• In the US: The sole published study in a white US population took place in Hawaii and estimated the incidence at 104 cases per 100,000. This study reported KA incidence equal to SCC and challenged the commonly reported incidence ratio of KA to SCC of 1:3. Peak incidence occurs in the seventh decade or beyond. KA is uncommon in darker-skinned patients.

• Internationally: Based on the Hawaiian data, the incidence of KA in ethnic Japanese, Filipino, and Hawaiian populations has been estimated to be 22, 7, and 6 per 100,000, respectively, approximately one fifth to one sixteenth of the incidence rate found in American whites. In other studies, the ratio of KA to SCC has ranged from 1:0.6 to 1:5 in different geographic locations.

Mortality/Morbidity: KA is believed to have a good prognosis; however, it recently was reclassified as SCC-KA type to reflect the difficulty in histologic differentiation, as well as the uncommon but potentially aggressive nature of KA. KA infrequently presents as multiple tumors and may enlarge (5-15 cm), become aggressive locally, or rarely, metastasize.

Race: KA is less common in darker-skinned individuals.

Sex: Male-to-female ratio is 2:1.

Age: KA has been reported in all age groups, but incidence increases with age. KA is rare in persons younger than 20 years.

History: KA typically grows rapidly, attaining 1-2 cm within weeks, followed by a slow involution period lasting up to 1 year and leaving a residual scar if not excised preemptively. Since expedient therapy almost always is instituted, the true natural course of the tumor cannot be confirmed with certainty.

Physical:

• Pertinent physical findings are limited to the skin. Lesions typically are solitary and begin as firm, roundish, skin-colored or reddish papules that rapidly progress to dome-shaped nodules with a smooth shiny surface and a central crateriform ulceration or keratin plug that may project like a horn

• Most KAs occur on sun-exposed areas. The face, neck, and dorsum of the upper extremities are common sites. Truncal lesions are rare.

• Lesions usually are skin-colored to pinkish-red. Unaffected skin retains its normal appearance.

Causes:

• The definitive cause of KA remains unclear; however, several potentiating factors should be considered.

• Epidemiologic data of KA is notably similar to SCC and Bowen disease (BD; SCC in situ) concerning age, sex, and the anatomic site of lesions. This data strongly supports a common etiology among KA, SCC, and BD. Epidemiologic data support sunlight as an important etiologic factor.

• Industrial workers exposed to pitch and tar have been well established as having a higher incidence of KA, as well as SCC.

• A recent study suggested a strong association between cigarette smoking and the development of KA.

• Trauma, human papilloma virus (specifically types 9, 11, 13, 16, 18, 24, 25, 33, 37, and 57), genetic factors, and immunocompromised status also have been implicated as etiologic factors.

• Recent work has identified that up to one third of keratoacanthomas harbor chromosomal aberrations. Recurrent aberrations include gains on 8q, 1p, and 9q with deletions on 3p, 9p, 19p, and 19q. One other report identified a 46,XY,t(2;8)(p13;p23) chromosomal aberration.

Procedures:

• One component of establishing the diagnosis is tissue examination for histopathology. Shave biopsy of KA is indistinguishable from invasive SCC; therefore, excisional or deep incisional biopsy of the lesion is preferred.

Pseudocarcinomatous infiltration in KA typically presents a smooth, regular, well-demarcated front that does not extend beyond the level of the sweat glands.

The term SCC-KA type has been introduced for otherwise classic KAs that reveal a peripheral zone formed by squamous cells with atypical mitotic figures, hyperchromatic nuclei, and loss of polarity to some degree. These marginal cells also may penetrate into surrounding tissue in a more aggressive pattern.

Medical Care: Treatment of KA is primarily surgical. Reserve medical treatment for exceptional cases where surgical intervention is either not feasible or desirable. For example, medical intervention may be appropriate in patients with multiple lesions, in lesions not amenable to surgery because of size or location, and in patients with comorbidities that dissuade surgical procedure.

Systemic retinoids, such as isotretinoin, are a consideration for patients with lesions too numerous for surgical intervention.

Intralesional methotrexate, 5-fluorouracil, bleomycin, and steroids have been used with success in patients who are either poor surgical candidates or have lesions not amenable to surgery because of size or location. Both topical imiquimod and 5-fluorouracil have been used with anecdotal success.

Note much of the literature concerning medical intervention for KA is limited to case reports and of unproved efficacy. Be cautious when making the decision to pursue medical in lieu of surgical intervention and perform appropriate follow-up.

Surgical Care:

• The primary therapy for KA is surgical excision of the tumor.

• Excise tumors with adequate margins (3-5 mm) and histopathologic evaluation to exclude invasive SCC.

• Partial shave biopsy usually inadequately distinguishes between KA and invasive SCC.

• In some patients, smaller lesions may be treated with deep excisional shave and curettage or other destructive techniques.

• Since the biological behavior of an individual KA cannot be predicted, many consider surgical treatment of KA to be equivalent to treatment for SCC.

• Mohs micrographic surgery may be indicated for large or recurrent KAs or KAs located in anatomic areas with cosmetic or functional considerations.

• KAs are radiosensitive and respond well to low doses of radiation (<10 Gy).

• Radiation therapy may be useful in selected patients with large tumors in whom resection will result in cosmetic deformity or for tumors that have recurred following attempted excisional surgery.

• Radiation therapy is less appealing in younger patients in whom radiation damage worsens with time.
• Radiation therapy is an important alternative treatment for selected patients who understand the risks and benefits, who are not good surgical candidates, or who lack access to Mohs surgery.

• Both laser therapy and cryotherapy have been used successfully in small KAs, in KAs found in difficult to treat locations, and as an adjunct to surgical removal.