Original Research

Handheld Reflectance Confocal Microscopy to Aid in the Management of Complex Facial Lentigo Maligna

Cutis. 2017 May;99(5):346-352

Brian P. Hibler, MD

Oriol Yélamos, MD

Miguel Cordova, MD

Heidy Sierra, PhD

Milind Rajadhyaksha, PhD

Kishwer S. Nehal, MD

Anthony M. Rossi, MD

Diagnosis and management of lentigo maligna (LM) and LM melanoma (LMM) is challenging. Novel noninvasive imaging technologies such as reflectance confocal microscopy (RCM) have advanced the ability to better diagnose and monitor challenging lesions. In addition, the new handheld RCM (HRCM) together with the use of videomosaics has allowed an accurate evaluation of large lesions in concave/convex areas of the body (eg, the face). Herein, we review the impact of HRCM in the detection, treatment decision-making, and monitoring of 5 cases of complex facial LM/LMM. In the cases presented, HRCM enabled the detection of subclinical margins, presence of invasion, detection of persistence/recurrence, and monitoring of surgical and nonsurgical therapies. In this preliminary report, our results suggest that HRCM is a versatile ancillary tool in pretreatment decision-making, intraoperative surgical mapping, and posttreatment monitoring of complex facial LM/LMM.

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Practice Points

Diagnosis and management of lentigo maligna (LM) and LM melanoma (LMM) is challenging due to their ill-defined margins and location mainly on the head and neck.
Handheld reflectance confocal microscopy (RCM) has high diagnostic accuracy for LM/LMM and can be used in curved locations to assess large lesions.
Handheld RCM can be a versatile tool in pretreatment decision-making, intraoperative surgical mapping, and posttreatment monitoring of both surgical and nonsurgical therapies for complex facial LM/LMM.

