Dermatology: Practical and Conceptual Review | Dermatol Pract Concept. 2022;12(4):e2022176 1 The Use of Dermoscopy in the Delineation of Basal Cell Carcinoma for Mohs Micrographic Surgery: a Systematic Review With Meta-Analysis Noureddine Litaiem1,2, Faten Hayder1,2, Imene Benlagha1,2, Manel Karray1,2, Chadli Dziri2,3, Faten Zeglaoui1,2 1 Department of Dermatology, Charles Nicolle Hospital, Tunis, Tunisia 2 University of Tunis El Manar, Faculté de Médecine de Tunis, Tunis, Tunisia; 3 Director of Honoris Medical Simulation Center, Tunisia Key words: Mohs micrographic surgery, Slow Mohs, dermoscopy, dermatoscopy, basal cell carcinoma Citation: Litaiem N, Hayder F, Benlagha I, Karray M, Dziri C, Zeglaoui F. The Use of Dermoscopy in the Delineation of Basal Cell Carcinoma for Mohs Micrographic Surgery: A Systematic Review with Meta-Analysis. Dermatol Pract Concept. 2022;12(4):e2022176. DOI: https://doi.org/10.5826/dpc.1204a176 Accepted: February 18, 2022; Published: October 2022 Copyright: ©2022 Litaiem N 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: Noureddine Litaiem, Department of dermatology, Charles Nicolle Hospital, Tunis, Tunisia. E-mail: Noureddine.litaiem@gmail.com Introduction: Several studies investigated the use of dermoscopy in the delineation of basal cell carci- noma (BCC) for Mohs micrographic surgery (MMS) with conflicting results. Objectives: The purpose of this systematic review with meta-analysis was to evaluate the effectiveness of the use of dermoscopy-guided MMS in the treatment of BCC. Methods: We included all comparative studies. Cases of BCC treated using dermoscopy-guided MMS (or slow MMS) were compared to those treated with curettage-guided MMS or “standard” MMS. Results: A total of 6 studies including 508 BCCs were reviewed. There was no statistically significant difference in the proportion of total margin clearance on the first MMS stage between BCCs removed using dermoscopy-guided MMS and those that had curettage or visual inspection. However, lateral margin involvement was significantly lower in BCCs that had dermoscopy-guided MMS. Conclusions: Dermoscopy allows visualization of structures up to 1mm into the dermis. Therefore, it is rational to use it for lateral margin evaluation. Currently, there are two comparative studies showing the efficacy of dermoscopy for lateral margin evaluation during MMS. Future studies are required to develop an evidence-based recommendation regarding the utility of dermoscopy in MMS. ABSTRACT 2 Review | Dermatol Pract Concept. 2022;12(4):e2022176 Introduction Basal cell carcinoma (BCC) is the most prevalent skin cancer worldwide [1]. The overall incidence has been steadily rising in the last decade throughout the world due to a burgeoning aging population and increased surveillance and diagnosis [2]. The biological behavior of BCC depends on the tumor subtype [1,2]. Undiagnosed and untreated BCC could lead to extensive local destruction and increase both functional and cosmetic morbidity making the treatment and repair ap- proach challenging for the physician. The National Comprehensive Cancer Network (NCCN) has established guidelines of care for BCCs [3]. High-risk BCCs include recurrent BCC, tumors with ill-defined borders, located on high-risk mask area of the face, arising on sites of prior radi- ation therapy or harboring aggressive histological features [3]. There are multiple treatment options for BCC such as ablative laser, photodynamic therapy, curettage, cryosurgery, imiquimod, and sonic hedgehog pathway inhibitors [12,2]. However, sur- gical excision remains the gold standard for treatment of most BCCs [1]. Standard excision is performed with a predefined clinical margin in order to achieve low recurrence rates. Mohs micrographic surgery (MMS) is a specialized surgical technique that combines surgery with pathology. MMS uses horizontal frozen sections to obtain complete margin control resulting in minimal tissue removal with low recurrence rates  [1]. MMS proved to be superior to standard excision for high-risk BCC [1]. Slow Mohs is a variant of