Dermatology & Oncology & Family Medicine
Erythroplasia
Erythroplasia - from the Greek erythros (red) and plasis (formation) - refers to a bright red, velvety, well-defined, persistent plaque of the oral or genital mucosa, which cannot be attributed to any other clinically identifiable cause. Unlike leukoplakia (white plaque), whose risk of transformation into invasive squamous cell carcinoma is 1 to 5 %, erythroplakia presents with severe dysplasia or carcinoma in situ on histology in 80 to 90 % of cases, and transformation into invasive carcinoma in 40 to 50 % of untreated cases. This exceptional malignant potential is due to the thinness of the erythroplastic epithelium - with little or no keratinization - which reveals dilated dermal capillaries (hence the red color) and whose cellular architecture is already profoundly altered. Oral erythroplasia, the best-known form, occurs most frequently in men over 60, who smoke or drink, and is most prevalent on the floor of the mouth, the ventral surface of the tongue and the soft palate. Queyrat's erythroplasia is the equivalent male genital form - red velvety plaque on the glans or prepuce of uncircumcised men, associated with human papillomavirus (HPV) infection, histologically a squamous cell carcinoma in situ. Current terminology tends to unify these entities under the term squamous cell carcinoma in situ (SCC) - the term erythroplasia remains widely used in clinical practice, however, and corresponds to a distinctive macroscopic presentation requiring systematic biopsy.
Clinical presentation, etiologies and differential diagnosis
- Clinical features of oral erythroplasia : bright red to crimson-red plaque, velvety or granular in appearance, well-defined, flat or slightly depressed, variable in size (a few mm to several cm); smooth, shiny surface, soft to palpation - contrasts sharply with normal surrounding mucosa (pinkish or pearly white appearance); generally asymptomatic or minimally symptomatic (slight sensitivity to spicy food, burning sensation) - absence of pain is a major diagnostic pitfall; preferential locations: floor of the mouth + ventral surface and lateral edges of the tongue + soft palate + retromolar area + cheek - areas at high carcinological risk; mixed erythroplasia (erythroleukoplakia or speckled lesion): red plaque interspersed with white areas - malignant potential intermediate between pure leukoplakia and pure erythroplakia - biopsy of red areas imperative; large, irregular, palpation-induced, ulcerated or spontaneously hemorrhagic lesions should raise suspicion of invasive transformation already underway
- Etiological risk factors : smoking (cigarettes, pipes, cigars, chewing tobacco): main risk factor for oral erythroplasia - risk multiplied by 3 to 6 - synergistic with alcohol; alcohol (regular consumption ≥2 glasses/d): potentiates the carcinogenic effect of tobacco - risk multiplied by 2 to 4 alone, up to × 15 in combination with tobacco; HPV (human papillomavirus) - HPV 16 and 18 mainly : major role in genital erythroplasia (Queyrat) + increasing role in oral erythroplasia of the oropharynx in young non-smoking patients (oro-genital sexuality); immunosuppression (HIV, transplantation, hematological diseases): increased risk of precancerous and cancerous mucosal lesions; chronic irritation (fractured tooth, ill-fitting prosthesis): favouring factor but not sufficient on its own
- Queyrat's erythroplasia - male genital form : bright-red, velvety, well-defined plaque on glans or prepuce - uncircumcised male over 40 - asymptomatic or mildly pruritic; histology: squamous cell carcinoma in situ (SCC) - complete architectural disorganization of the epithelium through the entire thickness without crossing the basement membrane; risk factors: HPV 16/18 + absence of circumcision (retention of smegma + chronic preputial inflammation) + immunodepression; differentiate from genital Bowen's disease (same histology - CIS - but more keratotic appearance in circumcised patient); work-up: biopsy + HPV test (genotyping) + STI work-up + partner(s) examination + HPV vaccination if unvaccinated (<45 years)
- Differential diagnosis : atrophic candidiasis erythematosus (depilated red tongue + pain + predisposing factor - antibiotics, corticoids, immunodepression → therapeutic antifungal test × 2 weeks); erosive lichen planus (white Wickham striae in periphery + symmetrical bilateral involvement + other skin localizations - biopsy to confirm); pemphigus vulgaris and pemphigoid (erosions + detachments + biopsy + direct immunofluorescence) ; oral discoid lupus erythematosus (central atrophy + peripheral striae + ANA antibodies); hemangioma / vascular malformation (clears with in vitro pressure - diascopy); thermal or chemical trauma (context - resolution in 2 weeks); mucosal melanosis (brown - not red - biopsy if in doubt); any differential diagnosis cannot be formally established without biopsy.
