Dermatology: Practical and Conceptual 198 Research | Dermatol Pract Concept 2018;8(3):10 DERMATOLOGY PRACTICAL & CONCEPTUAL www.derm101.com Dermatoscopy of flat pigmented facial lesions— evolution of lentigo maligna diagnostic criteria Miguel Costa-Silva1, Ana Calistru1, Ana Margarida Barros1, Sofia Lopes1, Mariana Esteves1, Filomena Azevedo1 1 Department of Dermatology and Venereology, Centro Hospitalar São João, EPE Porto, Portugal Key words: dermatoscopy, lentigo maligna, flat pigmented lesions, face Citation: Costa-Silva M, Calistru A, Barros AM, Lopes S, Esteves M, Azevedo F. Dermatoscopy of flat pigmented facial lesions—the evolution of lentigo maligna. Dermatol Pract Concept. 2018;8(3):198-203. DOI: https://doi.org/10.5826/dpc.0803a10 Received: January 20, 2018; Accepted: April 14, 2018; Published: July 31, 2018 Copyright: ©2018 Costa-Silva et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: None. Competing interests: The authors have no conflicts of interest to disclose. All authors have contributed significantly to this publication. Corresponding author: Miguel Costa e Silva, MD, Department of Dermatology and Venereology, Centro Hospitalar São João, EPE Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Email: miguelcostaesilva.dermato@gmail.com Introduction Flat pigmented facial lesions (FPFL) on chronic sun-damaged skin include a variety of melanocytic and nonmelanocytic, benign and malignant conditions with a similar clinical appearance presenting as a diagnostic challenge to physicians [1,2]. In many cases, diagnostic uncertainty is not resolved by clinical inspection, leading to biopsy or excision to rule out lentigo maligna (LM) [1]. Recognition of facial melanoma is often difficult, particu- larly in the early stages. Pigmented lesions of the face do not show the classic dermatoscopic findings characteristically observed elsewhere on the skin. A conventional pigment net- work is rarely found [2]. Instead, they are dermatoscopically characterized by the presence of a specific feature called a pseudonetwork [2-4]. The well-known “ABCDE rule” can- not be applied to facial locations [5,6]. Differential diagnosis includes solar lentigo (SL), postinflammatory hyperpigmen- Recognition of facial lentigo maligna (LM) is often difficult, particularly at early stages. Algorithms and multivariate diagnostic models have recently been elaborated on the attempt to improve the diag- nostic accuracy. We conducted a cross-sectional and retrospective study to evaluate dermatoscopic cri- teria aiding in diagnosis of flat pigmented facial lesions (FPFL). We examined 46 FPFL in 42 Caucasian patients and found that 4 of 20 dermatoscopic criteria reached the significance level required for fea- tures indicating malignancy namely, hyperpigmented follicular openings, obliterated follicular open- ing, annular-granular structures, and pigment rhomboids. Concomitant presence of at least 2 or 3 of the 4 mentioned criteria was significantly more frequent in LM than in pigmented actinic keratosis (PAK). However, despite more frequently seen in LM, these features were also displayed in some of the PAK and other FPFL, so we found them not specific for LM. Although dermatoscopy enhances the di- agnostic accuracy in evaluating FPFL, histopathology remains the gold standard for correct diagnosis, making evident the need for improvements in early noninvasive diagnosis of LM.  ABSTRACT Research | Dermatol Pract Concept 2018;8(3):10 199 • Obliterated follicular opening (OFO), when obliterated hair follicles were seen; • Pigment rhomboids, interfollicular lines that form a poly- gon (most commonly a rhomboid); • Moth-eaten borders, defined as concave areas at the edge of the lesion; • Sharp border when there was abrupt cessation of pigmen- tation; • Scale , evaluated from the dermatoscopic not the clinical image after application of fluid or gel; • Fingerprint-like structures, corresponding to different types of fissures which can be described as ridges, “fat fingers,” or cerebriform pattern; • Annular-granular structures, were considered when gran- ules were found regularly around the follicles; • Red rhomboidal structure, defined as lozenge-shaped vascular pattern occurring in the