Effect of Field Treatment of Actinic Keratosis With Ingenol Mebutate Gel on the Identification of Lesions for Biopsy

August 2015 | Volume 14 | Issue 8 | Original Article | 813 | Copyright © August 2015

Miriam S. Bettencourt MD

Advanced Dermatology and Cosmetic Surgery, Henderson, NV
University of Nevada, Las Vegas, NV

Actinic keratoses (AKs) are premalignant skin lesions caused by cumulative ultraviolet-light exposure that may progress to invasive squamous cell carcinoma (SCC). As the clinical presentation of AKs varies widely, only a histopathologic analysis of a biopsied sample can eliminate or confirm a diagnosis of invasive SCC. Reducing the burden of AK with a combination of lesion-directed and field-directed treatments may help to identify persistent, suspicious lesions that require further evaluation. We present 10 cases of SCC that were identified and histologically confirmed in 7 patients after complete or substantial clearance of AKs by sequential treatment of sun-damaged skin with cryosurgery and ingenol mebutate.

J Drugs Dermatol. 2015;14(8):813-818.


Actinic keratoses (AKs) are common epidermal lesions that usually manifest clinically as red, brown, or skin-colored, rough papules or plaques on sun-exposed skin sites.1,2 The presence of multiple AKs is associated with an increased risk for nonmelanoma skin cancer (NMSC), particularly squamous cell carcinoma (SCC).3 In the later stages, AKs can enlarge and become thick, hyperkeratotic lesions and, ultimately, invasive SCC.2 Reports estimate that the majority of SCCs originate from contiguous or concomitant AKs.4-7 The clinical presentation of AK is highly variable, and although certain signs in the lesions (related to size, induration, and bleeding) may suggest more invasive disease, only histopathologic analysis of a biopsied sample can confirm the diagnosis.8,9 In patients with extensive actinic disease, AK lesions may be numerous and present in contiguous widespread masses, which increases the difficulty of clinical characterization of lesions.8
Algorithms recommend use of a combination of both lesion- and field-directed therapies to treat multiple AKs in a small area.10,11 This strategy can reduce the burden of actinic damage and may make apparent persistent lesions that may warrant biopsy and histopathologic examination to confirm or eliminate a diagnosis of SCC. A study that used laser-mediated photodynamic therapy to treat patients (n=36) with many AKs (mean number, 98 lesions), followed by analysis of nonresponsive lesions, showed that the majority of lesions were non-AK neoplasms, including SCCs.12
A Phase 3 study of ingenol mebutate gel, 0.015%, used sequentially after cryosurgery demonstrated good tolerability and sustained clearance of AKs on the face and scalp that was superior to the clearance rate with cryosurgery alone.13,14 In our dermatology clinic, many of the patients with a long history of AK who were treated with ingenol mebutate used sequentially after cryosurgery have achieved complete or partial clearance of AK.15 In this report, we describe the identification of 10 suspicious lesions in 7 patients after substantial or complete clearance of AK following sequential treatment with cryosurgery and topical application of ingenol mebutate. Histopathologic evaluation of 10 biopsied samples from suspicious lesions in 7 patients confirmed the diagnosis of invasive SCC.


All information was obtained by retrospective patient chart review. Data on patient demographics, skin cancer history, history of AK, and past AK treatments were collected. Information on sequential treatment with cryosurgery and ingenol mebutate, including location of the treatment area, severity of local skin reactions, clearance of AK, and follow-up assessments, was summarized. For suspicious lesions, characteristics and location were described, as well as any information available on the tumor and the results of Mohs micrographic surgery (MMS) treatment.


Summary of Patient Cases

Between August 2012 and October 2013, 10 persistent, suspicious lesions were identified in 7 patients, 6 men and 1 woman. Median age of the patients was 70 years (range, 61-78 years). AK history was >10 years in 6 patients and >1 year in 1 patient. All 7 patients had a history of recurrent and hyperkeratotic AKs and prior treatment with cryosurgery. Two of the 7 patients also had a history of treatment with diclofenac gel and imiquimod