Dermatoscopy-guided therapy of pigmented basal cell carcinoma with imiquimod*

BACKGROUND Dermatoscopy is a non-invasive diagnostic tool used to examine skin lesions with an optical magnification. It has been suggested as a useful tool for monitoring therapeutic response in lentigo maligna patients treated with imiquimod. OBJECTIVE To examine the accuracy of dermatoscopy as a tool to monitor the therapeutic response of pigmented basal cell carcinoma treated with imiquimod. METHOD The authors designed a prospective study. Patients with pigmented basal cell carcinoma were included and data regarding the dermatoscopy features were collected following the Menzies criteria, prior to initiating the imiquimod treatment. Subsequent dermatoscopic evaluations were performed at weeks 4 and 8, following imiquimod discontinuation. RESULTS Twenty lesions were included. The most common pigmented dermatoscopy features were large blue-grey ovoid nests (80%), followed by blue-grey globules (50%) and leaf-like areas (30%). No spoke wheel areas were observed. In 17 out of 20 patients, a response was noted during the first evaluation at 4 weeks, while the clearance was noted at the second check-up after 8 weeks. In two patients, the clearance was found at the initial evaluation at 4 weeks, while in one patient, the response remained unchanged. Blue-grey globules were the fastest to exhibit clearance (50% at week 4), followed by leaf-like areas (15%) and large blue-grey ovoid nests (6.25%). CONCLUSION According to our results, dermatoscopic evaluation enhances the accuracy in the assessment of the clinical response to imiquimod in pigmented basal cell carcinoma.


INTRODUCTION
Basal cell carcinoma (BCC) is the most prevalent malignant skin cancer originating from the basal cell layer of the epidermis.
It rarely metastasizes and a proportion of these tumors may contain pigment. Most of the histological subtypes of basal cell carcinoma can exhibit pigmented varieties but this is rarely observed in morphoeic and infiltrative subtypes. 1 Histologically, melanin can be found in the tumour cells and surrounding stroma. Within the tumour mass, melanin is more often seen in the superficial component of the tumour, with melanosomes often confined to the melanocytes. However, they may be taken up by the surrounding malignant epithelial cells. [2][3][4] In the stroma, melanin is typically found at the tumour shoulders, in melanophages, but small amounts may lie free. Occasionally, melanocytes are found in the deep tumour nodules or in the overlying epidermis. 2 Because of its asymmetry of pigmentation and variety of growth patterns, pigmented basal cell carcinoma (PBCC) is includ-ed in the differential diagnosis of invasive melanoma, along with other benign, pigmented skin lesions.
Dermatoscopy is a non-invasive diagnostic tool used to examine skin lesions with an optical magnification. Using a polarized light, this technique allows a detailed examination of pigmented epidermis structures and the dermo-epidermal junction. Its use has become highly important among dermatologists in conducting a better clinical diagnosis of nearly all pigmented lesions. [5][6][7][8][9][10][11][12][13][14][15] Regarding pigmented basal cell carcinoma (PBCC), dermatoscopy has proven to be an effective diagnostic technique 2 . Most basal cell carcinomas have < 50% of their area pigmented, and only 7% of lesions have > 75% of pigmented tumour area. 16 Although dermatoscopy has already been used as a tool to control borders in the surgical management of BCC, to the authors' knowledge, it has not yet been used to control accurately the efficacy of topical treatments such as imiquimod. 17 This drug is an imid-DOI: http://dx.doi.org/10.1590/abd1806-4841.20165255 Abstract: Background:Dermatoscopy is a non-invasive diagnostic tool used to examine skin lesions with an optical magnification. It has been suggested as a useful tool for monitoring therapeutic response in lentigo maligna patients treated with imiquimod. oBjective: To examine the accuracy of dermatoscopy as a tool to monitor the therapeutic response of pigmented basal cell carcinoma treated with imiquimod. Method: The authors designed a prospective study. Patients with pigmented basal cell carcinoma were included and data regarding the dermatoscopy features were collected following the Menzies criteria, prior to initiating the imiquimod treatment. Subsequent dermatoscopic evaluations were performed at weeks 4 and 8, following imiquimod discontinuation. results: Twenty lesions were included. The most common pigmented dermatoscopy features were large blue-grey ovoid nests (80%), followed by blue-grey globules (50%) and leaf-like areas (30%). No spoke wheel areas were observed. In 17 out of 20 patients, a response was noted during the first evaluation at 4 weeks, while the clearance was noted at the second check-up after 8 weeks. In two patients, the clearance was found at the initial evaluation at 4 weeks, while in one patient, the response remained unchanged. Blue-grey globules were the fastest to exhibit clearance (50% at week 4), followed by leaf-like areas (15%) and large blue-grey ovoid nests (6.25%). conclusion: According to our results, dermatoscopic evaluation enhances the accuracy in the assessment of the clinical response to imiquimod in pigmented basal cell carcinoma. azoquinoline amide, which modifies immune response with both antitumor and antiviral activity. Its use was first approved in 2004 by the US Food and Drug Administration to treat actinic keratosis and superficial basal cell carcinoma. 18 In addition, nodular subtypes of basal cell carcinoma have been treated with this cream, entailing positive responses. [19][20][21][22][23] In the current literature, only one study reports a case of large PBCC, which was successfully resolved after imiquimod therapy. 24 This study aims to examine the accuracy of dermoscopy as a tool for monitoring the therapeutic response of PBCC treated with imiquimod.

