Version July 2025
INTRODUCTION —
Keratoacanthoma (KA) is a cutaneous squamoproliferative tumor that usually presents as a 1 to 2 cm dome-shaped or crateriform nodule with central hyperkeratosis (picture 1). A common and distinctive feature of KA is a clinical course characterized by phases of rapid growth, lesion stability, and spontaneous involution.
The treatment and prognosis of KA will be discussed here. The epidemiology, risk factors, and diagnosis of KA are reviewed separately. (See "Keratoacanthoma: Epidemiology, risk factors, and diagnosis".)
GENERAL CONSIDERATIONS —
A longstanding debate over the classification of KA as a benign, spontaneously resolving tumor versus a variant of cutaneous squamous cell carcinoma (cSCC) with a rare potential for metastasis has contributed to a lack of definitive guidelines on the treatment of these lesions. However, the well-recognized difficulty in distinguishing KA from cSCC, a common tumor associated with a risk for metastasis, leads many clinicians (including ourselves) to recommend treatment of these lesions [1-7].
We opt to treat KA based on the following considerations [2]:
●No clinical or pathologic features can reliably differentiate KA and cSCC.
●Treatment accelerates lesion resolution.
●Treatment is usually straightforward and efficient, with relatively minor risk.
●Early treatment may improve cosmetic outcomes by limiting damage to the skin and underlying structures, such as the nose, eyelids, or lips.
We defer therapeutic intervention and proceed with observation only in patients who refuse to proceed with treatment. (See 'Deferring therapy' below.)
SOLITARY KERATOACANTHOMA —
Surgical excision is the first-line treatment for patients with the most common clinical presentation of KA: a solitary lesion. Other therapeutic options for solitary KA include electrodesiccation and curettage (ED&C), intralesional injections, topical therapies, and radiation therapy.
Wide local excision — Wide local excision is the treatment of choice for solitary KA (picture 2 and picture 1) since it allows for pathologic confirmation of diagnosis and tumor removal. The excision should include a periphery of normal skin and should extend into the subcutaneous fat. Due to the well-accepted difficulty in distinguishing KA from cutaneous squamous cell carcinoma (cSCC), we typically excise these lesions with the recommended surgical margins for low-risk cSCC (4 to 6 mm) [8]. (See "Treatment and prognosis of low-risk cutaneous squamous cell carcinoma (cSCC)", section on 'Wide local excision'.)
The efficacy of wide local excision for the treatment of KA has not been evaluated in randomized trials. In a single-institution retrospective study that included 261 patients with 363 KA treated with different modalities and followed up for a median time of 2.3 years, the recurrence rate among 100 patients with 112 KA treated with standard surgical excision was 0.9 percent compared with rates of 12 to 33 percent with other treatment modalities, including ED&C, cryotherapy, and topical therapies [9].
Mohs surgery — Mohs surgery is usually reserved for patients in whom a tissue-sparing procedure is desired (see "Mohs surgery"). Thus, it is the preferred treatment for KA in areas such as the central face, ear, nose, and periocular and perioral skin (picture 3 and picture 4). Mohs surgery may also be used for lesions >2 cm in diameter (giant KA) since it allows for confirmation of tumor removal prior to wound closure and may minimize the size of the surgical defect [10].
Data on the efficacy of Mohs surgery for KA are limited. In a large series of 95 patients with 119 KA treated with Mohs surgery, the recurrence rate was 0.8 percent [9]. A similar recurrence rate (0.9 percent) was observed among 100 patients with 112 KA treated with conventional surgical excision. In another retrospective study of 127 consecutive patients with KA seen between 2020 and 2022 and treated with Mohs surgery, no recurrences were observed [11]. No recurrences were observed in another series of 83 KA treated with Mohs surgery [12].
Alternative therapies — Other therapies that have been used for the management of KA include ED&C, intralesional chemotherapy, ionizing radiation, and topical agents. Compared with surgical excision, the major disadvantage of these alternative procedures is the lack of histopathologic confirmation of the removal of the tumor.
Electrodesiccation and curettage — ED&C is a quick surgical procedure that is often used to treat KA, usually after a shave biopsy has been sent for histopathologic evaluation. The procedure involves three cycles in which curettage is followed by electrodesiccation of the lesion site. Only a few minutes are required to administer this therapy. (See "Minor dermatologic procedures", section on 'Curettage and electrodesiccation'.)
