Dermatology: Practical and Conceptual 200 Research | Dermatol Pract Concept 2019;9(3):5 Dermatology Practical & Conceptual Value of Dermoscopy in a Population-Based Screening Sample by Dermatologists Isabelle Hoorens1, Katrien Vossaert 1,2, Sven Lanssens2, Laurence Dierckxsens3, Giuseppe Argenziano4, Lieve Brochez1 1 Department of Dermatology, University Hospital Ghent, Belgium 2 Private Practice, Maldegem, Belgium 3 Department of Dermatology, AZ Sint-Lucas, Ghent, Belgium 4 Department of Dermatology, Second University of Naples, Italy Key words: dermoscopy, screening, melanoma, basal cell carcinoma, squamous cell carcinoma Citation: Hoorens I, Vossaert K, Lanssens S, Dierckxsens L, Argenziano G, Brochez L. Value of dermoscopy in a population-based screening sample by dermatologists. Dermatol Pract Concept. 2019;9(3):200-206. DOI: https://doi.org/10.5826/dpc.0903a05 Accepted: June 3, 2019; Published: July 31, 2019 Copyright: ©2019 Hoorens 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. Authorship: All authors have contributed significantly to this publication. Corresponding author: Isabelle Hoorens, MD, PhD, Department of Dermatology, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Gent, Belgium. Email: isabelle.hoorens@uzgent.be Background: The use of dermoscopy improves the diagnosis of skin cancer significantly in trained dermatologists. However, to evaluate its cost-effectiveness in daily practice, not only sensitivity but also the excision rate is important. Objective: We examined the diagnostic accuracy of cases from a true population-based sample scored by general dermatologists. Methods: One hundred twenty-six dermatologists were randomly assigned to  145  digital cases of lesions detected at a skin cancer screening. This resulted in 4,655 case evaluations using a web appli- cation. Accuracy of diagnosis and treatment was correlated with the histological diagnosis or expert opinion. Results: The larger portion (89.7%) of the participating dermatologists reported using their derma- toscope daily. The odds of making a correct diagnosis of melanoma using dermoscopy was 5.38 com- pared with naked-eye examination (NEE). Dermoscopy increased sensitivity for skin cancer diagnosis from  70.6% to  84.6%, but this was associated with a small but significant decrease in specificity of  3.5%. To detect  1  skin cancer, 5.23  lesions had to be biopsied/excised in this sample and this was not significantly improved by dermoscopic evaluation. Dermoscopy significantly increased the confidence about making a correct diagnosis, especially in seborrheic keratosis, Bowen disease, and melanoma. Conclusions: Dermoscopy significantly improved diagnostic accuracy, the sensitivity of skin cancer detection, and the confidence in diagnosis especially for seborrheic keratosis, Bowen disease, and melanoma. However, this finding was not reflected in a significant reduction in the number needed to excise in this sample. ABSTRACT Research | Dermatol Pract Concept 2019;9(3):5 201 cal or dermoscopy image. This study was approved by the Flemish government and by the medical ethical committee of the University Hospital Ghent. All screenees provided written informed consent. As a histological diagnosis was not available for most of the lesions, the following surrogate reference diagnosis was used in a hierarchical order: diagnosis of the pathologist in case of excision or biopsy of the lesion (n = 5; 3.4%), con- cordant diagnosis by 2 blinded expert dermoscopists (K.V., L. B. [n = 100; 68.5%]); in case of discordance in diagnosis by these 2 experts, a third independent and blinded expert dermoscopist (G.A.) was asked and the most concordant diagnosis was chosen (n = 41; 28.1%). The gold standard diagnoses of all cases are listed in Table 1. Recruitment of Dermatologists A personal invitation to participate in this study was sent to all 384 Flemish certified dermatologists. One hundred twenty-six (32.8%) dermatologists were included in the study. Participants were asked to register online and to evaluate 1 or more series of 25 cases each. Case series were presented