precancerous skin diseases

1. LEUKOPLAKIA
BY : Vincy Varghese,
Anubhav Agrawal
514

2. SYNOPSIS
• Introduction
• Etiology
• Classification
• Pathophysiology
• Clinical Features
• Diagnosis
• Treatment
• Prognosis

3. LEUKOPLAKIA
(LEUKO-WHITE; PLAKIA-PATCH)
• Oral leukoplakia is defined by the WHO as “a white patch or plaque that cannot be scrapped
off and also characterized clinically or pathologically as any other disease”.
• Leukoplakia generally refers to a firmly attached white patch on a mucous
membrane which is associated with an increased risk of cancer. The edges of
the lesion are typically abrupt and the lesion changes with time. Advanced
forms may develop red patches. There are generally no other symptoms. It
usually occurs within the mouth, although sometimes mucosa in other parts
of the gastrointestinal tract, urinary tract, or genitals may be affected.
• Mild leukoplakia is usually harmless and often goes away on its own. More
serious cases may be linked to oral cancer. These must be treated promptly.

6. STATISTICAL DATA
1. Affects 1.5 – 12% of total population
2. It usually affects people over the age of 40 years (average age is 60 years).
3. Prevalence increases rapidly with age particularly in males.
4. Approximately 8 % of the males over the age of 70 years are reportedly affected.
5. 17-25 % carcinoma in situ.
6. 5.4% may develop squamous cell carcinoma in smokers it rises to 16%

7. ETIOLOGY
• Chemical: alcohol, tobacco
• mechanical: sharp tooth or crown margins, irritating denture clasps
• Premalignant epithelial changes
• Candida Albicans
• Ultraviolet radiation
• Trauma
• Toothpaste or mouth rinses (sanguinaria)

8. SITES OF PREDILECTION
• Lateral and ventral tongue
• floor of the mouth
• alveolar ridge mucosa
• corner of the mouth
• less frequently:
• soft palate
• lip

9. Site % of leukoplakia at this
site
% of leukoplakia at this
site that show dysplasia
or carcinoma
Mandibular mucosa and
sulcus
25.2 14.6
Buccal musosa 21.9 16.5
Maxillary mucosa and
sulcus
10.7 14.8
Palate 10.5 18.8
Lips 10.3 24.0
Floor of the mouth 8.6 42.9
tongue 6.8 24.2
retromolar 5.9 11.7

10. CLINICAL FORMS
• Homogenous Leukoplakia
• Non Homogenous Leukoplakia
• Proliferative verrucous leukoplakia
• Erythroleukoplakia
• Sublingual keratosis
• Oral hairy leukoplakia
• Syphilitic leukoplakia

11. HOMOGENOUS
• Uniform flat appearance that may
exhibit shallow cracks and has a
smooth, plaque like, wrinkled or
corugated surface with a
consistent texture throughout.
• Image- Homogenous leukoplakia
in the floor of the mouth in a
smoker. Biopsy showed
hyperkeratosis

12. NON HOMOGENOUS
• Non-homogenous leukoplakia is a
lesion of non-uniform appearance.
The color may be predominantly
white or a mixed white and red.
The surface texture is irregular
compared to homogenous
leukoplakia, and may be flat
(papular), nodular or exophytic.
• Image- Exophytic leukoplakia on
the buccal mucosa

13. PROLIFERATIVE VERRUCOUS LEUKOPLAKIA
• Proliferative verrucous leukoplakia
(PVL) is a recognized high risk subtype
of non-homogenous leukoplakia. It is
uncommon, and usually involves the
buccal mucosa and the gingiva (the
gums).[22] This condition is
characterized by (usually) extensive,
papillary or verrucoid keratotic plaques
that tends to slowly enlarge into
adjacent mucosal sites. An established
PVL lesion is usually thick and
exophytic (prominent), but initially it
may be flat.

14. ERYTHROLEUKOPLAKIA
• Erythroleukoplakia (also termed speckled
leukoplakia, erythroleukoplasia or
leukoerythroplasia) is a non-homogenous lesion of
mixed white (keratotic) and red (atrophic) color.
Erythroplakia (erythroplasia) is an entirely red patch
that cannot be attributed to any other cause.
Erythroleukoplakia can therefore be considered a
variant of either leukoplakia or erythroplakia since
its appearance is midway between.
• Image- Erythroleukoplakia ("speckled leukoplakia"),
left commissure. Biopsy showed mild epithelial
dysplasia and candida infection. Antifungal
medication may turn this type of lesion into a
homogenous leukoplakia (i.e. the red areas would
disappear)

15. SUBLINGUAL KERATOSIS
• Sometimes this term is used to describe
leukoplakia of the floor of mouth or under the
tongue. It is not universally accepted to be a
distinct clinical entity from idiopathic
leukoplakia generally, as it is distinguished
from the latter by location only.
• Usually sublingual keratoses are bilateral and
possesses a parallel-corrugated, wrinkled
surface texture described as "ebbing tide".