Study design
The authors designed a study, conducted between January 1 st, 2011 and May 1 st, 2011. It was a prospective, open-label trial. The Menzies criteria were followed to diagnose PBCC; Absence of pigment network and at least, one of the following features: leaf-like areas, spoke wheel areas, large blue-gray ovoid nests and multiple blue-gray globules). 12 BCCs manifesting arborizing vessels and/ or ulceration, with no pigmentation features, were excluded. The authors included adult patients with dermatoscopy-confirmed diagnosis of PBCC.

Imiquimod therapy
The treatment protocol for the lesions included in our study was the dosing frequency recommended by the manufacturer: one daily application 5 days a week for 6 weeks. Rest periods were used as necessary to manage local skin reactions, and continued for up to 6 weeks.

Assessment of dermatoscopic features
Prior to initiating treatment, the team scanned the lesion using the Fotofinder® device and collected data regarding the dermatoscopy features, following the above-mentioned criteria. Subsequent evaluations were performed at weeks 4 and 8 after imiquimod discontinuation. The team compared the images before and after to assess the changes in the dermatoscopy features. Responses were classified as: clearance (complete clearance of features), response (decrease in number and/or intensity of features), unresponsive (no changes in features) and worsening (increase in number and/or intensity of features).
The study's protocol was approved by the hospital's medical ethics committee, and all participants gave their written informed consent before enrollment.

RESULTS
Twenty lesions from 20 subjects (9 women and 11 men) were included in the study. The median age was 68.73 (±9.11) years. Ten lesions were superficial BCC, and ten were of the nodular type. The most commonly affected site was the temple (5 lesions, 25%) followed by the nose (4 lesions, 20%). Table 1 summarizes the epidemiological data from our sample.
All patients completed the 6-week treatment cycle. Application site reactions were the most common adverse effects, seen in As regards arborizing vessels, complete dermatoscopic clearance was observed at week 8 in most lesions (9 out of 13, 69%).      biopsies are still required to confirm remission. Indeed, the main limitation of our study is that no biopsies were performed to assess histological remission. 30,31 However, a biopsy does not allow examination of the whole lesion because specimens are usually obtained from representative areas of a lesion to predict the histopathological condition. Hence, the authors suggest that dermatoscopic evaluation of treated lesions may enhance the accuracy of treatment response assessments: if dermatoscopic features remain on the treated lesion, a biopsy should be performed on that site. In this study, no signs of lesion recurrence were observed after one-year of follow-up and therefore no biopsies were needed.
Randomized controlled studies comparing dermatoscopic findings, as well as a histopathological evaluation of complete surgical excision, are required to confirm the real usefulness of dermatoscopy in monitoring imiquimod therapy for PBCC.
To the authors' knowledge, this is the first study to examine dermatoscopy as a therapeutic tool for monitoring PBCC treated with imiquimod. In conclusion, the data suggest that dermatoscopy is not only a diagnosis technique, but that it may also be useful in managing PBCC by facilitating the monitoring of response to topical treatments.

CONCLUSION
According to the findings, dermatoscopic evaluation enhances the accuracy in the assessment of the clinical response to imiquimod in PBCC.q