Mohs surgery for melanoma in situ

Mohs micrographic surgery is a valuable option for the treatment of melanoma in situ, especially lesions of the lentigo maligna subtype that are clinically ill defined. Complete peripheral margin assessment of a tumor's borders by means of frozen or permanent sections can help reduce the surgical defect size and maximize cure rate as compared with standard excision with preset 5-mm margins. This article reviews the different variations of Mohs micrographic surgery that are currently used for melanoma in situ.     

Lentigo maligna treated with 5% imiquimod cream

Lentigo maligna (LM) is considered to be an in-situ stage of lentigo maligna melanoma. Clinically, it presents as a pigmented macule, irregular in shape and tone. 30% to 35% of untreated lentigo malignas can progress into lentigo maligna melanoma. The treatment of choice for this pathology is surgical excision with margins of 0.5 cm. of clinically normal skin around the lesion, or Mohs microsurgery. Imiquimod is a topical immunomodulator that stimulates both acquired and innate immunity. We present the case of a patient with LM, treated with 5% imiquimod cream, with an excellent therapeutic response.     

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.     

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.     

[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.     

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.     

Tratamiento quirúrgico del lentigo maligno: cirugía convencional vs. Mohs diferida. Estudio retrospectivo de 62 casos

IntroductionSurgical excision with margins of 0.5 cm is the standard treatment for lentigo maligna (LM). Excision, however, is often incomplete as many of these tumors have indistinct borders.ObjectiveTo identify clinical predictors of subclinical extension in primary and recurrent LM of the head and thereby determine which lesions might require wider surgical margins.Material and methodsWe reviewed the clinical records of patients with LM of the head treated definitively with conventional surgical excision or slow micrographic Mohs surgery (MMS) at the dermatology department of Instituto Valenciano de Oncología between January 1993 and April 2011.ResultsSurgical margins larger than 0.5 cm were required in 69.2% of recurrent LM and 26.5% of primary LM. Factors associated with the need for wider margins were prior treatment that might have interfered with the clinical delineation of the border, lesions in the center of the face, and skin phototypes III to V.ConclusionsSurgical margins of 0.5 cm are inadequate for the treatment of a considerable number of LM lesions located on the head, particularly if these are recurrent. Slow MMS using paraffin-embedded sections appears to be the treatment of choice in such cases, particularly for recurrent lesions or lesions with poorly defined borders or possible subclinical extension.     

Mikrographisch kontrollierte Chirurgie (3D‐Histologie) beim Melanom

Frederic E. Mohs was the first to apply micrographic surgery in cutaneous surgery. As a result in the English literature, micrographic surgery (3D‐histology) is usually called Mohs micrographic surgery (MMS). Techniques of 3D‐histology have been applied in various skin tumours. The method is most suitable for tumours with continuous spread. Excisions with 3D‐histology can be performed with smaller initial safety margins. Thus less normal tissue is excised and often better cosmetic results can be obtained. Techniques of 3D‐histology such as the Mohs technique (MMS) and the “Tuebingen Cake” technique are compared with routine histopathology. In addition, the current status of 3D‐histology in cutaneous melanoma is assessed. Prospective randomized studies on 3D‐histology in cutaneous melanoma are not available. Nevertheless, 3D‐histology should usually be employed for lentigo maligna melanoma. In functionally and cosmetically important areas (face, hand, foot) 3D‐histology may allow reduced safety margins in other histological types of cutaneous melanoma.     

New approaches to surgery of lentigo maligna

Lentigo maligna (LM) is a pigmented lesion that occurs most commonly on the sun-exposed skin of the head and neck of an older patient. LM can be difficult to completely remove due to its occasional extensive subclinical extension. Surgical treatments, including standard excision and margin-controlled excision (Mohs micrographic surgery or rush permanent sections), are reviewed. Immunostains that can increase sensitivity and specificity of margin-controlled excision are discussed, and other nonscalpel treatments including destruction, topical imiquimod, radiation therapy and cryotherapy are briefly discussed. The gold standard treatment for LM is margin-controlled excision.     

