A keratoacanthoma is a rapidly growing, well-differentiated neoplasm of squamous epithelium. It assumes a distinct crater-shaped appearance and usually occurs as a solitary lesion on sun-exposed skin. It is considered by many to be a low-grade squamous cell carcinoma. Men are more commonly affected than women, individuals with lighter skin phototypes are at greater risk than those with darker skin phototypes, and peak incidence is between 65 and 71 years of age.

In contrast to squamous cell carcinomas, keratoacanthomas appear and grow rapidly over the course of a few weeks to a month. If left untreated, most keratoacanthomas spontaneously involute and resolve within 6 months, leaving an atrophic scar. It is thought that the immune system plays a role in spontaneous regression of keratoacanthomas.

Most keratoacanthomas are painless. Patients occasionally complain of pruritus within the lesion. They may cause mechanical or cosmetic deformity depending on the site of involvement. Most will cause only local destruction, but there are few that behave more aggressively. These are considered invasive variants. Metastases to draining lymph nodes, while seldom, have been reported.

Risk factors include ultraviolet (UV) light exposure and immunosuppression. Patients on immunosuppressants (eg, immunosuppression after solid organ transplantation) have increased numbers of more persistent and more chronic keratoacanthomas. Skin injury may also be a predisposing factor, as there are many reports of keratoacanthomas developing in sites of previous trauma, in surgical scars, after laser resurfacing, and following radiation therapy. Foreign bodies, such as tattoo ink, have also been identified as risk factors for keratoacanthomas.

While solitary typical keratoacanthomas are the most common presentation, there are also giant (2-15 cm in diameter), subungual, mucosal, and keratoacanthoma centrifugum marginatum (prominent horizontal growth pattern) variants.

In rare cases, multiple keratoacanthomas develop as part of a syndrome.

• Ferguson-Smith syndrome is an autosomal dominant inherited disease characterized by multiple self-healing keratoacanthomas. Lesions occur within one localized area, such as on the face or trunk. Each lesion clinically resembles a solitary keratoacanthoma, and lesions scar with resolution.
• In eruptive keratoacanthomas of Grzybowski, hundreds of lesions occur in a generalized distribution and may involve mucous membranes. Pruritus is a common feature, and lesions tend to heal without scarring.
• Keratoacanthomas may occur within Muir-Torre syndrome along with sebaceous neoplasms and adenomatous colon carcinoma or other low-grade internal malignancies.
• In familial keratoacanthomas of Witten and Zak, multiple larger and smaller keratoacanthomas are found.

Keratoacanthomas, including multiple eruptive keratoacanthomas, have been described in patients taking BRAF inhibitors such as vemurafenib and dabrafenib. Keratoacanthomas have also been associated with vismodegib and sorafenib use.