eMedicine Specialties > Dermatology > Malignant Neoplasms
Keratoacanthoma: Treatment & Medication
Updated: Mar 11, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Treatment of keratoacanthoma 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 (MTX), 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.8,16 A 2007 review of the use of intralesional injection of MTX on 38 patients, including 18 of the researchers' patients, showed a 92% clinical "resolution" rate; however, patients needed an average of 2.1 injections to achieve it. Only 13% (5 patients) obtained histological confirmation.17 Both topical imiquimod and 5-fluorouracil have been used with anecdotal success.18
Note much of the literature concerning medical intervention for keratoacanthoma 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 keratoacanthoma 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 keratoacanthoma 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 keratoacanthoma cannot be predicted, many consider surgical treatment of keratoacanthoma to be equivalent to treatment for SCC.
- Mohs micrographic surgery may be indicated for large or recurrent keratoacanthomas or keratoacanthomas located in anatomic areas with cosmetic or functional considerations.
- Keratoacanthomas 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 keratoacanthomas, in keratoacanthomas found in difficult to treat locations, and as an adjunct to surgical removal.
Consultations
Dermatologist: Consult to exclude invasive SCC.
Medication
Although primary consideration of treatment is surgical, in patients with clear-cut and multiple keratoacanthomas, a number of medical alternatives have been used with success.
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 MTX, interferon alfa-2a,19 and bleomycin) also have been used with some success in treating keratoacanthomas. 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.
Methotrexate (Folex, Rheumatrex)
Antimetabolite that inhibits DNA synthesis and cell reproduction in malignant cells. May suppress immune system. Satisfactory response seen within 3-6 wk following administration.
Marked response noticed after 2 injections (1 study).
Adult
0.4-1.5 mL of 12.5 mg/mL injected intralesionally q2wk
Pediatric
Not established
Oral aminoglycosides may decrease absorption and blood levels of concurrent oral MTX; charcoal lowers MTX levels; coadministration with other potentially hepatotoxic medications (eg, retinoids) may increase hepatotoxicity of MTX; folic acid or its derivatives contained in some vitamins may decrease response to MTX; coadministration with NSAIDs may be fatal; indomethacin and phenylbutazone can increase MTX plasma levels; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity of MTX; may increase plasma levels of thiopurines
Documented hypersensitivity; alcoholism; hepatic insufficiency; immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency; pregnancy or breastfeeding
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Excreted mainly via kidney; monitor CBC counts monthly, and liver and renal function q1-3mo during therapy (monitor more frequently during initial dosing, dose adjustments, or when risk of elevated MTX levels, eg, dehydration); MTX has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if significant drop in blood counts; aspirin, NSAIDs, or low dose steroids may be administered concomitantly with MTX (possibility of increased toxicity with NSAIDs including salicylates has not been tested); may cause mucositis or cutaneous ulceration
Fluorouracil (Efudex, Adrucil, Fluoroplex)
Fluorinated pyrimidine antimetabolite that inhibits thymidylate synthase (TS) and also interferes with RNA synthesis and function. Has some effect on DNA. Useful in symptom palliation for patients with progressive disease.
Adult
0.1 mL of 5% sol injected intralesionally qd into keratoacanthoma base and at 4 peripheral quadrants for 2 wk (1 study) or 0.1-0.3 mL (of 50 mg/mL sol) injected circumferentially and 0.1-0.2 mL (of 50 mg/mL sol) injected sublesionally qwk for 3 wk (second study)
Pediatric
Administer as in adults
Increased risk of bleeding with anticoagulants, NSAIDs, platelet inhibitors, thrombolytic agents; enhanced bone marrow toxicity with other immunosuppressive agents; may increase risk of infection by live vaccine; cimetidine may increase toxicity; thiazide diuretics may increase myelosuppressive effects of antineoplastic agents; increased risk of phenytoin toxicity exists with concomitant use; therapeutic efficacy may be enhanced by leucovorin coadministration; addition of cyclophosphamide, MTX, and fluorouracil to tamoxifen may increase risk of thromboembolic events in postmenopausal women being treated for breast cancer
Documented hypersensitivity; poor nutritional state, bone marrow suppression, pregnancy, severe renal function impairment, hepatic function impairment, chicken pox or herpes zoster, potentially serious infections; dihydropyrimidine dehydrogenase enzyme deficiency (topical route)
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Carcinogenic, mutagenic; monitor mouth for ulceration; monitor CBC counts; monitor for GI ulceration and bleeding; inflammatory reactions may occur with occlusive dressings; porous gauze dressing may be applied for cosmetic reasons without increase in reaction; caution in metastases involving bone marrow; caution if previous high-dose pelvic irradiation administered or previous treatment with alkylating agents; caution in renal or hepatic impairment; use proper procedures for handling and disposal of chemotherapy
Bleomycin (Blenoxane)
Glycopeptide antibiotic that inhibits DNA synthesis.
