KAs are well-differentiated, squamous cell carcinomas with potential for metastasis (7
). Therefore, it is important to treat these tumours. There have been many treatment options for KAs including surgical excision, radiation and MTX.
A study (12
) performed in Caucasians in the United States estimated the incidence of KAs at 104 cases/100,000 individuals. Peak incidence occurs in individuals 70 years of age or older. KAs are uncommon in dark-skinned individuals. In our practice, there seems to be an increasing number of patients between 30 and 69 years of age presenting with KAs. One factor for this increase within the younger age groups may be due to a potential relationship of KAs with the human papilloma virus (HPV). One study (13
) tested for HPV DNA in patients with KA biopsies using polymerase chain reaction. It was found that 37 of 72 (51%) patients with KAs were HPV DNA positive (13
The present retrospective study showed that using intralesional MTX after debulking the KA had an 88.9% resolution rate. Eight of nine patients had complete resolution after one to four injections. Each injection ranged from 12.5 mg to 25 mg of MTX. One patient initially responded after two injections. However, after the third MTX injection, there was no improvement in the lesion. At this time, a biopsy confirmed KA, and surgical excision was performed without delay.
Although it has been reported in the literature (7
) that pancytopenia related to MTX can occur, none of the patients in the present study experienced adverse effects from the treatment. One patient complained of pain at the site after the MTX injection; the pain lasted for approximately one week. The average follow-up period of the present study was 2.8 years.
The results of the study were consistent with previous studies using intralesional MTX for the treatment of KA. Intralesional MTX for the treatment of KA was first described in 1991 (10
). Nine patients with solitary KA, whose lesions resolved completely after one to two injections with a total dose ranging from 5 mg to 50 mg within two to four weeks, were reported. Subsequently, multiple case reports (6
) have confirmed successful resolution of KAs following intralesional injection of MTX.
In 2007, Annest et al (7
) published a series of KA cases treated with intralesional MTX using cases from their institution and those in the literature. MTX achieved resolution in 92% of cases, with an average of 2.1 injections for an average of 18 days. Limitations of the study included a short follow-up period, with an average of only 1.8 years. Furthermore, the initial diagnosis of KA in some of the patients in that study was not confirmed by histological studies. Third, the 92% resolution rate included the data from their institution and single case reports that were cited in the literature, thus including a favourable reporting bias (7
Our study was unique in that all the patients underwent a histological biopsy, which confirmed the diagnosis. Also, the treatment protocol used by our institution varied from previous studies in that all of the tumours were debulked during the first office visit with a shave, using a No. 10 blade scalpel. Once the tumour was debulked, at the same setting, MTX was injected at the base. This was performed with the hypothesis that by debulking the tumour, the MTX would be more effective. The procedures were all performed in the office. The initial shave required a local anesthetic. All subsequent injections were performed without the use of local anesthesia.
There are many advantages of using intralesional MTX for the treatment of KAs after a shave debulking. Intralesional MTX is inexpensive and noninvasive, and cosmetic outcomes are very satisfactory compared with surgical excision. Additionally, no hospitalization or general anesthesia is required. The cost of a 2 mL vial (25 mg/mL) of MTX when purchased in bulk is US$10. Each vial can be used multiple times.
We propose that intralesional MTX injection with initial debulking of the KA should be used as a first line of treatment when KAs are present on the extremities, on cosmetically sensitive areas and in elderly patients with multiple comorbities. These patients should first undergo a biopsy to confirm that the lesion is a KA. We recommend an initial injection of 0.5 mL of methotrexate (25 mg/mL) with 0.5 mL of sterile saline. Subsequent weekly injections can range from 0.5 mL to 1 mL of MTX (25 mg/mL) plus 0.5 mL of sterile saline, depending on the response. Patients should also be followed very closely with weekly visits. If there is any indication that the lesion is not responding to the MTX or there is residual tumour, patients should undergo surgical excision without any delay. Contraindications for intralesional MTX include pregnancy or breastfeeding, and individuals with active infection, blood dyscrasias, drug interactions, hepatic disease or renal disease (14