16. ORAL HAIRY LEUCOPLAKIA
• Oral hairy leukoplakia is a corrugated
("hairy") white lesion on the sides of the
tongue caused by opportunistic
infection with Epstein-Barr virus on a
systemic background of
immunodeficiency, almost always
human immunodeficiency virus (HIV)
infection. This condition is not
considered to be a true idiopathic
leukoplakia since the causative agent
has been identified.

17. SYPHILITIC LEUKOPLAKIA
• This term refers to a white lesion
associated with syphilis, specifically in
the tertiary stage of the infection. It is
not considered to be a type of idiopathic
leukoplakia, since the causative agent
Treponema pallidum is known. It is
now rare, but when syphilis was more
common, this white patch usually
appeared on the top surface of the
tongue and carried a high risk of
malignant transformation.

19. PATHOPHYSIOLOGY
• Tumor suppressor genes are genes involved in the regulation of normal cell turnover
and apoptosis (programmed cell death). One of the most studied tumor suppressor
genes is p53, which is found on the short arm of chromosome 17. Mutation of p53
can disrupt its regulatory function and lead to uncontrolled cell growth.
• Mutations of p53 have been demonstrated in the cells from areas of some
leukoplakias, especially those with dysplasia and in individuals who smoke and
drink heavily.

20. CLINICAL SIGNIFICANCE
• Leukoplakia is marked by unusual-looking patches inside mouth. They may be
sensitive to touch, heat, spicy foods, or other irritation. These patches can vary
in appearance and may have the following features:
• white or gray color
• thick, hard, raised surface
• hairy (hairy leukoplakia only)
• red spots (rare)
The patches may take several weeks to develop, and they’re rarely painful.
Some women may develop leukoplakia on the outside of their genitals in the
vulva area.

21. HISTOLOGIC APPEARANCE
Leukoplakia has a wide range of possible histologic appearances. The degree of hyperkeratosis,
epithelial thickness (acanthosis/atrophy), dysplasia and inflammatory cell infiltration in the
underlying lamina propria are variable.The following are commonly cited as being possible
features of epithelial dysplasia in leukoplakia specimens:
• Cellular pleomorphism
• Nuclear atypia
• Increased number of cells seen undergoing mitosis, including both normal and abnormal
mitoses.
• The distinction between the epithelial layers may be lost.
• Abnormal keratinization
• Alteration of the normal epithelial-connective tissue architecture - the rete pegs may become
"drop shaped". wider at their base than more superficially.

22. DIAGNOSIS
• Leukoplakia is usually diagnosed with an oral exam. During a physical exam, dentist or primary
care doctor can confirm if the patches are leukoplakia. One might mistake the condition for oral
thrush. Thrush is a yeast infection of the mouth. The patches it causes are usually softer than
leukoplakia patches. They may bleed more easily.
• Dentist or doctor may need to do other tests to confirm the cause of spots. This helps suggesting
a treatment that may prevent future patches from developing.
• If a patch looks suspicious, dentist or doctor will do a biopsy. To do a biopsy, they remove a small
piece of tissue from one or more of spots. They then send that tissue sample to a pathologist for
diagnosis. The goal is to look for signs of oral cancer.

23. BIOPSY
• Tissue biopsy is usually indicated to rule out
other causes of white patches and also to enable
a detailed histologic examination to grade the
presence of any epithelial dysplasia. This is an
indicator of malignant potential and usually
determines the management and recall interval.
The sites of a leukoplakia lesion that are
preferentially biopsied are the areas that show
induration (hardening) and erythroplasia
(redness), and erosive or ulcerated areas. These
areas are more likely to show any dysplasia
than homogenous white areas.
Microscopic examination of
keratinocytes scraped from
the buccal mucosa

24. TREATMENT
• Most patches improve on their own and don’t require any treatment. It’s important to avoid
any trigger that may have caused your leukoplakia, such as tobacco use. If it’s related to
irritation from a dental problem, dentist may be able to address this.
• If a biopsy comes back positive for oral cancer, the patch must be removed immediately.
This can help prevent the spread of the cancer.
• Small patches can be removed by a more extensive biopsy using laser therapy or a scalpel.
Large leukoplakia patches require oral surgery.
• Hairy leukoplakia may not require removal. dentist or doctor might prescribe antiviral
medications to help stop the patches from growing. Topical ointments containing retinoic
acid can also be used to reduce patch size.

25. HOW CAN LEUKOPLAKIA BE PREVENTED?
Many cases of leukoplakia can be prevented with lifestyle changes:
• Stop smoking or chewing tobacco.
• Reduce alcohol use.
• Eat antioxidant-rich foods such as spinach and carrots. Antioxidants may help
deactivate irritants that cause patches.

26. PROGNOSIS
• The annual malignant transformation rate of leukoplakia rarely exceeds 1%, i.e. the
vast majority of oral leukoplakia lesions will remain benign.
• A number of clinical and histopathologic features are associated with varying
degrees of increased risk of malignant transformation, although other sources argue
that there are no universally accepted and validated factors which can reliably
predict malignant change.
• It is also unpredictable to an extent if an area of leukoplakia will disappear, shrink
or remain stable.