References

Guitera P, Moloney FJ, Menzies SW, et al. Improving management and patient care in lentigo maligna by mapping with in vivo confocal microscopy. JAMA Dermatol. 2013;149:692-698.
Guitera P, Pellacani G, Crotty KA, et al. The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face. J Invest Dermatol. 2010;130:2080-2091.
Pellacani G, Guitera P, Longo C, et al. The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions. J Invest Dermatol. 2007;127:2759-2765.
Segura S, Puig S, Carrera C, et al. Development of a two-step method for the diagnosis of melanoma by reflectance confocal microscopy. J Am Acad Dermatol. 2009;61:216-229.
Hofmann-Wellenhof R, Pellacani G, Malvehy J, et al. Reflectance Confocal Microscopy for Skin Diseases. New York, NY: Springer; 2012.
Pellacani G, Farnetani F, Gonzalez S, et al. In vivo confocal microscopy for detection and grading of dysplastic nevi: a pilot study. J Am Acad Dermatol. 2012;66:E109-E121.
Nadiminti H, Scope A, Marghoob AA, et al. Use of reflectance confocal microscopy to monitor response of lentigo maligna to nonsurgical treatment. Dermatol Surg. 2010;36:177-184.
Alarcon I, Carrera C, Alos L, et al. In vivo reflectance confocal microscopy to monitor the response of lentigo maligna to imiquimod. J Am Acad Dermatol. 2014;71:49-55.
Fraga-Braghiroli NA, Stephens A, Grossman D, et al. Use of handheld reflectance confocal microscopy for in vivo diagnosis of solitary facial papules: a case series. J Eur Acad Dermatol Venereol. 2014;28:933-942.
Kose K, Cordova M, Duffy M, et al. Video-mosaicing of reflectance confocal images for examination of extended areas of skin in vivo. Br J Dermatol. 2014;171:1239-1241.
Menge TD, Hibler BP, Cordova MA, et al. Concordance of handheld reflectance confocal microscopy (RCM) with histopathology in the diagnosis of lentigo maligna (LM): a prospective study [published online January 27, 2016]. J Am Acad Dermatol. 2016;74:1114-1120.
Hibler BP, Connolly KL, Cordova M, et al. Radiation therapy for synchronous basal cell carcinoma and lentigo maligna of the nose: response assessment by clinical examination and reflectance confocal microscopy. Pract Radiat Oncol. 2015;5:E543-E547.
Hibler BP, Cordova M, Wong RJ, et al. Intraoperative real-time reflectance confocal microscopy for guiding surgical margins of lentigo maligna melanoma. Dermatol Surg. 2015;41:980-983.
Kose K, Gou M, Yelamos O, et al. Video-mosaicking of in vivo reflectance confocal microscopy images for noninvasive examination of skin lesions [published February 6, 2017]. Proceedings of SPIE Photonics West. doi:10.1117/12.2253085.
Hazan C, Dusza SW, Delgado R, et al. Staged excision for lentigo maligna and lentigo maligna melanoma: a retrospective analysis of 117 cases. J Am Acad Dermatol. 2008;58:142-148.
Etzkorn JR, Sobanko JF, Elenitsas R, et al. Low recurrence rates for in situ and invasive melanomas using Mohs micrographic surgery with melanoma antigen recognized by T cells 1 (MART-1) immunostaining: tissue processing methodology to optimize pathologic staging and margin assessment. J Am Acad Dermatol. 2015;72:840-850.
Gaudy-Marqueste C, Perchenet AS, Tasei AM, et al. The "spaghetti technique": an alternative to Mohs surgery or staged surgery for problematic lentiginous melanoma (lentigo maligna and acral lentiginous melanoma). J Am Acad Dermatol. 2011;64:113-118.
Guitera P, Menzies SW, Argenziano G, et al. Dermoscopy and in vivo confocal microscopy are complementary techniques for diagnosis of difficult amelanotic and light-coloured skin lesions [published online October 12, 2016]. Br J Dermatol. 2016;175:1311-1319.
Borsari S, Pampena R, Lallas A, et al. Clinical indications for use of reflectance confocal microscopy for skin cancer diagnosis. JAMA Dermatol. 2016;152:1093-1098.
Agarwal-Antal N, Bowen GM, Gerwels JW. Histologic evaluation of lentigo maligna with permanent sections: implications regarding current guidelines. J Am Acad Dermatol. 2002;47:743-748.
Gardner KH, Hill DE, Wright AC, et al. Upstaging from melanoma in situ to invasive melanoma on the head and neck after complete surgical resection. Dermatol Surg. 2015;41:1122-1125.
Champin J, Perrot JL, Cinotti E, et al. In vivo reflectance confocal microscopy to optimize the spaghetti technique for defining surgical margins of lentigo maligna. Dermatolog Surg. 2014;40:247-256.
Fogarty GB, Hong A, Scolyer RA, et al. Radiotherapy for lentigo maligna: a literature review and recommendations for treatment. Br J Dermatol. 2014;170:52-58.
Swetter SM, Chen FW, Kim DD, et al. Imiquimod 5% cream as primary or adjuvant therapy for melanoma in situ, lentigo maligna type. J Am Acad Dermatol. 2015;72:1047-1053.
Richtig E, Arzberger E, Hofmann-Wellenhof R, et al. Assessment of changes in lentigo maligna during radiotherapy by in-vivo reflectance confocal microscopy--a pilot study. Br J Dermatol. 2015;172:81-87.
Gerger A, Koller S, Kern T, et al. Diagnostic applicability of in vivo confocal laser scanning microscopy in melanocytic skin tumors. J Invest Dermatol. 2005;124:493-498.
Farnetani F, Scope A, Braun RP, et al. Skin cancer diagnosis with reflectance confocal microscopy: reproducibility of feature recognition and accuracy of diagnosis. JAMA Dermatol. 2015;151:1075-1080.
Rajadhyaksha M, Marghoob A, Rossi A, et al. Reflectance confocal microscopy of skin in vivo: from bench to bedside [published online October 27, 2016]. Lasers Surg Med. 2017;49:7-19.