ran- domly to each registered dermatologist. Upon registration, general information concerning their practice, previous train- ing in dermoscopy, and the frequency of use of dermoscopy in routine practice was elicited. Case Evaluation Each online case mentioned brief clinical information (age, gender, and location of the lesion). First dermatologists were Introduction The skin cancer epidemic has an important impact on health care budget. Early detection and treatment is assumed to give better cure rates and subsequently a more cost-effective treat- ment. Dermoscopy is a well-established technique for diag- nosis of melanoma and nonmelanoma skin cancer. Several meta-analyses have shown that dermoscopy, in the hands of experienced dermatologists, is superior to naked-eye exami- nation (NEE) to detect melanoma [1-3]. Dermoscopy also sig- nificantly increases the diagnostic accuracy of nonmelanoma skin cancer diagnosis [4]. For basal cell carcinoma (BCC) the dermoscopic diagnostic accuracy is up to 95%-99% [5-7]. It is known that the diagnostic accuracy of dermoscopy depends significantly on training of the examiners [8]. In the hands of untrained practitioners, dermoscopy provides no better diagnostic accuracy for melanoma than NEE [1]. Most of the studies on the additional diagnostic value of dermoscopy have been performed in a well-selected set of lesions, in which melanomas and other malignant lesions are usually overrepresented. Since skin cancer prevalence in real-life setting is usually much lower, this can influence the number of false-positive diagnoses and their related cost in an important way (Bayes’ theorem). For this reason we exam- ined diagnostic accuracy and treatment allocation by NEE alone and additional dermoscopy among dermatologists in a population-based screening sample in Belgium. Methods Study Design Cases and Determination of Reference Diagnosis The cases were collected during a population-based lesion- directed skin cancer screening. Screenees could register for a free-of-charge skin cancer check-up if they had a lesion meeting 1 or more of the following criteria: ABCD rule, ugly duckling sign, a new lesion lasting more than 4 weeks, or red nonhealing lesions. All the index lesions presented by the screenees were checked and photographed both clini- cally and dermoscopically, respectively with an EOS 1200 D camera (Canon, Giessen, Germany) and the DermLite Photo System (3Gen, San Juan Capistrano, CA, USA). Follow- ing this lesion- directed screening, a total body check was offered to all participants for ethical reasons. We did not photograph any lesions during this second phase of the screening. In total 248 lesions were screened and 8 of them were histologically proven to be skin cancers (3.2%). Fur- ther details on this screening initiative have been published elsewhere [9]. In total 145 of the 248 cases (58%) were selected for a web application. Exclusion of cases was due to suboptimal quality of the photographs or a missing clini- Table 1. Specific Diagnoses of Lesions in the 145 Cases No. % Diagnosis Melanoma 1 0.69 BCC 4 2.76 SCC/Bowen 1 0.69 Actinic keratosis 3 2.07 Angioma 5 3.45 Dermatofibroma 4 2.76 Atypical nevus 6 4.14 Blue nevus 3 2.07 Congenital nevus 6 4.14 Benign nevus 53 36.55 Solar lentigo 12 8.27 Seborrheic keratosis 40 27.69 Other 7 4.82 Total 145 100 SCC = squamous cell carcinoma. 202 Research | Dermatol Pract Concept 2019;9(3):5 shown the clinical picture and were asked to select a clinical diagnosis (multiple choice), to score the certainty of their diagnosis on a visual analogue scale from 0 to 100%, and to choose the best treatment action (no treatment, biopsy, surgical excision, curettage, cryotherapy, and other); after reg- istration of these answers they were shown the dermoscopy photograph and were asked to complete the same questions. Sample Size Calculation and Statistical Analysis A sample size of 1,630 case evaluations was required to achieve a power of 80% to detect a difference in specific- ity of 5% in the group of clinical evaluation compared with the group of additional dermoscopy evaluation