Dermatology: Practical and Conceptual Image Letter | Dermatol Pract Concept. 2024;14(3):e2024194 1 Early Emerging Lentigo Maligna and the Role of Confocal Microscopy in Guiding PRAME-Directed Immunohistochemical Staining Sebastián González-Valdés1, Alvaro Abarzúa-Araya1,2 1 Department of Dermatology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile 2 Melanoma and Skin Cancer Unit, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile Citation: González-Valdés S, Abarzúa-Araya A. Early Emerging Lentigo Maligna and the Role of Confocal Microscopy in Guiding the PRAME-Directed Immunohistochemical Staining. Dermatol Pract Concept. 2024;14(3):e2024194. DOI: https://doi.org/10.5826 /dpc.1403a194 Accepted: April 30, 2024; Published: July 2024 Copyright: © González-Valdés 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: Alvaro Abarzúa-Araya, MD, IFAAD, Department of Dermatology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Diagonal Paraguay 362, 6th floor, Santiago, Chile 8330077. E-mail: alvaroabarzuaaraya@gmail.com Case Presentation We present the case of a 59-year-old male patient who, during a skin exam in a dermatology consultation, was found to have a 4 × 3 mm brown macule on the left mandibular branch, with the presence of gray dots upon dermoscopy (Figure 1A). As it did not exhibit specific characteristics, a reflectance confocal microscopy (RCM) was performed, revealing atypical den- dritic cells with folliculotropism (“caput medusae” appear- ance) in a single follicle (Figure 1B). Subsequently, a biopsy of the lesion was conducted, initially showing histopathological evidence of a junctional melanocytic nevus. However, due to the clinicopathological discrepancy, an additional study was requested using anti-PRAME (preferentially expressed antigen in melanoma) immunostaining, which demonstrated intense positivity in over 80% of the melanocytes at the der- moepidermal junction and in the affected follicle previously visualized through RCM (Figure 1C), leading to the final di- agnosis of lentigo maligna. Finally, the lesion was excised using the slow Mohs technique. Teaching Point There are various signs described in reflectance confocal microscopy (RCM) to suspect a lentigo maligna, among which we find the alteration of the honeycomb pattern, poorly defined dermal papillae, pagetoid cells, and atypical cells at the dermoepidermal junction or around the follicles resembling a medusa head-like structure, among others [1]. As illustrated by the presented case, these signs could be de- tected in early lesions. Immunostaining with anti-PRAME antibodies proves to be of great diagnostic utility, possessing a sensitivity of 93.5% and specificity of 94.7% for diagnos- ing lentigo maligna, especially in complex cases [2]. The use of RCM can be a very useful tool for diagnosing early-stage lentigo maligna in clinically difficult lesions, allowing guided immunostaining to the initially delimited suspicious area by this non-invasive method, thus improving diagnostic ac- curacy and allowing early treatment with lower associated morbidity. 2 Image Letter | Dermatol Pract Concept. 2024;14(3):e2024194 References 1. Gamo R, Pampín A, Floristán U. Reflectance Confocal Micros- copy in Lentigo Maligna. Actas Dermosifiliogr. 2016;107(10): 830-835. DOI: 10.1016/j.ad.2016.07.012. PMID: 27614735. 2. Gradecki SE, Valdes-Rodriguez R, Wick MR, Gru AA. PRAME immunohistochemistry as an adjunct for diagnosis and histologi- cal margin assessment in lentigo maligna. Histopathology. 2021; 78(7):1000-1008. DOI: 10.1111/his.14312. PMID: 33280156. Figure 1. Early-stage lentigo maligna. (A) Brown macule with the presence of asymmetric gray dots. (B) Reflectance confocal microscopy showing atypical dendritic cells with folliculotropism resembling a medusa head-like structure. (C) Immunostaining with anti-PRAME antibodies displaying intense positivity in >80% of melanocytes at the dermoepidermal junction and the affected follicle (Courtesy of Dr. Miguel Villaseca).