oral White Lesions and keratosis 2024.pdf

Oral White Lesions Third yaer Prepaered y: Dr.Ebtesam Aldieb University of Tripoli Faculty of Dentistry ORAL PATHOLOGY DEPARTMENT )2024( [Type here] [Type...

Oral White Lesions Third yaer Prepaered y: Dr.Ebtesam Aldieb University of Tripoli Faculty of Dentistry ORAL PATHOLOGY DEPARTMENT )2024( [Type here] [Type here] [Type here] Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page1 Introduction in the normal oral mucosa: The normal colour of oral mucosa is ranged from pink in some areas & red in other areas, this appearance depends on the interplay between four factors: 1) Vascularity comes from submucosa  vascularity turns pink mucosa into red & decreases vascularity and turns pale mucosa. 2) Melanin pigmentation comes from the basal layer of epithelium  in the number of Melanocytes or an increase in the amount of melanin pigment turns pink mucosa into brown. 3) Epithelial thickness comes from the prickle layer of epithelium  increase in epithelial thickness turns mucosa into a paler structure because it doesn’t see blood vessels. 4) Keratinization comes from the keratin layer of epithelium  in keratinization, which turns mucosa into white because keratin will be soaked or bathed by water or saliva and reflect the light. Definition of oral white patch: ✓ White patch is the clinical term used to describe lesions that appear as white areas in oral mucosa and as many such lesions are associated with abnormal or increased keratin production, they are often described as keratosis. ✓ White patches caused by increased or abnormal production of keratin can’t be scrapped off. ✓ White patches caused by the accumulation of keratinous debris and desquamated epithelial cells on the surface of the mucosa can be scrapped off. White lesions obtain their characteristic appearance (white) because of: 1. Thickened layer of keratin (Hyperkeratosis). 2. Epithelial hyperplasia (Increase thickness in one or more layers of the epithelium as (Acanthosis). 3. Intracellular epithelial edema (Spongiosis). 4. Reduced vascularity of subjacent connective tissue. Yellow-white lesions obtain their appearance because: 1. Fibrinous exudate covering an ulcer. 2. Some white lesions are associated with accumulation of keratinous debris a desquamated cells that are retained on the surface of oral mucosa due to lack of the mechanical debridement that is normally achieved by the process of eating and the action of saliva. 3. Sub-mucosal deposits (tumour or anomalies). 4. Fungal colonies. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page2  Classification of Oral White Lesions I. Clinical classification of white lesions: 1) Normal oral mucosa with variation in structure and appearance as: (leukoderma, linea Alba, Fordyce’s granules). 2) Nonkeratotic white lesion (Non-epithelial white lesion): white lesions that can be rubbed off easily as (coated tongue, oral thrush, aspirin burn). 3) Keratotic white lesions: white lesions that can’t be rubbed off: (Leukoplakia, Oral keratosis). N.B Scrapping/wiping test using a piece of gauze: is a clinical test to use to diagnose white patches and tell whether it is caused by increased keratin production OR accumulation of mucosal debris. II. Histological classification of white lesions: They are grouped into those show epithelial dysplasia and those that don’t show it. III. Etiological classification of white lesions: according to causative agents: 1) Hereditary conditions (Hereditary Keratosis): a. Leukoedema b. White Sponge Nevus c. Hereditary Benign Intraepithelial Dyskeratosis d. Follicular Keratosis 2) Reactive / Inflammatory lesions: a. Mechanical Traumatic: Focal (Frictional) Hyperkeratosis b. Thermal Traumatic: Nicotine Stomatitis c. Chemical Traumatic: Aspirin burn d. Radiation Traumatic: Solar (Actinic keratosis) & Radiation mucositis e. White Lesions Associated with use. Smokeless tobacco (tobacco chewer, betel nut chewer, oral snuff). f. Hairy Tongue g. Dentifrice-Associated Slough 3) Preneoplastic (Premalignant) & Neoplastic lesions: a. Actinic Cheilitis b. Actinic Keratosis (Solar Keratosis) c. Idiopathic Leukoplakia d. Oral sub mucous fibrosis e. Chronic hyperplastic candidiasis f. Oral squamous cell carcinoma Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page3  4) Deramtosis (immunological) diseases: a. Lupus Erythematosus b. Lichen Planus c. Geographic tongue 5) Infectious: a. Bacterial infection ➔ (syphilitic leukoplakia) b. Fungal infection ➔ (candidiasis/candidosis) c. Viral infection ➔ (hairy leukoplakia) 6) Non-epithelial white lesions: a. Fordyce’s Granules b. Ectopic Lymphoid Tissue c. Gingival Cysts d. Pauli’s Mucosal burns e. Sub-mucosal fibrosis 7) White benign lesions caused by human papilloma virus (HPV): a. Squamous cell papilloma. b. Verrcuca vullgaris. Definition of histopathological terms used to describe some white lesions ▪ Orthokeratosis - The superficial cell layers (squamous) of the epithelium are flattened, anucleate (no nucleus), and have homogeneous, eosinophilic cytoplasm. ▪ Parakeratosis - The superficial cell layers of the epithelium are again flattened and eosinophilic, but contain pyknotic nuclei. ▪ Keratosis – Keratinization of epithelium that is not normally keratinized. ▪ Hyperkeratosis –  thickness of the keratin layer. ▪ Hyperparakeratosis -  thickness of the parakeratin. ▪ Spongiosis - (intercellular oedema ) ▪ Hyperplasia –  in number of cells without any cytological abnormality. ▪ Acanthosis - A type of epithelial hyperplasia in which  thickness is due to  number of cells in the prickle cell layers, producing broadening and lengthening of the rete ridges. ▪ Epithelial atrophy - Thinning of the epithelium, usually associated with loss of rete ridges. ▪ Cellular atypia - A group of cellular changes that cytologically characterize epithelial dysplasia and which are typically seen in premalignant lesions. ▪ Epithelial dysplasia - A term applied to describe epithelium when features of cellular atypia are present. Atypia refers to cells; dysplasia is used when referring to the tissue. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page4  I. HEREDITARY CONDITIONS (Hereditary Keratosis) 1-LEUKOEDEMA Definition: ✓ Leukoedema is a bilateral, diffuse, translucent greyish, white thickening, particularly of the buccal mucosa. It is a variation of normal, present in 90% of blacks and variable numbers of whites. ✓ The difference in racial predilection may be explained by the presence of background mucosal pigmentation in blacks that makes the edematous changes more noticeable. Etiology and Pathogenesis: The cause of leukoedema ➔ unknown o Factors such as genetic factors, smoking, chewing tobacco, alcohol ingestion, and bacterial infection have been implicated in the pathogenesis of leukoderma. Clinical Features: ▪ Leukoedema is usually discovered as an incidental finding (asymptomatic). ▪ It is typically present as bilateral, symmetrically distributed in the buccal mucosa. ▪ In the early stage: ➔ appears as a diffuse, translucent, milky whiteness of the surface of the mucosa with a slightly folded appearance. ▪ In the exaggerated (late) stage:➔ appears as a whitish cast with surface textural changes, including wrinkling or corrugation may be seen. N.B Leukoedema tends to disappear on stretching it is not hyperkeratinzation (keratin production) BUT rather it represents intracellular edema of the prickle cell layer (accumulation of fluid within epithelial cells). Histopathological features: ▪ The epithelium is thickened by acanthosis with marked intracellular edema of spinous cells with broad rete ridges. ▪ The characteristic edematous cells in the superficial prickle layer appear extremely large and pale (vacuolated cells) and they present a reticular pattern. The cytoplasm appears lost and nuclei appear absent Leukoedema with marked or pyknotic. intracellular edema and acanthosis Treatment& prognosis: (thickness of epithelium). Treatment is not necessary because asymptomatic so considered a normal variation (developmental condition) and benign no malignant potential exists. Differential Diagnosis: White sponge nevus, Hereditary benign intraepithelial dyskeratosis, Chronic cheek biting, and Lichen planus. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page5  2- WHITE SPONGE NEVUS (WSN) (Keratotic nevus, Oral Epithelial Nevus, Cannon’s disease) Definition: ✓ White sponge nevus is a relatively rare genodermatosis (genetically determined skin disorder) that is inherited as an autosomal dominant trait, it is a benign condition (it is not a premalignant lesion). Etiology and Pathogenesis: ✓ This condition is due to a defect in the normal keratinization of the oral mucosa. ✓ It is due to point mutation  expression in keratin genes coding for keratins 4 & 13 leading to keratin production on the mucosal surface. Clinical Features: ▪ Age: Noticed at birth or soon after and increases with age. ▪ Site: Any part of the oral mucosa may be affected, as well as other mucosal surfaces in the body (extra-orally sites such as the nose, esophagus, and genital mucosa) ▪ Oral lesions: o Are almost always bilateral and symmetric and usually appear early in life, typically before puberty. o It usually occurs on the buccal mucosa but may be widespread involving the lateral surface of a tongue, palate, gingiva, and vestibular mucosa. o The mucosa appears thickened and folded or corrugated appearance (due to the uneven thickness of the epithelium) with a soft or spongy texture and white hue. WSN: The keratosis is irregular o The lesion is almost asymptomatic. and folded and extends into o Its edges are NOT well-defined (ill-defined/diffuse) & merge areas that are not subject to gradually with the normal epithelium. friction. Histopathological features: ▪ Microscopically, the epithelium is greatly thickened, with marked spongiosis, acanthosis, and hyper parakeratosis (characteristic features). ▪ Within the stratum spinosum, marked hydropic change➔ intracellular edema with abnormally prominent epithelial cell membranes and pyoknotic produce a so-called (Basketweave appearance). ▪ Pathognomic Perinuclear eosinophilic condensation of cytoplasm characteristic of prickle cells in White spongy nevus. Treatment: No treatment is necessary for this condition because it is asymptomatic and benign condition. Differential Diagnosis: Hereditary benign epithelial dyskeratosis, Lichen planus, Lichenoid drug reaction, Lupus erythematosus (LE), Cheek chewing, and possibly Candidiasis Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page6  II. REACTIVE-INFLAMMATORY LESIONS (TRAUMATIC KERATOSIS) Introduction: III. ▪ Reactive white lesions ➔ are those white patches with defined etiological factors, if the etiology is eliminated the lesion is reversible. Irreversible Lesions are considered premalignant lesions. Lesions cannot be rubbed off (known as oral keratosis). ▪ Traumatic keratosis ➔ It is reactive white patches represented by the following: Mechanical Trauma-frictional keratosis + Chemical trauma + Thermal Trauma + Radiation trauma. ▪ The oral mucosa reacts to irritants or trauma in one of two ways: Acute trauma ➔ (sudden severing high-grade trauma) leads to  blistering & ulceration. Chronic trauma ➔ (continuous non-severing low-grade trauma) leads to  epithelial thickening and hyperkeratinization which is known as frictional keratosis). ▪ Hyperkeratinization & epithelial thickening are two defense mechanisms to protect the epithelium and underlying submucosa from irritant penetration. ▪ In hyperplasia the irritant  Pressurizes the mucosa while in hyperkeratinization the irritant  Rubs the mucosa. 1- FOCAL (FRICTIONAL) KERATOSIS & CHEEK BITING Definition: Frictional keratosis is a white lesion (keratotic) that is related to chronic rubbing or friction against an oral mucosal surface. Etiology: ✓ As a result of exposure to chronic and prolonged mechanical traumatic agents such as ➔ Sharp cusps, rough restoration, and mal-posed tooth, I'll fit denture. ✓ Habits such as ➔ Cheek chewing, lip biting, and tongue-thrusting habit. ✓ Clinical features ▪ White plaque with a rough surface clearly related to the source of mechanical friction stimulus. ▪ Seen commonly in areas frequently traumatized like ➔ lips, lateral margins of tongue, buccal mucosa along the occlusal line, and edentulous alveolar ridges. ▪ Chronic cheek or lip chewing may result in ➔ opacification (keratinization) of the affected area. ▪ Chewing on edentulous alveolar ridges produces the same Focal hyperkeratosis caused by cheek chewing. effect called  (ridge keratosis). Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page7 Histopathological features: ▪ Hyperkeratosis which may be accompanied by some acanthosis but there is no dysplasia. ▪ Few Chronic inflammatory cells in C.T Diagnosis and treatment: o To diagnose frictional keratosis ➔ a source of chronic irritation must be identified and should fit the size and shape of the lesion. o No treatment is required: removal of the cause and control of related habit, the lesion should disappear ➔ (Reversible). 