Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2022;12(4):e2022137 1 Benefits and Pitfalls of Using in Vivo Reflectance Confocal Microscopy in Lentigo Maligna Diagnostics: Case Reports Ieva Povilaite1, Giuseppe Argenziano2, Graziella Babino2, Claudio Conforti4, Elvira Moscarella2, Francesca Pagliuca3, Andrea Ronchi3, Iris Zalaudek4, Marina Agozzino4 1 Department of Skin and Venereal diseases, Lithuanian University of Health Sciences, Kaunas, Lithuania 2 Dermatology Unit, University of Campania, Naples, Italy 3 Department of Advanced Biomedical Sciences, Pathology Section, University of Naples Federico II, Naples, Italy 4 Dermatology and Venereology Department, Maggiore hospital, University of Trieste, Trieste, Italy Key words: lentigo maligna, in vivo reflectance confocal microscopy, pigmented facial lesion, diagnostic accuracy Citation: Povilaite I, Argenziano G, Babino G, et al. Benefits and pitfalls of using in vivo reflectance confocal microscopy in lentigo maligna diagnostics: case reports. Dermatol Pract Concept. 2022;12(4):e2022137. DOI: https://doi.org/10.5826/dpc.1204a137 Accepted: January 13, 2022; Published: October 2022 Copyright: ©2022 Povilaite et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding author: Ieva Povilaite, MD, Department of Skin and Venereal diseases, Eiveniu st.2, Kaunas, Lithuania; LT-50161. Email: ievapovilaite@gmail.com Introduction The differential diagnosis between lentigo maligna (LM) and pigmented facial lesions (PFL) might be challenging clinically and dermoscopically, especially in its early phases, because early melanoma may exhibit only subtle malignancy clues and may have overlapping features with PFL [1,2]. There- fore, new diagnostic tools such as Reflectance confocal microscopy (RCM) to improve early detection of LM in its initial growth phases are crucial. Herein reported two cases of LM and two different approaches of using RCM. Case Presentation A 47-year-old man presented at our department for la- ser treatment of some facial brownish macules. During routine examination using a dermatoscope a macule on the tip of the nose was noted (Figure 1A). Dermoscopically a structureless brownish color pigmentation and irregular grayish pigmentation around some follicles were present (Figure 1B). Due to the doubtful appearance in dermoscopy RCM examination was performed revealing the presence of several atypical melanocytes located mainly around hair fol- licles (Figure 1C). Based on confocal features, a total surgi- cal excision was performed and a final diagnosis of LM was confirmed (Figure  1D). The patient refused the re-excision, and adjuvant therapy with Imiquimod 5% cream once daily for 6 weeks was started. After 2 years of follow up, no mela- noma recurrence signs were noted. A 61-year-old woman presented at our clinic for evalu- ation of a pigmented macule on the left cheek (Figure 2A). The patient had no previous history of melanoma. Both DPC_1843.indd 1DPC_1843.indd 1 14/10/22 5:29 PM14/10/22 5:29 PM 2 Research Letter | Dermatol Pract Concept. 2022;12(4):e2022137 clinically and dermoscopically (Figure 2B) the lesion looked suspicious. Under RCM examination atypical dendritic cells were visible at the level of the epidermis, they were not located around follicles nor infiltrating them. Mela- nocytic nests forming cords were visible at the level of the dermal-epidermal junction, with no obvious melanoma fea- tures (Figure 2C). However, due to the suspicious dermo- scopic aspect, the lesion was excised and a final diagnosis of LM was confirmed by histology (Figure 2D). The patient is recurrence free after 2 years follow up. Conclusions In the first case presented, the lesion did not show any spe- cific features for melanoma. On dermoscopy the only sub- tle suspicious clue was the presence of greyish color around some follicles. This clue shows high sensitivity to malignancy (85, 1%), but quite low specificity (39, 7%) [1]. RCM helped us reveal characteristics suggestive of the melanocytic nature of the lesion. In the second case the lesion both clinically and dermo- scopically looked suspicious, however RCM findings were subtle. Indeed, on RCM, the lesion had regular epidermal architecture, which is noteworthy and in the early radial growth phase of melanoma, follicles were well defined with- out folliculotropism and widespread dendrites. In this case the confidence level of the dermatologist in making diagnosis of LM was higher with the dermatoscope. Therefore, this second case supported that clinical and dermoscopic criteria are extremely important for LM diagnosis. In conclusion, LM diagnosis still remains challenging. A combined clinical/dermoscopic/confocal approach should be used for the management of PFL in order to provide a more conclusive pre-histological diagnosis leading clinicians to a correct management. Figure 1. (A) Clinical appearance of a small brownish macule measuring 5 mm in diameter on the distal part of the nose (red arrow). (B) Dermoscopy showing light grey color around few hair follicles (red arrow). (C) RCM mosaic at level of the epidermis, showing infiltration of atypical melanocytes around adnexal structures (red square); pagetoid/dendritic melanocytes located mainly around hair follicles (red arrows). (D) Histopathology: a lentiginous intraepidermal melanocytic proliferation in the context a skin with severe actinic damage. A junctional nest is shown on the left (red arrow) (H&E, ×200). DPC_1843.indd 2DPC_1843.indd 2 14/10/22 5:29 PM14/10/22 5:29 PM Research Letter | Dermatol Pract Concept. 2022;12(4):e2022137 3 Figure 2. (A) Pigmented macule located on the left cheek (5 × 7 mm) with irregular borders and variegated color (red arrow). (B)  Dermoscopy showing an asymmetric pigmented macule with atypical infiltration of interspaces and adnexal structures (red stars). (C) RCM mosaic (1.5 × 2.5 mm) at the level of the DEJ showing junctional nesting (red arrows) without colonization of atypical cells around hair follicles. (D) Histopathology: the sublesional dermis shows marked solar elastosis and increased melanophages (black arrow: melanocytic nest; red arrows: melanophages; black stars: solar elastosis) (H&E, ×200). DPC_1843.indd 3DPC_1843.indd 3 14/10/22 5:29 PM14/10/22 5:29 PM