A. P. ULBRICH, B.S., D.O., and THOMAS H. keratoacanthoma resemble those of Grade I epi- BONINO, A.B., D.O., Detroit, Michigan dermoid carcinoma,9 the lesion is essentially a self- limiting pseudoepithelioma. We believe that a co- ordination of clinical and pathologic findings will do much to enlighten physicians and bring this disease entity out of the classification of a grievous Keratoacanthoma is a clinical entity that derma- malignancy. Adequate observation and care can tologists have long been able to recognize easily, then be afforded the patient without subjecting although not by that name but rather "squamous him to overtreatment. cell carcinoma." The variety of names that have A review of our records of patients with malig- been given this tumor reflects its position as a nant lesions disclosed a startling number of cases, "relative" that has not received full recognition. obviously keratoacanthomalike, which had been fol- It has frequently been discussed, but a name tag lowed as squamous cell carcinoma, some for as has been elusive. 1 ,2 American literature has tended long as 15 years (Fig. 1). The error is widespread to favor the designation "tumor-like keratosis of and long-standing; as late as 1954, a standard med- Poth,"3-5 or at least to associate this tumor with ical text10 showed keratoacanthoma as a typical Poth's original descriptions British writers have example of "squamous cell carcinoma, Grade I." used the term "self-healing epithelioma of Ferguson The problems of diagnosis and incidence are high- Smith,"7 although at present they use the term lighted by published opinions u ranging from "molluscum sebaceum." Even the relatively specific ... admitted one case of keratoacanthoma for every term "keratoacanthoma" should perhaps be quali- two cases of epidermoid carcinoma" to "It is im- fied by "solitary" or "multiple." A solitary lesion, possible ... to make a definite histopathologic diag- however, might turn out to be merely the first nosis of keratoacanthoma." That the incidence is in a given case; on the other hand, the fact that higher than has been assumed, and indeed may be a patient has one such lesion does not mean he will increasing, is indicated by the fact that during the have others, as is illustrated in the cases to be past 3 years our records included a total of 24 cases described in this article. Admittedly the problem of keratoacanthoma, the clinical diagnoses having of differentiating solitary versus multiple lesions, been confirmed by pathologists' reports. along with the problem of etiologic classification, gives rise to much academic debate and discussion.8 The prime consideration, however, should be the Fig. I. Patient seen in 1946; clinical diagnosis was made of a squamous cell carcinoma on biopsy and confirmed by a patholo- fundamental problem of differentiating keratoacan- gist. This is clinically a keratoacanthoma. thoma from squamous cell carcinoma, thus remov- ing a benign, self-healing lesion from the category of malignancy. In the past, general pathologists have readily confirmed a clinical diagnosis of low-grade squa- mous cell carcinoma for lesions that were actually keratoacanthoma. Occasionally the pathologist's diagnosis has been "verruca," particularly when the excised specimen included only a portion of the lesion. Although the histopathologic changes in °Address, 18820 Woodward Ave.
JOURNAL A.0 A., VOL. 61, NOV, 1961 189 flammation around the area, and telangiectasis is slight. In the early stages, there is some violaceous change in lesions occurring on unexposed portions of the body. The lesions grow rapidly, often from 1 to 1.5 cm. in a month or two, and as they age the edges become smaller and the central keratin plugs more elevated (Fig. 6). In the receding stages, the reduction continues and the plugs flatten until the lesion appears somewhat like the top of a flat pepper shaker, with numerous small black spots. Any surface area of the body may be involved, and sometimes the mucous membrane of the mouth. Lip lesions in particular offer a diagnostic challenge to
Fig. 2. Typical keratoacanthoma at a frequent site. both clinician and histopathologist. Many variations have been noted in the course of these tumors. Tremendous areas of involvement Clinical review have been reported—two thirds of the patient's chest, in one case. 12 In one 6-weeks-old lesion For this report, the records in a 1-year series of which we excised, the central keratin protruded 10 cases were reviewed in detail. Of these patients so far that the lesion gave the appearance of a the oldest was 85, the youngest 21, and the average cutaneous horn. Two of our cases involved associ- age 46; 5 were male and 5 female. One patient ated lesions which might have been a source of gave a history of a malignant neoplasm which had confusion, and which illustrated the fact that kera- been clinically diagnosed as squamous cell carci- noma, but tissue was not available for study. One patient had four lesions; the others each had a solitary lesion. The site of the lesion was the nose in 4 cases; cheek, 1 (Fig. 2); ear, 1; cervical area, 2; dorsum of hand, 1; and medial thigh, 1. The clinical picture of keratoacanthoma varies with the age of the lesion (Fig. 3). Among our patients the two earliest lesions observed were only 4 mm. in diameter; each lesion showed a centrally depressed area containing a keratogenous plug. One of these lesions was on the left ear and was of only 6 weeks' duration. In general, the lesions range up to 15 mm. in size; they tend to be hemispheric or dome-shaped, and slightly less elevated than they are wide (Figs. 4 and 5 ). The area of keratinization Fig. 4. Keratoacanthoma of dorsum of hand, with appearance of so-called typical squamous cell epithelioma. tends to enlarge as the lesions enlarge. Desquama- tion from this area results in the relative depression of the center of the lesion and discoloration from toacanthoma may readily precede or follow other the darkening debris. There is relatively little in- types of skin tumor. Details of these cases follow.