with a significance level of 5%. A specificity of 85.4% for the clinical diagnosis was expected and an interclass correlation of 0.814 was assumed (based on pilot data). Sample size cal- culation was adjusted for the clustered nature of the design by applying the method described by Killip et al [10]. Descriptive statistics were used to describe the cases and dermatologists participating. The related samples Wilcoxon signed rank test was used for continuous variables. Because of the clustered nature of the data, mixed logistic regression models were used to calculate sensitivity, specificity, and number needed to excise (NNE) and their relation to experience and training of the dermatologist. All statistical tests were 2-tailed and P values <0.05 were considered statistically significant. The analyses were conducted in SPSS version 21.0 (IBM, Armonk, NY, USA). Outcomes The primary outcome of this study was to evaluate the diagnostic accuracy of dermoscopy compared with NEE in a population-based setting. Furthermore, we wanted to evaluate whether dermoscopy can increase certainty of the correct diagnosis. Results Participant Characteristics In total 126 dermatologists randomly evaluated 1 or more series of cases with a mean of 32.1 evaluations per case. This resulted in 4,655 case evaluations; 80.2% of the par- ticipants were female and 19.8% were male. The median age was 45 years (interquartile range [IQR]: 38-52). The major- ity of dermatologists worked in a private practice (54.8%), 38.9% in a university center and 6.3% in a hospital setting. The reported median number of patients seen in routine practice was 100 per week (IQR: 70-130). Dermoscopy was used at least once a day in 89.7%, once a week but not daily in 7.9%, once a week up to once a month in 1.6%, and not at all in 0.8%. Thirty-seven (29.4%) used a nonpolarized dermatosope. Training in dermoscopy varied among par- ticipants: only 3 dermatologists (2.4%) had no training in dermoscopy, whereas 25 (19.8%) had 1-5 hours, 42 (33.3%) had 5-10 hours, and 44.4% had more than 10 hours of training. Diagnostic Accuracy and Certainty of Diagnosis Dermoscopy increased sensitivity for skin cancer diagnosis significantly from 70.6% to 84.6% (binomial generalized linear mixed model, P = 0.002; Table 2), associated with a small but significant decrease in specificity (96.9% for NEE vs 93.5% for dermoscopy, binomial generalized linear mixed model, P < 0.001; Figure 1). The sensitivity for the diagnosis Table 2. Diagnostic Performance of Dermoscopy According to Level of Training of the Dermatologist Clinical Dermoscopy Sens Spec 1 − Spec Sens Spec 1 − Spec All 0.706 (0.625-0.775)* 0.969 (0.959-0.977)** 0.031 0.846 (0.781-0.894) 0.935 (0.915-0.950)** 0.065 Training < 5 hrs 0.645 (0.461-0.795)1 0.915 (0.886-0.938)2 0.085 0.774 (0.593-0.890)3 0.861 (0.810-0.900)4 0.139 5-10 hrs 0.702 (0.588-0.796)1 0.921 (0.903-0.935)2 0.079 0.829 (0.726-0.899)3 0.885 (0.854-0.910)4 0.115 > 10 hrs 0.704 (0.593-0.795)1 0.940 (0.927-0.951)2 0.060 0.852 (0.755-0.915)3 0.887 (0.861-0.909)4 0.113 Sensitivity and specificity, binomial generalized linear mixed models. * P = 0.002 (odds ratio: 0.43 [95% confidence interval: 0.26-0.73]). ** P < 0.001 (OR: 2.18 [95% confidence interval: 1.84-2.58]). 1,2,3,4 P = NS. Research | Dermatol Pract Concept 2019;9(3):5 203 of melanoma with the use of dermoscopy increased even more from 76.0% to 94.0% (binomial generalized linear mixed model, P = 0.028). The odds for making a correct diagnosis of melanoma using dermoscopy was 5.38 (95% CI: 1.22-23.81) compared with NEE. Dermoscopy also increased sensitivity for diagnosis of BCC and squamous cell carcinoma/Bowen from 71.5% to 74.6%, and 58.9% to 71.0%, respectively, but this failed to reach statistical significance. A trend to increasing sensitivity/specificity was observed with increasing training level (Figure 2). The confidence about a correct diagnosis significantly increased from a median of 70% (IQR: 60-80) using NEE to 83.7% (IQR: 70-90) with dermoscopy (related samples Wilcoxon signed rank test (P < 0.001)). This increase was most