Lentigo maligna (LM) and LM melanoma (LMM) represent diagnostic and therapeutic challenges due to their heterogeneous nature and location on cosmetically sensitive areas. Newer ancillary technologies such as reflectance confocal microscopy (RCM) have helped improve diagnosis and management of these challenging lesions.^1,2

Reflectance confocal microscopy is a noninvasive laser system that provides real-time imaging of the epidermis and dermis with cellular resolution and improves diagnostic accuracy of melanocytic lesions.^2,3 Normal melanocytes appear as round bright structures on RCM that are similar in size to surrounding keratinocytes located in the basal layer and regularly distributed around the dermal papillae (junctional nevi) or form regular dense nests in the dermis (intradermal nevi).^4,5 In LM/LMM, there may be widespread infiltration of atypical melanocytes invading hair follicles; large, round, pagetoid melanocytes (larger than surrounding keratinocytes); sheets of large atypical cells at the dermoepidermal junction (DEJ); loss of contour in the dermal papillae; and atypical melanocytes invading the dermal papillae.² Indeed, RCM has good correlation with the degree of histologic atypia and is useful to distinguish between benign nevi, atypical nevi, and melanoma.⁶ By combining lateral mosaics with vertical stacks, RCM allows 3-dimensional approximation of tumor margins and monitoring of nonsurgical therapies.^7,8 The advent of handheld RCM (HRCM) has allowed assessment of large lesions as well as those presenting in difficult locations.⁹ Furthermore, the generation of videomosaics overcomes the limited field of view of traditional RCM and allows for accurate assessment of large lesions.¹⁰

Traditional and handheld RCM have been used to diagnose and map primary LM.^1,2,11 Guitera et al² developed an algorithm using traditional RCM to distinguish benign facial macules and LM. In their training set, they found that when their score resulted in 2 or more points, the sensitivity and specificity to diagnose LM was 85% and 76%, respectively, with an odds ratio of 18.6 for LM. They later applied the algorithm in a test set of 44 benign facial macules and 29 LM and obtained an odds ratio of 60.7 for LM, with sensitivity and specificity rates of 93% and 82%, respectively.² This algorithm also was tested by Menge et al11 using the HRCM. They found 100% sensitivity and 71% specificity for LM when evaluating 63 equivocal facial lesions. Although these results suggest that RCM can accurately distinguish LM from benign lesions in the primary setting, few reports have studied the impact of HRCM in the recurrent setting and its impact in monitoring treatment of LM.^12,13

Herein, we present 5 cases in which HRCM was used to manage complex facial LM/LMM, highlighting its versatility and potential for use in the clinical setting (eTable).