MMS using formalin-fixed par- affin-embedded sections with similar outcome [4]. Dermoscopy, also known as dermatoscopy or epilumi- nescence microscopy, is a non-invasive imaging technique widely employed for the diagnosis of skin cancers. Some specific dermoscopic patterns are helpful in the diagnosis of BCC [5]. The use of dermoscopy in the demarcation of surgical margins is another scope of its application. For in- stance, the use of dermoscopy in MMS might help reduce the number of Mohs stages and achieve surgical margin control within the 1st Mohs stage [4,6-11]. Many studies investigated the effectiveness of dermos- copy in tumor delineation for MMS but with varying out- comes [4,6-11]. While some  suggested that dermoscopy could help reduce the number of Mohs stages and there- fore shorten operative time and cost [4,9,11], others argued against the usefulness of this approach [6,12]. The ambiguity of these findings is further hampered by the lack of random- ized studies and systematic reviews. Objectives The purpose of this systematic review with meta-analysis was to evaluate the effectiveness of the use of dermoscopy-guided MMS in the treatment of BCC. Methods Search Strategy This systematic review with meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [13]. We searched the PubMed and Scopus databases from inception up to January 26, 2022 to identify eligible studies. We aimed to identify all relevant studies published in English language. We used the following search algorithm: (“Basal cell carcinoma”) AND (“Mohs surgery” or “Slow Mohs” or “micrographic surgery” or ”3‐D histology” or “microscopically controlled surgery”) AND (“dermoscopy” or “dermatoscopy” or “epi- luminescence microscopy”). The PubMed and Scopus search strategies are available as supplementary material. Inclusion and Exclusion Criteria of Studies Two review authors (NL and FH) independently screened titles and abstracts for eligible studies. Eligible articles were identified on the basis of the following inclusion criteria: (i) comparative studies having at least a group of BCCs treated with dermoscopy-guided MMS, (ii) studies that used a control group of BCCs treated with visual inspection and/or curet- tage-guided MMS, (iii) articles published in English language. For eligible studies, full articles were retrieved in full and ana- lyzed by two independent authors (NL and FH). Any discrep- ancy between the two investigators was resolved by consensus. PICO(S): Populations, Interventions, Comparison, Outcome Measures, Types of Studies We included all comparative observational as well as ran- domized clinical trials (RCT). Participants with BCC regard- less of the clinical and histological subtype of the tumor were eligible for inclusion. Cases of BCC treated using dermoscopy-guided MMS (or slow MMS) were compared to those treated with curettage-guided MMS or “standard” MMS. The latter uses visual inspection alone to delineate the tumors. All types of dermoscopy techniques were eligible, regardless of the po- larization mode (polarized vs. nonpolarized mode) and the device type (hand-held dermoscopy or video dermoscopy). The main outcome measure was the proportion of to- tal margin clearance on the first MMS stage. The secondary outcome measures included the: (i) number of Mohs stages required to achieve complete margin control, (ii) the lateral margin involvement rate, and (iii) the recurrence rate. If one or more outcome measures were missing, we con- tacted the corresponding author at least twice (with at least one-week interval) to ask whether full data were available. If the contact was unsuccessful, the corresponding article was excluded from the analysis. Review | Dermatol Pract Concept. 