2- CHEMICAL TRAUMATIC Definition: ✓ It is a transient scrapable (Non-keratotic) white lesion. ✓ Chemical insult to the oral mucosa may produce a variety of reactions depending on the severity of the insult and its duration. o A severe insult such as that produced by the topical use of aspirin (aspirin burn) is likely to  produce epithelial necrosis, sloughing, and ulceration. o Mild, low-grade, chronic insult may result in  hyperkeratosis. Etiology:- ✓ As a result of exposure of the oral mucous membrane to ➔ chemical agents such as aspirin tablets (aspirin burn), hydrogen peroxide O2H2, and acid etchants. Clinical Features: - ▪ Locally use of aspirin ➔ is to place the tablet against the offending tooth ➔ allowing the check or lip to hold it in position  within a few minutes burning sensations of oral mucosa due to ➔ Coagulative necrosis. ▪ The surface becomes ➔ blanched or whitened in appearance. ▪ Then ➔ becomes sloughing tissue leaving a painful and bleeding area. Aspirin burn: against affected tooth Histopathological features: ▪ Irritating agent to the oral mucosa ➔ leads to stimulate  thickness of epithelium and necrosis of the surface (pseudomembranous) ▪ Connective tissue is infiltrated by chronic inflammatory cells. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page8  3-White lesions associated with the use of Tobacco (Tobacco related keratosis) Introduction Tobacco affects the oral mucosa through: 1) Heat 2) Tobacco constitutes (tar and resin). 3) Material leach out of chewing tobacco (Nitrosonornicotine)  Carcinogenic. ✓ Regular smokers of cigarettes, cigars, and pipes often develop white plaques on their oral mucosa, particularly the anterior parts of the buccal mucosa, tongue, and palate. ✓ It is likely that both thermal and chemical factors are involved in the development of these hyperkeratotic lesions. Types of Tobacco-related Keratosis: 1. Smoker keratosis. 2. Keratosis associated with the use of smokeless tobacco. 1. Smoker keratosis: 1. Cigarettes smoker 2. Cigar smoker ▪ Smoker patches on the lip ▪ Hyperkeratosis of the anterior hard ▪ Leukodema like lesions. palate. ▪ Sometimes stomatitis nicotina ▪ Diffuse erythema of soft palate ▪ Stomatitis nicotina 3. Pipe smokers 4. reverse smoking ▪ Same as cigar smoker + facet between ▪ Same as pipe and cigar smokers, teeth and stain of teeth. however, the lesion is irreversible. A-Nicotine Stomatitis (Pipe smoker’s keratosis) Nicotine Palatinus; Smoker’s Palate Definition: ✓ Nicotine stomatitis is a generalized white palatal alteration (hard palate) ➔ that seems to be a hyperkeratotic response to the heat generated by tobacco smoking rather than a response to the carcinogens within the smoke. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page9 ✓ It is the common Tabaco-related form of keratosis which is commonly seen among heavy, long-term pipe-smokers and sometimes caused by cigar and cigarette smokers. ✓ Because pipe smoking generates more heat on the hard palate than other forms of smoking so nicotine stomatitis has been ➔ associated most often with this habit. Malignant transformation in (Pipe smoker’s keratosis): Although Nicotine Stomatitis is a white keratotic change  which is strongly associated with tobacco smoking  but it does not appear to have a premalignant nature ➔ because it develops in response to heat rather than the chemicals in tobacco smoke. Epidemiological evidence suggests  that pipe smoking raises the risk of cancer, but when oral cancer develops in association with pipe smoking ➔ it typically appears not in the keratotic area on the palate (one of the least common sites for cancer) but low down in the mouth, often in ➔ the lingual retromolar region. "Reverse smoking" habit produces  a pronounced palatal keratosis, or reverse smoker's palate ➔ this has a significant potential to develop dysplasia or carcinoma. Because ➔ Malignant transformation is markedly intensified when the combination of tobacco carcinogens and heat in reverse smoking. Clinical presentation: ▪ It is most commonly found in men older than 45 years. ▪ The appearances are distinctive ➔ The palate is affected, but any part protected by a denture is ➔ unaffected  Changes are then seen only on the soft palate. ▪ The palatal mucosa becomes diffusely gray or white. ▪ The palatal mucosa initially ➔ responds with an erythematous change followed by ➔ keratinization. Subsequent to keratinization of the palate along with numerous slightly elevated papules ➔ (white keratotic Stomatitis nicotina: There is a rings) with punctate red centers (red dots). The dots ➔ generalized whitening with punctate red centers (red dots) represent dilated and inflamed excretory duct openings of the minor salivary glands. Histopathological features: ▪ Epithelium of the palate showing  (Hyperkeratosis and Acanthosis). ▪ Salivary gland  (Mild to severe inflammation of the minor salivary gland, secretory ducts show ➔ squamous metaplasia. ▪ Keratin plugs in some of the duct orifices associated with mild periductal chronic inflammation. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page10  B- WHITE LESIONS ASSOCIATED WITH SMOKELESS TOBACCO (KERATOSIS ASSOCIATED WITH THE USE OF SMOKELESS TOBACCO) Introduction: Mainly two forms of smokeless tobacco: 1) Snuff tobacco ➔ two types (dry snuff + moist snuff) 2) Chewing tobacco ➔ as Betel quid chewing. ✓ Habitually chewing tobacco is an important established risk factor for the development of oral carcinoma. In India and UK ➔ smokeless tobacco (chewing tobacco) combined in quid with other products such as  Betel leaves + areca nuts + slaked lime ➔ giving (Betel quid chewing) ➔ which is associated with Oral submucous fibrosis ➔ which is a chronic, progressive, scarring, high-risk precancerous condition of the oral mucosa. The clinical results of long-term exposure to smokeless tobacco are: 1. Oral white patches (Keratosis)➔ characteristic white plaque of smokeless tobacco with a slightly malignant potential. 2. Alteration of smell and taste & Bad breath. 3.  Amount of gingival recession with periodontal destruction in the immediate area of contact. 4. Dental abrasion 5. Teeth discoloration and smoker’s Melanosis  (pigmentation of oral mucosa). 6. Dental caries ➔ (development of root surface decay) due to sugar content. 