area separating the hair follicles from each other; and • Increased density of the vascular network, defined as a vascular network of higher density within the lesion than in peripheral skin. Data Analysis All features were treated as binary values (present or absent). Statistical methods Chi-squared and Fisher’s exact tests were used to evaluate possible associations. Values of p ≤ 0,05 were considered significant. Data analysis was performed using the statistical software program SPSS 20.0 for Windows (SPSS Inc, Chicago, IL). Results We examined 46 FPFL in 42 Caucasian patients (30 women and 12 men; age range 30–94 years, mean 65,2). LM was diag- nosed in 5 (10.9%), PAK in 15 (32.6%), SL in 19 (41.3%), SK in 5 (10,9%), LPLK in 1 (2.2%) and PIH in 1 (2.2%) lesion—all of them histopathologically confirmed. Examples of SL, LM, and PAK are shown in figure 1a-d. Table 1 dem- onstrates the frequency of detected dermatoscopic features in our series. The most striking pattern in 34 of 46 (73.9%) FPFL was brown structureless areas, followed by HFO (24/46 52.2%). Streaks and milia were not present in any of the lesions observed. In LM, HFO (5/5, 100%), annular-granular structures (4/5, 80%), brown structureless areas (4/5, 80%), dots (4/5, 80%), OFO (3/5, 60%), pigment rhomboids (3/5, 60%) and increased density of the vascular network (3/5, 60%) were present in most of the lesions. Four features namely, HFO, OFO, annular-granular structures, and pigment rhomboids were significantly associated with tation (PIH), seborrheic keratosis (SK), pigmented actinic keratosis (PAK), and lichen planus-like keratosis (LPLK) [2]. Dermatoscopy has been demonstrated to be an efficient non- invasive technique for the preoperative assessment, as well as for differential diagnosis of pigmented lesions [5]. For all of these reasons, algorithms and multivariate diagnostic models have recently been elaborated on the attempt to improve the diagnostic accuracy [1,2,5,7]. The aim of the present study was to evaluate dermato- scopic criteria aiding in diagnosis of pigmented skin lesions on the face by blinded evaluation of a consecutive series of dermatoscopic images in order to emphasize their diagnostic value in the differentiation between LM and other FPFL. Methods We conducted a cross-sectional and retrospective study of the FPFL in patients attending one author’s office over a 24-month period, from January 2014 to December 2015. We excluded those lesions with equivocal histopathology reports, raised lesions, and lentigo maligna melanoma (LMM) lesions. Concerning this study, the authors refer to the entity as LM when confined to the epidermis (in situ) and as LMM when it invaded the dermis. The gold standard for diagnosis used in this study was the histopathologic report. Clinical and dermatoscopic images of each lesion were documented by a FotoFinder (FotoFinder Systems, Inc, Bad Birnbach, Germany) non-polarized, videodermatoscope and in some cases by a Handyscope (FotoFinder Systems, Inc, Bad Birnbach, Germany) polarized, dermatoscope. In the case of lesions larger than 14 mm in diameter, multiple dermatoscopic images of different areas of the lesion were obtained to provide data for all topographical areas. Immer- sion fluid, either 70% ethanol hand wash gel, or ultrasound gel, was always used when taking the photographs. All dermatoscopic images were assessed digitally and reviewed by 3 dermatologists (MCS, AC, AMB) before reviewing the histopathologic report. Dermatoscopic features were positively scored when a consensus of at least 2 of the 3 observers was achieved. Twenty dermatoscopically detectable criteria related to dif- ferent structures and combinations of colors and structures were analyzed, including scar-like areas, dots, yellow clods, globules, streaks, brown structureless areas, gray structure- less areas, milia and comedones [1,2,5,7-10]. Additionally we included other more controversial structures namely: • Rosettes, also called four-dot clods, which are defined as 4 white dots arranged in a square; • Hyperpigmented follicular openings (HFO), considered when fine, irregular, semi-, signet ring or double circles were present; 200 Research | Dermatol Pract Concept 2018;8(3):10 