2022;12(4):e2022176 3 Assessment of the risk of bias Two review authors (NL and FH) independently assessed the quality of consistency and the risk of bias in the eligible stud- ies. Any disagreement was resolved by discussion or by con- sensus with a third author (CD). MINORS score was used for observational studies [14]. RCT were evaluated using the Jadad score [15] . Data Synthesis and Statistical Analysis Results were reported as Odds ratio (OR) with 95% confi- dence intervals (CIs) for dichotomous data (proportion of to- tal margin clearance on the first MMS stage, lateral margin involvement, and recurrence rates) and standardized mean dif- ference with standard error of the mean for continuous data (number of Mohs stages). A random-effects model was used. Forest plots summarized the data. Funnel plot was used to investigate the existence of publication bias. Strategies for ad- dressing heterogeneity included performing a random-effects meta-analysis and subgroup analyses. We performed all calcu- lations using Comprehensive meta-analysis 3.0 package. We investigated heterogeneity using Cochran Q test. Evaluation of the percentage of variation between the sam- ple estimates was performed using the Higgins I2 statistic. Results Results of the Search The literature search identified 289 articles (Figure 1). After removing duplicates, 69 articles were screened for eligibil- ity. Fifty-five records were excluded, including not relevant articles (N = 30), papers not published in English (N = 3), editorials and commentary (N = 11), review articles (N = 10) and book chapters (N = 2). Fourteen full-text articles were assessed for eligibility. Among these, 4 were excluded (case reports and noncomparative studies) [16-19]. Three research letters were excluded [11,20,21]. Among these research Figure 1. Flow diagram. 4 Review | Dermatol Pract Concept. 2022;12(4):e2022176 The mean number of Mohs stages in each study group was specified in 5 articles [4,6-9]. However, related standard deviations were only available in 3 articles [4,6,7]. Contact with the corresponding authors of these studies was unsuc- cessful. Therefore, we did not have the required data to carry out the up-mentioned analysis for these articles [4,6,7]. Only two studies reported the number of positive lateral margins after the first Mohs stage [4,10]. Relapse rates were described in 2 articles [4,9], ranging between no relapse and 4%, after a follow-up period of 10 ± 5 and more than 62.5 months respectively. Assessment of Risk of Bias in Included Studies For RCT [6,7], the Jadad scale was 1 and 2. Overall, the methodological quality was poor. There was no disagree- ment between the review authors (NL and FH) about the studies quality. For non-randomized studies [4,8-10], the MINORS in- dex ranged between 14 and 16. Effects of Interventions When comparing dermoscopy-guided vs. standard MMS for BCC treatment, there was no statistically significant differ- ence in the proportion of total margin clearance on the first MMS stage (OR 0.86, 95% CI 0.41 to 1.15; five studies [4,7-10]) (Figure 2). There was no statistically significant difference in the number of Mohs stages when comparing dermoscopy-guided and standard MMS (The standardized mean difference -0.17, 95% CI -0.51 to 0.17; three studies [4,6,7]) (Figure 3). For this outcome measure, we found heterogeneity (Tau2 = 0220 et I2 = 70.334%). Subgroup analysis was performed based on the technique used for Mohs surgery (frozen sections versus formalin-fixed paraffin-embedded sections). After subgroup analysis, including studies using MMS [6,7], there was no heterogeneity (Tau2 = 0.000), the pooled standard difference in means showed no statistically significant differ- ence. Only one study reported the number of Mohs stages in patients treated using Slow Mohs [4]. Since iterative Mohs sessions rely on histopathological examination of excised tis- sue, it is possible that the type of tissue processing technique (frozen sections in MMS vs formalin-fixed paraffin-embed- ded sections in slow Mohs) is responsible for heterogeneity regarding the outcome measure (number of Mohs stages). A significantly lower proportion of positive lateral mar- gins was obtained with dermoscopy-guided MMS compared with standard MMS based on visual inspection (OR 0.16, 95% CI 0.06 to 0.83; 2 studies [4,10]) (Figure 4). With regards to recurrence rates, available data was insufficient for meta-analysis. Two