White Lesions

Sumamry Not another white lesion! This lesson will help you differentiate between the many white lesions you will come across.

Overview

White lesions result from: Thickened keratin Necrotic Epithelial hyperplasia, Intracellular epithelial oedema Reduced vascularity of subjacent connective tissue. White/ yellow-white lesions may be due to fibrinous exudate A is required for any persistent and unexplained oral white patch in order to exclude cancer

Key words¹

Keratosis Keratinisation of epithelium that is not usually keratinised The superficial cells of the stratified squamous epithelium are keratinised, Orthokeratosis anucleated and flattened More common in the . Superficial cells of the epithelium are ParakeratosisReviseDental.comkeratinised, flattened and have pyknotic nuclei. The granular cell layer isn't visible An abnormal quantity of keratin within the outer layer of the stratified squamous Hyperkeratosis epithelium that is usually keratinised Hyperplasia of stratum spinosum - prickle cell layer Acanthosis Increased thickness of epithelium Large and broad rete ridges Oedema Excess of watery fluid collecting in cells, tissues or cavities Decreased thickness of epithelium Atrophy Loss of rete ridges usually occur Dysplasia Mass of epithelial cells which are atypical Small red/ purple spots which are caused by bleeding into the oral mucosa - also Petechiae known as haemorrhage Similar to petechiae as they are caused by intradermal capillary bleeding Purpura Larger than petechiae and usually raised

Differential diagnosis of a white lesion

Hereditory Benign Intraepithelial Dyskeratosis (Witkop's disease) Dyskeratosis Congenita Frictional Keratosis Nicotinic Hairy Chemical burn Lichenoid reaction - For information, please find in the lesson Lupus erythematous Leukoplakia Proliferative Verrucous Leukoplakia Skin graft Submucous Fibrosis (Benign Migratory ) - For information, please find in the Normal Variations of the Oral Cavity lesson - For information, please find in the Normal Variations of the Oral Cavity lesson White Sponge Naevus - For information, please find in the Normal Variations of the Oral Cavity lesson Pseudomembranous Candidiasis -For information, please find in the Fungal Infections and the Oral Cavity lesson Chronic Hyperplastic Candidiasis - For information, please find in the Fungal Infections and the Oral CavityReviseDental.com lesson Hereditary benign intraepithelial dyskeratosis (Witkop Disease)

Aetiology and epidemiology Rare, autosomal dominant inheritance Early onset (within first year of life) Pathophysiology Three alleles for two linked markers exist on 4q35 chromosome Clinical features Asymptomatic, soft white folds and plaques of spongy mucosa On most oral surfaces apart from dorsum of the tongue Additionally: Bulbar conjunctivitis, conjunctival plaques at the corneal limbus Histopathology Epithelial hyperplasia and acanthosis are present within intracellular oedema Enlarged hyaline keratinocytes within superficial half of epithelium Diagnosis Biopsy usually to confirm diagnosis Management No treatment, condition is self-limiting and benign

Dyskeratosis congenita

Aetiology and epidemiology X-linked and autosomal, both dominant and recessive forms are recognised Patients undergo premature aging and have a predisposition to malignancy Manifestations appear in first 10 years of life Pathophysiology X-linked dyskeratosis encodes a protein called dyskerin, which is abnormal Clinical features Mucosal erosions and leukoplakia may develop ApproximatelyReviseDental.com 30% of the leukoplakia progress to oral cancer in 10-30 years Reticulated skin hyperpigmentation of the upper chest and dysplastic nail changes are characteristic Rapidly progressing , thrombocytopenia and aplastic anaemia may also be seen Histopathology Hyperkeratosis with epithelial atrophy Varying severity of dysplasia Diagnosis History, clinical presentation and biopsy Management Careful observation and biopsy of suspicious areas to detect any malignant change Dental implications Rapidly progressing periodontal disease

Focal (Frictional) hyperkeratosis

Aetiology and epidemiology Chronic rubbing or friction against oral mucosa Pathophysiology Due to irritation, a protective hyperkeratotic white lesions forms: analogous to a callous on the skin Clinical features Depending on the cause, may be well-demarcated or diffused Homogeneously white, may have a thickened corrugated appearance , lateral margins of the tongue, buccal mucosa along the occlusal line and edentulous alveolar ridges are mostly affected Histopathology Hyperkeratosis Thickening of granular cell layer A few chronic inflammatory cells may be seen in the subjacent connective tissue Diagnosis History, clinical presentation and biopsy if not cause known Management Removal of the cause