Diagnosis and treatment
| Appearance / Treatment | Technique, mechanism and procedures | Results, monitoring and precautions |
|---|---|---|
| Biopsy - histological examination Mandatory and systematic - diagnostic gold standard |
Any persistent red plaque >2 weeks on an oral or genital mucosa requires biopsy without delay - there is no acceptable trial treatment for erythroplasia; oral biopsy technique: incisional biopsy with cold scalpel or biopsy punch (4-6 mm) under local anaesthetic (lidocaine 2 % with epinephrine) - sampling at the junction of the lesion and normal mucosa + area of most suspicious appearance (granular, indurated, ulcerated) - sent in formalin 10 % for standard anatomopathology ; biopsy of entire lesion if small (<1 cm) - representative incisional biopsy if large lesion; special staining and immunohistochemistry: Ki-67 (proliferation index) + p53 + p16 (indirect HPV marker); WHO 2022 histological classification (mucosal epithelial dysplasia): mild + moderate + severe dysplasia + carcinoma in situ (CIS); expected result in erythroplasia: severe dysplasia or CIS in 80-90 % of cases - invasive carcinoma already present in 10-20 % of erythroplasia biopsies (requiring immediate extension work-up) | Biopsy is non-negotiable - no erythroplastic lesion should be monitored without prior histological confirmation; a negative biopsy (mild dysplasia or absence of dysplasia) does not exclude malignancy if the lesion is heterogeneous - repeat the biopsy in a different area or refer to an ENT or maxillofacial surgeon for biopsy guided by chromoendoscopy (acetic acid 3 % - toluidine blue) or autofluorescence (VELscope); staining with toluidine blue (tolonium chloride) : vital dye that binds preferentially to dyplastic or malignant cells (intense blue staining) - helps guide biopsy to the most suspicious area of a large lesion - sensitivity 93-97 % specificity 73 % for severe dysplasia and CIS; time between biopsy and treatment: as short as possible - do not exceed 2 to 4 weeks |
| Eliminating risk factors Priority measure - Smoking and alcohol cessation |
Immediate and complete smoking cessation: smoking is the most important modifiable risk factor - cessation significantly reduces the risk of malignant transformation and improves the results of local treatment; prescription of smoking cessation aid: varenicline (Champix 0.5 mg then 1 mg × 2/d × 12 weeks) + nicotine replacement therapy (NRT) + psycho-behavioural support + J'arrête (Québec) telephone hotline; alcohol cessation: reduction or cessation of alcohol consumption - refer to attending physician for withdrawal assistance (naltrexone, acamprosate) if dependent; correction of local irritant factors: adjustment or replacement of ill-fitting dentures + treatment of fractured teeth or irritating sharp edges + improved oral hygiene (brushing + flossing + antiseptic mouthwash); these measures do not replace treatment of the lesion, but are essential to prevent recurrences and improve mucosal healing | Smoking cessation alone can lead to partial regression of mild leukoplakia, but its effect on erythroplakia is insufficient to justify simple monitoring - severe dysplakia and CIS do not regress spontaneously with smoking cessation alone; however, weaning is mandatory before any surgical treatment to reduce the risk of post-operative complications (mucosal scarring, risk of infection) and recurrence; patients must be informed that erythroplasia is a serious precancerous lesion requiring immediate treatment, irrespective of their decision regarding tobacco and alcohol consumption |
| Surgical excision Reference treatment - mandatory healthy margins |
Complete surgical excision with healthy margins (resection margins >3-5 mm in histologically confirmed healthy tissue): 1st-line treatment for oral erythroplasia of severe dysplasia or CIS - performed by experienced ENT or maxillofacial surgeon or oral surgeon; approaches: cold scalpel excision (gold standard - best histological quality of margins) + CO₂ laser excision (advantage: intraoperative haemostasis + easier mucosal reconstruction - disadvantage: thermal artifacts on margins that can hamper histological interpretation); mucosal reconstruction: primary closure if exeresis small (<2 cm) + free mucosal graft (hard palate) or local flap if larger defect; exeresis of genital erythroplasia (Queyrat): complete local excision with scalpel ± plastic surgery (skin graft) if large surface area; circumcision: recommended if Queyrat's erythroplasia on uncircumcised foreskin (allows exposure and monitoring of glans + eliminates prepucial favouring factor) | The local recurrence rate after resection with healthy margins is 10-30 % at 5 years for oral erythroplasia - higher if margins are positive or close (<1 mm) - justifying prolonged surveillance; resection with positive margins requires reoperation or additional treatment (radiotherapy) ; if anatomopathological examination of the surgical specimen reveals an invasive carcinoma (already present in 10-20 % of erythroplasias) → full extension workup + specialized oncological treatment (surgery + radiotherapy ± chemotherapy); functional and aesthetic outcome of excision depends on lesion size and location - lesions of the floor of the mouth or mobile tongue may impact swallowing and phonation → postoperative orthophonic assessment if necessary |
| Alternative treatments to surgery Laser CO₂, PDT, imiquimod, topical 5-FU |