studies reported the number of recurrences after MMS [4-9]. One of these letters, two compared dermoscopy to naked eye examination in BCC margin evaluation but the number of Mohs stages in each study group expressed in mean with standard de- viation was not available [11,20]; and one article included only BCC evaluated using dermoscopy prior to MMS [21]. A randomized open-label study comparing visual inspection, curettage, and dermoscopy in tumor delineation for MMS was excluded because no outcome measure was available for each study group [12]. Contact with the corresponding authors of this study was unsuccessful. Six articles were ulti- mately included in the present systematic review. Of these, 2 studies were from Asia-Pacific region, 1 from North Amer- ica, 1 from South America, 1 from Europe, and 1 from Africa (Table 1) [4,6-10]. Description of Included Studies Of the 6 included studies, 2 were RCTs [6,7], and four were observational studies [4,8-10]. There was no randomized controlled study available for the present systematic review. All included studies were conducted in university‐setting cen- ters [4,6-10]. These studies had no funding support and cor- responding authors declared no conflicts of interest [4,6-10]. The number of BCCs evaluated ranged from 40 to 197 BCCs per study. The total number of evaluated BCCs was 508. Suzuki et al included both BCC (N = 40) and squamous cell carcinomas (N = 6). The latter were excluded from the analysis. Three studies specified BCC subtypes [6,7,9]. Asil- ian and Momeni included only nodular BCC [6], and Gur- gen and Gatti only infiltrative BCC [7]. Dika et al included various BCC subtypes including nodular (N = 40) and mor- pheiform BCCs (N = 40) [9]. Recurrent BCCs were excluded in three studies [4,6,7]. One study included only recurrent BCC following ablative laser treatment [10]. Two studies enrolled both primary and recurrent BCC (Table 1) [8,9]. Four studies compared 2 interventions for MMS: tumor delineation using naked eye examination versus dermosco- py-guided margin assessment [4,7,8,10]. One of the studies compared dermoscopy-guided MMS to curettage-guided MMS [9]. Asilian and Momeni compared 3 groups: tumor demarcation using naked eye examination (N = 20), dermos- copy (N = 20) and curettage (N = 20) [6]. For the primary outcome “total margin clearance on the first MMS stage”, we assumed that BCCs that underwent more than one Mohs stage showed at least one positive margin. Thereby, the number of BCCs showing total margin clearance on the first MMS stage was extracted from 5 arti- cles [4,7-10]. The secondary outcomes included the mean number of Mohs stages, the recurrence rate, and the number of positive lateral margins after the first Mohs stage. Ta b le 1 . Su m m ar y o f in cl u d ed s tu d ie s. A u th o r Y e a r C o u n tr y S tu d y o b je ct iv e S tu d y d e si g n C o v e ra g e p e ri o d In te rv e n ti o n g ro u p s B C C s u b ty p e s in e a ch g ro u p R e cu rr e n t B C C b e fo re M o h s su rg e ry C a se s in cl u d e d in t h e m e ta -a n a ly si s Fo ll o w -u p (m o n th s) A si li an a n d M o m en i [6 ] 2 0 1 2 Ir an T o c o m p ar e th re e w ay s (n ak ed e ye ex am in at io n , d er m o sc o p y, a n d cu re tt ag e) f o r d et er m in in g tu m o r ex te n si o n b ef o re in it ia ti o n o f M M S, R C T 2 0 1 1 - 2 0 1 2 3 g ro u p s: tu m o r d em ar ca ti o n u si n g n ak ed e ye ex am in at io n (N = 2 0 ), d er m o sc o p y (N = 2 0 ) an d cu re tt ag e (N = 2 0 ) n o d u la r B C C i n a ll in cl u d ed c as es n o t in cl u d ed i n th e st u d y 4 0 N D G u rg en a n d G at ti [ 7 ] 2 0 1 2 U n it ed St at es T o c o m p ar e th e fi n al n u m b er o f M M S st ag es p er fo rm ed u si n g d er m o sc o p y an d vi su al i n sp ec ti o n o f in fi lt ra ti ve b as al ce ll c ar ci n o m a R C T N D 2 g ro u p s: - d er m o sc o p y gr o u p ( N = 2 0 ) - vi su al in sp ec ti o n gr o u p ( N = 2 0 ) in fi lt ra ti ve B C C i n al l ca se s n o t in cl u d ed i n th e st u d y 4 0 N D Su zu k i et a l [8 ] 2 0 1 4 B ra zi l T o a ss es s th e im p ac t o f d er m o sc o p y o n th e d em ar ca ti o n o f su rg ic al m ar gi n s fo r M M S an d a sc er ta in w h et h er t h e u se o f th is m et h o d c an sh o rt en o p er at iv e ti m e o b se rv at io n al st u d y 2 0 0 9 -2 0 1 1 2 g ro u p s: - G ro u p 1 : M o h s su rg er y (N = 2 1 ) - G ro u p 2 : M o h s su rg er y w it h d er m o sc o p y- gu id ed m ar gi n s (N = 2 3 ) N D G ro u p 1 : 3 /2 1 G ro u p 2 : 4 /2 3 4 4 N D T ab le 1 c o n ti n u es 6 Review | Dermatol Pract Concept. 