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Improving Management and Patient Care in Lentigo Maligna by Mapping With In Vivo Confocal Microscopy

Pascale Guitera, MD, PhD; Fergal J. Moloney, MD; Scott W. Menzies, MBBS, PhD; Jonathan R. Stretch, MBBS, DPhil; Michael J. Quinn, MBBS; Angela Hong, MBBS, PhD; Gerald Fogarty, MBBS; Richard A. Scolyer, MD
JAMA Dermatol. 2013;149(6):692-698. doi:10.1001/jamadermatol.2013.2301.
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Importance Lentigo maligna (LM) is a clinical, pathologic, and therapeutic challenge with a higher risk of local recurrence than other types of melanoma correctly treated and also carries the cosmetically sensitive localization of head and neck.

Objective To determine whether in vivo reflectance confocal microscopy (RCM) mapping of difficult LM cases might alter patient care and management.

Design Analysis of LM and LM melanoma (LMM) in a series of patients with large facial lesions requiring complex reconstructive surgery and/or recurrent or poorly delineated lesions at any body sites were investigated.

Settings Two tertiary referral melanoma centers in Sydney, Australia.

Participants Thirty-seven patients with LM (including 5 with LMM) were mapped with RCM. Fifteen patients had a recurrent LM, including 9 with multiple prior recurrences. The LM was classified amelanotic in 10 patients, lightly pigmented in 9, and partially pigmented in 18.

Interventions The RCM images were obtained in 4 radial directions (allowing for anatomic barriers) for LM margin delineation using an RCM LM score previously described by our research team.

Main Outcome Measures Differences in the margin of LM as determined by RCM vs dermoscopy vs histopathologic analysis.

Results Seventeen of 29 patients (59%) with dermoscopically visible lesions had subclinical (RCM-identified) disease evident more than 5 mm beyond the dermoscopy margin (ie, beyond the excision margin recommended in published guidelines). The RCM mapping changed the management in 27 patients (73%): 11 patients had a major change in their surgical procedure, and 16 were offered radiotherapy or imiquimod treatment as a consequence of the RCM findings. Treatment was surgical in 17 of 37 patients. Surgical excision margins (based on the RCM mapping) were histopathologically involved in only 2 patients, each of whom had an LM lesion larger than 6 cm.

Conclusions and Relevance In vivo RCM can provide valuable information facilitating optimal patient care management.

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Figure 1. An 88-year-old man presented with macular pigmentation of the left cheek that had developed over many years. Purple lines indicate the length and width of the visible pigmentation. Yellow lines indicate the length and width of the tumor as determined by reflectance confocal microscopy (RCM). The center of 4 pen marks on the patient's skin indicates the site of biopsy. Areas examined by RCM correspond with the numbers on the image. This patient was surgically treated with complete excision (guided by RCM mapping), and no recurrence was found at 4-year follow-up. ND indicates not done; Pathol, pathologic assessment; +, diagnosed as lentigo maligna; −, diagnosed as negative margin.

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Figure 2. A 78-year-old woman with extensive pigmentation of her left cheek, 8 areas of which were examined by reflectance confocal microscopy (RCM). The area of lentigo maligna (LM) is delineated with the black line. The area mapped by RCM was excised, but a margin at the lower eyelid area was positive for LM. Subsequent re-excision of this margin was undertaken with no recurrence (at 18 months' follow-up). The facial areas marked X, Y, and Z are further illustrated in Figures 3, 4, and 5, each figure showing dermoscopic, RCM, and histopathologic images (histopathologic specimens taken from the RCM field). The facial area marked X showed atypical features of LM under all 3 evaluation techniques; the area marked Y is a negative margin; and the area marked Z showed features of an actinic lentigo.

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Figure 3. Images corresponding to area X in Figure 2. A, Dermoscopy image of the area of biopsy-proven lentigo maligna (LM). There are some areas of slate-gray globules and rhomboidal structures, and there are some asymmetric pigmented follicular structures (upper arrow). The lower arrow indicates artifact from a previous punch biopsy. B, Reflectance confocal microscopy (RCM) 8 × 8-mm mosaic at the dermoepidermal junction showing some atypical melanocytic cells and the distortion of the dermoepidermal junction (inset, detail of an RCM image, 0.5 × 0.5 mm, showing numerous bright, large [>20 μm], irregularly shaped cells [arrows] with a complete disorganization of the junction [nonedged papillae). C, Hematoxylin-eosin–stained specimen from the RCM field showing a lentiginous proliferation of atypical melanocytes with involvement of a skin appendage in chronically sun-damaged skin (original magnification ×100). These features are characteristic of LM.

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Figure 4. Images corresponding to area Y in Figure 2. A, Dermoscopy image showing ill-defined pigmentation with no clear feature of lentigo maligna (LM). B, Confocal image, 0.5 × 0.5 mm, showing a continuous layer of small monomorphous cells that are not very bright at the spinous layer. C, Hematoxylin-eosin–stained specimen from the RCM field showing atrophic epidermis with loss of rete ridges and severe dermal solar elastosis; there is mild patchy basal keratinocyte pigmentation but no evidence of LM (original magnification ×100).

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Figure 5. Images corresponding to area Z in Figure 2. A, Dermoscopy image showing poorly formed rhomboidal structures. B, Confocal image, 0.5 × 0.5 mm, showing some bright cells but not bigger than the surrounding keratinocytes (arrows); the honeycomb pattern of the keratinocytes is mildly distorted. C, Hematoxylin-eosin–stained specimen from the RCM field showing an actinic lentigo with increased basal keratinocyte pigmentation, elongated rete ridges, and focal mild keratinocyte atypia. There is no increase in melanocytes (original magnification ×100).




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