CO₂ laser vaporization: controlled thermal destruction of the lesion without excision - used for very extensive lesions that are surgically unresectable or multifocal - major drawback: no histological specimen to confirm margins → reserved for cases where prior biopsy has confirmed CIS without invasion + surgery impossible; photodynamic therapy (PDT): topical application of a photosensitizer (5-aminolevulinic acid - 5-ALA or its methyl ester Metvix) to the lesion + irradiation with red light (630 nm) → generation of free radicals → selective cell necrosis of dysplastic cells - effective for superficial CIS - complete response rate 70-85 % for CIS of the oral mucosa (Kubler 2001) - available in specialized ENT centers; imiquimod cream 5 % (Aldara): topical immunomodulator - induction of innate and adaptive immunity - used for Queyrat's erythroplasia (application × 3/week × 4-16 weeks) - complete response rate 30-50 % - significant local side effects (erosions, ulcerations, inflammation); 5-fluorouracil (5-FU) cream 5 %: topical antimitotic - limited use in oral mucosa (severe irritation) - more commonly used in dermatology for actinic keratoses | These alternatives to surgery are reserved for situations where surgical excision is impossible or inadvisable (extent of lesion, critical location, patient's general condition, patient refusal) - they do not replace reference surgical treatment and are associated with higher recurrence rates; PDT is probably the best non-surgical alternative for CIS of the oral mucosa - it is available in a few Canadian university centers (Toronto, Montreal); imiquimod for Queyrat's erythroplasia is supported by several case series and represents an acceptable non-surgical option in patients with extensive or recurrent lesions - to be used under close dermatological or urological supervision; whatever treatment is used, a follow-up biopsy at 3 months is imperative to confirm complete histological response |
| Post-treatment monitoring and prevention of recurrence Lifetime follow-up - risk of recurrence and second cancer |
Close clinical monitoring after treatment: examination of the oral cavity or genital region at 1 month + 3 months + 6 months + then every 6 to 12 months for life; systematic visual inspection of the entire oral mucosa (floor, tongue, cheeks, palate, oropharynx) + palpation of cervical lymph nodes at each consultation; biopsy any site suspected of recurrence (new red or mixed plaque) without delay - do not delay on a lesion suspected of recurrence; risk of second primary synchronous or metachronous cancer: patients with a history of erythroplasia have a 10-30 % risk of developing a second carcinoma of the upper aerodigestive tract (VADS) - concept of «field cancerization»: diffuse mucosal exposure to carcinogens → potential multifocal dysplasia; HPV vaccination: recommended for patients with HPV-associated erythroplasia not yet vaccinated - up to age 45 (Gardasil 9 - 3 doses) - may reduce risk of HPV-induced recurrence | The concept of field cancerization (Slaughter 1953) explains why recurrences after excision of oral erythroplasia are frequent (10-30 % at 5 years) - the mucosa exposed to carcinogens over a long period presents multifocal molecular alterations, some of which are not yet clinically visible at the time of index excision - hence the importance of complete smoking cessation and prolonged monitoring of the entire mucosa; patients must be informed of the need for lifelong monitoring, of the risk of local recurrence and second cancer, and of the vital importance of smoking and alcohol cessation in reducing this risk; consultation with a head and neck oncologist recommended for any erythroplasia with severe dysplasia or CIS - discussion in a multidisciplinary oncology consultation meeting (RCP) for complex or recurrent cases. |
ℹ️
2-week rule - any persistent red mucous lesion requires a biopsy: any red plaque or lesion of the oral or genital mucosa not clearly explained by recent trauma, candidal infection or a known inflammatory cause, and persisting after 2 weeks of observation, should be biopsied without delay. Clinical appearance alone - even for an experienced clinician - cannot distinguish a benign lesion from severe dysplasia or carcinoma in situ. Erythroplasia is asymptomatic in the majority of cases, which frequently delays diagnosis. The average delay between the appearance of a precancerous lesion and histological diagnosis often exceeds 6 to 12 months in the absence of systematic screening - each month's delay increases the risk of invasive transformation. A systematic examination of the oral cavity at every medical or dental consultation remains the most effective and accessible screening strategy.
Signs requiring urgent medical attention
Consult your doctor or an ENT specialist without delay if you present : persistent red plaque >2 weeks on buccal, lingual, palatal or genital mucosa - biopsy mandatory - never wait more than 2 weeks without consultation.
Red buccal plaque associated with palpable induration, spontaneous ulceration or bleeding on contact → strong suspicion of invasive carcinoma - urgent ENT or maxillofacial consultation.
Hard, fixed cervical adenopathy associated with a mucosal lesion → lymph node metastasis possible - immediate oncological extension assessment (cervico-thoracic CT + PET scan).
Consult at Clinique Omicron
Clinique Omicron's physicians examine suspected oral and genital mucosal lesions, refer without delay to an ENT, maxillofacial, dermatology or urology specialist for biopsy and treatment, and participate in post-treatment follow-up of patients with a history of precancerous lesions. Oral and genital screening is part of the periodic medical examination offered at our points of service in Quebec, and in telemedicine for referral consultations. To book an appointment, visit cliniqueomicron.ca.
The contents of this page are provided for information purposes only and do not replace the advice of a qualified healthcare professional. Erythroplasia is a high-risk precancerous lesion requiring systematic biopsy and specialized management without delay.
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