AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Keratoacanthoma (KA) is a relatively common low-grade malignancy that originates in the pilosebaceous glands and closely and pathologically resembles squamous cell carcinoma (SCC). In fact, strong arguments support classifying KA as a variant of invasive SCC. KA is characterized by rapid growth over a few weeks to months, followed by spontaneous resolution over 4-6 months in most cases. KA reportedly progresses, although rarely, to invasive or metastatic carcinoma; therefore, aggressive surgical treatment often is advocated. Whether these cases were SCC or KA, the reports highlight the difficulty of distinctly classifying individual cases.

Pathophysiology

Both sunlight and chemical carcinogens have been implicated as pathologic factors in growth of the tumor. Trauma, human papilloma virus, genetic factors, and immunocompromised status also have been implicated as etiologic factors.

Frequency

United States

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.

International

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.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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 (see Images 1-4).
• 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. See Human Papillomavirus.
• 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.

DIFFERENTIALS

Section 4 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Eruptive keratoacanthoma of Grzybowski: Generalized distribution of multiple KAs that typically do not involute.

Multiple Ferguson-Smith keratoacanthoma: Rare autosomal dominant self-healing type of KA, with lesions arising in early adulthood.

Internal malignancy

Muir-Torre syndrome: KA may be a component of Muir-Torre syndrome, which is a cancer-associated genodermatosis with multiple sebaceous neoplasms (adenomas, epitheliomas, carcinomas), keratoacanthomas, and gastrointestinal malignancies (most commonly colon), although other carcinomas have been reported (genitourinary, pulmonary, endometrial).

When Muir-Torre syndrome is diagnosed, an age-appropriate cancer screening workup is indicated. An approximately equal number of internal malignancies are diagnosed before and after the cutaneous neoplasm. These internal malignancies tend to be low grade, but early diagnosis is important. Colonoscopy, rather than flexible sigmoidoscopy, is recommended, since the colon cancer frequently is found in the right ascending colon, proximal to the hepatic flexure.

WORKUP

Section 5 of 11  

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• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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.

Histologic Findings

KAs are composed of singularly well-differentiated squamous epithelium that show only a mild degree of pleomorphism and likely form masses of keratin that constitute the central core of KA.

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.

TREATMENT

Section 6 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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.

Consultations

Dermatologist: Consult to exclude invasive SCC.

MEDICATION

Section 7 of 11  

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• Differentials
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• Follow-up
• Miscellaneous
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• References

Although primary consideration of treatment is surgical, in patients with clear-cut and multiple KAs, a number of medical alternatives have been used with success.

Drug Category: Antineoplastic agents

Useful in patients with large or multiple tumors or tumors that are inoperable because of anatomic location or the patient's poor medical status. Agents (eg, topical 5-fluorouracil, intralesional methotrexate, interferon alfa-2a, and bleomycin) also have been used with some success in treating KAs. When small amounts of medication are administered, the interactions and precautions listed below are less restrictive than when systemic doses are administered. As a rule, if after 4 wk the lesion has not responded fully to medical therapy, surgical removal is indicated.

Drug Category: Retinoids

Efficacious in treatment of KAs with good cosmetic outcome.

Decrease sebaceous gland size and sebum production. May inhibit sebaceous gland differentiation and abnormal keratinization.

FOLLOW-UP

Section 8 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Outpatient Care

• Patients who develop nonmelanoma skin cancer, such as KA, SCC, BD, or basal cell carcinoma, are at high risk for developing subsequent nonmelanoma skin cancer. Education, periodic follow-up examinations, and early detection and treatment of actinic keratosis and skin cancer are important in these patients.

Prognosis

• Prognosis is excellent following excisional surgery.
• Recurrent tumors may require more aggressive therapy.
• Follow patients with a history of KA for development of new primary skin cancers (SCC in particular).

Patient Education

• Educate patients about prevention (including sunscreen), sun-protection techniques, and skin self-examination.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to diagnose KA can result in substantial morbidity and, occasionally, mortality. Since both metastatic disease and local destruction have been reported with KA, accurate diagnosis is critical. Physicians diagnosing and/or treating KA are held legally responsible for actions (or actions not taken) that fall outside of the standard of care.
• Failure to treat KA appropriately may result in unacceptably high levels of recurrence and metastasis, or in other cases, may result in an unfavorable risk-to-benefit ratio. Since over or under treating KA can have untoward effects, physicians treating KA bear the liability for selecting and performing the appropriate level of treatment.
• Failure to educate patients about prevention, self-examination, and the nature of the tumor may result ultimately in an unacceptable level of morbidity and mortality. Since KA is a strong risk factor for future occurrences of nonmelanoma skin cancer and may be a marker for internal malignancy in the context of some syndromes, appropriate education and follow-up must be performed.