LM (p < 0.05). All LMs presented at least 2 out of these 4 features and 4 (80%) LMs had 3 of the 4. HFO (9/15, 60%), brown structure- less areas (9/15, 60%), and annular- granular structures (8/15, 53.3%) were the most common dermatoscopic find- ings in PAK. Despite being present in only 20% (3/15), rosettes were solely observed in PAK, and this difference was statistically significant when compared to all other FPFL (p < 0.05). No other dermatoscopic criteria were statistically associated with the diagnosis of PAK (p > 0.05). Concerning premalignant (PAK) a n d m a l i g n a n t l e s i o n s ( L M ) a l l together and compared to benign FPFL (namely SL, SK, LPLK and PIH), HFO (70% vs 38.5%, p < 0.05), annular- granular structures (60% vs 23.1%, p < 0,05), rosettes (15% vs 0%, p < 0.05), and increased density of the vascular network (50% vs 15.4%, p < 0.05) were significantly more frequent in the former. Distinguishing between LM and PAK lesions, pigment rhomboids and OFO were significantly more frequent in the former (60% vs 6.7% and 60% v s   6 , 7 % , r e s p e c t i v e l y, p < 0 . 0 5 ) . Concerning features indicating LM namely, HFP, OFO, annular-granular structures, and pigment rhomboids, the concomitant presence of  2  of the 4 mentioned criteria was signifi- cantly more frequent in LM than in PAK (100% vs 40%, p < 0,05). Simi- larly, the concomitant presence of 3 of the 4 mentioned criteria was signifi- cantly more frequent in LM than in PAK (80% vs 6.7%, p < 0,05). Discussion Caucasian skin chronically exposed to the sun is susceptible to both benign and malignant FPFL [1]. Lentigo maligna is the most common subtype of melanoma on the face with increasing incidence [5]. Despite a frequent delay in diagnosis, its prognosis at the time of diagnosis is globally good [5]. The high frequency of PAK observed in our study mainly reflects its relatively high frequency in the population when compared with LM [9]. Although dermatoscopic char- acteristics of LM on the face have been described before, knowledge of the significance of dermatoscopic patterns with regard to the differentiation of LM from other FPFL is limited and may be a challenge even for experienced clinicians [1,3,5,7-10]. Schiffner et al [8], found that using a combination of 4 features, asymmet- ric pigmented follicular openings, dark rhomboidal structures, slate-gray dots, and slate-gray globules resulted in a classification rate of 93% for LM, with a specificity of 96% and a sensitivity of 89%. These criteria differ fundamen- tally from those of Steiner et al [11], who reported that radial streaming, peripheral black dots, and an irregular prominent pigment network that stops abruptly and thins out at the periph- ery, were the characteristic features for LM. According to the former find- ings, a progression model of LM was developed which differentiates 4 steps of the LM invasion of the hair follicles observed by dermatoscopy. Initially HFO appear, then, fine gray dots and globules appear around the follicles, producing the annular-granular pat- tern. Next, rhomboid pigmented areas are formed in the areas located around the hair follicle openings. Lastly, with progression of the malignant cells within all follicular anatomical struc- tures, the hyperpigmentation coalesces, and OFO emerge [8,12]. Later, Pralong et al [5], confirmed the diagnostic value of the classic Stolz dermatoscopic crite- Figure  1. (a) Solar lentigo with brown structureless areas, (b) lentigo maligna with rhomboids (arrowhead) and annular-granular structures (arrow), (c) pigmented actin- ic keratosis with rosettes (arrow), (d) pigmented actinic keratosis with hyperpigmented follicular openings (arrow) and obliterated follicular opening (arrowhead). [Copyright: ©2018 Costa-Silva et al. Research | Dermatol Pract Concept 2018;8(3):10 201 TABLE 1. Dermatoscopic Features in a Series of 46 FPFL Feature LM N = 5 PAK N= 15 LM + PAK N=20 Benign Lesions N= 26 LM + PAK vs Benign Lesions p* LM vs PAK p* LM vs FPFL p* PAK vs FPFL p* Age (years, median, range) 66.6 (30-87) 71 (45-92) 69.9 (30-92) 61.6 (30-94) 0.515 0.172 0.090 0.501 Sex Male Female 2 (40%) 3 (60%) 5 (33.3%) 10 (66.7%) 7 (35%) 13 (65%) 8 (30.8%) 18 (69.2%) 0.762 0.787 