Keratoacanthoma

Introduction

Note: click on underlined words for more detail or photos.

Occasionally, an epithelial hyperplasias will strongly mimic the microscopic appearance of well-differentiated squamous cell carcinoma or verrucous carcinoma. Usually termed pseudoepitheliomatous hyperplasia, such a lesion may be primary (idiopathic) or secondary. The primary cutaneous lesion, referred to as keratoacanthoma ("self-healing" carcinoma; pseudocarcinoma), is a benign, self-limiting proliferation of the epithelial component of the follicular infundibulum. Intraoral examples have been reported, but are rare and obviously require a different theory to explain their origin. The average annual incidence rates in white males and females, respectively, are 144/100,000 and 73/100,000 population.

The etiology of this lesion is unknown. Sun damage is suggested by the fact that the vast majority of solitary lesions are found on sun-exposed skin, predominantly in elderly persons. Human papillomaviruses, usually the HPV-26 or HPV-37 subtypes, have been found in some lesions. Cutaneous keratoacanthoma-like lesions have been produced in animals by the application of known carcinogens.  The lesions occur with increased frequency in immunosuppressed patients and in the Muir-Torre syndrome (sebaceous neoplasms, keratoacanthomas, and gastrointestinal carcinomas), and multiple lesions tend to be hereditary in nature.

Intraoral pseudoepitheliomatous hyperplasia is usually the secondary type and lacks the distinctive appearance and behavior of keratoacanthoma. It is most often associated with chronic denture irritation and papillary hyperplasia of the palate or epulis fissuratum, but it is also associated with cases of chronic candidiasis, especially the form called median posterior atrophic candidiasis (median rhomboid glossitis) and with the deep fungi, blastomycosis and histoplasmosis.

Clinical Features

Keratoacanthoma occurs almost always in patients older than 45 years of age and shows a male predilection. Solitary lesions arise on sun-exposed skin in all but 5% of cases, and 8% of all cases are found on the outer edge of the vermilion border, affecting the upper and lower lips with equal frequency.

The skin or vermilion lesion appears as a firm, nontender, well-demarcated, dome-shaped nodule with a central plug of keratin, often resembling a volcano (Figures 1 & 2). Except for the yellow, brown or black keratin plug, the nodule has normal texture and color but may be erythematous. The central core has an irregular, crusted, often verruciform surface. Intraoral keratoacanthoma usually lacks this volcano-like appearance and has, rather, a simple verruciform surface change.

Rapid enlargement is typical, with the lesion attaining a diameter of 1-2 cm. within 6 weeks. This critical feature helps to distinguish keratoacanthoma from the much more slowly enlarging squamous cell carcinoma. When a large number of keratoacanthomas is seen early in life, it most likely represents the Ferguson Smith type, which is hereditary, and lesions are not likely to spontaneously involute. The eruptive Grzybowski type manifests as hundreds of small papules of the skin and upper digestive tract and has been associated with internal malignancy.

Pathology and Differential Diagnosis

The overall pattern of the tumor is diagnostically more important than the appearance of individual cells, hence, excisional or large incisional biopsy with inclusion of adjacent, clinically normal epithelium is suggested for proper histopathologic interpretation. The cells are mature and the epithelium shows good differentiation from the basal layer to the surface keratin (Figures 3 & 4), but dyskeratosis (abnormal or premature keratin production) is often seen as individually keratinizing lesional cells and keratin pearls identical to those of well-differentiated squamous cell carcinoma (Figure 5).

At the lip of the central crater an acute angle is formed between the overlying epithelium and the periphery of the lesion (Figure 6). The central crater is filled with keratin and the base of the crater shows broad, proliferating rete ridges which seldom extend below the level of the sweat glands in skin lesions or to the underlying muscle in oral lesions. A pronounced chronic inflammatory cell response may be found within adjacent stroma. Late stage lesions have considerably more keratinization of cells deep in the tumor than do early lesions.

Differentiation of keratoacanthoma from well-differentiated squamous cell carcinoma may be problematic. The malignancy, however, lacks the characteristic acute angle between normal and lesional epithelial margins of the keratoacanthoma, and both benign entities demonstrate a "pushing" extension into underlying stroma with none of the invading islands and individual dysplastic cells of the carcinoma.

The keratoacanthoma can easily be distinguished from crater-producing or volcano-like molluscum contagiosum of labial, buccal or other oral mucosa by the presence in the latter of large, basophilic viral inclusions (molluscum bodies) within keratinocytes at the base of the central "volcanic" core. These cells are commonly seen to be sloughing into the central cratered area.

Treatment and Prognosis

Keratoacanthoma tends to involute of its own accord, but surgical excision is often performed in order to confirm a benign diagnosis.  Large lesions of the vermilion or labial skin should be removed for esthetic reasons because significant scarring may result from involution. Recurrence occurs after excision in approximately 2% of skin cases. Aggressive behavior and malignant transformation into carcinoma have been reported in a few keratoacanthomas, but the similarity between this lesion and squamous cell carcinoma tends to raise doubts as to the appropriateness of the initial diagnosis in such cases.

References (Chronologic Order)

Note: Click on underlined author's names for additional detail. use back arrow to return here.

General references:

Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology. Philadelphia, W. B. Saunders; 1995.

Elder D, Elenitsas R, Jaworsky C, Johnson B Jr. Lever's Histopathology of the skin, 8th edition. Philadelphia; Lippincott-Raven, 1997.

Sapp JP, Eversole LR, Wysocki GP. Contemporary oral and maxillofacial pathology. Mosby; St. Louis, 1997.

Odell EW, Morgan PR. Biopsy pathology of the oral tissues. London; Chapman & hall Medical, 1998.

Specific references:

Pictures

Note: To see enlarged photo, click on the left-hand picture; 
return here with your BACK ARROW button.