4. white lesions

objectives of white lesion diagnosis (DDD)

• describe clinical features

• develop D/D

• differentiate btwn likely benign and potentially malignant

all white lesions are leukoplakias

false

flat, solid, raised area of the skin or mucosa >1cm in diameter

plaque

solid mass of tissue >1cm in diameter

tumor

rewatch: reactive, traumatic, and frictional lesions are

sharply demarcated or diffuse

four things that make oral mucosa look white (think layers)

• thick keratin - protective, calluses

• alteration to keratinocytes - pre-cancer, candida changes

• acanthosis - response to trauma, infection, pre-cancer

• fibrosis - scarring

acronym for white lesion categories

HIDEMAN

Hereditary, infectious, developmental, enviro/reactive, metabolic/med-induced, autoimmune/immune-mediated, neoplastic

• white sponge nevus

• (BLANK) benign intraepithelial dyskeratosis

• darier disease/warty dyskeratosis

• dyskeratosis congenita

hereditary

oral candidiasis and oral hairy leukoplakia

infectious

• leukoedema

• contact desquamation

• hairy tongue

• frictional keratosis

• benign alveolar ridge keratosis

• nicotine stomatitis

• smokeless tobacco keratosis

environmental/reactive

• oral lichen planus

• lupus erythematosus

• oral graft vs host disease

autoimmune/immune mediated

• oral leukoplakia

• oral submucous fibrosis

• oral squamous cell carcinoma

neoplastic

most often seen

environmental/reactive

least often seen

autoimmune and hereditary

which hereditary lesion:

• Rare autosomal dominant genodermatosis

• Mutation in keratin 4 and keratin 13

• Defective keratinization of oral mucosa

white sponge nevus

which hereditary lesion clinical features:

• Appears at birth or early childhood

• Asymptomatic, bilateral and symmetrical, thickened, white, corrugated or velvety, diffuse plaques of the buccal mucosa

• Other oral mucosal sites

• Extra oral mucosal sites less common

• No treatment required

white sponge nevus

which hereditary lesion histopathological features:

• Prominent hyperparakeratosis and marked acanthosis with clearing of the cytoplasm of the cells in the spinous layer

• Perinuclear condensation of keratin tonofilaments (K4 and K13 mutation → clumping and spongy)

white sponge nevus

waxy fissured thick white plaques often bilateral hereditary

white sponge nevus

which hereditary lesion:

• Rare autosomal dominant genodermatosis

• Descendants of Native Americans who originally lived in North Carolina

• Duplication of chromosome 4q35

hereditary benign intraepithelial dyskeratosis

which hereditary lesion clinical features:

• Develops during childhood

• Thick, corrugated white plaques, buccal and labial mucosa

• Other oral mucosal sites

• Ocular involvement:

  • Thick, opaque, gelatinous plaques affecting the bulbar conjunctiva adjacent to the cornea

• No treatment required

hereditary benign intraepithelial dyskeratosis

hereditary

hereditary benign intraepithelial dyskeratosis

cell w/in cell appearance hereditary

hereditary benign intraepithelial dyskeratosis

Darier disease/warty dyskeratoma aka

keratosis follicularis

which hereditary lesion:

• Autosomal dominant disorder

• Mutation in ATP2A2 gene - calcium channels

• Alters normal function of

• White, painless, keratotic papules desmosomes (glue) and keratin or plaques, and cobblestoning of the oral mucosa

• 1/3 parotid or submandibular swelling

• Erythematous, papules on the skin of the trunk and the scalp

• Treated with topical steroids

Darier disease/warty dyskeratoma

which hereditary lesion:

Darier disease/warty dyskeratoma

hereditary

Darier disease/warty dyskeratoma

which hereditary lesion:

• Rare X-linked recessive genodermatosis (think young and severe)

• Mutations in the DKC1 gene

• Other mutations have been identified

• Disrupt the normal maintenance of telomerase

• Risk of oral cancer and aplastic anemia

dyskeratosis congenita (DKC)

which hereditary lesion clinical features:

• Apparent during first decade

• Nail dystrophy

• Oral leukoplakia

• Abnormal skin pigmentation

dyskeratosis congenita (DKC)

which infectious lesion:

• Opportunistic fungal infection

• Antibiotics, inhaled/topical steroids, immunosuppression, dry mouth, denture

• Clinical features:

  • Pseudomembranous

  • Erythematous

  • Hyperplastic

• Antifungals

  • Nystatin suspension

  • Clotrimazole troches

  • Fluconazole

oral candidiasis

infectious lesion: hyphae w/in keratinocytes, biomorphic forms and cytology of epithelial cells

oral candidiasis

which infectious lesion:

• Caused by Epstein-Barr virus (EBV)

• Not a premalignant lesion

• HIV/AIDS with low CD4 counts, immunocompromised, topical steroids, healthy individuals - 10%

• Clinical features: White, vertical, linear lesion or plaque, lateral border of tongue

