What is the recommended treatment for eruptive keratoacanthomas of the tongue?

Treatment of Lingual Eruptive Keratoacanthomas

For eruptive keratoacanthomas of the tongue, systemic retinoids combined with intralesional therapies (5-fluorouracil or methotrexate) represent the most practical approach, as surgical excision is often impractical for multiple lingual lesions and evidence-based guidelines specifically for this rare presentation are lacking.

Primary Treatment Strategy

Systemic Retinoids as Foundation Therapy

• Systemic retinoids should be initiated as first-line therapy for eruptive keratoacanthomas, as they treat existing lesions while reducing the risk of subsequent lesions 1.
• Retinoids can be combined with targeted intralesional treatments for individual problematic lesions 1.

Intralesional Therapies for Individual Lesions

• Intralesional 5-fluorouracil (5-FU) is highly effective for keratoacanthomas refractory to other approaches, with injections every 3-4 weeks over 12 weeks achieving clinical clearance 2.
• The traditional weekly injection protocol may not be necessary; less frequent dosing (every 3-4 weeks) provides excellent results with better patient convenience 2.
• Intralesional methotrexate represents an alternative option for multiple keratoacanthomas, particularly those occurring in traumatized areas 3.
• Intralesional bleomycin has been reported as another off-label option, though safety data in specific populations remain limited 1.

Important Caveats and Considerations

Limitations of Topical Therapies

• Topical 5-FU and imiquimod are NOT recommended for lingual lesions despite showing efficacy for cutaneous keratoacanthomas 1, 4.
• Topical therapies cause marked erythema, erosions, and crusting lasting over a month, which would be intolerable on the tongue 1.
• The mucosal environment of the tongue makes topical application impractical and potentially dangerous due to systemic absorption 1.

Surgical Considerations

• Surgical excision remains the gold standard for solitary keratoacanthomas but is problematic for multiple eruptive lingual lesions 1, 5.
• Wide local excision with 3-10 mm margins is recommended for standard cutaneous lesions 1.
• For lingual lesions, surgical excision may compromise tongue function and is impractical when lesions are numerous 1.
• Liquid nitrogen cryotherapy or deep shave/saucerization followed by electrodesiccation and curettage can be considered for accessible individual lingual lesions, though complete surgical excision is generally not required for keratoacanthomas 1.

Critical Diagnostic Point

• Biopsy confirmation is essential before initiating conservative therapy, as keratoacanthomas are histologically similar to well-differentiated squamous cell carcinoma and should be considered a clinically distinct variant capable of rare metastasis 5.
• Lesions treated conservatively should undergo repeat biopsy after 5-8 weeks to confirm histopathological remission and potentially shorten treatment duration 4.

Radiation Therapy

• Radiation is reserved for inoperable cases or when patients cannot tolerate surgery 1.
• Radiation may be useful as a palliative modality but carries risks of tissue damage and is not first-line for benign eruptive keratoacanthomas 1.

Management Algorithm

1. Confirm diagnosis histologically via biopsy of representative lesion(s) 5
2. Initiate systemic retinoids as foundation therapy 1
3. Add intralesional 5-FU (every 3-4 weeks) for symptomatic or rapidly growing individual lesions 2
4. Consider intralesional methotrexate as alternative if 5-FU unavailable or ineffective 3
5. Reserve surgical excision for solitary accessible lesions where function can be preserved 1
6. Perform follow-up biopsy at 5-8 weeks if using conservative therapy to confirm histopathological response 4