Smokeless tobacco-associatedReviseDental.com lesions

Aetiology and epidemiology Snuff (particulate, finely divided, or shredded tobacco) appears to much more likely cause oral lesions than chewing tobacco Tobacco-containing preparations are generally of a higher pH (alkaline) and often mixed with other ingredients e.g. betel nut, lime, camphor, spice Pathophysiology Oral mucosa responds with inflammation and keratosis Altered cell signalling and subsequent cell damage have been demonstrated Dysplastic changes may follow with a risk of malignant change Clinical features White asymptomatic lesions develop in the immediate area where the tobacco was placed, most commonly mucobuccal fold Mucosa develops a granular to wrinkled appearance Advanced cases, a heavy folded character may be seen Histopathology Slight to moderate parakeratosis Superficial epithelium may demonstrate vacuolisation or oedema Slight to moderate chronic inflammatory cell infiltrate Epithelial dysplasia may develop Diagnosis Clinical presentation, history Biopsy not necessarily required unless lesions persistent after discontinuation of smokeless tobacco use Management Discontinuation of smokeless tobacco use Dental implications These patients will have acceleration of periodontal disease

Nicotinic stomatitis

Aetiology and epidemiology Pipe and cigar smoking Pathophysiology Inflammation surrounding the minor salivary gland excretory ducts Clinical features Initial erythematous change followed by keratinisation of the Red dots surrounded by white keratotic rings appear Histopathology Epithelial hyperplasia, hyperkeratinization ChronicReviseDental.com inflammatory cell infiltration of sub epithelial connective tissue Excretory ducts show squamous metaplasia Diagnosis History and clinical presentation Management Smoking cessation Smokers Palate

Hairy leukoplakia

Aetiology and epidemiology 20% of patients with have AIDS Pathophysiology HasReviseDental.com been associated with Epstein-Barr Virus Candidal infections co-exist in approximately half of the cases Clinical features Unilateral or bilateral on the margins of the tongue but can develop at other sites e.g. buccal and labial mcuosa Well-demarcated white lesion Varies from a flat and plaque-like to a papillary/ filiform or corrugated lesion Histopathology Viral inclusions or peripheral displacement of chromatin with a resultant smudgy nucleus Marked hyperparakeratotic surface with irregularities and ridges C.albicans hyphae often seen extending into the superficial epithelium Cells show ballooning degradation and perinuclear clearing in the spinous cell layer Very low numbers of subepithelial inflammatory cells Diagnosis Biopsy can be taken for histopathological examination however it is preferable to substantiate the diagnosis with electron microscopy or DNA-hybridisation Management Lesion responds to antiviral therapy and does not respond to antifungal therapy

Chemical burn

Aetiology and epidemiology Commonly caused due to the application of aspirin to the site of a toothache or on the fitting surface of the denture Pathophysiology The low pH of aspirin causes erythema and tissue necrosis Clinical features White, friable slough that can be easily removed leaving a bed of erythema and ulceration Histopathology Areas of focal coagulative necrosis of the epithelium Ulceration Intra and extra-cellular oedema Sub-epithelial acute inflammatory infiltrate Diagnosis Clinical examination and history. No biopsy required Management Remove application of chemical Use of antiseptic mouthwash to keep mouth clean Dental implications AssessmentReviseDental.com of toothache if present

Lichenoid reaction

Aetiology and epidemiology Caused typically by a restorative dental material, most commonly amalgam or an adverse reaction from systemic drug therapy e.g. NSAIDs, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, oral hypoglycaemic agents and antimalarials Pathophysiology Delayed-type Hypersensitivity reaction to a component within the dental material e.g. mercury within amalgam Clinical features Asymmetry and involvement of the palate distinguish it from lichen planus Reaction will be adjacent to the restoration is related to a restorative material Histopathology Nearly identical to lichen planus Acanthosis and inflammatory exocytosis, with perivascular inflammation Inflammation generally extends deeper into the lamina propria than oral lichen planus Diagnosis Histopathological examination from a biopsy can help suggest lichenoid reaction over lichen planus Management Replacement of the restorative material with alternative materials can result in resolution Dental implications Avoidance of amalgam