7. Oral mucosal ulceration B-SMOKELESS TOBACCO KERATOSIS (TOBACCO POUCH KERATOSIS Snuff pouch, Snuff dipper’s keratosis, spit tobacco keratosis Definition: ✓ Habitually chewing tobacco leaves or dipping snuff results in the development of a well- recognized white mucosal lesion in the area of tobacco contact, called smokeless tobacco keratosis, snuff dipper’s keratosis, or tobacco pouch keratosis. Etiology: ▪ The Causal relationship has been documented between the use of smokeless tobacco and white tissue changes: ▪ Direct contact of mucosa with smokeless tobacco and contaminants ➔ Snuff form of tobacco most commonly likely to induce lesions. Dry snuff placed on buccal mucosa Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page11 Tobacco pouch keratosis: hence name from: The altered mucosa typically has a soft velvety feel to palpation and stretching of the mucosa often reveals a distinct "pouch" (snuff pouch. tobacco pouch) caused by flaccidity in the chronically stretched tissues in the area of tobacco placement. Clinical Features: ▪ White lesions associated with smokeless tobacco develop in the immediate area where the tobacco is habitually placed. ▪ Most commonly area➔ anterior mandibular vestibule followed by posterior mandibular vestibule. ▪ Asymptomatic, White area of granular or wrinkled appearance developed immediately where the tobacco is habitually placed. ▪ Stretched mucosa appears fissured or rippled & a “Pouch” Tobacco pouch keratosis: is usually present. appears as soft fissured and gray- white lesion in buccal (left picture) ▪ The white pouch may become leathery or nodular in long- and labial mucosa (right picture). term heavy users. Histopathological features: ▪ Hyperparakeratosis of surface epithelium with formation of parakeratin Chevrons ➔ seen as pointed projections of keratin above of surface epithelium. ▪ Acanthosis and Vacuolization (intracellular edema of superficial layers). ▪ Epithelial hyperplasia is typical. ▪ Epithelial dysplasia is uncommon in smokeless tobacco keratosis and when present, is typically mild. Tobacco pouch keratosis. Showing hyperkeratosis with ▪ Occasionally, significant dysplasia or SCC may be present "chevron" formation. on first biopsy. ▪ NB... All types of smokeless tobacco ➔ associated with epithelial dysplasia (potential premalignant disorders). Treatment and Prognosis: ▪ Discontinuation of smokeless tobacco use some lesions may disappear after several weeks. ▪ A long period of exposure to smokeless tobacco increases the risk of transformation to verrucous or squamous cell carcinoma, although this risk is probably low. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page12  4-RADIATION TRAUMA (ACTINIC CHEILITIS) SOLAR CHEILITIS Definition: ✓ Actinic, or solar, cheilitis represents accelerated tissue degeneration of the vermilion (dry mucous membrane) of the lips, especially the lower lip, as a result, ➔ of chronic exposure to sunlight; it is considered to represent a potentially premalignant condition. ✓ Keratotic lesions secondary to ➔ prolonged exposure to sunlight. Etiology: Overexposure to ultraviolet light (esp. UVB [2900 to 3200 nm]). Clinical features ▪ Occurs almost exclusively in white people particularly those with fair skin. ▪ The vermilion border of the lower lip appears ➔ atrophic, pale gray or silver gray, glossy appearance. ▪ Fissuring and wrinkling at cutaneous -vermilion junction. Actinic cheilits in vermilion border of lower lip ▪ Areas of hyperpigmentation ▪ Superficial scaling, erosion ,ulceration, and crusting ➔ observed in advanced cases. Histopathological features: ▪ Irregular hyperplastic epithelium with Orthokeratosis or Parakeratosis ▪ Various dysplastic changes ranged from slight atypia to carcinoma in situ. ▪ Basophilia of the submucosa (replacement of collagen with elastin). ▪ Appearance of Telangiectasia vessels. VII. Premalignant (Precancerous) Oral White lesions ✓ Premalignant (Precancerous) lesions: is" a morphologically altered tissue in which oral cancer is more likely to occur than its apparently normal counterpart. ✓ Precancerous condition is" a generalized state associated with significantly increased risk of cancer". ✓ Malignant transformation potential: The risk of cancer being present in a precancerous lesion or condition, either at initial diagnosis or in the future (usually expressed in percentages). ✓ Oral epithelial dysplasia: Dysplasia refers to abnormal epithelial growth characterized by a spectrum of cytological, maturational, and architectural changes. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page13  Oral White Premalignant lesions vs Premalignant Conditions Premalignant lesions Premalignant conditions 1) Dysplastic leukoplakia 1) Oral submucous fibrosis 2) Speckled leukoplakia 2) Oral lichen planus 3) Erythoplakia 3) Discoid lupus erythemtosus 4) Syphilitic leukoplakia 4) Plummer-Vison syndrome 5) Palatal keratosis associated with reverse 5) Actinic keratosis smoking. 6) Actinic cheilitis 7) Smokeless tobacco keratosis 8) Carcinoma in situ LEUKOPLAKIA (LEUKOKERATOSIS) Definition: ✓ Leukoplakia (leuko = white, plakia = patch). ✓ Oral leukoplakia: defined by the World Health Organization (WHO) as a "predominately white, irreversible, non-scrapable lesion of the oral mucosa that cannot be characterized clinically or histopathologically as any other lesion/disease (any other definable lesion) and increased risk of cancer than its normal counterpart". ✓ Idiopathic (True) leukoplakia ON definitive cause or etiology ✓ Leukoplakia Clinical Term. ✓ Diagnosis of leukoplakia clinically and arrived by exclusion (exclusion of other definable lesions which present as oral white patches or plaques). ✓ Leukoplakia is not associated with specific histopathological features, it may range from benign hyperkeratosis to invasive squamous cell carcinoma, so a biopsy is mandatory to establish a definitive diagnosis. ✓ Importance of Leukoplakia: it is the most common premalignant (precancerous) lesion of the oral mucosa (accounts for 85% of the premalignant lesions). Etiology: - ▪ The etiology of idiopathic oral leukoplakia is by definition unknown ▪ But predisposing factors (risk factors) can be identified. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page14 1) Tobacco: - Tobacco is the most common etiological factor in patients with leukoplakia. - Smokers are much more likely to have leukoplakia than non-smokers. - 80% of tobacco users develop leukoplakia. - Both smoke & smokeless tobacco users ➔ develop leukoplakia - Prevalence  with the amount of tobacco & duration of smoking. - Distribution of lesions may vary with the particular type of habit e.g:- o Cigarette smoking: leukoplakia may be diffuse on cheeks, lips, and tongue. o Reverse smoking: a wide variety of changes (white patches, red areas, or ulceration) in the palate. o Smokeless tobacco: leukoplakia may be in the lower buccal sulcus. N.B ✓ In the patients with tobacco-associated keratosis regresses on cessation of the habit, the lesion ➔ should not be classified as leukoplakia. ✓ In leukoplakia tobacco may be a predisposing factor for the changes taking place but it is not the cause that if removed the lesion would regress. 2) Alcohol: It strong synergistic effect with tobacco ➔ to developed oral cancer ➔ it has not associated with  develop of leukoplakia. 3) Candida: - Candidal hyphae frequently found in chronic hyperplastic candidiasis which called (Candidal Leukoplakia). - Candida occasionally found in association with ➔ idiopathic leukoplakia but not known whether this candida produces dysplasia or secondarily ➔ in previously altered (dysplastic) epithelium. 