Erythroplakia

Clinical and Pathologic Features

Causes and Risk Factors

Erythroplakia shares its causes with leukoplakia, but reflects far heavier toxic exposure and a greater build-up of genetic mutations:

• Combined tobacco and alcohol use: Long-term smoking together with heavy drinking is the main cause (over 90% of cases). Alcohol dissolves the protective lipid layer of the mucosa, allowing tobacco carcinogens to penetrate down to the basal cells.
• Betel quid and chewing tobacco: Proven to cause early mutations in the TP53 and CDKN2A genes in the mucosa.
• High-risk HPV infection: HPV-16 and HPV-18 act as cofactors that switch on the pathway to malignant transformation.
• Chromosomal loss and accumulated mutations: Cytogenetic studies show that erythroplakia has high rates of loss of heterozygosity (LOH) at chromosomes 3p, 9p (p16INK4a) and 17p (TP53), clearly higher than in leukoplakia.

Clinical Features

• Appearance: A bright red, deep red or velvety red patch that is fairly flat or slightly depressed, with a very sharp border against the surrounding healthy mucosa.
• Surface and sensation: Smooth and velvety, soft to the touch (before deep infiltration), and may bleed slightly when touched. Most patients feel no pain at all; some notice mild stinging or burning with spicy or hot food.
• High-risk sites:
  • Floor of the mouth.
  • Lateral and ventral surfaces of the tongue.
  • Soft palate and retromolar trigone.
• Erythroleukoplakia (speckled leukoplakia): A red patch interspersed with white spots or granules. This mixed form carries a risk of malignancy similar to pure erythroplakia.

Histopathology

Why is erythroplakia so distinctly red? Under the microscope, two changes combine: epithelial atrophy, which removes the protective keratin layer, and vascular hyperemia with new vessel formation (neovascularization) in the superficial lamina propria just beneath it.

• Severe dysplasia / carcinoma in situ (CIS): More than 50% of cases. Atypical cells replace the full thickness of the epithelium:
  • Large, irregular, hyperchromatic nuclei with a reversed nuclear-to-cytoplasmic (N/C) ratio.
  • Numerous atypical mitotic figures, including in the upper layers of the epithelium.
  • Complete loss of basal cell polarity.
  • Disrupted intercellular bridges and abnormal keratinization of single cells (dyskeratosis).
• Microinvasive oral squamous cell carcinoma (OSCC): 30–40% of cases. Nests of atypical tumor cells break through the basement membrane and invade the underlying lamina propria to a depth of < 1–2 mm.
• Atrophic epithelium: The overlying epithelium is thinned to just a few cell layers with no keratin at all, letting light pass through and reveal the network of new vessels below.

Differential Diagnosis and Immunohistochemistry (IHC)

Our Approach to Treating Erythroplakia

At Haute-Derma, we manage erythroplakia with the utmost urgency:

• No watchful waiting: Unlike mild leukoplakia, which can sometimes be monitored, erythroplakia must be biopsied within 24–48 hours of being found.
• Treated as an early-stage cancer: Because up to 90% are malignant, every biopsy-confirmed erythroplakia must be completely removed by surgery or ultrapulse CO2 laser, with properly clear microscopic margins.
• Screening of the entire upper aerodigestive tract (pan-endoscopy): People with erythroplakia have a high risk of a second primary tumor in the esophagus, larynx or bronchi because of field cancerization.

How We Diagnose Erythroplakia at Haute-Derma

• Magnified mucosal examination and VELscope fluorescence: Identifies areas of fluorescence visualization loss (FVL), which appear distinctly dark under 400–460 nm light.
• 1% toluidine blue staining to map the lesion: Toluidine blue stains erythroplakia an intense royal blue, because severely dysplastic cells have a high DNA content and bind the dye strongly. This marks the microscopic boundary for surgery.
• Immediate mucosal biopsy (punch / incisional): Samples are taken from the center and edge of the lesion. Small lesions (< 5 mm) are removed whole as an excisional biopsy.
• Immunohistochemistry (p53, Ki-67, p16, p40): Confirms carcinoma in situ or invasive OSCC and helps estimate the risk of progression.

Specialized Treatments at Haute-Derma

• Wide local excision:
  • The gold standard for erythroplakia. The whole lesion is removed with a 5 mm clinical safety margin beyond the toluidine blue–stained border.
  • Frozen-section margins are checked during surgery to make sure no tumor cells remain at any edge.
• UltraPulse CO2 laser excision: An excellent alternative to the scalpel for lesions on the floor of the mouth, the side of the tongue or the soft palate. The laser removes the lamina propria precisely without harming deeper vessels or nerves, so tongue movement and swallowing recover quickly and there is no contracting scar.
• Photodynamic therapy (PDT): A photosensitizer (5-ALA or MAL) is applied and left for 3 hours, then activated with red laser light (630 nm). Used as an adjunct for extensive multifocal erythroplakia or when surgery is not possible.
• Removing risk factors and long-term follow-up:
  • Stop smoking and drinking completely.
  • Follow-up visits with mucosal examination are essential: every 1–2 months in the first year and every 3–6 months thereafter.