RECURRENT LENTIGO MALIGNA: CONSERVATIVE CONTINUOUS TREATMENT WITH IMIQUIMOD OR REPEATED SURGERY? A LONG-TERM FOLLOW-UP DERMOSCOPIC CASE STUDY.

A case of recurrent lentigo maligna in a 45-year-old woman is presented. The disease relapsed several times following the surgical excision of the lesion. An alternative treatment with imiquimod 5% cream was then used. After 4 years of follow-upfrom the last surgery, this treatment achieved total clearance of the lesion. The problems of lentigo maligna diagnosis and treatment are discussed.

Efficacy of imiquimod in the management of lentigo maligna.

BACKGROUND: Lentigo maligna (LM) is a melanocytic proliferation occurring on photo-exposed skin that may progress to LM melanoma. Surgery is recommended as first-line treatment. Excision margins of 5-10 mm remain, without international consensus. Several studies have shown that imiquimod, an immunomodulator, induces LM regression. This study investigated the effect of imiquimod versus placebo in neoadjuvant settings. PATIENTS AND METHODS: We performed a prospective, randomized, multicentre, phase III clinical study. Patients were randomly assigned in 1:1 ratio to receive imiquimod or placebo for 4 weeks, followed by LM excision 4 weeks after the last application of imiquimod or placebo. The primary endpoint was extra-lesional excision, with a 5 mm margin from the residual pigmentation after imiquimod or vehicle. Secondary endpoints included the gain on the surface removed between the two groups; number of revision surgeries to obtain extra-lesional excisions; relapse-free time; and number of complete remissions after treatment. RESULTS: A total of 283 patients participated in this study; 247 patients, 121 patients in the placebo group and 126 in the imiquimod group, accounted for the modified ITT population. The first extralesional extirpation was performed in 116 (92%) imiquimod patients and in 102 (84%) placebo patients; the difference was not significant (p = 0.0743). Regarding the surface of LM, imiquimod reduced the LM surface (4.6-3.1 cm2 ) significantly (p < 0.001) more compared to the placebo (3.9-4.1 cm2 ). CONCLUSION: Imiquimod reduces the lentigo maligna surface after 1 month of treatment, without a higher risk of intralesional excision and with a positive aesthetic outcome.

Treatment of periocular lentigo maligna with topical 5% Imiquimod: a review.

Lentigo Maligna is a benign subtype of melanoma in situ and can progress to lentigo maligna melanoma, which is invasive. Complete surgical excision is the gold standard of treatment but requires large margins. If affecting the peri-ocular region, surgical excision leads to extensive defects, complex reconstructions, and functional impairment of the protection of the ocular surface. Here we review the reported literature about the use of Imiquimod 5% topical cream for lentigo maligna of the eyelid, the treatment outcomes, side effects and tolerance. In addition, the side effects of imiquimod treatment of non-LM lesions are described to help better inform the decision-making process. Treatment for peri-ocular Lentigo maligna showed a 56-86% complete treatment response and a 90% tolerability rate. However, reported treatment protocols vary and histopathological confirmation of clearance was only obtained in 56%. Further studies are required to determine the optimal treatment protocol to maximise clearance rates. Overall, Imiquimod was well tolerated in the peri-ocular area.

Series of Fourteen Cases of Topical Imiquimod 5% in Lentigo Maligna: Treatment Modalities and Clues for Detecting Recurrences. / [Artículo traducido] Serie de 14 casos de tratamiento con imiquimod tópico al 5% en lentigo maligno: modalidades terapéuticas y claves para detectar recidivas.

Topical imiquimod has been used off-label as monotherapy or adjuvant treatment for lentigo maligna. Our aim is to describe treatment modalities, clinical outcomes, and management of recurrence in patients receiving imiquimod for lentigo maligna. Patients from our unit with lentigo maligna or lentigo maligna melanoma treated with imiquimod 5% as monotherapy or in combination with surgery were included in this study. Fourteen cases were recruited (85.7% lentigo maligna and 14.3% lentigo maligna melanoma). Eight patients (57.1%) received imiquimod without surgery, and six (42.9%) underwent narrow excision before beginning treatment. During the follow-up period, pigmentation reappeared in 6 patients (4 postinflammatory hyperpigmentation and 2 relapses). Relapses were managed with very narrow excision (1 mm margin) and retreatment with imiquimod 5%. All imiquimod modalities showed well-tolerated side effects and low recurrence rates, with long periods of follow-up. Imiquimod appears to be a versatile option for treating LM in suitable candidates.

