[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 (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.     

Cryotherapy for lentigo maligna

Eleven patients, 10 with lentigo maligna (LM) and one with lentigo maligna melanoma (LMM), were treated with cryotherapy. The symptoms cleared in all patients except one with LM. There were recurrences in four patients and three cleared with further treatment.     

The risk of progression of lentigo maligna to lentigo maligna melanoma

An analysis is presented which estimates the risk of progression of lentigo maligna (LM) to lentigo maligna melanoma (LMM) in U.S. whites using three data sources: the Health and Nutrition Examination Survey I for estimation of the age-specific prevalence of LM; the Surveillance, Epidemiology, and End Results Program for estimation of the age-specific incidence of melanoma; and the data from three melanoma registries for estimation of the age-specific case fraction of LMM among all invasive melanomas. The risk varies with age and is likely to be greater than estimated here for patients who present themselves for evaluation of changes in a lesion of LM. Our analysis suggests that the risk of progression from LM to LMM is substantially lower than is commonly believed.     

Increasing incidence of lentigo maligna melanoma subtypes: northern California and national trends 1990-2000

Worldwide, lentigo maligna melanoma (LMM) comprises 4%-15% of cutaneous melanoma and occurs less commonly than superficial spreading or nodular subtypes. We assessed the incidence of melanoma subtypes in regional and national Surveillance, Epidemiology, and End Results (SEER) cancer registry data from 1990 to 2000. Because 30%-50% of SEER data were not classified by histogenetic type, we compared the observed SEER trends with an age-matched population of 1024 cases from Stanford University Medical Center (SUMC) (1995-2000). SEER data revealed lentigo maligna (LM) as the most prevalent in situ subtype (79%-83%), and that LMM has been increasing at a higher rate compared with other subtypes and to all invasive melanoma combined for patients aged 45-64 and > or =65 y. The SUMC data demonstrated LM and LMM as the only subtypes increasing in incidence over the study period. In both groups, LM comprised > or =75% of in situ melanoma and LMM > or =27% of invasive melanoma in men 65 y and older. Regional and national SEER data suggest an increasing incidence of LM and LMM, particularly in men > or =age 65. An increased incidence of LM subtypes should direct melanoma screening to heavily sun-exposed sites, where these subtypes predominate.     

Topical imiquimod immunotherapy in the management of lentigo maligna

Melanoma in situ of the lentigo maligna (LM) type is a precursor lesion of LM melanoma. It most commonly occurs in elderly individuals, on the head and neck. Although surgical excision is recommended, this may not be practical for large lesions at cosmetically sensitive sites. In addition, histological changes commonly extend beyond the clinical margins of the lesion. This study describes the use of imiquimod 5% cream as topical immunotherapy in the management of lentigo maligna. Twelve patients (average age 63 years, 10 female), of biopsy-proven facial LM were treated with topical imiquimod, three times a week for 6 weeks. In the absence of an inflammatory response, patients were asked to apply the treatment daily. Seven showed clearance of the LM clinically and histologically. A further three patients showed clearance histologically with persisting pigmentation due to dermal melanin and melanophages. Thus, 10 of 12 patients cleared with no relapse after a median follow-up of 6 months. Two patients failed to respond to imiquimod and their lesions were treated with surgical excision. Imiquimod was well tolerated, except in three patients who experienced an intense inflammatory response. Two of these also developed secondary infection. Imiquimod 5% cream appears to offer a potential noninvasive method for the treatment of lentigo maligna.     

Prolonged evolution of a lentigo maligna

Lentigo maligna (LM) is a melanocytic lesion which is a potential precursor to melanoma and often has a prolonged intraepidermal growth phase before evolving into lentigo maligna melanoma (LMM). LM is also noted for its tendency to locally recur after treatment. We present a patient who had a persistent LM on her left cheek which, despite multiple excisions, persisted and transformed into a partially amelanotic LMM roughly three decades later. Our patient's course was also notable for this melanoma recurring at the edge of, and subsequently migrating into, a previously placed skin graft.     

Following lentigo maligna may not prevent the development of life-threatening melanoma.

BACKGROUND--Management of lentigo maligna (Hutchinson's melanotic freckle, in situ lentigo maligna melanoma) by regular observation relies on the detection of invasive melanoma before it has developed significant life-threatening potential. Recent studies indicate that lentigo maligna melanoma does not have a better prognosis than other forms of melanoma. OBSERVATIONS--A case is reported of an amelanotic lentigo maligna that evolved from a macular lesion to a deeply invasive, amelanotic, lentigo maligna melanoma within 6 months. The melanoma was Clark level IV and measured 3.0 mm in maximum tumor thickness. CONCLUSIONS--Observation of lentigo maligna at 6-month intervals would not seem to be sufficiently reliable in detecting the development of invasive lentigo maligna melanoma before it becomes a life-threatening disease. Early surgical excision is the treatment of choice.     

