> Table of Contents > Keratoacanthoma
Carl Bryce, MD, Capt, USAF
Matthew J. Snyder, DO
image BASICS
  • Rapidly proliferating, solitary, dome-shaped, erythematous or flesh-colored papule or nodule with a central keratinous plug, typically reaching 1 to 2 cm in diameter
  • Highly debated as to whether keratoacanthoma (KA) is a benign or malignant variant of squamous cell carcinoma (SCC). Majority are benign and resolve spontaneously, but lesions do have the potential for invasion and metastasis; therefore require treatment.
  • Three clinical stages of KAs (1):
    • Proliferative: rapid growth of the lesion over weeks to several months
    • Maturation/stabilization: Lesion stabilizes and growth subsides.
    • Involution: spontaneous resolution of the lesion, leaving a hypopigmented, depressed scar; most but not all lesions will enter this stage.
  • System(s) affected: integumentary
  • Greatest incidence over the age of 50 years but may occur at any age
  • Presentation increased during summer and early fall seasons
  • Most frequently on sun-exposed, hair-bearing skin but may occur anywhere
  • Predominant sex: male > female (2:1)
  • Most commonly in fair-skinned individuals; highest rates in Fitzpatrick I-III
  • 104 cases per 100,000 individuals
  • Derived from an abnormality causing hyperkeratosis within the follicular infundibulum
  • Squamous epithelial cells proliferate to extend upward around the keratin plug and proceed downward into the dermis; followed by invasion of elastic and collagen fibers
  • Cellular mechanism responsible for the hyperkeratosis is currently unknown; role of human papillomavirus has been discussed but has no established causality (2).
  • Regression may be due to immune cytotoxicity or terminal differentiation of keratinocytes.
  • Multiple etiologies have been suggested:
    • UV radiation
    • May be provoked by surgery, cryotherapy, chemical peels or laser therapy
    • Viral infections: human papillomavirus (HPV) or Merkel cell polyomavirus
    • Genetic predisposition: Muir-Torre syndrome, xeroderma pigmentosum, Ferguson-Smith syndrome
    • Immunosuppression
    • Chemical carcinogen exposure
  • Mutation of p53 or H-ras
  • Ferguson-Smith (AD)
  • Witten-Zak (AD)
  • Muir-Torre (AD)
  • Xeroderma pigmentosum (AR)
  • Gzybowski (sporadic)
  • Incontinentia pigmenti (XLD)
  • UV exposure/damage: outdoor and/or indoor tanning
  • Fitzpatrick skin type I-III
  • Trauma (typically appears within 1 month of injury): laser resurfacing, surgery, cryotherapy, tattoos
  • Chemical carcinogens: tar, pitch, and smoking
  • Immunocompromised state
  • Discoid lupus erythematosus
Sun protection
  • Frequently, the patient has concurrent sun-damaged skin: solar elastosis, solar lentigines, actinic keratosis, nonmelanoma skin cancers (basal cell carcinoma, SCC)
  • In Muir-Torre syndrome, KAs are found with coexisting sebaceous neoplasms and malignancy of the GI and GU tracts.
  • Firm, solitary, erythematous or flesh-colored, domeshaped papule or nodule with a central keratin plug, giving a crateriform appearance
  • Surrounding skin and borders of lesion may show telangiectasia, atrophy, or dyspigmentation.
  • Solitary; although multiple lesions can occur.
  • Most commonly seen on sun-exposed areas: face, neck, scalp, dorsum of upper extremities, and posterior legs
  • May also be seen on areas without sun exposure: buttocks, anus, subungual, mucosal surfaces
  • Subungual KAs are very painful and seen on the first 3 digits of the hands.
  • Examine for regional lymphadenopathy due to chance of lesion invasion and metastasis.