Series of Fourteen Cases of Topical Imiquimod 5% in Lentigo Maligna: Treatment Modalities and Clues for Detecting Recurrences.

Topical imiquimod has been used off-label as monotherapy or adjuvant treatment for lentigo maligna. Our aim is to describe treatment modalities, clinical outcomes, and management of recurrence in patients receiving imiquimod for lentigo maligna. Patients from our unit with lentigo maligna or lentigo maligna melanoma treated with imiquimod 5% as monotherapy or in combination with surgery were included in this study. Fourteen cases were recruited (85.7% lentigo maligna and 14.3% lentigo maligna melanoma). Eight patients (57.1%) received imiquimod without surgery, and six (42.9%) underwent narrow excision before beginning treatment. During the follow-up period, pigmentation reappeared in 6 patients (4 postinflammatory hyperpigmentation and 2 relapses). Relapses were managed with very narrow excision (1mm margin) and retreatment with imiquimod 5%. All imiquimod modalities showed well-tolerated side effects and low recurrence rates, with long periods of follow-up. Imiquimod appears to be a versatile option for treating LM in suitable candidates.

Series of Fourteen Cases of Topical Imiquimod 5% in Lentigo Maligna: Treatment Modalities and Clues for Detecting Recurrences / Serie de 14 casos de tratamiento con imiquimod tópico al 5% en lentigo maligno: modalidades terapéuticas y claves para detectar recidivas

Topical imiquimod has been used off-label as monotherapy or adjuvant treatment for lentigo maligna. Our aim is to describe treatment modalities, clinical outcomes, and management of recurrence in patients receiving imiquimod for lentigo maligna. Patients from our unit with lentigo maligna or lentigo maligna melanoma treated with imiquimod 5% as monotherapy or in combination with surgery were included in this study. Fourteen cases were recruited (85.7% lentigo maligna and 14.3% lentigo maligna melanoma). Eight patients (57.1%) received imiquimod without surgery, and six (42.9%) underwent narrow excision before beginning treatment. During the follow-up period, pigmentation reappeared in 6 patients (4 postinflammatory hyperpigmentation and 2 relapses). Relapses were managed with very narrow excision (1mm margin) and retreatment with imiquimod 5%. All imiquimod modalities showed well-tolerated side effects and low recurrence rates, with long periods of follow-up. Imiquimod appears to be a versatile option for treating LM in suitable candidates (AU)

Imiquimod tópico ha sido utilizado como monoterapia o tratamiento adyuvante fuera de indicación para el lentigo maligno (LM). Nuestro objetivo es describir las modalidades de tratamiento, los resultados clínicos y el manejo de la recidiva en los pacientes que reciben imiquimod para lentigo maligno. Se incluyó en este estudio a los pacientes de nuestra unidad con lentigo maligno o lentigo maligno melanoma tratados con imiquimod 5% en régimen de monoterapia o junto con cirugía. Se seleccionaron 14 casos (el 85,7% de lentigo maligno y el 14,3% de lentigo maligno melanoma). Ocho pacientes (57,1%) recibieron imiquimod sin cirugía, y seis (42,9%) fueron sometidos a resección antes de iniciar el tratamiento. Durante el periodo de seguimiento, reapareció la pigmentación en seis pacientes (cuatro con hiperpigmentación postinflamatoria y dos recidivas). Las recidivas fueron tratadas con un margen de resección muy estrecho (1mm) y retratamiento con imiquimod 5%. Todas las modalidades de imiquimod reflejaron buena tolerancia de efectos secundarios y bajas tasas de recidiva. Imiquimod parece ser una opción muy versátil para tratar LM en candidatos idóneos (AU)

[Artículo traducido] Serie de 14 casos de tratamiento con imiquimod tópico al 5% en lentigo maligno: modalidades terapéuticas y claves para detectar recidivas / Series of Fourteen Cases of Topical Imiquimod 5% in Lentigo Maligna: Treatment Modalities and Clues for Detecting Recurrences