Oestrogen and progesterone receptors in lentigo maligna

We have measured oestrogen and progesterone binding in specimens of histopathologically confirmed lentigo maligna (LM) lesions excised from five elderly white men, using a dextran-coated charcoal method. Oestrogen binding was observed in four of the five specimens, and progesterone binding in all five. Marginal normal skin showed only non-specific binding for oestrogen and progesterone. The presence of steroid hormone receptors in LM suggests the possibility that hormone responsiveness may be relevant in the transformation of a lentigo maligna into malignant melanoma.     

Recurrent lentigo maligna as amelanotic lentigo maligna melanoma

Amelanotic lentigo maligna and lentigo maligna melanoma are extremely rare tumours. Even rarer is a recurrent amelanotic lentigo maligna or amelanotic lentigo maligna melanoma at the site of a previously removed pigmented lentigo maligna. We describe two cases of recurrent amelanotic lentigo maligna melanoma manifesting as erythematous plaques evolved from previously excised pigmented lentigo maligna.     

Lentigo maligna and lentigo maligna melanoma

Lentigo maligna (LM) is a pigmented lesion that occurs on the sun-exposed skin, particularly the head and neck areas, of an older patient. The lesion increases in size and at some point, often many years after its onset, may become lentigo maligna melanoma (LMM). For this reason, most authors consider LM a form of melanoma in situ. Treatment includes surgical or destructive modalities; the preferred form of therapy is surgical removal. Histopathologic features include a proliferation of atypical melanocytes along the basal layer of the epidermis and adnexal structures. This article discusses the clinical, histopathologic, and epidemiologic features of LM. The prognosis and treatment of LM are reviewed. Although the lifetime risk of the development of LMM is unclear, LMM is discussed briefly.     

Fractionated radiotherapy of lentigo maligna and lentigo maligna melanoma in 64 patients

Between 1987 and 1998, 64 patients with lentigo maligna (LM) (n = 42) or lentigo maligna melanoma (LMM) (n = 22) were treated by fractionated radiotherapy. In all 22 patients with LMM, excision of the nodular part of the LMM was performed before radiation of the residual lentiginous tumor. During the follow-up period of 1 to 96 months (mean, 23 months; median, 15 months), none of the 42 patients with LM displayed any signs of recurrence of LM after radiation therapy alone. Of the 22 patients with LMM, only 2 patients showed local recurrence of the tumor, salvaged by excision in both cases. One patient with LMM suffered from metastatic disease without local recurrence of the melanoma 44 months after radiation therapy. The cosmetic results of radiotherapy were good or excellent in the vast majority of patients, with only a few experiencing hypopigmentation or hyperpigmentation in the irradiated area. Fractionated radiation therapy with superficial x-rays is an effective method of treatment of LM associated with low morbidity and leading to clinical results comparable to those of surgical excision.     

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.     

Lentigo maligno

Lentigo maligna is a type of in situ melanoma. It develops mainly in middle-aged and elderly individuals on areas of the skin chronically exposed to sunlight. It progresses to its invasive form, lentigo maligna melanoma, in 5% to 50% of cases. Management of lentigo maligna is open to debate, with a notable lack of randomized trials and specific guidelines and protocols. Early diagnosis and treatment is necessary to achieve cure if possible and prevent progression to invasive melanoma with the corresponding risk of metastasis. The treatment of choice for lentigo maligna is surgery. When surgery is not possible, other alternatives are available although outcomes and rates of recurrence are variable. The objective of this study was to review the diagnostic methods and criteria for lentigo maligna, as well as the different surgical options and alternatives to surgery, in order to provide information on the best approach in each case.     