References

Guitera P, Moloney FJ, Menzies SW, et al. Improving management and patient care in lentigo maligna by mapping with in vivo confocal microscopy. JAMA Dermatol. 2013;149:692-698.
Guitera P, Pellacani G, Crotty KA, et al. The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face. J Invest Dermatol. 2010;130:2080-2091.
Pellacani G, Guitera P, Longo C, et al. The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions. J Invest Dermatol. 2007;127:2759-2765.
Segura S, Puig S, Carrera C, et al. Development of a two-step method for the diagnosis of melanoma by reflectance confocal microscopy. J Am Acad Dermatol. 2009;61:216-229.
Hofmann-Wellenhof R, Pellacani G, Malvehy J, et al. Reflectance Confocal Microscopy for Skin Diseases. New York, NY: Springer; 2012.
Pellacani G, Farnetani F, Gonzalez S, et al. In vivo confocal microscopy for detection and grading of dysplastic nevi: a pilot study. J Am Acad Dermatol. 2012;66:E109-E121.
Nadiminti H, Scope A, Marghoob AA, et al. Use of reflectance confocal microscopy to monitor response of lentigo maligna to nonsurgical treatment. Dermatol Surg. 2010;36:177-184.
Alarcon I, Carrera C, Alos L, et al. In vivo reflectance confocal microscopy to monitor the response of lentigo maligna to imiquimod. J Am Acad Dermatol. 2014;71:49-55.
Fraga-Braghiroli NA, Stephens A, Grossman D, et al. Use of handheld reflectance confocal microscopy for in vivo diagnosis of solitary facial papules: a case series. J Eur Acad Dermatol Venereol. 2014;28:933-942.
Kose K, Cordova M, Duffy M, et al. Video-mosaicing of reflectance confocal images for examination of extended areas of skin in vivo. Br J Dermatol. 2014;171:1239-1241.
Menge TD, Hibler BP, Cordova MA, et al. Concordance of handheld reflectance confocal microscopy (RCM) with histopathology in the diagnosis of lentigo maligna (LM): a prospective study [published online January 27, 2016]. J Am Acad Dermatol. 2016;74:1114-1120.
Hibler BP, Connolly KL, Cordova M, et al. Radiation therapy for synchronous basal cell carcinoma and lentigo maligna of the nose: response assessment by clinical examination and reflectance confocal microscopy. Pract Radiat Oncol. 2015;5:E543-E547.
Hibler BP, Cordova M, Wong RJ, et al. Intraoperative real-time reflectance confocal microscopy for guiding surgical margins of lentigo maligna melanoma. Dermatol Surg. 2015;41:980-983.
Kose K, Gou M, Yelamos O, et al. Video-mosaicking of in vivo reflectance confocal microscopy images for noninvasive examination of skin lesions [published February 6, 2017]. Proceedings of SPIE Photonics West. doi:10.1117/12.2253085.
Hazan C, Dusza SW, Delgado R, et al. Staged excision for lentigo maligna and lentigo maligna melanoma: a retrospective analysis of 117 cases. J Am Acad Dermatol. 2008;58:142-148.
Etzkorn JR, Sobanko JF, Elenitsas R, et al. Low recurrence rates for in situ and invasive melanomas using Mohs micrographic surgery with melanoma antigen recognized by T cells 1 (MART-1) immunostaining: tissue processing methodology to optimize pathologic staging and margin assessment. J Am Acad Dermatol. 2015;72:840-850.
Gaudy-Marqueste C, Perchenet AS, Tasei AM, et al. The "spaghetti technique": an alternative to Mohs surgery or staged surgery for problematic lentiginous melanoma (lentigo maligna and acral lentiginous melanoma). J Am Acad Dermatol. 2011;64:113-118.
Guitera P, Menzies SW, Argenziano G, et al. Dermoscopy and in vivo confocal microscopy are complementary techniques for diagnosis of difficult amelanotic and light-coloured skin lesions [published online October 12, 2016]. Br J Dermatol. 2016;175:1311-1319.
Borsari S, Pampena R, Lallas A, et al. Clinical indications for use of reflectance confocal microscopy for skin cancer diagnosis. JAMA Dermatol. 2016;152:1093-1098.
Agarwal-Antal N, Bowen GM, Gerwels JW. Histologic evaluation of lentigo maligna with permanent sections: implications regarding current guidelines. J Am Acad Dermatol. 2002;47:743-748.
Gardner KH, Hill DE, Wright AC, et al. Upstaging from melanoma in situ to invasive melanoma on the head and neck after complete surgical resection. Dermatol Surg. 2015;41:1122-1125.
Champin J, Perrot JL, Cinotti E, et al. In vivo reflectance confocal microscopy to optimize the spaghetti technique for defining surgical margins of lentigo maligna. Dermatolog Surg. 2014;40:247-256.
Fogarty GB, Hong A, Scolyer RA, et al. Radiotherapy for lentigo maligna: a literature review and recommendations for treatment. Br J Dermatol. 2014;170:52-58.
Swetter SM, Chen FW, Kim DD, et al. Imiquimod 5% cream as primary or adjuvant therapy for melanoma in situ, lentigo maligna type. J Am Acad Dermatol. 2015;72:1047-1053.
Richtig E, Arzberger E, Hofmann-Wellenhof R, et al. Assessment of changes in lentigo maligna during radiotherapy by in-vivo reflectance confocal microscopy--a pilot study. Br J Dermatol. 2015;172:81-87.
Gerger A, Koller S, Kern T, et al. Diagnostic applicability of in vivo confocal laser scanning microscopy in melanocytic skin tumors. J Invest Dermatol. 2005;124:493-498.
Farnetani F, Scope A, Braun RP, et al. Skin cancer diagnosis with reflectance confocal microscopy: reproducibility of feature recognition and accuracy of diagnosis. JAMA Dermatol. 2015;151:1075-1080.
Rajadhyaksha M, Marghoob A, Rossi A, et al. Reflectance confocal microscopy of skin in vivo: from bench to bedside [published online October 27, 2016]. Lasers Surg Med. 2017;49:7-19.

Handheld Reflectance Confocal Microscopy to Aid in the Management of Complex Facial Lentigo Maligna

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