Imiquimod tópico ha sido utilizado como monoterapia o tratamiento adyuvante fuera de indicación para el lentigo maligno (LM). Nuestro objetivo es describir las modalidades de tratamiento, los resultados clínicos y el manejo de la recidiva en los pacientes que reciben imiquimod para lentigo maligno. Se incluyó en este estudio a los pacientes de nuestra unidad con lentigo maligno o lentigo maligno melanoma tratados con imiquimod 5% en régimen de monoterapia o junto con cirugía. Se seleccionaron 14 casos (el 85,7% de lentigo maligno y el 14,3% de lentigo maligno melanoma). Ocho pacientes (57,1%) recibieron imiquimod sin cirugía, y seis (42,9%) fueron sometidos a resección antes de iniciar el tratamiento. Durante el periodo de seguimiento, reapareció la pigmentación en seis pacientes (cuatro con hiperpigmentación postinflamatoria y dos recidivas). Las recidivas fueron tratadas con un margen de resección muy estrecho (1mm) y retratamiento con imiquimod 5%. Todas las modalidades de imiquimod reflejaron buena tolerancia de efectos secundarios y bajas tasas de recidiva. Imiquimod parece ser una opción muy versátil para tratar LM en candidatos idóneos (AU)

Topical imiquimod has been used off-label as monotherapy or adjuvant treatment for lentigo maligna. Our aim is to describe treatment modalities, clinical outcomes, and management of recurrence in patients receiving imiquimod for lentigo maligna. Patients from our unit with lentigo maligna or lentigo maligna melanoma treated with imiquimod 5% as monotherapy or in combination with surgery were included in this study. Fourteen cases were recruited (85.7% lentigo maligna and 14.3% lentigo maligna melanoma). Eight patients (57.1%) received imiquimod without surgery, and six (42.9%) underwent narrow excision before beginning treatment. During the follow-up period, pigmentation reappeared in 6 patients (4 postinflammatory hyperpigmentation and 2 relapses). Relapses were managed with very narrow excision (1mm margin) and retreatment with imiquimod 5%. All imiquimod modalities showed well-tolerated side effects and low recurrence rates, with long periods of follow-up. Imiquimod appears to be a versatile option for treating LM in suitable candidates (AU)

Clinical and histologic features associated with lentigo maligna clearance after imiquimod treatment.

BACKGROUND: Imiquimod cream may be used as a non-surgical treatment for lentigo maligna or as adjuvant therapy following excision to decrease the risk of recurrence. OBJECTIVES: To evaluate histologic and clinical factors associated with clinical clearance of lentigo maligna treated with imiquimod. METHODS: We performed a retrospective review of all patients diagnosed with lentigo maligna and treated with imiquimod between 1997 and 2019 at our academic institution. RESULTS: We observed clinical clearance in 93% (66/71) of participants who received adjuvant imiquimod following surgery and 79% (19/24) in the primary non-surgical treatment group over a median of 38 months of follow-up. In the adjuvant therapy group, positive surgical margins were associated with a decreased rate of clinical clearance when compared to cases with close (<1 mm) margins or background melanocytic dysplasia (83.3 vs. 100%, p = .01). The presence of an inflammatory response during treatment was associated with increased clearance (94.1 vs. 66.7%, p = .02). CONCLUSIONS: Adjuvant imiquimod treatment may decrease LM recurrence rates in cases with background melanocytic dysplasia or close margins. LM cases with positive surgical margins need close clinical follow-up given higher recurrence rates.

Case of large lentigo maligna melanoma of the scalp treated with 5% and 3. 75% Imiquimod

Abstract The paper presents a case of lentigo maligna melanoma of the scalp in an elderly patient treated for the nodular part with surgery and the residual melanoma in situ with 5% Imiquimod and subsequently with 3.75% Imiquimod (each concentration for 4 months, 5 times per week), with complete regression of the lesion. 3.75% Imiquimod, which is already used for the treatment of actinic keratosis, could be a useful weapon with the same effectiveness and fewer side effects compared to 5% Imiquimod.

A practical guide on the use of imiquimod cream to treat lentigo maligna.

