Imiquimod in the treatment of lentigo maligna

BACKGROUND: Lentigo maligna (LM) is treated to prevent progression to lentigo maligna melanoma (LMM). Surgery remains the treatment of choice, although topical immunotherapy with imiquimod has recently become a popular alternative. OBJECTIVES: In this review, we have analysed the published literature relating to the use of imiquimod for LM, in order to understand better the utility of this treatment. METHODS: All English language studies relating to the use of imiquimod for LM were analysed up to January 2006. RESULTS: Eleven case reports and four open-label studies were identified, comprising a total of 67 patients who completed treatment with imiquimod for LM. There was significant variability in treatment schedules and regimens. Eight patients failed to respond, with LMM developing in two of these. In certain cases there were discrepancies between clinical and histological response with some patients clearing clinically but not histologically, and vice versa. Follow-up periods were short, exceeding 12 months in only five cases. CONCLUSIONS: Although imiquimod clearly has an effect on LM, this analysis of available studies has helped to identify concerns about its use. Without controlled evidence and prolonged follow up, the use of imiquimod for LM must still be considered experimental.     

Immunocryosurgery as monotherapy for lentigo maligna or combined with surgical excision for lentigo maligna melanoma

The incidence of lentigo maligna (LM), in situ (LM) or invasive (lentigo maligna melanoma, LMM), has increased during the last decades. Due to functional or cosmetic outcomes, optimal treatment with surgical excision may not be appropriate in some cases. We tried less invasive therapy, immunocryosurgery, as a single treatment for LM or combined with surgery for LMM, with better aesthetic results. Three patients with LM or LMM not amenable to complete surgical excision were selected. LMM patients underwent limited surgical resection of the invasive area. Subsequently, a combined treatment with topical imiquimod and cryosurgery was performed. The LM patient received immunocryosurgery directly. All of them were free of local and systemic disease at 48, 42 and 41 months after discontinuation of therapy. We consider that immunocryosurgery is an alternative option for LM or even for LMM (after removal of the invasive tissue with narrow margins) in poor surgical candidates, with good therapeutic, functional and cosmetic results.     

A pilot study of clinical efficacy of imiquimod and cryotherapy for the treatment of basal cell carcinoma with incomplete response to imiquimod

Background Cryotherapy is a physical procedure whose immunogenic capability enables it to destroy tumour cells, at least partially. Consequently, it can boost the effect of imiquimod. Objective The objective of the present study was to evaluate the efficacy of combining cryotherapy and imiquimod in patients who did not achieve a complete response after treatment of basal cell carcinoma with imiquimod. The study sample comprised 22 patients with 23 basal cell carcinomas. The tumours were treated with liquid nitrogen (one cycle, 20–30 s) before application of imiquimod (five times weekly for 6 weeks). Results A maintained complete clinical response was observed in 19 of the 23 tumours (83%), a partial response in three and no response in one. One tumour presented signs of persistence/recurrence during follow‐up. Conclusions Cryotherapy applied to treat imiquimod‐refractory basal cell carcinoma seems to sensitize the tumour to the effect of the drug, thus reducing the percentage of patients who need surgery after an incomplete response to imiquimod. Further studies are necessary to confirm these findings.     

Dermoscopic features of actinic keratosis and follow up with dermoscopy: A pilot study

Actinic keratosis (AK) is a common precursor of sun‐related squamous cell carcinoma. AK is difficult to be differentiated from other malignancies with the naked eyes. Dermoscopic features of AK were previously described in some studies, but not extensively investigated. We investigated the dermoscopic features of AK in Asians and assessed dermoscopy as a post‐treatment monitoring tool of AK. We retrospectively examined 34 AK lesions which had been diagnosed by histology. The changes of dermoscopic features and histopathological findings were assessed in all these lesions before and after treatment. Before treatment, 18 lesions were pigmented and 16 lesions were non‐pigmented AK dermoscopically. The frequent dermoscopic features of AK were keratin/scales (79.4%), red pseudonetwork (73.5%), targetoid‐like appearance (55.9%), rosette sign (38.2%) and absent fissures/ridges, crypts and milia‐like cysts. All the lesions had been treated with either photodynamic therapy, cryotherapy or 5% imiquimod cream. After treatment, dermoscopic features of 33 AK lesions were decreased or disappeared, and skin biopsies confirmed that atypical keratinocytes disappeared. One lesion showed accentuated and new dermoscopic features after treatment, and skin biopsy also showed progressing squamous cell carcinoma. In conclusion, scales, red pseudonetwork, targetoid‐like appearance and rosette sign were common dermoscopic findings of AK in Asians. In most cases, the treatment response correlated with the changes in dermoscopic features. These findings suggest that dermoscopy is a useful tool to monitor AK.     