  • Dermoscopy (3)[B]
    • Central keratin
    • White circles, blood spots
    • Cannot reliably distinguish between AK and SCC
  • SCC
  • Nodular or ulcerative basal cell carcinoma
  • Cutaneous horn
  • Hypertrophic actinic keratosis
  • Amelanotic melanoma
  • Merkel cell carcinoma
  • Metastasis to the skin
  • Molluscum contagiosum
  • Prurigo nodularis
  • Verruca vulgaris
  • Verrucous carcinoma
  • Sebaceous adenoma
  • Hypertrophic lichen planus
  • Hypertrophic lupus erythematosus
  • Deep fungal infection
  • Atypical mycobacterial infection
  • Nodular Kaposi sarcoma
  • Excisional biopsy including the center of the lesion as well as the margin is the best diagnostic test (2)[C].
  • A shave biopsy may be insufficiently deep to distinguish KA from an SCC.
  • If unable to perform an excisional biopsy, a deep shave (saucerization) of the entire lesion, extending into the subcutaneous fat, can be done.
  • Punch biopsies should be avoided because they give an insufficient amount of tissue to represent the entire lesion.
Initial Tests (lab, imaging)
  • Subungual KA: radiograph of the digit to monitor for osteolysis (cup-shaped radiolucent defect)
  • Aggressive tumors may need CT with contrast for evaluation of lymph nodes and MRI if there is concern of perineural invasion.
  • Most lesions do not need any form of imaging.
Test Interpretation
  • Pathology of biopsy: a well-demarcated central core of keratin surrounded by well-differentiated, mildly pleomorphic, atypical squamous epithelial cells with a characteristic glassy eosinophilic cytoplasm
  • May see elastic and collagen fibers invading into the squamous epithelium
  • P.577

  • Histologic differentiation of a KA from an SCC may be difficult and unreliable, although immunochemical staining for cellular protein Ki-67 may help do this (4).
  • KAs have a greater tendency than SCC to display fibrosis and intraepidermal abscesses of neutrophils and eosinophils.
  • Regressing KA shows flattening and fibrosis at base of lesion.
  • Treatment of choice is an excisional procedure plus electrodessication and curettage; however, there are many treatment options available (2)[C].
  • Aggressive tumors (>2 cm) or lesions in cosmetically sensitive areas (face, digits, genitalia) that require tissue sparing, consider Mohs micrographic surgery
    • Mohs is the treatment of choice in cases with perineural or perivascular invasion.
  • Small lesions (<2 cm) of the extremities may undergo electrodessication and curettage.
  • Immunocompromised patients should receive immediate surgical treatment.
  • Nonsurgical management is a viable and relatively cost-effective option in these select cases not amenable to surgery due to lesion number, size, or location; also for patients with multiple comorbidities who are unwilling or unable to withstand surgery
  • Evidence for the following treatments based on case reports and retrospective reviews:
    • Intralesional methotrexate 12.5 to 25 mg in 0.5 mL normal saline every 2 to 3 weeks for one to four treatment sessions (5)[B]
      • Monitor for pancytopenia with complete blood count (5)[C].
    • 5% Imiquimod cream 3 times per week for 11 to 13 weeks (5)[B]
    • Topical 5% 5-fluorouracil cream daily, 61-92% cure rate (5)[B]
    • Intralesional 5-fluorouracil of 50 mg/mL on a weekly basis for three to eight treatment sessions—98% cure rate (5)[B]
    • Intralesional IFN a-2a or a-2b (83%, 100% cure rate, respectively) (5)[B]
    • Intralesional bleomycin—100% cure rate (5)[B]
    • Isotretinoin oral 0.5 to 1 mg/kg/day
Dermatology referral if lesions are >2 cm, numerous, mucosal, or subungual
  • Photodynamic therapy with methyl aminolevulinic acid and red light, successful case reports (6)[B] but also reported aggravation following treatment
  • Cryotherapy
  • Argon or YAG lasers
  • Radiotherapy, primary or adjuvant: KAs may regress with low doses of radiation but may require doses up to 25 to 50 Gy in low-dose (5 to 10 Gy) fractions for possible SCC (7)[B].