0.079 0.942 HFO 5 (100%) 9 (60%) 14 (70%) 10 (38.5%) 0.034 0.091 0.023 0.460 Annular-granular structures 4 (80%) 8 (53.3%) 12 (60%) 6 (23.1%) 0.011 0.292 0.047 0.170 Pigment rhomboids 3 (60%) 1 (6.7%) 4 (20%) 2 (7.7%) 0.219 0.010 0.001 0.372 OFO 3 (60%) 1 (6.7%) 4 (20%) 4 (15.4%) 0.682 0.010 0.008 0.182 Combination of 2/4† LM features 5 (100%) 6 (40%) 11 (55%) 5 (19.2%) 0.012 0.020 0.001 0.605 Combination of 3/4‡ LM features 4 (80%) 1 (6.7%) 5 (25%) 2 (7.7%) 0.105 0.001 0.001 0.261 Scar-like areas 1 (20%) 1 (6.7%) 2 (10%) 0 0.099 0.389 0.069 0.592 Dots 4 (80%) 6 (40%) 10 (50%) 10 (38.5%) 0.434 0.121 0.081 0.741 Scale 0 6 (40%) 6 (30%) 5 (19.5%) 0.396 0.091 0.184 0.072 Yellow clods 1 (20%) 6 (40%) 7 (35%) 4 (15.4%) 0.122 0.417 0.828 0.075 Rosettes 0 3 (20%) 3 (15%) 0 0.041 0.278 0.532 0.010 Globules 2 (40%) 2 (13.3%) 5 (25%) 3 (11.5%) 0.232 0.132 0.087 0.613 Streaks 0 0 0 0 - - - - Brown structureless areas 4 (80%) 9 (60%) 12 (60%) 22 (84.6%) 0.159 0.292 0.743 0.075 Fingerprint-like structures 0 1 (6.7%) 1 (25%) 7 (26.9%) 0.052 0.554 0.277 0.182 Sharp border 2 (40%) 5 (33.3%) 7 (35%) 11 (42.3%) 0.615 0.787 0.966 0.575 Moth-eaten borders 0 3 (20%) 3 (15%) 8 (30.8%) 0.214 0.278 0.184 0.665 Milia 0 0 0 0 - - - - Comedo 0 0 0 1 (3.8%) 0.375 - 0.724 0.482 Red rhomboidal structure 0 1 (6.7%) 1 (5%) 0 0.249 0.554 0.724 0.146 Increased vascular network 3 (60%) 7 (46.7%) 10 (50%) 4 (15.4%) 0.011 0.606 0.128 0.096 Gray structureless areas 1 (20%) 3 (20%) 4 (20%) 3 (11.5%) 0.428 1 0.752 0.530 HFO- hyperpigmented follicular openings; OFO- obliterated follicular opening; LM – lentigo maligna; PAK – pigmented actinic kera- tosis; FPFL- flat pigmented facial lesions * Chi-squared and Fisher’s exact tests were used to evaluate possible associations. † Combination of 2 out of the 4 features significantly associated to LM (HFO, OFO, annular-granular structures, and pigment rhomboids). ‡ Combination of 3 out of the 4 features significantly associated to LM (HFO, OFO, annular-granular structures, and pigment rhomboids). 202 Research | Dermatol Pract Concept 2018;8(3):10 This study reviewed retrospectively a relatively small series of lesions and a larger number of patients and found that facial lesions are important to give more definite results. Also, the lack of a uniform dermatoscopic nomenclature makes it difficult to compare different studies. Conclusions Although dermatoscopy improves diagnostic accuracy in evaluating FPFL, it remains a challenge. Histopathology remains the gold standard for correct diagnosis. Improve- ments in early noninvasive diagnose of LM are needed. Using combinations of dermatoscopic structures may enhance the diagnosis value of dermatoscopy of FPFL. References 1. Tschandl P, Rosendahl C, Kittler H. Dermatoscopy of flat pigment- ed facial lesions. J Eur Acad Dermatol Venereol. 2015;29(1):120- 127. doi: 10.1111/jdv.12483. 2. Carbone A, Ferrari A, Paolino G, et al. Lentigo maligna of the face: A quantitative simple method to identify individual patient risk probability on dermoscopy. Australas J Dermatol. 2017;58(4):286-291. doi: 10.1111/ajd.12595. 3. Pehamberger H, Binder M, Steiner A, Wolff K. In vivo epilumines- cence microscopy: improvement of early diagnosis of melanoma. J Invest Dermatol. 1993;100(3)(suppl):356S-362S. doi: 10.1038/ jid.1993.63. 4. Argenziano G, Soyer HP, Chimenti S, et al. Dermoscopy of pigmented skin lesions: results of a consensus meeting via the In- ternet. J Am Acad Dermatol. 2003;48(5):679-693. doi: 10.1067/ mjd.2003.281. 5. Pralong P, Bathelier E, Dalle S, Poulalhon N, Debarbieux S, Thomas L. Dermoscopy of lentigo maligna melanoma: re- port of 125 cases. Br J Dermatol. 2012;167(2):280-287. doi: 10.1111/j.1365-2133.2012.10932.x. 6. Thomas L, Tranchand P, Berard F, Secchi T, Colin C, Moulin G. Semiological value of ABCDE criteria in the diagnosis of cutane- ous pigmented tumors. Dermatology. 1998;197(1):11-17. doi: 10.1159/000017969. 7. Goncharova Y, Attia EAS, Souid K, Vasilenko IV. Dermoscop- ic features of facial pigmented skin lesions. ISRN Dermatol. 2013;2013:546813. doi: 10.1155/2013/546813. 8. Schiffner R, Schiffner-Rohe J, Vogt T, et al. Improvement of early recognition of lentigo maligna using dermatoscopy. J Am Acad Dermatol. 