Solitary Keratoacanthoma

The most common type begins as a small, solitary, firm, hemispherical papule of skin color that rapidly grows into a round or oval exophytic nodule on a broad base. The color is reddish, sometimes with a bluish tinge, or normal skin color, with a size of 0.5-3 cm in diameter. A molluscum-like appearance is characteristic. A crater-like depression filled with loose or dense brownish keratinous masses (pseudoulcers) forms in the center of the tumor. The peripheral high rim surrounding the keratin plug has a smooth surface and appears pink or skin-colored. Keratotic masses are easily removed to reveal underlying papillomatous growths. Typically a keratoacanthoma is a solitary lesion, but in some cases multiple (up to 10) lesions may be present.

The usual localization is on sun-exposed areas (head, hands, forearms, and less commonly, upper trunk and lower extremities). Rare sites include the genitals, oral mucosa (cheeks, hard palate, tongue, gums), conjunctiva, and periocular area. On the conjunctiva, keratoacanthoma appears as a white nodule with central hyperkeratosis and surrounding dilated episcleral vessels.

The active growth phase may be followed by a stabilization phase during which the size of the tumor does not change. Typically, spontaneous regression occurs within 3-9 months with disappearance of the tumor nodule and formation of an atrophic scar. In some cases, the stabilization phase does not occur and the tumor can reach giant sizes (up to 10-20 cm in diameter).

It has been reported that squamous cell carcinoma occurs in 5-6% of cases with metastasis to parathyroid glands and regional lymph nodes.

Giant Keratoacanthoma

Clinically identical to the classic type, but larger than 3 cm, often oval in shape, and located mainly on the dorsum of the hands, nose, and cheeks. Females predominate among patients. It is characterized by rapid growth and vertical spread, sometimes with tissue destruction (facial muscles may be involved, accompanied by infiltration of cranial nerves). It tends to undergo spontaneous involution, albeit slower, but with significant anatomical changes.

Keratoacanthoma centrifugum marginatum

A rare variant characterized by progressive horizontal growth with central healing. It begins as small papules that slowly evolve into annular or polycyclic patches with raised margins, sometimes with papulo-nodular elements. Dense pigmented mini-papules may be present in the center of the scarred patches. Such keratoacanthomas are predominantly solitary and can sometimes reach 20 cm or more in diameter. In some cases, the tumors are multiple, unilateral or bilateral, primarily on the extremities, often the lower extremities, although localization can be anywhere. Spontaneous regression occurs within 6-12 months, but in some cases it may last for several years. Cases have been described in which keratoacanthoma centrifugum marginatum coexisted with giant and multiple tumors.

The tumor can simulate annular elastolytic giant cell granuloma, elastosis perforans serpiginosa, discoid lupus erythematosus, squamous cell carcinoma, tuberculosis, syphilis, deep mycoses.

Keratoacanthoma en plaque

Characterized by a flat, plaque-like eruption without a sharply defined crater and with a uniform distribution of keratotic masses on its surface. It occurs with equal frequency in males and females. On average, its duration does not differ from that of typical tumors.

Subungual Keratoacanthoma

A rare, aggressive form seen primarily in middle-aged men. It is often preceded by trauma. The first finger of the hand is most commonly affected. The tumor is characterized by rapid growth, pain, and destruction of the underlying bone. The nodule becomes visible after detachment of the nail plate. It is similar to a wart and squamous cell carcinoma. Spontaneous involution is rarely seen.

Persistent Keratoacanthoma

A rare, aggressive form seen primarily in middle-aged men. It is often preceded by trauma. The first finger of the hand is most commonly affected. The tumor is characterized by rapid growth, pain, and destruction of the underlying bone. The nodule becomes visible after detachment of the nail plate. It is similar to a wart and squamous cell carcinoma. Spontaneous involution is rarely seen.

Recurrent Keratoacanthoma

A rare, aggressive form seen primarily in middle-aged men. It is often preceded by trauma. The first finger of the hand is most commonly affected. The tumor is characterized by rapid growth, pain, and destruction of the underlying bone. The nodule becomes visible after detachment of the nail plate. It is similar to a wart and squamous cell carcinoma. Spontaneous involution is rarely seen.

Multinodular Keratoacanthoma

A rare form that forms as a result of the fusion of several closely located keratoacanthomas. The initially isolated craters may also coalesce over time to form irregularly shaped pseudo-ulcers.