Fig. 3. Early keratoacanthoma, 4 mm., not having reached its Case 1 • The patient was a 21-year-old male "maturity." schoolteacher. He was typically rufous—red-haired, fair-skinned, and freckled. There was marked tel- angiectasis between freckles. He had had two basal cell epitheliomas removed before we saw him. In July 1958, we excised three lesions, one anterior to the right ear, one from the right fore- head, and one from the right side of the chin. These too were basal cell epitheliomas. A lesion which was removed the following November, however, was diagnosed clinically and pathologically as kera- toacanthoma. There had been no exposure to sun- light or other irritants before this lesion appeared.
Case 2 (Fig. 7) • The patient, a 21-year-old man, was first seen in September 1955, when he was found to have verruca acuminata and hidradenitis suppurativa of the right groin. The verrucae were cauterized, and after an A.S.T. the hidradenitis re-
190 sponded to antibiotic agents and autogenous vac- cine. In March 1958 the patient returned for ex- amination of an indurated area on the lower right side of the abdomen, a change which he had first noticed 2 months before. There was no break in the dermis and no keratinization. The clinical im- pression was that of an infected sebaceous cyst. There was no capsule and the involved tissue seemed firm and unlike granulation. Treatment consisted of curette debridement followed by cau- tery; the lesion healed without further therapy. Histopathologic consultation resulted in a diagnosis of basal cell "pseudo-epitheliomatous hyperplasia," which corroborated the clinical findings. In Sep- Fig. 6. Aging keratoacanthoma beginning to show adherent tember 1958 the patient was again seen because type of scale. of a lesion on the right thigh. Clinically, the diag- nosis was keratoacanthoma, and this was confirmed contagiosum. Histopathologic examination of kera- by a histopathologist. Comparison with the patho- toacanthomatous tissue shows changes like those logical slides from the previous episode showed of Grade I (Broders) epidermoid carcinoma.9 no similarity between the lesions. Within a month, Histologic detail leads to the emergence of this four more keratoacanthomatous lesions appeared on relatively common entity from the diagnosis of the back of the thigh. Because the patient was a squamous cell epithelioma. Under the low-power student at a distant college, excision at that time objective, or preferably a scanning lens, the but- tress formation is at once apparent if the lesion is bisected in its greatest diameter. There is nothing diagnostic about this formation, but the appearance is responsible for one of the synonyms for kera- toacanthoma, molluscum sebaceum. The molluscum contagiosum possesses this configuration, but so also do many squamous epitheliomas. The forma- tion represents the smooth epidermis reflected back upon itself in response to the rapid proliferation of the cells composing the central plug. Under higher power, the central plug is seen to be made up of parakeratotic keratinocytes; epithelial hyper- plasia and increased mitotic activity are observed, Fig. 5. Keratoacanthoma in the posterior lateral cervical area but no hyperchromatism or differences in nucleus staining qualities which would indicate malignant change. The lack of hyperchromatism and varied was impractical. Podophyllin was applied once to staining qualities of the nucleus represent a uni- the lesions, and thereafter they remained static. formity in both chromosomal pattern and protein At the end of 3 months the lesions were slightly moiety of the nuclear structure. dome-shaped, with crusts resembling the top of a Occasional single-cell keratinization may be seen pepper shaker; after 3 more months, only small atrophic scars remained. Fig. 7. Case 2: (A) Scar left by a spontaneously healed kera- toacanthoma; (B) scar in an old area of hidradenitis suppura- Discussion tiva.