pronounced for seborrheic keratosis, Bowen disease, and melanoma (Figure 3). Number Needed to Excise Dermoscopy resulted in 43 additional excisions for skin cancer and 252 extra excisions for benign lesions (on a total of 1,675 excisions or biopsies performed) compared with the clinical evaluation without dermoscopy. This resulted in a NNE of 4.77 for clinical evaluation alone and 5.23 when using dermoscopy (binomial generalized linear mixed model, P = not significant [NS]). The NNE did not seem to be influ- enced by training level (0-5 hours, NNE 5.15; 5-10 hours, NNE 4.89; and >10 hours, NNE 5.62; binomial generalized linear mixed model, P = NS; Table 3). Also for specific sub- categories of lesions (melanocytic lesions and BCC) the NNE did not change significantly between clinical diagnosis and dermoscopy diagnosis (Table 3). Figure  1. Sensitivity and 1  minus specificity for a malignant diagnosis made clinically and using der- moscopy. Dermoscopy increased sensitivity for skin cancer diagnosis significantly from  70.6% to  84.6% (binomial generalized linear mixed model, P = 0.002), associated with a small but significant decrease in specificity (96.9% for NEE vs 93.5% for dermoscopy, binomial generalized linear mixed model, P < 0.001). [Copyright: ©2019 Hoorens et al.] Figure  2. Sensitivity and  1  minus specificity for a malignant diagnosis according to level of training of the dermatologist. Sensitivity and specificity for skin cancer diagnosis increased with advanced level of training, although this failed to reach statistical sig- nificance (binomial generalized linear mixed model, P = NS). [Copyright: ©2019 Hoorens et al.] 204 Research | Dermatol Pract Concept 2019;9(3):5 Discussion In this study the additional value of dermoscopy over NEE diagnosis by 126 dermatologists was evaluated in a popu- lation-based series of 145 cases. In the past many similar studies have used very selected case series in which skin cancer was usually overrepresented. Although the intention is not to miss any skin cancer (100% sensitivity), especially in melanoma, the importance of not overdiagnosing skin cancer (high specificity) may also be an important issue to avoid the individual (fear, unnecessary intervention) and societal (cost) disadvantages of false-positive diagnoses. In non–high- risk populations the specificity will have a higher impact on cost-effectiveness. In this study we therefore included a case series based on a population-based lesion-directed skin cancer screening program, in which skin cancer prevalence was only 6/145 (4.1%). Nearly one third of all Flemish dermatologists evaluated at least 25 of the 145 cases. Cases were randomly presented to the participants, leading to a total of 4,655 case evaluations. In this way this study reflects the additional value of dermoscopy in the hands of general dermatologists in a population-based setting. The results of this study demonstrate that dermoscopy is frequently used in Belgian dermatology practice: almost 90% of participants use their dermatoscope daily. This is compa- rable with large studies performed in France and Australia (94.6%-98%) [11,12]. In accordance with other studies, we observed that der- moscopy significantly increases sensitivity for malignant lesions [1-4,6]. However, this results also in a small but sig- nificant decrease in specificity, thus increasing the number of false-positive diagnoses. In this study dermoscopy resulted in 43 additional excisions for skin cancer and 252 extra excisions for benign lesions over clinical diagnosis. The sensitivity/specificity tended to increase with increased level of training, confirming the results of previous studies [1-4,6]. Confidence about making a correct diagnosis was significantly higher using dermoscopy, especially in mela- noma, seborrheic keratosis, and Bowen disease. However, this did not result in a reduction of unnecessary excisions as the NNE did not significantly differ between clinical diag- nosis and dermoscopy nor did it seem to be influenced by training. Subanalyses with years of dermoscopy experience, daily use, in