  • Erlotinib (EGFR inhibitor) 150 mg daily for 21 days, single case report (8)[B]
Excisional and office-based procedures as discussed above.
After the surgical site has healed or lesion has resolved, patient should be seen every 6 months due to increased risk of developing new lesions or skin cancers, annually at minimum (3)[C].
Patient Monitoring
  • Skin self-exams should be routinely performed with detailed instructions (see “Additional Reading”).
  • If multiple KAs are present in patient or family members, evaluate for Muir-Torre syndrome and obtain a colonoscopy beginning at age 25 years, as well as testing for genitourinary cancer (3)[C].
  • Sun protection measures: sun block with SPF >30, wide-brimmed hats, long sleeves, dark clothing, avoiding indoor tanning
  • Arc welding may produce harmful UV radiation and skin should not be exposed.
  • Tar, pitch, and smoking should be avoided.
  • Atrophic scarring and hypopigmentation can occur with self-resolution but may be significantly reduced by intervention.
  • 52 of 445 cases (12%) spontaneously regressed without treatment and none of these recurred (2).
  • 393 (88%) regressed following medical or excisional treatment (2).
  • 445 cases reported with no metastases or deaths attributable to the KA (2).
  • 4-8% recurrence
  • Mucosal and subungual lesions do not regress, must undergo treatment
1. Zalaudek I, Bonifazi E, Ferrara G, et al. Keratoacanthomas and spitz tumors: are they both “self-limiting” variants of malignant cutaneous neoplasms? Dermatology. 2009;219(1):3-6.
2. Savage JA, Maize JC Sr. Keratoacanthoma clinical behavior: a systematic review. Am J Dermatopathol. 2014;36(5):422-429.
3. Rosendahl C, Cameron A, Argenziano G, et al. Dermoscopy of squamous cell carcinoma and keratoacanthoma. Arch Dermatol. 2012;148(12):1386-1392.
4. Scola N, Segert HM, Stücker M, et al. Ki-67 may be useful in differentiating between keratoacanthoma and cutaneous squamous cell carcinoma. Clin Exp Dermatol. 2014;39(2):216-238.
5. Chitwood KL, Etzkorn J, Cohen G. Topical and intralesional treatment of nonmelanoma skin cancer: efficacy and cost comparisons. Dermatol Surg. 2013;39(9):1306-1316.
6. Jeon HC, Choi M, Paik SH, et al. Treatment of keratoacanthoma with 5% imiquimod cream and review of the previous report. Ann Dermatol. 2011;23(3):357-361.
7. Bruscino N, Corradini D, Campolmi P, et al. Superficial radiotherapy for multiple keratoacanthomas. Dermatol Ther. 2014;27(3):163-167.
8. Reid DC, Guitart J, Agulnik M, et al. Treatment of multiple keratoacanthomas with erlotinib. Int J Clin Oncol. 2010;15(4):413-415.
Additional Reading
  • The American Academy of Dermatology: https://www.aad.org/spot-skin-cancer/learn-about-skin-cancer/types-of-skin-cancer
  • The Skin Cancer Foundation: http://www.skincancer.org/
See Also
Squamous Cell Carcinoma, Cutaneous
  • D23.9 Other benign neoplasm of skin, unspecified
  • D48.5 Neoplasm of uncertain behavior of skin
  • L85.8 Other specified epidermal thickening
Clinical Pearls
  • Suspect KA with a solitary, dome-shaped, erythematous or flesh-colored papule or nodule with a central keratinous plug.
  • If KA is in the differential diagnosis, elicit time frame of onset during patient encounter; rapid onset supports diagnosis.
  • Due to the broad differential diagnosis of a suspected KA and unreliable clinical differentiation between these, strongly consider surgical excision as first-line diagnostic test and therapy.
  • Medical and radiation therapies are reasonable and effective options available for patients who are not surgical candidates or for lesions that are not amenable for surgery.