The pathogenesis of keratoacanthoma is unknown, although there seems to be a relationship to active irritation. The lesions are found predominantly on the exposed parts of the body, and they have been reported to occur after sunburn or exposure to heat. There are tumors produced by tar and arsenic which cannot be distinguished from keratoacan- thoma in either clinical or histopathologic examina- tion. Lesions resembling keratoacanthoma have been artificially induced in chicken skin. 13 Reports have been published concerning a viruslike agent" resembling that of molluscum contagiosum but one third as large.15 Indeed, if we were to select a skin lesion that might clinically most resemble kerato- acanthoma, it would be giant solitary molluscum
JOURNAL A.O.A., VOL. 61. NOV. 1961 191 in the central plug. One prickle cell may separate epithelioma which formerly was almost routinely itself from the neighboring cells and begin to kera- diagnosed as squamous cell carcinoma. Co ordina- tinize, or mature. It may appear like a foreign body tion of clinical and pathologic findings is needed in the basal-cell layer; the nucleus shrinks and to insure correct diagnosis and appropriate treat- eventually the whole process becomes fixed as an ment. The typical lesion is hemispheric, something cosinophilic body in the keratin, an epithelial pearl. less than 15 mm. wide, and marked by a central The inflammatory infiltrate consists of poly- keratin plug which is depressed at first but becomes morphs, monomorphs, and clusters of lymphocytes; elevated as the lesion grows. The lesions may be particularly lacking are the plasma cells and giant solitary or multiple, and may precede or follow cells which are a constant feature of epithelioma. other types of skin tumor. In 3 cases the authors This infiltrate, particularly the peripheral lympho- have seen keratoacanthoma followed by basal cell cytic clusters, may indicate the body's immunologic epithelioma; in another case, multiple keratoacan- response as well as the host's inflammatory reaction thoma appeared several years after verruca acumi- to the causative agent. nate and several months after basal cell pseudoepi- The keratoacanthoma is always an invasive re- thelioma. The cause is unknown, although there is action, as evidenced by the destruction of elastic evidence that a virus similar to that of molluscum fibers of the dermis. This is best seen with orcein- giemsa stain, 16 a stain with great affinity for elastic contagiosum may be involved; chemical or actinic fibers. The spontaneous resolution also results in irritation may be contributory. The diagnosis can scar formation, clinical verification of elastic-fiber be established only by histopathologic examination destruction. Here we have justification for early of excised tissue. A solitary lesion should be ex- and adequate removal of the lesion; that is, the cised, since there is a possibility that it may repre- prevention of an undesirable cosmetic feature that sent carcinoma. Multiple lesions may be treated by would result from destruction of tissue by this curet and cautery, after the diagnosis has been invasive lesion. established by examination of an adequate patho- Histologically, then, keratoacanthoma represents logic specimen. a tissue reaction tending to progress until the lesion is effectively sequestered by the immunologic de- 1. Fliegelman, M. T., and Loveman, A. B.: Tumor-like keratoses; fenses of the skin and of the body as a whole. Telma of case. A.M.A. Arch. Dermat. Syph. 66:353-357, Sept. 1952. For clinical purposes the lesion may be defined 2. De Moragas, T. M., Montgomery, H., and McDonald, J. R.: Keratoacanthoma v.rsos sallamous-cell carcinoma. A.M.A. Arch. as a benign self-healing pseudoepithelioma which Dermat. 77:390-395. April 1958. leaves a residual scar. Since the clinical appearance 3. New, W. M., and Horton, S. H.: Multiple acanthoma (tumor- like keratosis of Poth). A.M.A. Arch. Dermat. Syph. 68:475-478, is only suggestive, the solitary lesion should be Oct. 1953. excised whenever possible; there is always the 4. Andrews. G. C.: Diseases of skin. Ed. 4. W. B. Saunders Co., Philadelphia, 1954. possibility that it represents an early anaplastic 5. Sutton, R. L.: Diseases of skin. Ed. 11. C. V. Mosby Co., St. carcinoma. The clinician should bear in mind that Louis, 1956. 6. Poth, D. 0.: Tumor-like keratoses; report of case. Arch. Dermat. the pathologist must have adequate tissue for an Syph. 39:228-238, Feb. 1939. accurate diagnosis. From the standpoint of the 7. Smith, J. F.: Case of multiple primary squamous-celled carci- noma of skin in young man, with spontaneous healing. Brit. J. Dermat. patient, lesions should be removed as early as 46:267-272, June 1934. possible, to prevent or minimize scarring. In the 8. Jackson, R.: Keratoacanthoma (ed. comment). Canad. M. A. J. 80:5.51-552, April 1, 1959. case of multiple lesions, curettement and cautery 9. Bowman, H. E., and Pinkus, H.: Keratoacanthoma (Molluscum sebaceum). A.M.A. Arch Path. 60:19-25, Tuly 1955. suffice for treatment after an adequate pathologic 10. Ormsby, 0. S., and Montgomery, H.: Diseases of skin. Ed. 8. specimen has been obtained. Multiple lesions tend Lea Febiger, Philadelphia, 1954. 11. Epstein, N. N., Biskind, G. R., and Pollack, R. S.: Multiple toward gradual loss of the ability to heal. primary self-healing squamous cell "epitheliomas" of skin; general- Although differential diagnosis is highly impor- ized keratoacanthoma. A.M.A. Arch. Dermat. 75:210-223, Feb. 1957. 12. Puente Duany, N.: squamous cell pseudoepithelioma (kerato- tant in keratoacanthoma, the responsibility is not acanthoma). A.M.A. Arch. Dermat. 78:703-709, Dec. 1958. the clinician's alone, for if the lesion is suspected 13. Rigdon, R. H.: Keratoacanthoma (experimentally induced with methylcholanthrene in chicken). A.M.A. Arch. Dermat. 79:139-147, it is to be removed and the responsibility shared Feb. 1959. with a pathologist. 14. Zelickson, A. S., and Lynch, F. W.: Electron microscopy of virus-like particles in keratoacanthoma. J. Investigative Derm. 37:79- 83, Aug. 1961. 15. Ereaux, L. P., Schopflocher, P., and Fournier, C. J.: Kerato- Summary acanthomata. A.M.A. Arch. Dermat. 71:73-79, Jan. 1955. 16. Pinkus, H., and Hunter, R.: Simplified acid orcein and Giemsa technique for routine staining of skin sections. A.M.A. Arch. Dermat. Keratoacanthoma is a benign, self-limiting pseudo- 82:699-700, Nov. 1960.
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