addition to level of training taken into account, also could not reveal a significant difference in the NNE. However, the NNE of the experts in the real-life setting on the screening (K.V., L.B.) was clearly lower than the NNE reached in the online case evaluation (ie, NNE 1.25 in real- life screening) [9]. The use of both clinical and dermoscopic photographs with the added information of gender, age, and lesion loca- tion to evaluate pigmented skin lesions remains somewhat artificial. In the absence of a total body inspection, individual lesions may be interpreted in a different way. An individual with multiple nevi, for instance, usually displays similar lesions (signature nevi); on the other hand there should be caution about lesions with a different pattern (ugly duckling sign). This was illustrated by 2 prominent nevi that were considered nonsuspicious by the 2 experts (K.V., L.B.) on the screening and were scored as potential melanoma in the online case series by at least 2 of 3 experts (G.A., K.V., L.B.). Digital follow-up of these lesions by means of new clinical and dermoscopy photographs about 20 months after screen- Figure 3. Median certainty of diagnosis clinically vs dermoscopy per diagnostic group. Certainty diagnosis median on visual analogue scale from 0 to 100%. AK = actinic keratosis; VS = seborrheic keratosis. [Copyright: ©2019 Hoorens et al.] Research | Dermatol Pract Concept 2019;9(3):5 205 ing showed no change, hence suggesting that these lesions have a benign behavior. This finding illustrates that some of the false-positive skin cancer diagnoses may have been due to the artificial conditions in which these lesions were evaluated. Compared with previous studies, a NNE of 1 out of 6 was obtained in this study. Evaluation of the large SCREEN cam- paign in Germany in a partially nonspecialized setting not using dermoscopy resulted in 17 excisions of melanocytic lesions for the detection of 1 melanoma [13]. Our data are comparable with those of a large multicentric study examin- ing excision rates over a period of 10 years in specialized clinical settings, with a NNE of 6.8 [14]. Table 3. NNE Dermoscopy vs Clinical Situation According to Level of Training All Lesions Level of Training Excision/Biopsy Malignant Excision/Biopsy Benign Total Excisions (NNE) Method Clinical <5 hrs 31 100 131 (4.22) 5-10 hrs 58 230 288 (4.96) >10 hrs 61 235 296 (4.85) Total 150 565 715 (4.77)* Dermoscopy <5 hrs 33 137 170 (5.15) 5-10 hrs 81 315 396 (4.89) >10 hrs 79 365 444 (5.62) Total 193 817 1010 (5.23)* Melanocytic Lesions Level of Training Excision/Biopsy Malignant Excision/Biopsy Benign Total Excisions (NNE) Method Clinical <5 hrs 14 51 65 (4.57) 5-10 hrs 22 126 148 (6.73) >10 hrs 29 136 165 (5.69) Total 65 313 378 (5.81)* Dermoscopy <5 hrs 15 79 94 (6.26) 5-10 hrs 36 195 231 (6.41) >10 hrs 43 240 283 (6.58) Total 94 514 608 (6.46)* BCC Level of Training Excision/Biopsy Malignant Excision/Biopsy Benign Total Excisions (NNE) Method Clinical <5 hrs 10 32 42 (4.20) 5-10 hrs 18 71 89 (4.94) >10 hrs 17 54 71 (4.18) Total 45 157 202 (4.49)* Dermoscopy <5 hrs 13 28 41 (3.15) 5-10 hours 27 62 89 (3.30) >10 hrs 20 47 67 (3.35) Total 60 137 197 (3.28)* NNE to find 1 confirmed skin cancer, melanoma, or BCC, binomial generalized linear mixed models. *P = NS. 206 Research | Dermatol Pract Concept 2019;9(3):5 There was a trend toward increased sensitivity and speci- ficity with increased training; however, training of >10 hours did not reach statistically significant superior results. In the recent NICE guidelines it is recognized that dermoscopy is unequivocally useful in the diagnosis of melanoma, but only in the hands of trained users [15]. The required amount of training, however, is a topic of debate. It has been shown that despite the frequent use of dermoscopy, training seems to be insufficient and that even among dermatologists who consider themselves experienced in dermoscopy, repeated training can increase diagnostic accuracy [8,11]. In addition, currently a lot of training courses in dermoscopy mainly focus on red flags (increased sensitivity for