4) Viruses: - Human Papilloma Virus (HPV) HPV 18 & 16 strains. - Their role in the pathogenesis is uncertain but evidence exists of association of HPV16 strain with develop risk of malignant transformation. 5) Oral epithelial atrophy: - Atrophy ➔ weakens the mucosa and  its sensitivity to chemicals & traumatic agents. - Any condition that may cause epithelial atrophy  risk of leukoplakia such as: a) Iron deficiency. b) Some vitamin deficiencies (folic acid, vitamin B12) c) Submucosa fibrosis (which is a premalignant condition characterized by an epithelial inflammatory reaction and progressive fibrosis of the sub-mucosal tissues. The condition is linked ➔ to the areca nut chewing habit. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page15  d) Tertiary syphilis ➔ atrophic glossitis ➔ syphilitic leukoplakia. e) Patterson-Kelly OR Plummer-Vinson syndrome: in which patients develop iron- deficiency anemia, dysphagia (difficulty in swallowing), and esophageal webs (thin membranes that make swallowing painful). Orally it is associated with epithelial atrophy, leukoplakia, or carcinomas. 6) Tumour suppressor genes: - These genes are involved in the regulation of the normal cell-proliferation cycle. - Mutations in tumour suppressor genes mainly p53 on chromosome 17q result in ➔ uncontrolled cell proliferation and such mutations are seen in a wide range of malignancies and in some leukoplakia. 8) Sanguinaria-associated leukoplakia: - Sanguinaria Canadensis (type of flower) has been found to be effective against plaque buildup and gingivitis. - Sanguinaria-associated leukoplakia is a unique form of oral leukoplakia attributed to the chronic use of oral rinses and toothpastes containing the extract of this plant. - It is usually located on the attached gingiva & the alveolar mucosa of the maxillary vestibule. Clinical features: ▪ Age: Middle & old age ➔ Majority of cases occur after the age of 40 years. ▪ Sex: Prevalence for male (M>F). ▪ Size: Small well-defined to extensive. ▪ Sites: Any site of oral mucosa but most common sites ➔ lip vermillion, buccal mucosa, gingiva (account 70% of cases) ➔ mandibular mucosa, tongue, the floor of the mouth and retromolar area➔ Second common sites but maxillary ridge and palate ➔ less frequently involved. ▪ ▪ N.B High-risk sites of leukoplakia for malignant transformation: The floor of mouth > tongue > lip vermillion > retromolar ➔ exhibits a relatively high percentage of dysplastic OR neoplastic change. ▪ The surface appearance: - Ranged from Vague white patch to definitive white on a base of un-inflamed, normal- appearing tissue that can't be rubbed off. - The lesion may have ➔ leathery, fissured, verrucous, or wart-like appearance. - On palpation they may ➔ soft, smooth, or granular texture OR ➔ may be rough, nodular, or indurated. - Red zones are sometimes seen in leukoplakia ➔ it is termed speckled leukoplakia. - They usually ➔sharply demarcated borders but occasionally blend gradually into normal mucosa. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page16  Clinical classification of leukoplakia: Oral leukoplakia is classified into two main types: Homogenous leukoplakia VS Non-homogenous leukoplakia The lesion ➔ flat, thin, smooth surface The lesion ➔ shows variations in the Shape or fissured, wrinkled, a corrugated surface contour they may➔ granular or surface which alters or not with nodular and verrucous surface normal mucosa Color Uniform white patch They may ➔ show variation in colour whit red areas interspersed with white areas Types 1.Mild, thin leukoplakia 1.Granular or nodular leukoplakia 2.Thick, plaque leukoplakia 2.Verrucous leukoplakia 3.Proliferative verrucous leukoplakia 4.Speckled leukoplakia PMD Low malignant transformation ➔1-7% It has high risk malignant transformation ❖ Clinical Variants of Leukoplakia: 1 Mild or thin leukoplakia. 2. Homogenous or Thick leukoplakia. 3. Granular or Nodular Leukoplakia. 4. Verrucous or Verruciform Leukoplakia. 5. Proliferative Verrucous Leukoplakia (PVL). 6. Erythroleukoplakia or Speckled Leukoplakia. 7. Erythoplakia Homogenous thick Proliferative verrucous Speckled leukoplakia or leukoplakia leukoplakia (PVL) Erythroleukoplakia Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page17  ❖ Clinical Variants of Leukoplakia: 1) Mild or thin leukoplakia: 2) Homogenous or Thick Leukoplakia: o Affected mucosa➔ Thin smooth surface o Mucosa ➔ thicker + distinctly white o Seldom shows dysplasia on biopsy appearance. o May disappear or continuously changed o It may become ➔leathery to palpation➔ fissures may deepen & become more numerous o Some of which ➔ regress or disappear 3) Granular or Nodular Leukoplakia: 4)Verrucous or Verruci-form Leukoplakia: o Few of lesions become severe to develop o lesions that demonstrate sharp or blunt increased surface irregularities to be further projections called Granular leukoplakia. 5) Proliferative Verrucous Leukoplakia (PVL) o A special high-risk form of leukoplakia characterized by the development of multiple keratotic plaques with roughened surface projections. o This type of leukoplakia begins as simple keratosis and eventually becomes ➔ verrucous in nature. o Lesions tend to be persistent, multifocal, recurrent, and sometimes locally infiltrative. o Multiple PVL plaques tend to slowly spread involve additional oral mucosal sites o The cause of PVL is ➔ unknown, although early reports suggest a relationship in some lesions with human papillomavirus. o These lesions progress to develop dysplastic changes and transform into ➔ SCC (usually within 8years of initial diagnosis of PVL). (Malignant potential is high in PVL occur up to 08% of cases). o They are having strong female predilection  (F: M 4:1). o It has minimal association with tobacco use. 6) Erythroplakia also called Erythoplasia: 7) Erythro-leukoplakia or Speckled o Some lesions of leukoplakia➔ eventually Leukoplakia: demonstrate scattered patches of redness called o Also called (Non-Homogenous leukoplakia) erythroplakia. o Such areas usually represent sites in which o Erythroplakia are red patches. The surface is epithelial cells are so immature or atrophic frequently velvety in texture and the margin that they can no longer produce keratin. may be sharply defined o Intermixed red-and-white lesion pattern of o Erythroplasia is uncommon in the mouth but leukopla kia that frequently reveals advanced carries the highest risk of malignant dysplasia on biopsy. transformation and lesions are often already o Risk of malignant transformation of speckled malignant on the first biopsy. leukoplakia is greater than lesions that are homogeneous Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page18 Histopathological features: ▪ Histological grading of leukoplakia: ➔ range from hyperkeratosis  dysplasia  carcinoma in