Reflectance confocal microscopy allows in vivo real‐time noninvasive assessment of the outcome of methyl aminolaevulinate photodynamic therapy of basal cell carcinoma

Background Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is an approved noninvasive treatment option for basal cell carcinoma (BCC). In vivo reflectance confocal microscopy (RCM) is a noninvasive imaging technique that has proved useful for in vivo real‐time cytomorphological analysis of BCC cells infiltrating the epidermis. Objectives To investigate the use of in vivo RCM to assess the persistence of BCC cells surviving MAL‐PDT. Methods In vivo RCM images of 20 biopsy‐proven BCCs were taken before patients underwent a treatment cycle with MAL‐PDT. Follow‐up after 3 months was performed using clinical examination, RCM and conventional dermoscopy. Treated areas also underwent a targeted 3‐mm punch biopsy for standard haematoxylin and eosin histology stain to establish the clinical and instrumental correlation of the treatment outcome. Results Three months after PDT, clinical examination established that two out of 20 BCCs were persistent; dermoscopy found three out of 20 residual BCCs, but RCM showed that one of these lesions was a false positive, and showed persistent BCC foci in five out of 20 lesions. Histological analysis of targeted biopsies confirmed these results. Conclusions RCM provided noninvasive, early detection of incipient recurrences of BCC after MAL‐PDT. RCM findings steered targeted biopsies and surgical removal, or a new MAL‐PDT, of these subclinical recurrences with minimal invasiveness.     

A systematic review of non‐surgical treatments for lentigo maligna

Lentigo maligna (LM) is the most common melanocytic malignancy of the head and neck. If left untreated, LM can progress to lentigo maligna melanoma (LMM). Complete surgical excision is the gold standard for treatment, however, due to the location, size, and advanced age of patients, surgery is not always acceptable. As a result, there is ongoing interest in alternative, less invasive treatment modalities. The objective was to provide a structured review of key literature reporting the use of radiotherapy, imiquimod and laser therapy for the management of LM in patients where surgical resection is prohibited. An independent review was conducted following a comprehensive search of the National Library of Medicine using MEDLINE and PubMed, Embase, Scopus, ScienceDirect and Cochrane Library databases. Data were presented in tabular format, and crude data pooled to calculate mean recurrence rates for each therapy. 29 studies met the inclusion criteria: radiotherapy 10; topical imiquimod 10; laser therapies 9. Radiotherapy demostrated recurrence rates of up to 31% (mean 11.5%), with follow‐up durations of 1–96 months. Topical imiquimod recurrence rates were up to 50% (mean 24.5%), with follow‐up durations of 2–49 months. Laser therapy yielded recurrence rates of up to 100% (mean 34.4%), and follow‐up durations of 8–78 months. in each of the treatment series the I² value measuring statistical heterogeneity exceeded the accepted threshold of 50% and as such a meta‐analysis of included data were inappropriate. For non‐surgical patients with LM, radiotherapy and topical imiquimod were efficacious treatments. Radiotherapy produced superior complete response rates and fewer recurrences than imiquimod although both are promising non‐invasive modalities. There was no consistent body of evidence regarding laser therapy although response rates of up to 100% were reported in low quality studies. A prospective comparative trial is indicated and would provide accurate data on the long‐term efficacy and overall utility of these treatments.     

Cryosurgery during topical imiquimod: a successful combination modality for lentigo maligna

Background Either cryosurgery or topical imiquimod have been used to treat patients with lentigo maligna in cases where surgery is not feasible. Methods We report a patient with lentigo maligna, who was treated with the combination of topical imiquimod and cryosurgery, and review the rationale, which led us to design the present combined cryo‐immunological treatment modality. Results Sustained clearance of lentigo maligna to date (26 months after treatment). The successful treatment of this patient was based on the following rationale: A cryosurgery session during continuing imiquimod application may: (i) reinforce apoptosis of tumor cells; (ii) strengthen antiangiogenesis in the treated tumor; and (iii) build‐up a potent tumor‐destructive immune response by a cascade of events starting with imiquimod‐promoted attraction of immature dendritic antigen‐presenting cells (DCs) into the tumor. DCs further mature within the tumor‐antigen‐rich environment of subsequently cryo‐destructed tumor and upon imiquimod‐driven migration into the peripheral lymph nodes can stimulate a specific antineoplastic cell‐mediated immunity. Finally, continuing imiquimod application after cryosurgery may increase recruitment of activated effector cells into the tumor tissue leading to its destruction. Conclusion Cryosurgery during continued topical imiquimod seems to be a promising treatment for lentigo maligna.     

