* Skin tumors
* Increased risk for **Internal Malignancy**