Surgical margins for lentigo maligna and lentigo maligna melanoma: the technique of mapped serial excision

OBJECTIVES: To assess the margins required for excision of lentigo maligna (LM) and lentigo maligna melanoma (LMM) by the technique of mapped serial excision (MSE), and to assess the efficacy of MSE. DESIGN: An interventional, prospective, noncontrolled case series. SETTING: Tertiary referral, dermatologic surgery unit. PATIENTS: Consecutive patients with head and neck LM or LMM who underwent MSE between March 1, 1993, and October 31, 2002. INTERVENTION: The MSE of LM or LMM. MAIN OUTCOME MEASURES: The number of 5-mm levels for excision of LM and LMM and recurrence. RESULTS: One hundred sixty-one LMs or LMMs in 155 patients were treated. Thirty percent (37 of 125) of LMs required more than 5-mm margins. For LMMs less than 1 mm in Breslow thickness, 12% (4/32) required more than 10-mm margins. For primary tumors, 20% of LMs (18 of 91) required more than 5-mm margins, while 10% of LMMs less than 1 mm in Breslow thickness (2 of 21) required more than a 10-mm margin. For recurrent tumors, 56% of LMs (19/34) required more than a 5-mm margin. Mean follow-up of 38 months (range, 5-100 months) showed 4 recurrences (2%) after MSE. The extrapolated recurrence at 5 years was 5.0%. CONCLUSIONS: The current recommendations of 5-mm margins for LM and 10-mm margins for LMM less than 1 mm in Breslow thickness are often insufficient. Our results demonstrate the importance of margin-controlled excision, particularly in recurrent lesions. The use of MSE offers a high cure rate, in conjunction with tissue conservation.     

Management of lentigo maligna and lentigo maligna melanoma with staged excision: a 5-year follow-up

OBJECTIVE: To assess the long-term cure rate for treatment of lentigo maligna (LM) and lentigo maligna melanoma (LMM) by means of a staged, margin-controlled, vertical-edged excision with rush permanent specimens and a radial sectioning technique. DESIGN: Retrospective follow-up study. SETTING: University-affiliated and private-practice dermatologic surgery clinics. PATIENTS: Fifty-nine patients treated for 55 LMs and 7 LMMs between January 1, 1990, and December 31, 2001. INTERVENTIONS: The technique included vertical excision with initial 2- to 3-mm margins examined by rush permanent sections (prepared and read within 24 hours). Further excision took place as guided by histologic findings. Data on patient and lesion characteristics were obtained via a medical chart review. Patients were then contacted and examined for local recurrence. Biopsies were performed on all patients with possible recurrence on clinical examination. MAIN OUTCOME MEASURES: Local recurrence of LM or LMM. RESULTS: After a mean follow-up of 57 months (median, 54 months; 293.8 person-years), 95% of patients were free of recurrence. Three patients had local recurrence and no patients had evidence of metastasis. Two of the 3 local recurrences were of previously excised LM, and 1 was of an LMM. Half (32) of all lesions required 2 or more stages. One required more than 4 stages. The average margin of excision was 0.55 cm. Three of the 58 lesions read as LM on biopsy were found to have invasive disease (LMM) at the time of definitive excision. CONCLUSIONS: The technique described herein for the treatment of LM and LMM provides a long-term disease-free survival of 95%. The cure rate is greater than that reported for standard excision and is similar to that for other margin-control techniques. To our knowledge, this is the largest reported study and has the longest follow-up for this excision method for LM and LMM.     

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.     

Use of digital epiluminescence microscopy to help define the edge of lentigo maligna

OBJECTIVE: To compare identification of the border of lentigo maligna (LM) with digital epiluminescence microscopy (DELM) with clinical and Wood light assessment. DESIGN: The borders of lesions identified clinically with the Wood light, with DELM, and after excision by Mohs micrographic surgery were traced onto plastic sheets. The borders defined on the tracings were compared for congruence and mean surface area. SETTING: Cardinal Bernardin Cancer Center for Skin Cancer, Loyola University Health System, Maywood, Ill. PATIENTS: Twenty-six consecutive patients with LM of the head and neck. MAIN OUTCOME MEASURES: Results of the comparison of the outlines of the borders and the mean surface area identified by the 4 methods. RESULTS: The border determined by clinical examination was smaller than that determined with the Wood lamp or by DELM. Most lesions underwent an additional excision 5 mm beyond the DELM-defined border. The DELM pattern of LM with asymmetric follicular openings and dark brown rhomboidal structures changed at the periphery and became a pigmented thin mesh that was associated with the histopathological features of melanoma in situ. More homogeneous pigmented areas extending from the LM were associated with the pathologic features of melanocytic hyperplasia. CONCLUSIONS: Visualization of LM by DELM (dermoscopy) helps to guide resection. Because LM arises in sun-damaged skin with melanocytic hyperplasia, determining the tumor-free margin requires the judgment of an experienced physician.     

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.     