Multimodal in vivo optical imaging, including confocal microscopy, facilitates presurgical margin mapping for clinically complex lentigo maligna melanoma

Knowledge of the accurate margins of a lentigo maligna melanoma (LMM) is crucial in the presurgical evaluation of the patient. Towards this end clinicians have utilized the Wood's lamp and dermoscopy to help delineate the borders of the LMM. However, many LMMs arise on photodamaged skin, making it difficult to determine the border of the LMM and separate it from the background lentiginous skin. We present a case of a patient with a recurrent LMM on the scalp that developed in a background of photodamage with diffuse melanocytic atypia and lentigines, making it virtually impossible to determine the precise margins of the LMM by clinical, Wood's lamp or dermoscopic examination. To avoid subjecting the patient to multiple staged excisions we attempted to determine the margins of the LMM by utilizing in vivo confocal laser scanning reflectance microscopy. Using this, it was apparent that there were increased numbers of atypical/dendritic intraepidermal melanocytes in all layers of the epidermis within the LMM. In contrast, skin not involved with the LMM, as viewed under confocal laser examination, had normal honeycomb architecture and no abnormal melanocytes. The confocally determined border was further confirmed by obtaining multiple punch biopsies that were evaluated by haematoxylin and eosin histology and immunohistochemistry. Based on this information, the presurgical margins were marked and the tumour excised accordingly. The excised tissue was examined with multiple-step sections and the margins were determined to be clear. There has been no evidence of tumour recurrence after 1 year. In conclusion, this case illustrates that confocal reflectance microscopy, in conjunction with other in vivo optical instruments, can be utilized to enhance the accuracy for the presurgical margin mapping of LMM.     

Topical Imiquimod for the Treatment of Childhood Cutaneous Langerhans Cell Histiocytosis

Although topical steroids are considered first‐line treatment for cutaneous Langerhans cell histiocytosis (LCH), the appropriate therapy for refractory cases remains controversial. We report a 16‐month‐old girl with isolated cutaneous LCH refractory to treatment with topical corticosteroids and topical tacrolimus. Treatment was initiated with 5% topical imiquimod cream and the rash completely resolved after 5 months of therapy. There was no disease recurrence after more than 2 years of follow‐up. We present this case to highlight imiquimod as a novel therapeutic agent for the management of isolated cutaneous LCH in children.     

Peculiar clinical and dermoscopic remission pattern following imiquimod therapy of basal cell carcinoma in seborrhoeic areas of the face

Imiquimod is a 240.3-Da synthetic imidazoquinolinamine (C14H16N4), developed in 1983 and approved in 1997 by the US Food and Drug Administration for the topical treatment of external genital and perianal warts and, more recently, also for actinic keratosis and superficial basal cell carcinomas. We report five cases of patients affected by basal cell carcinomas localized in seborrhoeic areas of the face, successfully treated with topical imiquimod and characterized by the occurrence of eruptive epidermoid cysts at the end-point of therapy. The dermatoscopic evaluation disclosed the presence in all lesions of a common feature characterized by a hyperkeratotic yellow-withish area, resembling 'popcorn', excluding dermoscopic basal cell carcinoma features. Furthermore, histological proof confirmed the diagnosis of epidermoid cysts. As reported in the literature and as observed in our clinical experience, the occurrence of epidermoid cysts, after the topical treatment of basal cell carcinomas with imiquimod, may represent a local immune reaction that is drug-related and is a typical remission pattern in particular anatomical areas. We also emphasized the usefulness of dermoscopy in supporting the clinical diagnosis of epidermoid cysts, excluding the presence of tumoural residue or recurrence. In the future, it will be possible to follow-up the lesions after treatment avoiding the post-control biopsy punch.     