Multiple keratoacanthoma Ferguson Smith type

Sporadic cases and familial cases with an autosomal dominant inheritance pattern have been reported. The gene responsible for the development of the disease is mapped between D9529 (9q31) and D9S1 (9q22.1 - q22.2). According to recent data, the spectrum of mutations occurs in the TGFBR1 gene. The first appearance of multiple keratoacanthomas is observed between the ages of 8 and 62 years, but most patients experience the onset of the disease in childhood and adolescence. It is characterized by the eruption of dozens to hundreds of typical and atypical keratoacanthomas on any part of the skin, mainly on the limbs, including the palms and soles. The eruptions have a typical gradual evolution, but new lesions appear simultaneously with the spontaneous disappearance of some elements, leading to the formation of irregularly shaped atrophic scars. Cases have been reported in association with keratoacanthoma centrifugum marginatum and acrokeratosis verruciformis of Hopf.

Generalized Eruptive Keratoacanthomas of Grzybowski

The disease usually develops in individuals between the ages of 50 and 60 with equal frequency in men and women. It is characterized by the sudden eruption of hundreds of thousands of follicular papules of skin color, densely packed or scattered on the face, upper body, sometimes in body folds. Hyperkeratotic plugs are found in the center of some elements. In some patients, the oral mucosa and larynx are involved. Koebner's phenomenon is positive. The face often has a mask-like appearance with bilateral ectropion. Intense pruritus is subjective. The disease is chronic, spontaneous regression of eruptions is rare. Cases of invasive growth and progression to squamous cell carcinoma have not been described. Cases have been documented in association with typical solitary keratoacanthomas.

Multiple Familial Keratoacanthoma of Witten and Zak

An intermediate type between Ferguson-Smith and Grzybowski keratoacanthomas. The hereditary nature of the disease is presumed. It is characterized by simultaneous eruption of multiple milia-sized and larger self-resolving elements. In some cases, nodular-ulcerative formations of medium and large size and eruptions on the mucous membrane of the oral cavity are observed.

Keratoacanthomas in Other Diseases

Solitary and multiple keratoacanthomas can also be observed in Muir-Torre syndrome and xeroderma pigmentosum.

Diagnosis is based on clinical manifestations; excisional biopsy is performed for solitary or multiple lesions; diagnostic biopsy of the raised margin is performed for large lesions.

Histopatology: Considered by some to be a highly differentiated form of squamous cell carcinoma, histological examination reveals a circumscribed proliferation of well-differentiated keratinocytes. This has been described as multilobular exophytic or endophytic cyst-like invagination of the epidermis. The epidermis extends over the tumor, and there is a central horn plug of keratin. Peripheral to the keratin-filled crater are lip-like, peripheral borders of the epidermis. Intraepidermal neutrophilic abscesses are visualized in addition to horn pearls. The cells of the keratoacanthoma tumor are enlarged and atypical keratinocytes. They have a cytoplasm described as eosinophilic. Due to 3 stages of solitary keratoacanthoma, the histological examination can vary between stages. In comparison to squamous cell carcinoma, keratoacanthoma has intraepidermal microabscesses and tissue eosinophilia more commonly found. Recently keratoacanthoma has been reclassified as squamous cell carcinoma keratoacanthoma type (SCC-KA).

Cite: Zito PM, Scharf R. Keratoacanthoma. [Updated 2023 Mar 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499931/

• Squamous cell carcinoma
• Common warts
• Giant molluscum contagiosum
• Actinic keratosis
• Cutaneous horn
• Basal cell carcinoma.
• The multiple form should be differentiated from Darier's disease.

Due to the spontaneous involution of keratoacanthomas, waiting for 3-6 months is possible.

For solitary tumors, surgical excision, curettage, electro-, cryo-, or laser destruction (CO2, Er:YAG, Argon laser) are performed.

Alternative methods include:

• 5-fluorouracil cream
• Pirospidine cream
• Imiquimod
• Intralesional injection of methotrexate, interferon-alpha 2a

Due to the aggressive nature of subungual keratoacanthomas, amputation of the distal phalanx may sometimes be necessary.

In keratoacanthoma centrifugum marginatum , after surgical excision, reconstructive procedures may be necessary, retinoids are used for up to 5-6 months, and sometimes radiotherapy is prescribed.

Good results are observed in multiple keratoacanthomas of Ferguson-Smith type with intravenous administration of 5-fluorouracil (12 mg/kg/day in 5-day cycles with 2-day intervals for 6 weeks).

For Grzybowski and Witten-Zak keratoacanthomas, the use of retinoids is preferred: Acitretin oral 50-75 mg once daily for 4-11 weeks.

If there is no effect, cyclophosphamide is prescribed (200 mg/day for 3 months, followed by dose reduction to 100 mg, continued for another month; good effect was observed with pulse therapy - 1 g/month for 6 months).

In recent years, photodynamic therapy and EGFR tyrosine kinase inhibitor - erlotinib are being tested for various variants of keratoacanthoma.