Data on the efficacy of ED&C are limited. In a retrospective study of 111 KA followed for 3 to 26 months, recurrence was detected in four lesions (4 percent) [13]. A separate retrospective study of 75 patients treated with this modality reported an overall recurrence rate of 8 percent [3].
Although ED&C is well tolerated, the round, hypopigmented scar typically left after healing makes it a less favorable option for tumors located in cosmetically sensitive areas.
Intralesional chemotherapy — Intralesional chemotherapy is a treatment option infrequently used for KA [14-17].
●Chemotherapy agents
•Fluorouracil – Intralesional fluorouracil is typically administered undiluted at a concentration of 50 mg/mL weekly for three to eight treatment sessions.
The efficacy of fluorouracil is supported by case reports and case series [18,19]. In the largest series that included 41 lesions, a complete response rate of 98 percent was achieved with a dose of 40 to 75 mg per lesion [20]. In another series of 30 patients with eruptive KA (also called eruptive squamous atypia), 20 patients (67 percent) achieved complete resolution with intralesional fluorouracil at a dose of up to 50 mg per lesion [19].
•Methotrexate – Intralesional methotrexate 12.5 or 25 mg/mL is administered as individual injections of 0.1 to 2 mL every two to three weeks for one to four treatment sessions. One or two treatments are usually sufficient for resolution.
In a series of 54 patients with 73 KA treated with intralesional methotrexate (dose range 0.1 to 1 mL of a 12.5 mg/mL solution), 64 (88 percent) resolved with one to four injections [12]. In another series of 29 patients with 69 tumors, complete resolution occurred for 66 lesions (96 percent) after a mean of two injections [21].
Intralesional methotrexate and fluorouracil have been compared in a small trial that included 20 patients with biopsy-proven KA treated with intralesional methotrexate 25 mg/mL or intralesional fluorouracil 50 mg/mL every two weeks until complete clearance or up to five sessions [22]. Complete lesion resolution occurred in 7 of 10 patients treated with methotrexate and 8 of 10 treated with fluorouracil.
Intralesional methotrexate has also been used as neoadjuvant therapy prior to surgical excision, resulting in reduced lesion size by 50 to 80 percent [23].
•Other – Intralesional bleomycin [24-27] and interferon alfa-2a and alfa-2b [28,29] have been used in a few cases.
●Injection technique – A common technique used to perform intralesional injection of a KA is to deliver a total of five injections per lesion per session: a single injection into the center and one injection into each quadrant. The goal is to blanch the entire rim of the lesion [15,30].
Due to discomfort associated with the injection of fluorouracil and bleomycin, local anesthesia is frequently given prior to these injections. In contrast, anesthesia is not usually necessary for the administration of methotrexate and interferon [18].
●Adverse effects – Potential adverse effects common to intralesional therapy include local pain, erythema, necrosis, ulceration, and crusting. The possibility that adverse effects associated with systemic absorption of these agents may occur must also be considered [18]. Pancytopenia has occurred in two patients with kidney failure after KA treatment with 25 mg of intralesional methotrexate [31,32]. Thus, some authors have suggested obtaining a complete blood count before treatment and one week after injection of methotrexate [15].
Topical therapies — Topical fluorouracil and imiquimod have been successfully used for the treatment of KA. Their efficacy is supported by case reports and case series [33-35].
●Topical fluorouracil – A 5% formulation of fluorouracil is typically applied daily, and resolution usually occurs within eight weeks.
●Imiquimod – Imiquimod 5% cream is applied three to four times per week. Resolution is expected to occur within 4 to 11 weeks [35].
Significant local inflammation is a common adverse effect of both topical fluorouracil and imiquimod.
Radiation therapy — Radiation therapy is infrequently employed for the treatment of KA due to the multiple visits required and the potential long-term adverse effects. It is usually reserved for older adult patients for whom surgical treatment is not an option.
The efficacy of radiation therapy for KA is supported by case series and case reports [36-40]. There is a report of radiation therapy induction of numerous new lesions in a patient with multiple self-healing squamous epithelioma (Ferguson-Smith disease), a genetic disorder characterized by the development of multiple KA [41]. (See "Keratoacanthoma: Epidemiology, risk factors, and diagnosis", section on 'Multiple keratoacanthomas'.)
Other — Other therapies that have been reported as effective in small numbers of patients with KA include curettage alone, cryotherapy, an argon laser [42], erbium-doped yttrium aluminum garnet (Er:YAG) laser in combination with topical fluorouracil [43], and photodynamic therapy [44]. Of note, KA has been reported to occur as a consequence of trauma related to treatment with a fractional laser [45], a carbon dioxide (CO2) laser [46], and cryotherapy [47,48]. Worsening of a KA lesion has also been documented after photodynamic therapy [49].
