Leukoplakia

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.

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

5. 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 )

6. Sites of predilection Lateral and ventral tongue floor of the mouth alveolar ridge mucosa corner of the mouth less frequently: soft palate lip

7. 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

8. Clinical Forms Homogenous Leukoplakia Non Homogenous Leukoplakia Proliferative verrucous leukoplakia Erythroleukoplakia Sublingual keratosis Oral hairy leukoplakia Syphilitic leukoplakia

9. 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

10. 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

11. 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.

12. 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)

13. 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".

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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

21. 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.

22. 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.

23. 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.