situ invasive squamous cell carcinoma. ▪ At first diagnosis microscopic features are: o Hyperkeratosis— accounts for 80% of cases o Dysplasia— accounts for 12% of cases o In situ carcinoma— accounts for 3% of cases o Squamous cell carcinoma— account for 5% of cases ▪ Epithelial dysplasia: o NOT all leukoplakias are dysplastic. o Dysplastic changes can be  mild, moderate, or severe dysplasia. o Severe dysplasia has a higher risk for malignant transformation. ▪  Thickness of oral mucosa as a result of ➔ hyperkeratosis and acanthosis in the leukoplakia. ▪ Chronic inflammatory cells infiltrate the connective tissue stroma. ▪ Erythroplakia➔ appears as atrophic epithelial + severe dysplasia or carcinoma in situ. ▪ In about 25 % of the leukoplakia contain ➔ Epithelial Dysplasia in contrast, about 50 % of the erythroplakia contain ➔Epithelial Dysplasia. ▪ It must be remembered that leukoplakia is a clinical diagnosis arrived at after the exclusion of other diseases and is not based on any specific histopathological features. The term leukoplakia has no histological connotation. Prognosis& Potential malignant transformation of Leukoplakia: ✓ It depends on many factors such as ➔ a high -risk sites, size & nature of the lesion, severity, and duration of predisposing factors, clinical appearance, and histopathological features with epithelial dysplasia and cellular atypia. SO leukoplakia has a bad prognosis when ➔ female non-smoking patient + duration of the lesion + large size + non-homogenous type + lesion in tongue or floor of the mouth + dysplastic changes or carcinoma in microscopic features. ✓ Potential for malignancy is greater in high-risk sites as:➔ ventral surface of the tongue, flour of mouth, lingual aspect of lower alveolar mucosa. ✓ Dysplastic lesions ➔  risk of malignant transformation (10%-30%). ✓ Speckled and other non-homogenous types ➔  rate of malignant transformation (30%). ✓ Erythroplakia is a highly malignant transformation potential than leukoplakia. ✓ Erythroplakia (alone or as part of specked leukoplakia)➔ shows invasive carcinoma or carcinoma in situ on 50% of initial biopsies, and most of remaining show ➔ severe dysplasia. ✓ Candida leukoplakia ➔ high incidence of dysplasia or malignant transformation (30%). ✓ Recent studies show that leukoplakias with abnormal DNA content of epithelial cells are more likely to undergo ➔ malignant transformation. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page19  Differential Diagnosis of leukoplakia: leukoplakia keratotic white lesions Non-keratotic white lesions (pseudomemebern) Bilateral buccal Solitary white lesions: 1.fungus colony mucosal dieases: 1.Frictional keratosis 2. Food debris 1.Lichen planus 2.Tobacco pouch 3. Chemical burns 2.WSN keratosis 3.leukoedema 3.Candidial leukoplakia 4.DLE 4.Hiary leukoplakia 5.Cheek chewing 5.Syphilitic leukoplakia 6.Nicotine stomatitis VI. Infectious white lesions Infectious white lesions: 1) Candidal infection (Oral Condidiasis) caused by candida albicans. a) Acute ➔ Pseudomembranous (Thrush). b) Chronic hyperplastic candidiasis ➔ Candidal leukoplakia. c) Chronic mucocutanoeous candidiasis 2) Bacterial infection Syphilitic Leukoplakia caused by Treponema pallidum. 3) Viral infection Oral Hairy Leukoplakia caused by EBV. 4) V. DERMATOSIS (IMMUNOLOGICAL) (Dermokeratosis) ✓ A number of primarily dermatological diseases in addition to the genodermatoses have oral lesions which may present as white patches (deramokeratosis). Lichen planus is by far the commonest, but it is convenient here to include lupus erythematosus since, clinically and histologically, the chronic discoid type may mimic lichen planus. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page20  1- ORAL LICHEN PLANUS (OLP) Introduction ✓ Lichen planus (LP) ➔ (plant flat) is derived from the Greek lichen meaning tree moss (plant) and the Latin planus meaning flat. ✓ Erasmus Wilson  first described LP in 1869 as a chronic disease affecting the skin, scalp, nails, hair, and mucosa with possible rare malignant degeneration. ✓ Erasmus Wilson 1896  The LP is a relatively common disorder of stratified squamous epithelia. Definition: ✓ Lichen planus (LP): is a relatively common chronic inflammatory immunologically mediated disorder in which epidermal or epithelial basal cell damage produces mucocutaneous lesions that vary in appearance from keratotic to erythematous and ulcerative. ✓ The condition can affect either the skin or mucosa or both. ✓ Oral lichen planus (OLP) ➔ the disease manifested in the oral cavity as ➔ bilateral white striations, papules, or plaques on the buccal mucosa, tongue, and gingiva. Erythema, erosion, and blisters may or may not be present. ✓ Oral lesions frequently precede the appearance of lesions of the skin. ✓ OLP can be a source of sever morbidity and has a small potential to be malignant. Etiology and Pathogenesis: Etiology of the condition is ➔ unknown Many factors are believed to be implicated in etiology of OLP: 1) Emotion stress and anxiety but  the relationship of stress or anxiety to the development of OLP is controversial. 2) Genetic influence. 3) Infective disease ➔ Hepatitis C infection but  more recent carefully controlled epidemiologic studies do not appear to support the association of OLP with hepatitis. 4) Systemic disease ➔ Grinspan’s syndrome  triad of (LP + DM + vascular hypertension) 5) Drug eruption ➔ variety of medications may induce lesions that can appear clinically very similar to LP which is termed  (Lichenoid drug reaction/ lichenoid mucositis). 6) Hypersensitivity to dental materials ➔ (Contact hypersensitivity reaction). 7) Autoimmune disease: Recent data suggest OPL is a T-cell-mediated autoimmune disease in which cytotoxic CD8 T-cells trigger the apoptosis of oral epithelial cells. Pathogenesis of autoimmune mechanism: - Pathogenesis of lichen planus is not fully understood but it is widely accepted that cell- mediated immune responses (hypersensitivity type VI) to an external antigen or to internal antigenic ➔ changes in the epithelial cells. - In most cases the precipitating or stimulating factors are unknown and the disease is idiopathic. - TARGET in OLP is ➔ Oral Epithelial Basal Cells. - Cell-mediated immune process involving ➔ Langerhans cells, T-lymphocytes, macrophages, and major histocompatibility complex (MHC1). Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page21 Clinical features: ▪ Incidence: o 40%- of patients have ➔ Both Oral & Cutaneous lesions. o 35%- of patients have ➔ Cutaneous lesions only. o 25%- of patients have ➔ Mucosal lesions only. ▪ Prevalence of oral lichen planus is between 0. 