Deferring therapy — Given the possibility for spontaneous resolution of solitary KA, some patients may elect to defer therapy. In a single-institution retrospective study that included 22 patients with 27 KA who underwent active surveillance, 4 of 27 tumors (15 percent) were persistent after an average of four months and were subsequently excised with Mohs surgery [9].
When the observation approach is taken, close patient follow-up is recommended [50].
●Follow-up from presentation through resolution should be performed by a single clinician experienced in the natural history of these lesions.
●The course of the lesion should be documented with photographs every two to three weeks until lesion resolution.
●The patients must be informed that resolution may take six months or longer.
●Patients should be informed of the option for surgical excision and other treatments.
●We also inform patients who are considering deferring therapy of the possibility of aggressive lesion behavior and the chance for misdiagnosis of squamous cell carcinoma as KA.
If, during the course of observation, the lesion develops an atypical appearance, growth fails to cease, or the tumor fails to regress as expected, surgical excision with histopathologic examination of the lesion is indicated [4]. (See "Keratoacanthoma: Epidemiology, risk factors, and diagnosis", section on 'Solitary keratoacanthoma'.)
SPECIAL SITUATIONS
Multiple or large keratoacanthomas — The management of patients with numerous KA (picture 5), such as those seen in the rare multiple KA syndromes (see "Keratoacanthoma: Epidemiology, risk factors, and diagnosis", section on 'Multiple keratoacanthomas'), or with very large KA (eg, keratoacanthoma centrifugum marginatum [KCM] (picture 6)) is challenging [51]. Although surgery and other therapies, including intralesional fluorouracil [19], remain treatment options, they are usually impractical in patients with hundreds or thousands of lesions.
Systemic pharmacologic therapy is an alternative option for such patients.
●Oral retinoids – We suggest oral retinoids for the treatment of multiple or eruptive KA. Acitretin at a dose of 25 to 60 mg per day or isotretinoin at a dose of 20 mg per day up to 1.5 mg/kg per day are given for two to several months to achieve a satisfactory response. Atrophic scars may remain at the sites of healed lesions.
Multiple case reports have documented their efficacy in patients with multiple self-healing squamous epithelioma or generalized eruptive KA of Grzybowski [41,52-65]. Although long-term maintenance therapy may be required [53,60,62,66], sustained remission after therapy discontinuation has been reported in individual patients with multiple self-healing squamous epithelioma, eruptive KA of Grzybowski, and KCM [54-56].
Adverse effects associated with systemic retinoids include cheilitis, xerosis, visual changes, transaminitis, hyperlipidemia, and teratogenicity. Pregnancy should be avoided for one month after isotretinoin therapy and for three years after the discontinuation of acitretin. Thus, treatment with acitretin is usually avoided in women of childbearing age. In the United States, prescribing and receipt of isotretinoin requires participation in the iPLEDGE program. The iPLEDGE program provides detailed guidelines for pregnancy prevention counseling, pregnancy screening, and contraceptive use during treatment. (See "Oral isotretinoin therapy for acne vulgaris", section on 'iPLEDGE program'.)
●Other agents – Agents that have been successfully used include methotrexate [67,68], cyclophosphamide [69], and intravenous fluorouracil [70].
Subungual keratoacanthoma — Although spontaneous resolution of subungual KA has been reported [71,72], these lesions typically persist [5]. Surgical en bloc excision down to the bone or Mohs surgery are the preferred therapeutic interventions [73].
Curettage with or without electrodesiccation and systemic methotrexate have also been utilized [72,74]. Digital amputation is reserved for lesions that fail to respond to other therapies [72,74].
Muir-Torre syndrome — The Muir-Torre variant of Lynch syndrome may present with sebaceous tumors, visceral malignancies, and KA. The management of patients with this syndrome is reviewed separately. (See "Muir-Torre syndrome".)
PROGNOSIS
Recurrence — Incomplete removal of KA may result in lesion recurrence. The overall recurrence rate after excision or electrodesiccation and curettage (ED&C) is estimated to be between 3 and 8 percent [9,50,75]. Recurrence rates of <1 percent have been reported with both wide local excision and Mohs surgery [9].
Involution — Although it is generally well accepted that solitary KA can spontaneously regress, detailed documentation of lesions followed through to regression is limited [50,76]. In a retrospective review of 14 patients followed with serial photographs until lesion involution by a single clinician, the mean time to resolution was 27 weeks [50]. No recurrences were observed during patient follow-up, which ranged from nine months to eight years.