Lentigo Maligna: Review of Salient Characteristics and Management

Lentigo maligna is a melanocytic neoplasm, often regarded as ‘melanoma in situ,’ which may progress to lentigo maligna melanoma. Lentigo maligna clinically presents as a pigmented, asymmetric macule that originates on the head and neck and spreads slowly. The preferred method for diagnosing lentigo maligna is excisional biopsy. Histology shows proliferation of atypical melanocytes at the epidermal–dermal junction in small nests or single cells. The differential diagnosis includes solar lentigo, seborrheic keratosis, lichen planus-like keratosis, pigmented actinic keratosis, and melanocytic nevus. Stains used in diagnosis include hematoxylin and eosin, HMB-45, MART-1/Melan-A, Mel-5, and S-100. Surgical excision is the preferred treatment for lentigo maligna. Second-line techniques include medical (topical imiquimod) and destructive therapy.     

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.     

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.     

Use of in vivo confocal microscopy in malignant melanoma: an aid in diagnosis and assessment of surgical and nonsurgical therapeutic approaches

BACKGROUND: Melanomas with poorly defined borders, lack of pigmentation, lentiginous extension, and location in cosmetically sensitive regions represent diagnostic and therapeutic challenges. Repeated surgical reexcisions are frequently required to achieve tumor-free margins. The use of reflectance mode confocal microscopy as an noninvasive method has shown to be a promising tool for diagnosing pigmented lesions in vivo. OBSERVATIONS: We report 3 clinical cases of melanoma: amelanotic melanoma (case 1), locally recurrent melanoma (case 2), and lentigo maligna melanoma (case 3). In case 1, in vivo confocal microscopy was instrumental in making the diagnosis and in monitoring the response to imiquimod therapy for in situ residual disease. It was also used to successfully delineate preoperative surgical margins in cases 2 and 3. CONCLUSION: As new methods for treating melanoma emerge and become more available, confocal microscopy can play a significant role by improving sensitivity in diagnosis, by increasing rates of successful initial excision, and by serving as a noninvasive means of monitoring therapy.     

Imiquimod and lentigo maligna: a search for prognostic features in a clinicopathological study with long-term follow-up

Background  Melanoma in situ /lentigo maligna (LM) is a potential precursor of LM melanoma. It occurs most commonly in elderly individuals on sun-exposed skin of the head and neck. Although surgical excision is the treatment of choice, this may not be desirable or feasible for large lesions at functionally or cosmetically important sites. Imiquimod is a topical immunomodulator which can generate a local cytotoxic response with potentially antiviral and antitumour effects.
Objectives  To present our experience of LM treated with imiquimod.
Methods  A retrospective review was performed of all patients with facial LM treated in our unit with topical imiquimod between January 2001 and December 2006. Pretreatment diagnostic biopsies were also reviewed and histologically graded.
Results  Forty-eight patients were treated with imiquimod. There were 37 responders and 11 treatment failures (of whom two were 'partial responders'). Of the 37 responders, 31 showed a clinical inflammatory response to imiquimod. One patient in whom treatment failed subsequently developed invasive disease. The mean follow-up duration was 49 months. We could not identify histological features of prognostic significance. However, the ability to develop an inflammatory reaction to imiquimod was a strong predictor of therapeutic benefit.
Conclusions  We consider imiquimod to have a role in the treatment of LM in patients in whom surgery may be contraindicated or for those in whom the cosmetic or functional consequences may be considerable. Until better characterized, its use should probably be confined to centres with experience in the detection and treatment of LM and melanoma.     

Mohs' micrographic surgery using frozen sections alone may be unsuitable for detecting single atypical melanocytes at the margins of melanoma in situ

BACKGROUND: It remains questionable whether micrographic surgery with frozen sections is an appropriate technique for excision of melanoma in situ (MIS) of the lentigo maligna type. Advocates of the technique have interpreted MIS as being histologically defined by nests and contiguous atypical melanocytes on the basal layer. Others, however, have viewed the periphery of MIS as consisting of scattered single atypical melanocytes, a finding that may be difficult or impossible to establish on frozen sections. OBJECTIVES: To examine the reliability of micrographic surgery using frozen sections interpreted by an experienced Mohs' surgeon, in the excision of MIS. METHODS: From a total of 154 specimens, frozen sections from the 50 specimens with margins that were considered difficult to interpret were thawed, sent for routine processing and then examined 'blind' by a dermatopathologist. RESULTS: Using the dermatopathologist's report on paraffin-embedded sections as a reference point, the sensitivity and specificity of frozen sections were calculated to be 59% and 81%, respectively. CONCLUSIONS: Using these histological criteria, micrographic surgery with frozen sections alone is unreliable in the excision of MIS.