1% and 2.2% of population. ▪ Age: Disease of middle age & Children rarely affected. ▪ Sex: Females > Males 3: 2. No racial predilection ▪ Symptoms: 2/3 of cases are asymptomatic. ▪ Usually present bilaterally distributed. Oral manifestations of LP (OLP): - Most common site is ➔ posterior buccal mucosa. Other locations ➔ tongue, gingiva, (the gingival lesion appears as Desquamative Gingivitis), alveolar mucosa, palate, lip (mucosal side). - Distribution of oral lesions: o Buccal mucosa 80%,Tongue  65%, Lips20%, Gingiva and palate10% - Signs and symptoms: Asymptomatic, except in erosive and atrophic types ➔ they have a burning sensation. - Characteristic feature: presence of Wickham’s striae. Wickham striae: is very fine white or gray lines or dots seen on the top of the papular rash (skin lesions) and oral mucosal lesions of Lichen planus (Reticular OLP). It is typically seen in oral mucosa. ❖ Clinical forms of OLP: Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page22 1) Reticular OLP: ✓ The most common and most readily recognized form. ✓ Reticular OLP is named because  characteristic pattern of numerous interlacing white keratotic lines or striae (so- called Wickham’s striae) that produce an annular or lacy pattern. ✓ Lines are wavy and parallel. ✓ The buccal mucosa posteriorly is the site most commonly involved. Reticular OLP: with ✓ Striae ➔ occurring typically in a symmetric pattern on the Wickham’s striae (arrow) buccal mucosa bilaterally, but may also be noted on ➔ the tongue and less commonly on the gingiva and lips. ✓ This form generally presents with minimal clinical symptoms and is often an incidental discovery. 2) Papular OLP: ✓ The popular type of OLP is usually present in the initial phase of the disease. ✓ It is clinically characterized by small white dots ➔ which in most occasions intermingle with the reticular form. 3) Plaque OLP: ✓ Plaque type of OLP shows ➔ a homogenous well demarcated white plaque often but not always surrounded by striae. ✓ It resemble leukoplakia clinically but has a multifocal distribution. ✓ Such plaques generally range from slightly elevated to smooth and flat. ✓ The primary sites for this variant are the dorsum of the Plque OPL in dersoum surface tongue and the buccal mucosa. of the tongue. 4) Erythematous or Atrophic OLP: ✓ It is characterized by a homogenous red area. ✓ It appears as ➔ smooth, poorly defined erythematous patches with very fine white striae. ✓ It may be seen in conjunction with reticular or erosive variants. ✓ The proportion of keratinized areas to atrophic areas varies from one area to another. The attached gingiva, commonly involved in this form of lichen planus, exhibits a patchy Erythematous OLP: in buccal distribution, often in four quadrants. mucosa ✓ Usually associated with Desqumative gingivitis. ✓ Patients may complain of ➔burning, sensitivity, and generalized discomfort. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page23 5) Erosive OLP: ✓ More significant for the patient because ➔ the lesions are usually symptomatic. ✓ Atrophic areas with central ulceration of vary degree. ✓ Peripheral of atrophic regions is usually bordered by fine, white radiating striae. ✓ The process is a rather dynamic one, with changing patterns of involvement noted from week to week. ✓ Fibrinous plaque or pseudomembrane covers the ulcerations Erosive OLP: Ulceration of with keratosis and erythema. the buccal mucosa shows ✓ Patients complain of ➔ PAIN, burning sensation, bleeding, peripheral radiating keratotic Desquamative gingivitis. striae 6) Bullous OLP: ✓ A rarely form of lichen planus is the bullous variant. ✓ Vesciculobullous presentation combined with reticular or erosive pattern. ✓ Bullae range from a few millimeters to centimeters in diameter. ✓ Such bullae usually develop within an erythematous base which rupture immediate leaving painful ulcer. ✓ Sever form with extensive degeneration and separation of epithelium from CT. ✓ Lesions are usually seen on ➔ the buccal mucosa, especially in the posterior and inferior regions adjacent to the second and third molars. Lesions are less common on the tongue, gingiva, and inner aspect of the lips. ✓ Reticular or striated keratotic areas should be seen with this variant of lichen planus. Skin lesions features of LP: ▪ On the skin, lichen planus ➔ is characterized by the presence of small, violaceous, polygonal, flat-topped, pruritic papules on the flexor surfaces of the forearm and anterior tibial surfaces. ▪ Other clinical varieties ➔ include hypertrophic, atrophic, bullous, follicular, and linear forms. ▪ Cutaneous lesions have been reported in 20% to 60% of patients with oral lichen planus. ▪ Although the oral changes are relatively persistent over time, corresponding skin lesions tend to wax and wane and exhibit a relatively short natural history (1 to 2 years). ▪ Characteristic 4p’s- Purple, Polygonal, Pruritic, and Papule. Wickhams striae the classic appearance of skin lesions consists of erythematous to violaceous papules that are flat-topped and occasionally polygonal in form. A network of white lines often overlies the papules. Koebners phenomena- it refers to the development of papules along the line of trauma in a linear fashion  Most commonly seen on the skin. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page24 Histopathological features: 1. Varying degrees of Hyperorthokeratosis or Hyperparakeratosis of epithelium surface. 2. Thickening of the granular cell layer. 3. Acanthosis of the spinous layer. 4. Liquefaction degeneration of the basal cells. 5. Apoptotic (degenerated) basal keratinocytes may be seen in are of epithelium connective tissue interface and celled Civatte, cytoid or colloid bodies. 6. Saw tooth configuration of the rete ridges (pointed rete ridges)  why? 7. Intense band-like of lymphocytic infiltration (mainly T-lymphocyte-CD8) immediately subjacent to the epithelium. Epithelium CT junction ➔ change into (zig-zag pattern). Malignant transformation of OLP: ✓ Almost all cases of oral lichen planus ➔ run a benign course, but malignant transformation has been described in a very small proportion. ✓ Some studies have suggested that the atrophic/erosive forms are more likely to undergo such change ➔ because of the decreased barrier presented to potential carcinogens. ✓ In others studies have found malignant transformation to be associated mainly with plaque lesions which associated with dysplastic changes. ✓ It ranges from about 0.5 to 2.5 per cent over a 5-year period. Differential Diagnosis: ▪ Other diseases with a multifocal bilateral presentation that should be included in a clinical differential diagnosis are ➔ lichenoid drug reaction, LE, white sponge nevus, hairy leukoplakia, cheek chewing, graft-versus-host disease, and candidiasis. ▪ Idiopathic leukoplakia and squamous cell carcinoma might be considered when lesions are plaque-like. ▪ Erosive or atrophic lichen planus affecting the attached gingiva must be differentiated from cicatricial pemphigoid, pemphigus vulgaris, chronic LE, contact hypersensitivity, and chronic candidiasis. 