Concentration usually is 1 mg/mL and diluted further with local anesthetic.
Adult
0.2-0.4 mg as single intralesional injection (case reports) or 0.2 mg qwk for 4 wk (other reports)
Pediatric
Not established
May decrease plasma levels of digoxin and phenytoin; cisplatin may increase toxicity of bleomycin; increases risk of infection with live vaccine
Documented hypersensitivity; significant renal function impairment; compromised pulmonary function; pregnancy or breastfeeding
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in renal impairment; possibly secreted in breast milk; may cause mutagenesis and pulmonary toxicity (10%); idiosyncratic reactions similar to anaphylaxis (1%) may occur; monitor for adverse effects during and after treatment; vaso-occlusive phenomenon with distal necrosis of digit; permanent damage to nail matrix may occur; pain with injection, local urticaria, tissue necrosis, and Raynaud phenomenon may occur; bleomycin can cause decrease in platelets, hemorrhagic cystitis, and thrombotic microangiopathy; caution in coronary artery disease, myocardial infarction, arterial thrombosis, and cerebrovascular accidents; flagellate pigmentation (a typical form of localized skin hyperpigmentation) occurs in 8-38% of patients
Retinoids
Efficacious in treatment of keratoacanthomas with good cosmetic outcome.20 Decrease sebaceous gland size and sebum production. May inhibit sebaceous gland differentiation and abnormal keratinization.
Isotretinoin (Accutane)
Oral agent that treats serious dermatologic conditions. Synthetic 13-cis isomer of naturally occurring tretinoin (trans-retinoic acid). Both agents are structurally related to vitamin A.
FDA–mandated registry now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information, see iPLEDGE. Registry aims to further decrease risks of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.
Adult
20 mg PO qd; can increase to 80 mg PO qd if tolerated and lab results allow
Pediatric
Not recommended
Toxicity may occur with vitamin A coadministration or excessive alcohol intake; pseudotumor cerebri or papilledema may occur when coadministered with tetracyclines; may reduce plasma levels of carbamazepine
Documented hypersensitivity; pregnancy; significant liver disease
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Monitor CBC counts, blood sugar in patients with diabetes, triglycerides, hepatic function, and pregnancy in women of childbearing age; adverse effects include teratogenicity, hepatotoxicity, hypertriglyceridemia, hyperostosis, pseudotumor cerebri; may decrease night vision; may be associated with development of hepatitis; occasional exaggerated healing response of acne lesions (excessive granulation with crusting) may occur; patients with diabetes may experience problems in controlling blood sugar; avoid exposure to UV light or sunlight until tolerance achieved
More on Keratoacanthoma |
| Overview: Keratoacanthoma |
| Differential Diagnoses & Workup: Keratoacanthoma |
 Treatment & Medication: Keratoacanthoma |
| Follow-up: Keratoacanthoma |
| Multimedia: Keratoacanthoma |
| References |
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References
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Annest NM, VanBeek MJ, Arpey CJ, Whitaker DC. Intralesional methotrexate treatment for keratoacanthoma tumors: a retrospective study and review of the literature. J Am Acad Dermatol. Jun 2007;56(6):989-93. [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].
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].
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Further Reading
Keywords
keratoacanthoma, KA, squamous cell carcinoma, SCC, invasive SCC, invasive squamous cell carcinoma, squamous cell cancer, skin cancer, skin malignancy, pilosebaceous gland cancer, pilosebaceous glands