Effectiveness of cross polarized light and fluorescence diagnosis for detection of sub‐clinical and clinical actinic keratosis during imiquimod treatment

Please cite this paper as: Effectiveness of cross polarized light and fluorescence diagnosis for detection of sub‐clinical and clinical actinic keratosis during imiquimod treatment. Experimental Dermatology 2010; 19: 641–647. Background: During treatment of actinic keratosis (AK) lesions with imiquimod sub‐clinical lesions often become visible. It is, however, unclear whether these sub‐clinical lesions would be detectable beforehand. Objective: The aim of this pilot study was to compare two techniques, cross polarized light photography (CPL) and fluorescence diagnosis (FD) using methyllevulinic acid and illumination with Wood’s lamp for their ability to detect sub‐clinical lesions. These findings were also compared with biopsy results taken before and after treatment with imiquimod 5% cream or vehicle. Methodology: Twelve patients with at least five clinically visible AK lesions in a single contiguous 20 cm² area on the head were recruited. Patient eligibility was determined at the screening visit, when they were randomized to treatment. The randomization was 3:1, active to vehicle (nine treated with imiquimod, three with vehicle cream) for a total duration of 24 weeks (six clinic visits). Patients were assessed for baseline AK lesion counts (clinical and sub‐clinical) at the screening visit and final counts at week 20. Results: The number of clinically observed AK lesions was significantly lower at week 12 and week 20 compared with baseline following imiquimod treatment versus vehicle. The number of counted lesions were significantly higher using the CPL method compared with clinical counting with imiquimod treatment at baseline (8.3 ± 3.4 vs 5.8 ± 1.3; P = 0.027) and week 20 (4.8 ± 2.4 vs 3.0 ± 1.7; P = 0.02) but not in the vehicle group. The FD lesion counting method did not show a significant increase in the number of detected lesions compared with clinical analysis in the imiquimod and placebo groups but when comparisons were performed using pooled data (treatments and visits combined) the results were significant. Conclusion: The number of sub‐clinical and clinical AK lesions detected during treatment with imiquimod can be better demonstrated using the methods of CPL and FD, but statistical significance was reached only using the CPL method. This is only a preliminary study with a small number of patients and as a result it is difficult to conclude both statistical and clinical significance. However, results were encouraging and indicate that larger studies are needed to demonstrate the relevance of these two new methods for improved detection of clinical and especially sub‐clinical AK lesions.     

乳房外Paget病的研究进展

乳房外Paget病是一种少见的表皮内腺癌.检查方法有组织病理、免疫组化、非侵入性检查(包括皮肤镜和反射式共聚焦激光扫描显微镜).Mohs显微外科手术被认为是首选治疗方法,其他疗法有咪喹莫特、光动力疗法、曲妥珠单抗以及全身化学疗法等.本文对乳房外Paget病的流行病学、发病机制和诊治等内容进行综述,以期提高临床诊治水平.     

A cost analysis of photodynamic therapy with methyl aminolevulinate and imiquimod compared with conventional surgery for the treatment of superficial basal cell carcinoma and Bowen’s disease of the lower extremities

Background Superficial basal cell carcinoma (sBCC) and Bowen’s disease (BD) are usually slow‐growing, low‐grade malignancies that mainly affect older persons. Surgery is often the first choice of treatment and the modality with the lowest failure rate. However, non‐invasive procedures, such as topical methyl aminolevulinate photodynamic therapy (MAL‐PDT) and imiquimod, are increasingly demanded by dermatologists and patients, because of their generally favourable efficacy and adverse effects profile and their excellent cosmetic outcome. Objective To assess the cost of MAL‐PDT and of treatment with imiquimod for primary non‐melanoma superficial cutaneous carcinomas compared with conventional surgery, thereby calculating the total medical cost, and the direct and indirect costs. Setting We collected data on 67 patients with 86 tumours (32 sBCC, 54 BD). Patients were treated between May 2006 and April 2007 at the Dermatology Department of the Costa del Sol Hospital in Marbella, Spain. The mean cost and mean cost per complete clinical response were calculated for each therapeutic option. Results After 2 years of follow‐up, a complete response was observed in 89.5% of the MAL‐PDT group, 87.5% of the imiquimod group and 97.5% of the surgery group. The difference in costs when compared with the surgery group was a mean saving per lesion treated of 307 euros for the imiquimod group, and 322 euros for the MAL‐PDT group. Conclusions Although surgery proved to be more effective treatment, our results suggest that its average cost is greater than that of non‐invasive therapy for the treatment of non‐melanoma superficial cutaneous carcinomas on the lower limbs, at least after the first 2 years of follow‐up.     