2000;42(1 Pt 1):25-32. doi: 10.1016/S0190- 9622(00)90005-7. 9. Akay BN, Kocyigit P, Heper AO, Erdem C. Dermatosco- py of flat pigmented facial lesions: diagnostic challenge be- tween pigmented actinic keratosis and lentigo maligna. Br J Dermatol. 2010;163(6):1212-1217. doi: 10.1111/j.1365- 2133.2010.10025.x. 10. Stante M, Giorgi V, Stanganelli I, Alfaioli B, Carli P. Dermoscopy for early detection of facial lentigo maligna. Br J Dermatol. 2005;152(2):361-364. doi: 10.1111/j.1365-2133.2004.06328.x. 11. Steiner A, Pehamberger H, Wolff K. In vivo epiluminescence microscopy of pigmented skin lesions. II. Diagnosis of small pig- ria and described 4 additional features, such as the increased density of the vascular network, red rhomboidal struc- tures, target-like pattern, and darkening at dermatoscopic examination. Akay et al [9], found that 3 dermatoscopic criteria were statistically significant for malignant growth, namely, dark rhomboidal structures, dark streaks, and black blotches. On the other hand, slate-gray globules, annular- granular structure, HFO, and black globules were not sta- tistically significant for either benign or malignant growth. All dermatoscopic findings, except for black blotches, were observed in PAK, leading the authors to conclude that the value of dermatoscopy in differentiating between melano- cytic lesions and PAK was limited [3,9]. Recently, Tschandl et al [1], confirmed this assertion, noting that PAK and LM are similar in clinical and dermatoscopic features, sharing the presence of a gray color, although a pattern of pigmented circles is the most common pattern in early LM, while the presence of scales, white circles, and a sharply demarcated border were more in favor of PAK. Tschandl et al [1] saw the presence of gray color in lesions on the face as a strong clue to a malignant process, which is in accordance with the findings of Tiodorovic-Zivkovic et al [13], who postulated that gray color, regardless of the pattern, was the single most sensitive feature for the dermatoscopic recognition of early facial melanoma that can be detected even before the forma- tion of the characteristic LM structures, such as circles or rhomboids. They concluded that its presence should always prompt the clinician to perform a biopsy. Lastly, Carbone et al [2] developed a scoring system to improve the diagno- sis of LM with 7 dermatoscopic criteria: HFO, rhomboidal structures, target-like pattern, perifollicular gray color, dark blotches, moth-eaten border, and fingerprint-like structures. Our analysis is in accordance with the first findings of Schiffner et al and Stolz et al [8,12]. Four of 20 dermatoscopic criteria for analysis of facial pigmented skin lesions reached the significant level required for features indicating malig- nancy namely, HFO, OFO, annular-granular structures, and pigment rhomboids. The concomitant presence of 2 or 3 of the 4 dermatoscopic criteria enhances the diagnostic value of dermatoscopy in differentiating LM from PAK or from other FPFL. However, despite more frequently seen in LM, these features were also displayed in some of the PAK and other FPFL, so we found them not specific for LM. Rosettes were solely observed in PAK. However, they can also be found in other non-melanocytic FPFL [1,9]. It must be emphasized that most dermatoscopic images were taken with non-polarized dermatoscope. Because rosettes are mainly vis- ible with polarized light, we might have underestimated the presence of this structure. We found that pigment rhomboids and OFO were significantly more frequent in LM then in PAK but, again, were not specific. Research | Dermatol Pract Concept 2018;8(3):10 203 13. Tiodorovic-Zivkovic D, Zalaudek I, Lallas A, Stratigos AJ, Piana S, Argenziano G. The importance of gray color as a dermoscopic clue in facial pigmented lesion evaluation: a case report. Dermatol Pract Concept. 2013;3(4):37-39. doi: 10.5826/dpc.0304a09. mented skin lesions and early detection of malignant melanoma. J Am Acad Dermatol. 1987;17(4):584-591. doi: 10.1016/S0190- 9622(87)70240-0. 12. Stolz W, Schiffner R, Burgdorf WH. Dermatoscopy for facial pigmented skin lesions. Clin Dermatol. 2002;20(3):276-278. doi: 10.1016/S0738-081X(02)00221-3.