Video
Comment
Diagnosis and choice of treatment modality for cases of facial LM is a challenge, and there are a number of factors that may create even more of a clinical dilemma. Surgical excision is the treatment of choice for LM/LMM, and better results are achieved when using histologically controlled surgical procedures such as Mohs micrographic surgery, staged excision, or the "spaghetti technique."15-17 However, advanced patient age, multiple comorbidities (eg, coronary artery disease, deep vein thrombosis, other conditions requiring anticoagulation therapy), large lesion size in functionally or aesthetically sensitive areas, and indiscriminate borders on photodamaged skin may make surgical excision complicated or not feasible. Additionally, prior treatments to the affected area may further obscure clinical borders, complicating the diagnosis of recurrence/persistence when observed with the naked eye, dermoscopy, or Wood lamp. Because RCM can detect small amounts of melanin and has cellular resolution, it has been suggested as a great diagnostic tool to be combined with dermoscopy when evaluating lightly pigmented/amelanotic facial lesions arising on sun-damaged skin.18,19 In this case series, we highlighted these difficulties and showed how HRCM can be useful in a variety of scenarios, both pretreatment and posttreatment in complex LM/LMM cases.
Pretreatment Evaluation
Blind mapping biopsies of LM are prone to sample bias and depend greatly on biopsy technique; however, HRCM can guide mapping biopsies by detecting features of LM in vivo with high sensitivity.11 Due to the cosmetically sensitive nature of the lesions, many physicians are discouraged to do multiple mapping biopsies, making it difficult to assess the breadth of the lesion and occult invasion. Multiple studies have shown that occult invasion was not apparent until complete lesion excision was done.15,20,21 Agarwal-Antal et al20 reported 92 cases of LM, of which 16% (15/92) had unsuspected invasion on final excisional pathology. A long-standing disadvantage of treating LM with nonsurgical modalities has been the inability to detect occult invasion or multifocal invasion within the lesion. As described in patients 1, 4, and 5 in the current case series, utilizing real-time video imaging of the DEJ at the margins and within the lesion has allowed for the detection of deep atypical melanocytes suspicious for perifollicular infiltration and invasion. Knowing the depth of invasion before treatment is essential for not only counseling the patient about disease risk but also for choosing an appropriate treatment modality. Therefore, prospective studies evaluating the performance of RCM to identify invasion are crucial to improve sampling error and avoid unnecessary biopsies.
Surgical Treatment
Although surgery is the first-line treatment option for facial LM, it is not without associated morbidity, and LM is known to have histological subclinical extension, which makes margin assessment difficult. Wide surgical margins on the face are not always possible and become further complicated when trying to maintain adequate functional and cosmetic outcomes. Additionally, the margin for surgical clearance may not be straightforward for facial lesions. Hazan et al15 showed the mean total surgical margins required for excision of LM and LMM was 7.1 and 10.3 mm, respectively; of the 91 tumors initially diagnosed as LM on biopsy, 16% (15/91) had unsuspected invasion. Guitera et al2 reported that the presence of atypical cells within the dermal papillae might be a sign of invasion, which occasionally is not detected histologically due to sampling bias. Handheld RCM offers the advantage of a rapid real-time assessment in areas that may not have been amenable to previous iterations of the device, and it also provides a larger field of view that would be time consuming if performed using conventional RCM. Compared to prior RCM devices that were not handheld, the use of the HRCM does not need to attach a ring to the skin and is less bulky, permitting its use at the bedside of the patient or even intraoperatively.13 In our experience, HRCM has helped to better characterize subclinical spread of LM during the initial consultation and better counsel patients about the extent of the lesion. Handheld RCM also has been used to guide the spaghetti technique in patients with LM/LMM with good correlation between HRCM and histology.22 In our case series, HRCM was used in complex LM/LMM to delineate surgical margins, though in some cases the histologic margins were too close or affected, suggesting HRCM underestimation. Lentigo maligna margin assessment with RCM uses an algorithm that evaluates confocal features in the center of the lesion.1,2 Therefore, further studies using HRCM should evaluate minor confocal features in the margins as potential markers of positivity to accurately delineate surgical margins.
Nonsurgical Treatment Options
For patients unable or unwilling to pursue surgical treatment, therapies such as imiquimod or radiation have been suggested.23,24 However, the lack of histological confirmation and possibility for invasive spread has limited these modalities. Lentigo malignas treated with radiation have a 5% recurrence rate, with a median follow-up time of 3 years.23 Recurrence often can be difficult to detect clinically, as it may manifest as an amelanotic lesion, or postradiation changes can hinder detection. Handheld RCM allows for a cellular-level observation of the irradiated field and can identify radiation-induced changes in LM lesions, including superficial necrosis, apoptotic cells, dilated vessels, and increased inflammatory cells.25 Handheld RCM has previously been used to assess LM treated with radiation and, as in patient 2, can help define the radiation field and detect treatment failure or recurrence.12,25
Similarly, as described in patient 5, HRCM was utilized to monitor treatment with imiquimod. Many reports use imiquimod for treatment of LM, but application and response vary greatly. Reflectance confocal microscopy has been shown to be useful in monitoring LM treated with imiquimod,8 which is important because clinical findings such as inflammation and erythema do not correlate well with response to therapy. Thus, RCM is an appealing noninvasive modality to monitor response to treatment and assess the need for longer treatment duration. Moreover, similar to postradiation changes, treatment with imiquimod may cause an alteration of the clinically apparent pigment. Therefore, it is difficult to assess treatment success by clinical inspection alone. The use of RCM before, during, and after treatment provides a longitudinal assessment of the lesion and has augmented dermatologists' ability to determine treatment success or failure; however, prospective studies evaluating the usefulness of HRCM in the recurrent setting are needed to validate these results.
Limitations
Limitations of this technology include the time needed to image large areas; technology cost; and associated learning curve, which may take from 6 months to 1 year based on our experience. Others have reported the training required for accurate RCM interpretation to be less than that of dermoscopy.26 It has been shown that key RCM diagnostic criteria for lesions including melanoma and basal cell carcinoma are reproducibly recognized among RCM users and that diagnostic accuracy increases with experience.27 These limitations can be overcome with advances in videomosaicing that may streamline the imaging as well as an eventual decrease in cost with greater user adoption and the development of training platforms that enable a faster learning of RCM.28
Conclusion
The use of HRCM can help in the diagnosis and management of facial LMs. Handheld RCM provides longitudinal assessment of LM/LMM that may help determine treatment success or failure and has proven to be useful in detecting the presence of recurrence/persistence in cases that were clinically poorly evident. Moreover, HRCM is a notable ancillary tool, as it can be performed at the bedside of the patient or even intraoperatively and provides a faster approach than conventional RCM in cases where large areas need to be mapped.
In summary, HRCM may eventually be a useful screening tool to guide scouting biopsies to diagnose de novo LM; guide surgical and nonsurgical therapies; and evaluate the presence of recurrence/persistence, especially in large, complex, amelanotic or poorly pigmented lesions. A more standardized use of HRCM in mapping surgical and nonsurgical approaches needs to be evaluated in further studies to provide a fast and reliable complement to histology in such complex cases; therefore, larger studies need to be performed to validate this technique in such complex cases.