Overall treatment success after treatment of primary superficial basal cell carcinoma: a systematic review and meta-analysis of randomized and nonrandomized trials

Background Several noninvasive treatment modalities are available for superficial basal cell carcinoma (sBCC). Objectives This systematic review aims to determine residue, recurrence and tumour‐free survival probabilities of patients with primary sBCC treated with the currently most frequently used therapies. Methods The PubMed (January 1946 to October 2010), EMBASE (January 1989 to October 2010) and Cochrane (January 1993 to October 2010) databases, and reference lists were searched without date restriction. Inclusion criteria were studies that included primary, histologically proven sBCCs, that reported on residue and/or recurrence probabilities after treatment, and had a minimum follow‐up period of 12 weeks. Both randomized and nonrandomized studies were included. The primary and secondary outcomes were the probability of complete response and tumour‐free survival, respectively. Two independent reviewers selected 36 studies (14 randomized and 22 nonrandomized), and extracted residue, cumulative recurrence and tumour‐free survival probabilities. Results Pooled estimates of percentages of sBCC with complete response at 12 weeks post‐treatment, derived from 28 studies, were 86·2% [95% confidence interval (CI) 82–90%] for imiquimod treatment, and 79·0% (95% CI 71–87%) for photodynamic therapy (PDT). With respect to tumour‐free survival at 1 year, the pooled estimates derived from 23 studies were 87·3% for imiquimod (95% CI 84–91%) and 84·0% for PDT (95% CI 78–90%). Only a small number of studies reported on the results of sBCC treatment with 5‐fluorouracil (one), surgical excision (one) and cryotherapy (two). Conclusions Pooled estimates from randomized and nonrandomized studies showed similar tumour‐free survival at 1 year for imiquimod and PDT. The PDT tumour‐free survival was higher in studies with repeated treatments. However, these results were largely derived from nonrandomized studies, and randomized studies with head‐to‐head comparison of imiquimod and PDT are lacking. There is a need for head‐to‐head comparison studies between PDT, imiquimod and other treatments with long‐term follow‐up to enable better recommendations for optimal sBCC treatment.     

Treatment of superficial basal cell carcinoma with 7.8% 5‐aminolaevulinic acid nanoemulsion‐based gel (BF‐200 ALA) and photodynamic therapy: Results in clinical practice in a tertiary hospital

Photodynamic therapy (PDT) is an effective treatment option for the treatment of superficial basal cell carcinoma (sBCC). Recent publications have demonstrated that PDT with 7.8% 5‐aminolaevulinic acid nanoemulsion‐based gel (BF‐200 ALA‐PDT) is an effective and safe alternative for the treatment of sBCC). To investigate the efficacy and safety of 7.8% 5‐aminolaevulinic acid nanoemulsion‐based gel (BF‐200 ALA)‐PDT for the treatment of sBCC. A non‐controlled, open‐label single centre study was conducted. Patients received one PDT cycle with two PDT sessions one‐week apart. In case that clinical‐dermoscopy evaluation of treatment outcome revealed remaining lesions, a second PDT cycle was performed. The clinical results at the dermoscopy and fluorescence diagnosis level were histologically confirmed in all patients. Treatment response was evaluated 3, 6, and 12 months after last PDT session. A total of 31 patients (12 men and 19 women), with a median age of 63.74 years were included in this study. 3‐month after PDT‐session, 23/31 patients were complete responders (74.19%) after two BF‐200 ALA ‐PDT sessions. Esthetic outcome was considered good‐to‐excellent. 5 Aminolevulinic acid 7.8% nanoemulsion‐based gel (BF‐200 ALA) PDT is an effective therapy option for the treatment of sBCC. Complete clearance rates were higher in those patients who received only one PDT cycle. These results show a similar tendency as shown in other publications.     