Lentigo maligna (LM) is a common in situ melanoma subtype arising on chronically sun-damaged skin and mostly affects the head and neck region. Localisation in cosmetically sensitive areas, difficulty to obtain wide resection margins and advanced patient age/comorbidities have encouraged investigation of less invasive therapeutic strategies than surgery in managing complex cases of LM. Radiotherapy and imiquimod have emerged as alternative treatment options in this context. The treatment of LM with imiquimod cream can be challenging due to the nature of the disease including its often large size, variegated appearance, involvement of adnexal structures, poorly defined peripheral edge and frequent localisation close to sensitive structures such as the eyes and lips, and elderly patients with multiple comorbidities. Prolonged and unpredictable inflammatory reaction and side effects and compliance with a patient-delivered therapy can also be challenging. In the literature to date, studies evaluating the use of imiquimod to treat LM have utilised varying methodologies and provided short follow-up and these limitations have impaired the development of clear guidelines for dosage and management of side effects. Based on our multidisciplinary experience and review of the literature, we propose practical clinical strategies for the use of imiquimod for treating LM, detailing optimal administration procedures in various clinical scenarios and long-term management, with the aim of facilitating optimal patient outcomes.

Case of large lentigo maligna melanoma of the scalp treated with 5% and 3.75% Imiquimod.

The paper presents a case of lentigo maligna melanoma of the scalp in an elderly patient treated for the nodular part with surgery and the residual melanoma in situ with 5% Imiquimod and subsequently with 3.75% Imiquimod (each concentration for 4 months, 5 times per week), with complete regression of the lesion. 3.75% Imiquimod, which is already used for the treatment of actinic keratosis, could be a useful weapon with the same effectiveness and fewer side effects compared to 5% Imiquimod.

Topical Imiquimod for Lentigo Maligna: Survival Analysis of 103 Cases With 17 Years Follow-up.

Topical imiquimod 5% cream has been investigated as off-label primary or adjuvant treatment for melanoma in situ, lentigo maligna type (LM). Herein, we present the largest known case series of lentigo maligna treated with topical imiquimod, with up to 17 years of follow-up, and include a recurrence-free survival analysis. In this case series, 103 lesions were retrospectively evaluated for treatment response and recurrence following a course of topical imiquimod with or without tazarotene gel 0.1% pretreatment between January 1, 2002 and March 31, 2019, and prospectively followed through November 15, 2019. Over median follow-up of 5.1 years (mean = 6.2 years, S = 5.2 years, range, 0.08–17.1 years), including 29.1% LM with >10 years follow-up, we observed a response rate of 97.1% (100/103), with 8 local recurrences (8/100, 8.0%) developing at mean 2.9 years (SD: 2.7 years). Local recurrence was significantly associated with a history of failed excision (P= 0.001), <60 applications of imiquimod (P= 0.04) and partial clinical clearance (P= 0.0003). Recurrence-free survival analysis demonstrated significant risk-stratification for low and high-risk groups (P= 0.0001). Long term risk for recurrence showed significant differences among low- and high-risk cases, with low-risk cases demonstrating favorable long-term outcomes, comparable to conventional and staged surgery. Our observed low recurrence in a large case series with long-term follow-up suggests the efficacy of topical 5% imiquimod for LM and emphasizes the need for randomized control trials comparing imiquimod with, or as an adjunct to, surgical treatment. J Drugs Dermatol. 2021;20(3):346-348. doi:10.36849/JDD.5660.

Reflectance confocal microscopy and its role in the follow-up of a topical treatment for lentigo maligna.

BACKGROUND: In recent years, there has been an ongoing interest in topical treatment for lentigo maligna (LM) as imiquimod 5% cream owing to the localization of this tumor and the advanced age of patients; however, the efficacy of imiquimod 5% cream is controversial, and the rate of local relapses is about 25-53%. Reflectance confocal microscopy (RCM) is a noninvasive diagnostic tool useful not only for diagnostic purpose but also for monitoring the response to the local treatment of LM. Our aim was to demonstrate the role of RCM in the follow-up of a topical treatment with imiquimod 5% cream in clinical practice. METHODS: We report three patients with histopathologically confirmed LM who were not candidates for surgery and were successfully treated with imiquimod 5% cream. In such patients, dermatoscopic images and reflectance confocal microscopy were useful to evaluate treatment response and to verify long-term clinical benefits during the follow-up visits. RESULTS: No relapses were observed in our patients 18 months after the end of treatment; although, continuous follow-up visits are needed in these patients. CONCLUSIONS: In the case series presented herein, we highlight the importance of RCM as a noninvasive tool to monitor the efficacy of imiquimod to treat LM during and after treatment. Detailed confocal images of two of our patients allowed us to establish the persistence of atypical cells and to continue treatment, although clinical and dermatoscopic examinations showed "apparent complete remission" after the first cycle of therapy.