Oral Erythroplakia

A fiery red patch of the oral mucosa that cannot be characterised clinically or pathologically as any other definable disease. It is far less common than leukoplakia but is by a wide margin the most dangerous oral potentially malignant disorder.

Why it matters more than leukoplakia

• Prevalence is low, at around 0.02 to 0.2 percent.
• At first biopsy, 80 to 90 percent already show severe dysplasia, carcinoma in situ or invasive squamous cell carcinoma. This is the single most important fact about the lesion.
• Malignant transformation rates for those without invasion at presentation are quoted at 14 to 50 percent, far exceeding leukoplakia.
• Every erythroplakia must therefore be regarded as carcinoma until histology proves otherwise, and biopsy is urgent rather than elective.

Why it appears red

The epithelium is atrophic and thin, with reduced or absent keratin production and loss of the normal epithelial thickness, so the underlying connective tissue vasculature shows through. The subepithelial connective tissue also shows increased vascularity and inflammation. The redness therefore reflects epithelial atrophy and dysplasia, which is precisely why it correlates so strongly with severe histological change, in contrast to leukoplakia where the white appearance reflects hyperkeratosis that may be entirely benign.

Sites

• Floor of mouth, ventral and lateral tongue, and the soft palate complex including the retromolar trigone and anterior tonsillar pillar. These are the same high risk sites as for oral carcinoma, which is not coincidental.
• Erythroplakia of the floor of mouth in an older male smoker and drinker carries a very high probability of malignancy.

Risk factors

Tobacco in all forms, alcohol, areca nut and betel quid, with tobacco and alcohol acting synergistically. Chronic candidal infection and human papillomavirus contribute in a proportion.

Erythroleukoplakia, or speckled leukoplakia, is a mixed red and white lesion which behaves similarly to erythroplakia and carries a comparably high risk. It should be managed with the same urgency.

• Often asymptomatic and detected on examination, which is why systematic oral examination in at risk patients is essential.
• A soreness or burning sensation.
• A velvety texture noticed by the patient.
• Pain, bleeding on contact and ulceration, which are late and indicate invasion.
• Referred otalgia, dysphagia, loose teeth, numbness and a neck mass, which indicate established carcinoma.

Examination

• A well demarcated, flat or slightly depressed, bright red patch with a velvety or granular surface, which does not rub off and which bleeds readily on gentle contact.
• The margins are usually well defined, distinguishing it from inflammatory erythema.
• Palpate for induration, which indicates invasion.
• Full systematic examination of the entire oral cavity including the ventrolateral tongue lifted with gauze, the floor of mouth, the retromolar trigone and the soft palate.
• Neck palpation for lymphadenopathy, with the level and characteristics of any node recorded.
• Flexible nasoendoscopy in every patient to assess the oropharynx, hypopharynx and larynx for a second primary.

• Urgent biopsy in every case, on a suspected cancer pathway, with an incisional biopsy from the most suspicious area including the margin with adjacent normal tissue.
• Multiple biopsies for large or heterogeneous lesions, since invasion may be focal.
• Do not use brush cytology, toluidine blue or autofluorescence as a substitute for biopsy. They may guide biopsy site selection in a large lesion but they must never delay or replace scalpel biopsy in a red patch.
• Do not attempt a trial of treatment before biopsy. Prescribing an antifungal or an anti inflammatory and reviewing in a month is a recognised and serious error in the management of a red oral patch, and it costs weeks in a lesion with a high probability of already being malignant.
• Periodic acid Schiff staining for candida.
• Full upper aerodigestive tract examination with flexible endoscopy, and panendoscopy under anaesthesia where malignancy is confirmed, given synchronous second primaries in around 3 to 5 percent.
• Where carcinoma is confirmed: contrast enhanced computed tomography or magnetic resonance imaging of the head and neck, computed tomography of the chest, ultrasound guided fine needle aspiration of any suspicious node, and consideration of positron emission tomography, with staging and multidisciplinary team discussion.
• Full blood count, haematinics, glucose, liver function and coagulation.
• Nutritional assessment and dental assessment before any planned treatment.