Dubreuilh melanoma: and epidemiologic and prognostic study

BACKGROUND: Lentigo maligna melanoma is a specific histoclinical type of melanoma. We studied the epidemiologic features of lentigo maligna melanoma (Dubreuilh's melanoma) and compared prognosis with other types of melanoma. PATIENTS AND METHODS: A retrospective review of 516 cases of cutaneous melanomas, seen from 1985 to 1997, identified 29 cases of lentigo maligna melanoma. Epidemiologic, clinical and prognostic data were collected using a common scoring system for all patients. The chi-squared test, univariate log rank analysis, Cox multiple regression model for multivariate analysis, and actuarial survival curves were applied. RESULTS: The 29 cases of lentigo maligna melanoma (16 women, 13 men) accounted for 5.9 p. 100 of all melanomas. Mean age at diagnosis was 73 years compared with 54 years for others melanomas. Predominant localization was head and neck. There was no prior history of nevi compared with 50 p. 100. Mean delay to diagnosis was 4 years versus 1 year. All patients have had an occupation with to sun exposure. Mean tumoral thickness was 2 mm. Survival was the same as for extensive superficial melanomas and better than for nodular melanomas. Multivariate analysis showed that prognosis was not better in case of lentigo maligna melanoma. Tumoral thickness was the main prognosis factor. DISCUSSION: Our findings confirmed the specific nature of lentigo maligna melanoma and suggested that sun exposure plays an important role. Multivariate analysis did not show that prognosis was any better in case of lentigo maligna melanoma than in other types of melanoma. The thickness of the tumor must be taken into account as for other melanomas.     

Cryotherapy for lentigo maligna — is clinical acumen combined with a single punch biopsy good enough for staging?

Aim We aimed to clarity the effectivenes of our staging of LM over a I-year period. Background Cryosurgery has become accepted as a simple and effective treatment for lentigo maligna (LM) but not necessarily lentigo maligna melanoma (LMM). Pigmented epithelial cells are extremely sensitive to cold injury. If adequate freezing is delivered to the proper depth into the dermal appendages, LM should be eradicated. However, if the initial staging does not detect invasion the lesion may be inadequately treated. Methods Over 1 year prospectively. all patients presenting with LM(n= 12) wore stayed clinically by experienced dermatologists and by a single punch biopsy. This was then checked by complete excision of the lesion. Results In 9 patients the clinical and punch biopsy diagnosis was confirmed after excision. Two melanomas were missed clinically but detected on punch biopsy. In one patient the punch biopsy described a “LM with probable invasion elsewhere in the lesion”. Surgical excision yielded a melanoma, 0.8 mm thick. Clark's level 4. In a second patient, punch biopsy diagnosed superficial spreading melanoma (-SSM) in situ, confirmed on excision. Conclusions We therefore feel that clinical diagnosis combined with a single punch biopsy will diagnose invasion when present. We emphasise that cryotherapy should not be performed without punch biopsy confirmation of the clinical diagnosis.     

Amelanotic lentigo maligna managed with topical imiquimod as immunotherapy

Clinically amelanotic lentigo maligna often resembles an inflammatory lesion rather than a melanoma in situ. We present two cases of extensive amelanotic lentigo maligna presenting as gradually enlarging erythematous patches on the faces of women following incomplete excisions of lentigo maligna. Because of their site and size, therapeutic options were limited; the lesions have, however, resolved (clinically and histologically) following the topical application of 5% imiquimod cream. We discuss the rationale for the use of imiquimod in the treatment of lentigo maligna.     

Amelanotic lentigo maligna melanoma manifesting as a dermatitislike plaque

A 72-year-old man with a previous history of an amelanotic melanoma on his left forearm had an erythematous plaque excised from his right shoulder. Although the clinical impression was a dermatitis, a biopsy specimen revealed an amelanotic lentigo maligna melanoma. To our knowledge, this is the first patient described with an amelanotic lentigo maligna melanoma as a second primary tumor to an apparent previous amelanotic melanoma, manifesting as a dermatitislike plaque.     

Amelanotic malignant melanoma following cryosurgery for atypical lentigo maligna

Cryosurgery is an alternative treatment option to surgical excision for lentigo maligna. Clinical evidence of recurrence is usually characterized by repigmentation at the treated site. We report two patients who developed amelanotic malignant melanoma following cryosurgery for a pigmented lentigo maligna. These cases illustrate the potential risk of treating lentigo maligna with cryosurgery.     

Utilidad clínica de la microscopia confocal de reflectancia en el manejo del lentigo maligno melanoma

Facial lentigo maligna melanoma can be a diagnostic challenge in daily clinical practice as it has similar clinical and morphological features to other lesions such as solar lentigines and pigmented actinic keratoses. Confocal microscopy is a noninvasive technique that provides real-time images of the epidermis and superficial dermis with cellular-level resolution. We describe 3 cases of suspected facial lentigo maligna that were assessed using dermoscopy and confocal microscopy before histopathology study. In the first case, diagnosed as lentigo maligna melanoma, presurgical mapping by confocal microscopy was performed to define the margins more accurately. In the second and third cases, with a clinical and dermoscopic suspicion of lentigo maligna melanoma, confocal microscopy was used to identify the optimal site for biopsy.