2-LUPUS ERYTHEMATOSUS (LE) Definition: It is a dermatological disease that occurs when your body's immune system attacks your own tissues and organs (autoimmune disease) with oral manifestations. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page25 Types or forms of LE: o Lupus erythematosus (LE) may be seen in one of two well-recognized forms: A. Systemic (Acute) LE (SLE): ✓ SLE is a chronic, autoimmune, multisystem, inflammatory disease that may involve almost any organ but characteristically affects kidneys, joints, serous membranes, and skin. ✓ SLE is caused by tissue damage resulting from auto-antibody and complement complex deposition. ✓ It is characterized by states of exacerbation and remission. ✓ Is particular importance because ➔ disseminated disease involved multiple organs. B. Discoid (Chronic) LE (DLE): is the less aggressive form, predominantly affecting the skin. But can be involved oral mucous membrane. C. Third form, known as (sub-acute cutaneous LE) ➔ described as lying intermediate between SLE and DLE, results in skin lesions of mild to moderate severity Etiology and Pathogenesis: Etiology  unknown Hormones But Pathogenesis of SLE Genetics Environment o LE is believed to be an auto-immune disease involving both humeral and cell-mediated arms of the immune system. o There is  in the activity of humoral (B-lymphocytes) of immune system  production Autoantibodies (mainly Ig G) directed against self-Antigens: - Nuclear components ➔ ANA, anti-ds-DNA. - Cytoplasmic components. - Cell surface antigens of blood elements. o Hormone Estrogen is ➔ a stimulator of B-cell activity. o There is impaired T cell regulation of the immune response. SO ➔ Abnormal function of the T-lymphocytes  failure to remove immune complex from circulation leads to ➔ deposition of complexes in the tissues causing ➔ vasculitis  inflammation  injury to the tissue. o SLE is a prototype of type III hypersensitivity reactions. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page26  The presence of immune complexes containing nuclear antigen in injured tissues lends strong support to the concept that the bulk of the injury in lupus is ➔ due to the deposition of circulating immune complexes against self-antigens, particularly against DNA. Other clinical manifestations (e.g., thrombocytopenia or the secondary antiphospholipid syndrome) are caused by ➔ autoantibodies against serum components or molecules on cell membranes. Clinical Features: ▪ 80-90% of LE patients are female. ▪ The main age of diagnosis is 30 years. A) Discoid Lupus Erythematosus (DLE) Chronic cutaneous lupus erythematosus: ▪ Patients with DLE usually have few or no systemic signs or symptoms, with lesions being limited to skin or mucosal surfaces. ▪ The face and scalp are usually affected, in addition to oral and vermillion lesions. ▪ Skin lesions: ➔ appear as disk-shaped erythematous plaques with hyperpigmented margins. As the lesion expands peripherally, the center heals, and formation of scar and loss of pigment are noted. The skin lesions are Disk-shaped rash exacerbated by sun exposure. ▪ Oral Lesions: ➔ o Appear as erythematous or ulcerative with delicate white; keratotic striae radiating from the periphery of the lesions, similar to those of OLP are present. o Unlike the oral lesions of lichen planus ➔ the oral lesions of DLE rarely occur in the absence of skin lesions. o The buccal mucosa, gingiva, and vermilion are most commonly affected. B) Systemic Lupus Erythematosus: ▪ Multiple systemic involvements ➔ can affect any organ but commonly ➔ (joints, kidney, heart, lungs, blood and nervous system) cause wide variety of clinical signs and symptoms. ▪ Can range from mild to life threatening. ▪ Common findings include ➔ fever, weight loss, arthritis, fatigue, and general malaise. ▪ In 40% to 50% of affected patients have  Characteristic Butterfly rash or Malar rash an erythematous rash involves the skin over the malar process and bridge of nose, giving  butterfly distribution typically sparing the naso-labial folds. Sunlight often makes the lesion worse. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page27 ▪ Oral lesions in SLE: o Oral lesions of SLE develop in  5% to 25% of these patients. Although some studies indicate a prevalence as high as 40%. o The lesions usually affect ➔ the palate, buccal mucosa, and gingivae. o Typical lesions ➔ white, often striate areas with irregular atrophic areas or shallow erosions, but the patterns, particularly those of the striae are typically far less sharply defined than in lichen planus. o They are often patchy and unilateral and may be in the vault of the palate which lichen planus typically spares. o Involvement of the vermilion zone of the lower lip called ➔ (lupus cheilitis). o Other oral complaints such as ➔ xerostomia, candidiasis, periodontal disease. Histopathological features: ▪ The skin lesions ➔ are characterized by hyperkeratosis, basal cell degeneration and patchy to dense aggregate of chronic inflammatory cells in the underlying CT. ▪ The oral lesions ➔ demonstrate hyperkeratosis, alternating atrophy and thickening of the spinous cell layer, subepithelial lymphocytic infiltration. ▪ Perivascular lymphocytic infiltration in Discoid LE. In SLE the inflammatory cell infiltrate are less evident and more diffuse. ▪ Vascular dilatation with edema of the upper dermis. Diagnosis of SLE: 1. By the Direct immunofluorescence technique: A. It shows granular-linear deposits of immunoglobulins, complement and fibrinogen along the basement membrane. These are non-specific being present in several other conditions. B. Immunoglobulins granular-linear deposits demonstrated in sub-epidermis are relatively specific (Lupus band tesThe most important diagnostic disease- associated autoantibodies are those against nuclear antigens—in particular, antibody to double stranded DNA (ds-DNA) and to a soluble nuclear antigen complex that is part of the spliceosome, termed Sm (Smith) antigen. High titers of these two antinuclear antibodies (ANAs) are nearly pathognomonic of SLE but are not directly cytotoxic. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page28 References: 1. Oral and Maxillofacial Pathology" by Neville BW, Damm DD, Allen CM, Chi AC. 2. "Oral Pathology: Clinical Pathologic Correlations" by Regezi JA, Sciubba JJ, Jordan RCK. 3. "Color Atlas of Oral Diseases: Diagnosis and Treatment" by Langlais RP, Miller CS. 4. "Diagnosis and Management of Oral Lesions and Conditions: A Resource Handbook for the Clinician" by Sciubba JJ. Oral White Lesions/ Dr.Ebtesam Aldieb (2024) Page29