The type of KA influences the likelihood of spontaneous resolution. While spontaneous involution can occur in solitary KA and individual lesions in multiple self-healing squamous epithelioma (Ferguson-Smith disease) and generalized eruptive KA of Grzybowski, it is unlikely to occur in mucosal KA, subungual KA, and keratoacanthoma centrifugum marginatum (KCM). (See "Keratoacanthoma: Epidemiology, risk factors, and diagnosis", section on 'Clinical variants'.)
Metastasis — Metastases from KA are exceedingly rare [77-79]. Moreover, whether some or all of the few cases reported as metastatic KA actually represent the misdiagnosis of cutaneous squamous cell carcinoma (cSCC) has not been ascertained [1,80,81].
The relevance of the histopathologic detection of perineural invasion in 1 to 4 percent of KA, a finding associated with an increased risk for local recurrence and metastasis in cSCC, is uncertain [82-84]. Perineural invasion in KA has generally been considered an incidental finding with little impact on prognosis [83,85]. In the largest series documenting cases of KA with perineural invasion, 1 out of 40 lesions recurred, and no metastases were noted [82]. However, aggressive local behavior of a KA with histopathologic evidence for perineural invasion has also been reported [83].
FOLLOW-UP —
Patients should be instructed to return for re-evaluation if signs of lesion regrowth occur after treatment. The appropriate interval for routine clinical follow-up has not been determined. We typically see patients with small, uncomplicated, solitary KA six months after treatment for re-evaluation of the treatment site and a full skin examination. We then follow these patients once yearly.
Certain clinical scenarios may demand more frequent follow-up. Earlier and more frequent follow-up is appropriate for patients with large, aggressive, or multiple lesions.
PREVENTION —
Since ultraviolet light exposure likely contributes to the development of KA, daily sun-protective measures (application of sunscreen, use of sun-protective clothing, and midday sun avoidance) are recommended as a preventive measure. Patients with multiple KA syndromes may benefit from long-term systemic retinoid therapy to reduce the development of new lesions.
SUMMARY AND RECOMMENDATIONS
●General considerations – Although keratoacanthoma (KA) is a cutaneous squamoproliferative tumor with the potential for spontaneous resolution, we opt to treat KA based on the following considerations (see 'General considerations' above):
•No clinical or pathologic features can reliably differentiate KA and cutaneous squamous cell carcinoma (cSCC).
•Treatment accelerates lesion resolution.
•Treatment is usually straightforward and efficient, with relatively minor risk.
•Early treatment may improve cosmetic outcomes by limiting damage to the skin and underlying structures, such as the nose, eyelids, or lips.
●Solitary keratoacanthoma
•Surgery – For most solitary KA, we suggest wide local excision rather than observation or other therapies (Grade 2C). The excision should include margins of 4 to 6 mm of normal skin and should extend into the subcutaneous fat. For lesions in areas where tissue sparing is desired, such as the central face, ear, nose, and periocular and perioral skin, we suggest Mohs surgery, if available, rather than wide local excision (Grade 2C). (See 'Wide local excision' above and 'Mohs surgery' above.)
•Other therapies – Alternative options include electrodesiccation and curettage (ED&C), intralesional chemotherapy, topical therapies, and radiation therapy. Disadvantages of these interventions compared with surgical excision include the lack of histopathologic confirmation of tumor removal, longer healing times, and worse cosmetic outcomes. (See 'Alternative therapies' above.)
•Deferring therapy – For patients who elect to defer therapy and prefer to wait for the lesion's spontaneous resolution, close clinical follow-up should be implemented. Spontaneous resolution may take several months or longer. If lesions deviate from the expected clinical course, surgical excision to confirm the diagnosis is indicated. (See 'Deferring therapy' above.)
●Multiple keratoacanthomas – For patients with numerous KA, such as those seen in the rare multiple KA syndromes (eg, multiple self-healing squamous epithelioma, generalized eruptive KA of Grzybowski, eruptive squamous atypia), we suggest treatment with oral retinoids rather than surgery or other therapies (Grade 2C). Acitretin 25 to 60 mg per day or isotretinoin 20 mg per day up to 1.5 mg/kg per day are given for several months to achieve a satisfactory response. (See 'Multiple or large keratoacanthomas' above.)
●Prognosis – Incomplete removal of KA may result in lesion recurrence. Metastasis is exceedingly rare. (See 'Prognosis' above.)