Special Concerns

• Be sure to rule out SCC.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Keratoacanthoma (squamous cell carcinoma-keratoacanthoma or SCC-KA type) on inner canthus.
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Media file 2:  Keratoacanthoma of the left forehead.
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Media file 3:  Close-up view of the keratoacanthoma lesion seen in Image 2.
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Media file 4:  Keratoacanthoma lesion (squamous cell carcinoma-keratoacanthoma or SCC-KA type).
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Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Canas GC, Robson KJ, Arpey CJ. Persistent keratoacanthoma: challenges in management. Dermatol Surg. Dec 1998;24(12):1364-9. [Medline].
• Chuang TY, Reizner GT, Elpern DJ, et al. Keratoacanthoma in Kauai, Hawaii. The first documented incidence in a defined population. Arch Dermatol. Mar 1993;129(3):317-9. [Medline].
• Chuang TY, Reizner GT, Elpern DJ, et al. Non-melanoma skin cancer and keratoacanthoma in Filipinos: an incidence report from Kauai, Hawaii. Int J Dermatol. Oct 1993;32(10):717-8. [Medline].
• Clausen OP, Beigi M, Bolund L, et al. Keratoacanthomas frequently show chromosomal aberrations as assessed by comparative genomic hybridization. J Invest Dermatol. Dec 2002;119(6):1367-72. [Medline].
• Dendorfer M, Oppel T, Wollenberg A, Prinz JC. Topical treatment with imiquimod may induce regression of facial keratoacanthoma. Eur J Dermatol. Jan-Feb 2003;13(1):80-2. [Medline].
• Fitzpatrick T, Eisen A, Wolff K, et al, eds. Keratoacanthoma. In: Dermatology in General Medicine. 4th ed. New York, NY:. McGraw-Hill;1993:848-855.
• Frank TL, Maguire HC Jr, Greenbaum SS. Multiple painful keratoacanthomas. Int J Dermatol. Sep 1996;35(9):648-50. [Medline].
• Grob JJ, Suzini F, Richard MA, et al. Large keratoacanthomas treated with intralesional interferon alfa-2a. J Am Acad Dermatol. Aug 1993;29(2 Pt 1):237-41. [Medline].
• Hsi ED, Svoboda-Newman SM, Stern RA, et al. Detection of human papillomavirus DNA in keratoacanthomas by polymerase chain reaction. Am J Dermatopathol. Feb 1997;19(1):10-5. [Medline].
• Kim DK, Kim JY, Kim HT, et al. A specific chromosome aberration in a keratoacanthoma. Cancer Genet Cytogenet. Apr 1 2003;142(1):70-2. [Medline].
• Letzel S, Drexler H. Occupationally related tumors in tar refinery workers. J Am Acad Dermatol. Nov 1998;39(5 Pt 1):712-20. [Medline].
• Lu S, Syrjanen SL, Havu VK, Syrjanen S. Known HPV types have no association with keratoacanthomas. Arch Dermatol Res. Mar 1996;288(3):129-32. [Medline].
• Manstein CH, Frauenhoffer CJ, Besden JE. Keratoacanthoma: is it a real entity?. Ann Plast Surg. May 1998;40(5):469-72. [Medline].
• Meffert JJ. Cutaneous sporotrichosis presenting as a keratoacanthoma. Cutis. Jul 1998;62(1):37-9. [Medline].
• Miot HA, Miot LD, da Costa AL, et al. Association between solitary keratoacanthoma and cigarette smoking: a case-control study. Dermatol Online J. 2006;12(2):2. [Medline].
• Reizner GT, Chuang TY, Elpern DJ, et al. Keratoacanthoma in Japanese Hawaiians in Kauai, Hawaii. Int J Dermatol. Dec 1995;34(12):851-3. [Medline].
• Reizner GT, Chuang TY, Elpern DJ, et al. Basal cell carcinoma and keratoacanthoma in Hawaiians: an incidence report. J Am Acad Dermatol. Nov 1993;29(5 Pt 1):780-2. [Medline].
• Sanders S, Busam KJ, Halpern AC, Nehal KS. Intralesional corticosteroid treatment of multiple eruptive keratoacanthomas: case report and review of a controversial therapy. Dermatol Surg. Oct 2002;28(10):954-8. [Medline].
• Sayama S, Tagami H. Treatment of keratoacanthoma with intralesional bleomycin. Br J Dermatol. Oct 1983;109(4):449-52. [Medline].
• Schwartz RA. Keratoacanthoma. J Am Acad Dermatol. Jan 1994;30(1):1-19; quiz 20-2. [Medline].

Article Last Updated: Mar 29, 2007