Differential diagnosis and the discriminating feature

• Erythematous candidiasis: diffuse rather than well demarcated, often on the palate under a denture or on the tongue dorsum, associated with inhaled corticosteroids, and responds to antifungal treatment. Any red patch that does not resolve completely after a 2 week antifungal course must be biopsied.
• Erosive and atrophic lichen planus: bilateral, with white striae at the margins.
• Mucous membrane pemphigoid: desquamative gingivitis with blistering and a positive Nikolsky sign, confirmed by direct immunofluorescence.
• Pemphigus vulgaris.
• Denture induced stomatitis: conforms exactly to the denture outline and resolves when the denture is left out and treated.
• Median rhomboid glossitis: a well defined rhomboid depapillated area on the midline dorsum anterior to the circumvallate papillae, candidal in origin.
• Geographic tongue: migrating areas with white serpiginous borders that change over days.
• Kaposi sarcoma: purple to red macules and nodules, typically on the palate, in HIV infection.
• Haemangioma and vascular malformation: blanch on pressure.
• Contact and chemical stomatitis.
• Vitamin B12, folate and iron deficiency causing atrophic glossitis, which is generalised rather than a discrete patch.

Every erythroplakia is treated as a high grade lesion until histology says otherwise, and the default is complete excision.

Risk factor elimination

• Complete tobacco cessation with structured support and pharmacotherapy.
• Complete cessation of areca nut and betel quid.
• Alcohol cessation or substantial reduction.
• Remove chronic trauma and treat candidal infection, though neither should delay biopsy.
• Dental assessment and oral hygiene optimisation, which is also a prerequisite before radiotherapy if that becomes necessary.

Management by histology

• Invasive squamous cell carcinoma: treat on the head and neck cancer pathway with staging, multidisciplinary team discussion, and surgery with or without adjuvant therapy.
• Carcinoma in situ and severe dysplasia: complete excision with clear margins, with intensive lifelong surveillance.
• Moderate dysplasia: complete excision.
• Mild or no dysplasia, which is uncommon in erythroplakia: complete excision remains the usual recommendation given the high transformation rate and the risk that the biopsy has undersampled the lesion. At minimum, intensive surveillance at 3 monthly intervals with a low threshold for re biopsy.

Excision

• Scalpel excision with a margin of clinically normal mucosa, generally 3 to 5 mm for a dysplastic lesion, which provides a complete specimen and allows margin assessment. This is the preferred approach.
• Carbon dioxide laser excision, which offers haemostasis and reduced morbidity, and which should be used in excisional rather than ablative mode so that a specimen is obtained. Ablative techniques must not be used for erythroplakia, since destroying the tissue without histology in a lesion with an 80 to 90 percent chance of harbouring severe dysplasia or carcinoma is indefensible.
• Reconstruction as required with primary closure, secondary intention healing, a buccal fat pad flap or a split skin graft.
• Where the specimen shows invasion, formal oncological resection with neck management is required, and the initial excision is regarded as an excisional biopsy rather than definitive treatment.

No role for medical therapy

There is no medical treatment for erythroplakia. Topical and systemic retinoids, antioxidants and other agents have no established role and must not be offered in place of excision. Prescribing them delays diagnosis in a lesion where delay is measured in cancers.

Surveillance

• Lifelong follow up in every patient, since field change means the entire mucosa is at risk and new lesions arise at other sites.
• Review at 3 monthly intervals for the first 2 years, then 6 monthly, with full oral examination, palpation, photography and measurement, and biopsy of any change.
• Periodic flexible endoscopy of the upper aerodigestive tract in patients with tobacco and alcohol exposure.
• Recurrence at the excision site occurs in a significant minority, and new primary lesions occur elsewhere, so a normal examination at one visit provides no reassurance for the future.
• Teach self examination and instruct the patient to present immediately with any new red or white patch, any ulcer lasting more than 3 weeks, any lump, any bleeding, any numbness or any loosening tooth.
• Reinforce tobacco and alcohol cessation at every visit, since continued exposure drives new lesions and second primaries.