Lentigo maligna (LM) is a subtype of melanoma in situ that typically develops on sun-damaged skin. Presentation may be quite subtle and delayed diagnosis is common. Clinical margins are often ill defined. Histologic evaluation can be difficult due to the widespread atypical melanocytes that are present in the background of long-standing sun damage. Recurrence following standard therapies is common.
To review the clinical features, histopathology, and treatment options for LM. Emphasis is placed on recent advances in the treatment of LM.
The estimated lifetime risk of LM progressing to LM melanoma is 5%. Standard excision of LM with 5 mm margins is insufficient in 50% of cases. The recurrence rate with standard excision ranges from 8 to 20%. Mohs surgery and staged excision may offer better margin control and lower recurrence rates (4-5%). Estimates of recurrence rates following nonsurgical therapies such as cryosurgery, radiotherapy, electrodessication and curettage, laser surgery, and topical medications range from 20 to 100% at 5 years.
Adequate treatment of LM requires a comprehensive knowledge of the diagnostic features, histopathology, and treatment options. Surgical modalities with meticulous evaluation of tissue margins appears to offer the lowest rates of disease recurrence.
"As with SSM, it is only after vertical spread into the dermis that the lesions present a serious threat (Smoller, 2006). Nevertheless, LMM is very different from SSM. Lentigo maligna melanoma is less frequently derived from naevi, has a much later age-of-onset, exhibits characteristic changes in the epidermis (atrophy) and dermis (solar elastosis), and shows a distinct pattern of MC distribution (lentiginous versus pagetoid spread) (reviewed in McKenna et al., 2006). Hence, LMM appears to develop via a unique pathogenic mechanism dominated by chronic sun damage (CSD) over many decades. "
[Show abstract][Hide abstract] ABSTRACT: Phenotypic and molecular heterogeneity in human melanoma has impaired efforts to explain many of the clinically important features of melanoma. For example, many of the underlying mechanisms that might predict age-of-onset, time to metastasis and other key elements in melanoma progression remain unknown. Furthermore, melanoma staging used to predict outcome and treatment has not yet moved beyond a basic phenotypic classification. While molecularly targeted therapies show great promise for melanoma patients, establishing accurate animal models that recapitulate human cutaneous melanoma progression remains a priority. We examine the relevance of mice as models for human melanoma progression and for key molecular and histopathologic variants of melanoma. These mice may be used as preclinical models to probe the relationships between causative mutations, disease progression and outcome for molecularly targeted therapeutics. We ask how new mouse models, or more detailed histopathologic and molecular analyses of existing mouse models, may be used to advance our understanding of genotype-phenotype correlations in this tumour type. This necessarily involves a consideration of the utility of mice as models for ultraviolet radiation-induced melanoma, and how this might be improved.
"Furthermore, determination of the peripheral margins of LM clinically and pathologically also represents another challenge . Clinically, LM is often amelanotic peripherally, and can spread far beyond the visible margins (McKenna et al., 2006). Dermoscopy (Schiffner et al., 2000; Robinson, 2004; Stante et al., 2005) and Wood's light examination (Jeneby et al., 2001) have been described as useful techniques to better define the extent of the lesion. "
[Show abstract][Hide abstract] ABSTRACT: Limited studies have reported the in vivo reflectance confocal microscopy (RCM) features of lentigo maligna (LM). A total of 64 RCM features were scored retrospectively and blinded to diagnosis in a consecutive series of RCM sampled, clinically equivocal, macules of the face (n=81 LM, n=203 benign macules (BMs)). In addition to describing RCM diagnostic features for LM (univariate), an algorithm was developed (LM score) to distinguish LM from BM. This comprised two major features each scoring +2 points (nonedged papillae and round large pagetoid cells > 20 microm), and four minor features; three scored +1 point each (three or more atypical cells at the dermoepidermal junction in five 0.5 x 0.5 mm(2) fields, follicular localization of atypical cells, and nucleated cells within the dermal papillae), and one (negative) feature scored -1 point (a broadened honeycomb pattern). A LM score of > or = 2 resulted in a sensitivity of 85% and specificity of 76% for the diagnosis of LM (odds ratio (OR) for LM 18.6; 95% confidence interval: 9.3-37.1). The algorithm was equally effective in the diagnosis of amelanotic lesions and showed good interobserver reproducibility (87%). In a test set of 29 LMs and 44 BMs, the OR for LM was 60.7 (confidence interval: 11.9-309) (93% sensitivity, 82% specificity).
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