Lichen Planus

Aetiology and epidemiology Mucocutaneous disorder affecting 1-2% of the population in the UK Pathophysiology T-lymphocyte mediated destruction of basal keratinocytes and hyperkeratinisation produces characteristic lesions Clinical features Bilateral and symmetrical white patches or striae PrincipallyReviseDental.com affect the buccal mucosa, lips, tongue and attached gingivae Can be divided into subtypes: reticular, erosive, plaque-like, atrophic and bullous Histopathology Hyperkeratinised epithelium Basal cell destruction Dense band-like infiltrate of T lymphocytes in the superficial connective tissue Deposition of fibrinogen along the basement membrane but no deposition of antibodies or complement Diagnosis Clinical examination - especially in cases with skin involvement Not absolute requirement to take a biopsy If biopsy to be taken, sample should be taken from 'typical area' of buccal mucosa and not from areas of erosion Management If asymptomatic: no treatment required Symptomatic: topical streroid preparations can be used e.g. Beclomethasone spray 50 ug/metered spray, twice daily and reviewed after 4 weeks. If no improvement, refer to specialist

Erosive Lichen Planus

ReviseDental.com Leukoplakia

Aetiology and epidemiology A whitish patch/ plaque that does not have a specific characteristic or pathology similar to any other disease and not associated with any causative agent Most significant aetiological factors include tobacco use, alcohol ingestion, nutritional deficiency and candidal infection Pathophysiology 1-5% of homogenous leukoplakia will show malignant change 20% of non-homogenous leukoplakia will show malignant change Clinical features Can vary from a minimal localised lesion to extensive involvement There is no relationship between clinical appearance and malignant change Histopathology Presence of epithelial dysplasia (details on epithelial dysplasia can be found in the biology of cancer lesson!) Diagnosis Biopsy required to exclude the presence of carcinoma and should be taken from the worst site New techniques have been used to detect potentially malignant lesions. This includes toluidine blue staining, chemiluminescent visualisation, tissue florescence and brush biopsy for Management Patient to be kept under continued review Mildly dysplastic lesion: conservative management with smoking cessation or treatment of candida infections Moderate and severely dysplastic lesions should be excised

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Extensive Leukoplakia Submucous Fibrosis

Aetiology and epidemiology Mainly affects South-East Asia or India, 20-40 years old Primary cause is chewing betal nut (areca nut) Other factors that contribute include chronic exposure to chili peppers and prolonged deficiency of iron and vitamin B complexes, particularly folic acid 1/3rd patients develop oral cancer Pathophysiology Excessive production and insufficient degradation of collagen by fibroblasts Fibrous bands result in the loss of elasticity of the tissues which in turn limits opening of the mouth Clinical features Irregular, flat, white patches Presence of marked fibrous bands in the cheeks and soft palate Limited mouth opening Histopathology Atrophy of the epithelium and subjacent fibrosis Epithelial dysplasia may be evident Lamina propria is poorly vascularised and hyalinised Lack of fibroblasts Diffuse mild to moderate inflammatory infiltrate Type 1 collagen predominates in the submucosa Diagnosis Clinical assessment and manual detection of the fibrous bands Biopsy worsens the condition but may be necessary if any suspicious mucosa abnormality is present Management Discontinuation of betel nut consumption Manual stretching exercises Review patient closely

ReviseDental.com Proliferative Verrucous Leukoplakia

Aetiology and epidemiology Rare form of leukoplakia High malignant transformation rate Aetiology is unknown Clinical features Initial white patch which develops into multiple areas of exophytic/ -like lesions Common sites affected are buccal mucosa, gingivae and tongue Histopathology Similar to leukoplakia, with or without dysplasia Diagnosis Clinical presentation and biopsy Management Treatment is difficult due to progressive recurrence following surgical removal