Dermoscopic features of Bowen’s disease in Asians

Background Previously, dermoscopic features of Bowen’s disease (BD) were extensively investigated in two studies, but there were some discrepancies. The dispute necessitated a further study concerning the dermoscopic features of BD. Objective To describe the dermoscopic features of BD in Asians and to assess dermoscopy as a post‐treatment monitoring tool of BD. Materials and methods Dermoscopic examinations of histopathologically diagnosed 26 BD lesions were performed to evaluate for the presence of various dermoscopic features. In addition, the correlating changes of dermoscopic features and histopathological results before and after treatments were assessed in five patients with BD. Results Dermoscopically, 10 lesions were pigmented and 16 lesions were non‐pigmented. The most frequent dermoscopic findings of BD were vascular structures (96%) and a scaly surface (96%). Among vascular structure, glomerular vessels were most frequently observed (77%). The other vascular structures in our study were linear irregular vessels, dotted vessels, polymorphous/atypical vessels and arborizing vessels. Among five patients who had been treated with either photodynamic therapy or 5% imiquimod cream, four patients revealed disappearance of dermoscopic vascular structures, but one patient showed remaining vascular structures after treatment. Skin biopsy from treated lesions disclosed clearance of BD in four patients who had no vascular structures but remaining BD in the patient whose dermoscopic finding displayed no disappearance of vascular structures. Conclusions Vascular structures, especially glomerular vessels plus a scaly surface, were common dermoscopic findings of BD in Asians. In addition, existence of dermoscopic vascular structures after treatment appears to be associated with residual disease.     

Possible advantage of imiquimod and diphenylcyclopropenone combined treatment versus diphenylcyclopropenone alone: An observational study of nonresponder patients with alopecia areata

The topical contact sensitiser diphenylcyclopropenone (DCP) remains one of the most effective treatment modalities for alopecia areata (AA). However, some patients (nonresponders) do not respond to this treatment because they do not have an allergic reaction to DCP. The aim of this study was to investigate the potential role of imiquimod in inducing an allergic reaction to DCP in nonresponders. In all, 20 nonresponders were recruited from a group of DCP‐treated AA patients. Of these patients, 10 were treated with DCP and topical imiquimod and 10 were treated with DCP alone. A significantly better therapeutic outcome was measured in the DCP plus imiquimod group than in the group treated with DCP alone. The potential mechanism of imiquimod may involve the role of interleukin‐12, as previously suggested in an animal model. These findings suggest that imiquimod may have the potential to improve prognosis in nonresponder AA patients treated with DCP.     

Eruptive squamous cell carcinoma in a patient treated with concomitant pembrolizumab and imiquimod

Pembrolizumab, a humanized monoclonal antibody against programmed cell death 1, is used for various malignant neoplasms. Toll‐like receptor (TLR) agonists, specifically targeting the TLR9 subfamily (TLR7–9), are treatment options for solid tumors and hematological malignancies. We experienced a case of eruptive squamous cell carcinoma (SCC) in a patient treated concomitantly with pembrolizumab and imiquimod, a TLR7 agonist. A 75‐year‐old woman who was given a diagnosis of bladder cancer with lung metastasis received pembrolizumab for 3 months when she was referred to our department for the evaluation of skin rashes on her hands. Her skin lesions were diagnosed as well‐differentiated SCC and treated with topical imiquimod. Two months after the start of imiquimod, more than 10 reddish papules appeared on her hands. The histological diagnosis of a new plaque was the same as an earlier biopsy. We herein describe this case in detail and provide a published work review.     

Increased number of mast cells in the dermis in actinic keratosis lesions effectively treated with imiquimod

Actinic keratosis (AK) is a cutaneous cancer in situ which develops as a result of excessive exposure to ultraviolet (UV). Toll‐like receptor (TLR)7 agonist imiquimod is a topical immune response modifier and is effective for the treatment of non‐melanoma skin cancers. Recently, the diagnostic role of the dermatoscope has been reported in the course of treatment of AK. In addition, mast cells are now considered to contribute to both the innate and adaptive immune systems in topical imiquimod therapy. We assessed the effect of imiquimod treatment by dermatoscopic and immunohistochemical findings in 14 patients with a total of 21 AK lesions. With the dermatoscope, though the mean erythema score was not significantly different between the cured lesions and the unresponsive lesions, the erythema/red pseudo‐network (“strawberry”) pattern was decreased significantly in the cured lesions. By immunohistochemistry, the number of Ki‐67‐positive proliferative cells in the epidermis was decreased and that of CD117‐positive mast cells in the dermis was increased in the responding lesions. To the best of our knowledge, this is the first study demonstrating that the number of mast cells in the dermis was increased in AK lesions effectively treated with imiquimod. Our present result suggests that mast cells may contribute an antitumor effect in human skin treated with topical imiquimod.