melanoma). However, when used in low-prevalence populations, it could be interest- ing to put more focus on green flags (recognition of harmless lesions), thereby reducing the number of false-positive diag- noses and hence unnecessary excisions. Conclusions The current study evaluated the additional value of dermos- copy in the hands of general dermatologists in a population- based setting using a series of photos in a web application. These results demonstrate that dermoscopy clearly increases sensitivity for malignant lesions in a population-based setting at the expense of a small but significant decrease in specific- ity. Although dermoscopy significantly increased confidence about a diagnosis, especially in melanoma, seborrheic kera- tosis and Bowen disease, this did not result in a reduction of NNE. There was a trend toward higher sensitivity and specificity according to training level (<5 hours, 5-10 hours, or >10 hours). We suggest that continuous training for der- moscopy is necessary and that training courses should also pay enough attention to the recognition of benign lesions to avoid unnecessary excisions and in that way benefit cost- effectiveness ratios. References 1. Kittler H, Pehamberger H, Wolff K, Binder M. Diagnostic accu- racy of dermoscopy. Lancet Oncol. 2002;3(3):159-165. 2. Bafounta ML, Beauchet A, Aegerter P, et al. Is dermoscopy (epi- luminescence microscopy) useful for the diagnosis of melanoma? Results of a meta-analysis using techniques adapted to the evalu- ation of diagnostic tests. Arch Dermatol. 2001;137(10):1343- 1350. 3. Vestergaard ME, Macaskill P, Holt PE, Menzies SW. Dermoscopy compared with naked eye examination for the diagnosis of pri- mary melanoma: a meta-analysis of studies performed in a clinical setting. Br J Dermatol. 2008;159(3):669-676. 4. Pehamberger H, Binder M, Steiner A, et al. In vivo epilumines- cence microscopy: improvement of early diagnosis of melanoma. J Invest Dermatol. 1993;100(3):356S-362S. 5. Altamura D, Menzies SW, Argenziano G, et al. Dermatoscopy of basal cell carcinoma: morphologic variability of global and local features and accuracy of diagnosis. J Am Acad Dermatol. 2010;62(1):67-75. 6. Menzies SW, Westerhoff K, Rabinovitz H, et al. Surface mi- croscopy of pigmented basal cell carcinoma. Arch Dermatol. 2000;136(8):1012-1016. 7. Pan Y, Chamberlain AJ, Bailey M, et al. Dermatoscopy aids in the diagnosis of the solitary red scaly patch or plaque-features distinguishing superficial basal cell carcinoma, intraepidermal carcinoma, and psoriasis. J Am Acad Dermatol. 2008;59(2):268- 274. 8. Chevolet I, Hoorens I, Janssens A, et al. A short dermoscopy training increases diagnostic performance in both inexperi- enced and experienced dermatologists. Australas J Dermatol. 2015;56(1):52-55. 9. Hoorens I, Vossaert K, Pil L, et al. Total-body examination vs lesion-directed skin cancer screening. JAMA Dermatol. 2016;152(1):27-34. 10. Killip S, Mahfoud Z, Pearce K. What is an intracluster correlation coefficient? Crucial concepts for primary care researchers. Ann Fam Med. 2004;2(3):204-208. 11. Breton AL, Amini-Adle M, Duru G, Poulalhon N, Dalle S, Thomas L. Overview of the use of dermoscopy in academic and non- academic hospital centres in France: a nationwide survey. J Eur Acad Dermatol Venereol. 2014;28(9):1207-1213. 12. Venugopal SS, Soyer HP, Menzies SW. Results of a nationwide dermoscopy survey investigating the prevalence, advantages and disadvantages of dermoscopy use among Australian dermatolo- gists. Australas J Dermatol. 2011;52(1):14-18. 13. Waldmann A, Nolte S, Geller AC, et al. Frequency of excisions and yields of malignant skin tumors in a population-based screening intervention of 360,288 whole-body examinations. Arch Derma- tol. 2012;148(8):903-910. 14. Argenziano G, Cerroni L, Zalaudek I, et al. Accuracy in melanoma detection: a 10-year multicenter survey. J Am Acad Dermatol. 2012;67(1):54-59. 15. National Institute for Health and Care Excellence. Melano- ma—assessment and management of melanoma. (NG14) 2015. Availible at: http://www.nice.org.uk/guidance/ng14. Accessed March 15, 2019.