• Adjustment of HIV medications and systemic immunosuppressants

• May be treated with topical antivirals

oral hairy leukoplakia

infectious virally modified ballooned cells

oral hairy leukoplakia

which environmental/reactive lesion:

• Delicate lacy, gray-white lines on the buccal mucosa or ventral tongue

• Disappears on stretching the mucosa

• Very common

• Mildly irritating substances

  • Smoke from tobacco products or marijuana

  • caustic oral rinses, or toothpaste

• Traumatic, parafunctional habit such as mucosal sucking

• No treatment required

leukoedema

which environmental/reactive lesion: acanthotic edematous change

leukoedema

which environmental/reactive lesion:

• Painless, thready white tissue on the mucosa, peels off leaving normal mucosa

• Caustic mouth washes high in alcohol content

• Strong toothpastes (whitening)

• Other contactants that are irritants the mucosa

• Discontinuation of offending agent

contact desquamation

which environmental/reactive lesion:

• “Hairy tongue”

• Elongated filiform papillae on the dorsal surface of the tongue

• Yellowish white, can be discolored

• Heavy smokers, poor PO intake, dehydration, poor oral hygiene

• Benign, esthetic concerns

coated/hairy tongue

which environmental/reactive lesion:

hairy tongue

which environmental/reactive lesion:

• Linea alba- buccal mucosa

• Morsicatio mucosae oris- chronic chewing of the oral mucosa

• Biopsy is rarely indicated

• No treatment required

frictional keratosis

which environmental/reactive lesion: morsicatio buccarum

increased parakeratin → protective and acantosis make lesion white

frictional keratosis

which environmental/reactive lesion:

• Poorly demarcated, rough white plaque of the keratinized mucosa

• Friction with food

• Often confused with leukoplakia

• No treatment required

benign alveolar ridge keratosis

which environmental/reactive lesion:

benign alveolar ridge keratosis

which environmental/reactive lesion:

• Leathery, white change of the hard palatal mucosa in long term smokers

• Mucosal response to heat

• No treatment required

• Reversible after smoking cessation

nicotine stomatitis

which environmental/reactive lesion: prominent salivary ducts from heat

nicotine stomatitis

which environmental/reactive lesion:

• Contact with caustic agents within the tobacco

• Early: grayish-white wrinkles and parallel ridges and fissures in the area where the tobacco is placed - Reversible

• Advanced: well-demarcated, keratotic plaques

  • Must be biopsied for evaluation of dysplasia

  • Regular follow up

smokeless tobacco keratosis

which environmental/reactive lesion:

smokeless tobacco keratosis

which environmental/reactive lesion: pale almost necrotic and edematous

smokeless tobacco keratosis

which autoimmune/immune-mediated/allergic lesion:

• 1% to 2% of middle-aged adults

• 2–3 : 1 female predominance

• Idiopathic, medication-induced; hep C virus oral manifestations

• T-cell destruction of the basal cells

• Clinical features:

• Typically, bilateral and symmetrical

• Reticular/keratotic: Wickham striae

• Ulcerative

• Erythematous/erosive

• Contact lichenoid reactions to dental amalgams

• Treatment: Topical and systemic steroids or steroid-sparing agents (but pt can’t be on them forever), Replacing amalgam restorations

• Controversial malignant transformation potential 0.1-1% of cases

oral lichen planus

REU score

reticular, erythematous, ulcerative

which autoimmune/immune-mediated/allergic lesion: A-ulcers D-desquamative gingivitis and reticulations around erythema

oral lichen planus

which autoimmune/immune-mediated/allergic lesion:

oral lichen planus

which autoimmune/immune-mediated/allergic lesion:

oral lichen planus

which autoimmune/immune-mediated/allergic lesion: T cell mediated basal cell destruction; blue band lymphocytes; stellate looking on edges bc keratin layer acanthosis

oral lichen planus

which autoimmune/immune-mediated/allergic lesion:

• Autoimmune disease, unknown etiology

• Affects multiple organs

• SLE and DLE

• Circulating antibodies in SLE:

  • ANA, anti-Smith, anti–double-stranded DNA, and anti ribonucleoprotein

• 20% and 45% of patients with DLE and SLE, respectively, have oral lesions

• Oral lesions resemble oral lichen planus

• Not always bilateral and symmetrical

• Treatment as in OLP

lupus erythematosus

which autoimmune/immune-mediated/allergic lesion:

lupus erythematosus

which autoimmune/immune-mediated/allergic lesion: ulcer w raised border, erythema and striations surround it

lupus erythematosus

which autoimmune/immune-mediated/allergic lesion:

• Complication following hematopoietic stem cell transplant for treatment of hematologic malignancies

• Acute and chronic > 100 days

• Mouth is commonly affected

• Oral mucosal lesions essentially resemble OLP

• Treated similarly to OLP

oral graft-vs-host disease

which autoimmune/immune-mediated/allergic lesion:

• acute: ulcerative and erythematous changes diffusely, lip crusting

• chronic: xerostomia, lichen planus-like features, SICCA syndrome-like features, trismus, mucoceles

oral graft-vs-host disease

which autoimmune/immune-mediated/allergic lesion:

oral graft-vs-host disease

which neoplastic white lesion:

• White plaque of questionable risk having excluded other known diseases or disorders that carry no increased risk for cancer

• Highly associated with dysplasia and development of cancer

• High risk sites: Ventral tongue, floor of mouth, buccal mucosa, soft palate, and gingiva

• 43% to 47% represent dysplasia, carcinoma-in-situ, or invasive SCC

• Homogenous: 16% MT malignant transformation

• Non-homogenous

• Proliferative leukoplakia: 70-100% MT

oral leukoplakia

which neoplastic white lesion risk factors:

• Smoking

• Excessive alcohol consumption

• H/o cancer and cancer therapy

• Family h/o cancer

• H/o autoimmune disorder or prolonged immunosuppression

• Areca nut chewing

• Older age

• Human Papilloma Virus

oral leukoplakia

which neoplastic white lesion:

oral leukoplakia

which neoplastic white lesion:

• 25-27% of (BLANK) become/are dysplasia/SCC - show variable malignant transformation

  • homogenous 16%

  • proliferative leukoplakia 70-100%

oral leukoplakia

which neoplastic white lesion:

oral leukoplakia

which neoplastic white lesion histological features of dysplasia

oral leukoplakia

which neoplastic white lesion:

oral leukoplakia

which neoplastic white lesion:

oral leukoplakia

which neoplastic white lesion treatment:

• Surgical excision of small lesions

• Laser ablation

• Novell off label use of topical chemotherapy: 5% imiquimod, TLR-4 activation

• Monitoring

• Clinical trial of immune checkpoint inhibitor (nivolumab) for proliferative leukoplakia

oral leukoplakia

which neoplastic white lesion:

• 70% malignant transformation

• mortality rate of 30-40%

• Patients in their 6th decade (or older) and females (4x likely)

• Unclear associated risks Gingiva, alveolar and palatal mucosa

• ?prognosis

proliferative oral leukoplakia

which neoplastic white lesion:

R: oral leukoplakia L: benign alveolar ridge keratosis

which neoplastic white lesion: OPMDs are clinical presentations that carry a risk of cancer development in the oral cavity, whether in a clinically definable precursor lesion or in clinically normal oral mucosa

WHO oral potentially malignant disorders (OPMD)

ranking of OPMD WHO 2017

which neoplastic white lesion:

• High-risk, precancerous condition

• Chronic, progressive scarring of the oral mucosa

• Associated with betel quid chewing and related products

• Commonly used in eastern and south-east Asia, and among immigrants from these countries

• Estimated malignant transformation rate is 7%-13% (high) over variable periods of time

Oral submucous fibrosis (OSMF)

which neoplastic white lesion:

• associated with arce nut, betel leaf, betel quid which has been classified as a Group 1 carcinogen by IARC

• could be addictive

• commercially available: simple betel quid, spices and other additives with or w/o tobacco

Oral submucous fibrosis (OSMF)

which neoplastic white lesion:

areca nut:

• Increased collagen synthesis

• Reduced collagenase activity

• Inhibition of collagen phagocytosis

• Collagen cross-linking with lysyl oxidase (LOX is a copper-dependent enzyme)

Oral submucous fibrosis (OSMF)

which neoplastic white lesion clinical features:

• Mucosal blanching

• Burning sensation (dry mouth)

• Fibrous bands

• Restriction in mouth opening

• Shrunken and everted uvula

• The tongue appears depapillated

• could have precancerous mass but not the white lesion in question

Oral submucous fibrosis (OSMF)

which neoplastic white lesion:

• 90% of oral malignancies

• Male predilection

• High risk sites: Ventral tongue and floor of mouth

• Clinical features: indurated mass, endo or exophytic ulcer w rolled borders; leukoplakia, erythroplakia

oral squamous cell carcinoma

which neoplastic white lesion risk factors and treatment:

• Cigarette smoking

• Excessive alcohol consumption

• Areca nut chewing

• H/o cancer and cancer therapy

• H/o autoimmune disorder or prolonged immunosuppression

• Family h/o cancer

• Older age

• Treatment: excision +/-chemo/RT

oral squamous cell carcinoma

which neoplastic white lesion:

oral squamous cell carcinoma

which neoplastic white lesion:

oral squamous cell carcinoma

which neoplastic white lesion:

infiltration to underlying tissue → basement membrane broken

oral squamous cell carcinoma

which neoplastic white lesion::

• Five-year survival is:

  • 83% with local disease

  • 55% with loco-regional disease

  • 32% with distant metastases

• Long-term follow-up is highly importance

  • Second primary tumors occur in 7% to 33% of patients

oral squamous cell carcinoma