Lupus Erythematous

Aetiology and epidemiology Occurs in two forms: systemic or discoid Systemic (SLE): usually in women under 30 years and affects most systems of the body when salivary glands are affected, it forms the connective tissue component of secondary Sjogren's syndrome Patients have high titres of circulating antinuclear factor Discoid lupus erythematosus (DLE) More frequent in women than men, usually 30s/40s Any area of the skin is involved, lesions more common in the ear Oral lesions develop in 15% Pathophysiology Chronic autoimmune disorder characterized by the production of antinuclear autoantibodies Immune complexes (type III hypersensitivity) are formed and deposited along the basement membrane, leading to basal cell damage Clinical features White, striated, keratotic and erythematous patches which resemble lichen planus Butterfly rash of SLE Histopathology Basal cell destruction BasementReviseDental.com membrane thickening Lymphocytic infiltrates in the superficial connective tissues and in a perivascular distribution IgG and IgM along basement membrane Diagnosis Serological evidence of autoantibodies is important for diagnosis - several method, most frequent being indirect immuno-fluorescence Management Topical steroid Dental implications Many suffer from xerostomia: consequences include increased caries risk and fungal infections Skin Graft

Aetiology and epidemiology Skin grafts are used to repair the site of tumour excision Pathophysiology Grafting is usually from the arm or thigh Clinical features Pale, wrinkled area Hair may be present Histopathology Would replicate normal skin tissue Diagnosis History and clinical examination Management No treatment apart from observation as skin grafts may become secondarily infected with candida Dental implications Difficulty in providing dentures due to loss of alveolar ridge and mucosal adhesion- cohesion

Pyostomatitis vegetans

Aetiology and epidemiology Chronic, pustular, mucocutaneous disorder often seen in association with inflammatory bowlReviseDental.com diseases, e.g. Crohn's disease and Cause of oral lesions is unknown Clinical features Can be seen anywhere in the mouth, but most frequently the buccal or labial mucosa Erythema progresses into tiny 2-3mm yellow pustules The pustules evolve to larger vegetating papillary lesions of friable mucosa Histopathology Biopsy shows a nonspecific chronically-inflamed mucosa Superficial abscesses, ulceration and necrosis Diagnosis Made on clinical examination and the history of inflammatory bowel disease Management Management of the bowel involvement can show improvements in the oral lesions Test Yourself!

ReviseDental.com Red and white lesion

Based on the information above, we know that lesions can be a mix of red and white. We also know the various characteristics associated with mixed lesions.

Therefore what would your differential diagnosis for this lesion be? Do you need any additional information?

Is this lesion at risk of malignancy?

The questions above are always the questions you should be asking yourself when a lesion falls into a difficult diagnosis.

The differential diagnosis for this lesion include:

Erythro-leukoplakia - this would be the provisional diagnosis Erosive Lichen Planus

Do you need any additional information?

Is the lesion bilateral? Is the lesion painful? Can it be scraped away? Biopsy indicated

Is this lesion at risk of malignancy?

Erythro-leukoplakiaReviseDental.com has a high chance of transforming to become malignant. Therefore for diagnostic reasons, but also due to the high association with this lesion and dysplasia/malignancy a biopsy would be indicated. This can confirm the diagnosis and therefore management options can be explored.

Conclusion White lesions result from:

Thickened keratin Necrotic epithelium Epithelial hyperplasia Intracellular epithelial oedema Reduced vascularity of subjacent connective tissue.

White/ yellow-white lesions may be due to fibrinous exudate A biopsy is required for any persistent and unexplained oral white patch in order to exclude cancer

Third Party Links

References Specific references: ¹Rosales C. Common pathologic terms. PathologyOutlines.com Accessed May 1st, 2020. Resources used for this information: Felix DH, Luker J, Scully C. : 6. White lesions. Dental update. 2013 Mar 2;40(2):146-54. Gilvetti C, Porter SR, Fedele S. Traumatic chemical oral ulceration: a case report and review of the literature. British dental journal. 2010 Apr;208(7):297. Lewis MA, Lamey PJ. Oral Medicine in Primary Dental Care. Springer; 2019 Jun 21. link Lewis MA, Jordan RC, Ryan D. A colour handbook of oral medicine; 2012. link Müller S. Oral lichenoid lesions: distinguishing the benign from the deadly. Modern Pathology. 2017 Jan;30(1):S54-67. Odell EW. Cawson's Essentials of Oral Pathology and Oral Medicine E-Book. Elsevier Health Sciences; 2017 May 2. link

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