2022;12(4):e2022176 A u th o r Y e a r C o u n tr y S tu d y o b je ct iv e S tu d y d e si g n C o v e ra g e p e ri o d In te rv e n ti o n g ro u p s B C C s u b ty p e s in e a ch g ro u p R e cu rr e n t B C C b e fo re M o h s su rg e ry C a se s in cl u d e d in t h e m e ta -a n a ly si s Fo ll o w -u p (m o n th s) D ik a et a l [9 ] 2 0 1 7 It al y to e va lu at e th e ro le o f vi d eo - d er m o sc o p y an d c u re tt ag e in M S fo r a b et te r m ar gi n e va lu at io n in tr ao p er at iv el y o b se rv at io n al st u d y 2 0 0 5 -2 0 1 0 2 g ro u p s: - G ro u p 1 : P at ie n ts t re at ed w it h v id eo d er m o sc o p y gu id ed M o h s su rg er y (N = 1 0 2 ) - G ro u p 2 : P at ie n ts t re at ed w it h c u re tt ag e- gu id ed M o h s su rg er y (N = 9 5 ) G ro u p 1 : - n o d u la r B C C s (N = 2 1 ) - p ig m en te d B C C s (N = 2 8 ) - m o rp h ei fo rm B C C s (N = 2 0 ) G ro u p 2 : - n o d u la r B C C s (N = 1 9 ) - p ig m en te d B C C s (N = 2 8 ) - m o rp h ei fo rm B C C s (N = 2 0 ) Su b ty p es o f p ri m ar y tu m o rs ( n o d u la r, p ig m en te d , o r m o rp h ei fo rm B C C s) w er e eq u al ly d is tr ib u te d i n t h e 2 g ro u p s (p ri m ar y B C C i n G ro u p A 7 1 G ro u p B 6 9 ) G ro u p 1 (3 1 /1 0 2 ) G ro u p 2 (2 6 /9 5 ) 1 9 7 G ro u p 1 (8 2 .6 ) G ro u p 2 (6 2 .5 ) Sh in e t al [1 0 ] 2 0 2 0 K o re a T o e va lu at e th e u se fu ln es s o f d er m o sc o p y in d et er m in in g M M S su rg ic al m ar gi n s o f B C C s w it h a h is to ry o f ab la ti ve la se r tr ea tm en t. o b se rv at io n al st u d y 2 0 0 9 - 2 0 1 6 2 g ro u p s: - C li n ic al s u rg ic al m ar gi n (N = 6 9 ) - D er m o sc o p ic su rg ic al m ar gi n (N = 6 4 ) N D A ll c as es w er e re cu rr en t B C C (p re vi o u sl y tr ea te d b y ab la ti ve l as er ). R ec u rr en t ca se s af te r ra d io th er ap y o r su rg ic al re se ct io n w er e ex cl u d ed . 1 3 3 N D Ta b le 1 . Su m m ar y o f in cl u d ed s tu d ie s. ( co n ti n u ed ) Review | Dermatol Pract Concept. 2022;12(4):e2022176 7 A u th o r Y e a r C o u n tr y S tu d y o b je ct iv e S tu d y d e si g n C o v e ra g e p e ri o d In te rv e n ti o n g ro u p s B C C s u b ty p e s in e a ch g ro u p R e cu rr e n t B C C b e fo re M o h s su rg e ry C a se s in cl u d e d in t h e m e ta -a n a ly si s Fo ll o w -u p (m o n th s) L it ai em et a l [4 ] 2 0 2 0 T u n is ia T o e va lu at e th e u se o f d er m o sc o p y in th e d em ar ca ti o n o f su rg ic al m ar gi n s in sl o w M o h s su rg er y. o b se rv at io n al st u d y 2 0 1 6 - 2 0 1 9 2 g ro u p s: G 1 : tu m o r d em ar ca ti o n u si n g n ak ed e ye ex am in at io n (N = 2 8 ) G 2 : tu m o r d em ar ca ti o n u si n g n ak ed e ye ex am in at io n + d er m o sc o p y (N = 2 6 ) N D n o t in cl u d ed i n th e st u d y 5 4 1 0 ± 5 B C C = b as al c el l ca rc in o m a; N D = n o t d es cr ib ed ; R C T = r an d o m iz ed c li n ic al t ri al . 8 Review | Dermatol Pract Concept. 2022;12(4):e2022176 Figure 2. Comparison of the proportion of positive margins after the first Mohs stage using dermoscopy-guided vs. standard or curettage guided MMS for BCC treatment META ANALYSIS (OUTCOME: POSITIVE MARGINS) (Q TEST) P=0,164 - I2: 38,4% FUNNEL PLOT OF STANDARD ERROR BY LOG ODDS RATIO LOG ODDS RATIO 0,8 0,0-0,5-1,0-1,5 0,5 1,0 1,5 2,0-2,0 ST A N D A R D E R R O R Standard and curettage-guided MMSDermoscopy-guided MMS STATISTICS FOR EACH STUDY 1,222 0,372 4,018 0,741 0,521 0,295 0,921 0,01 0,1 1 10 100 0,958 0,463 1,983 0,909 0,025 0,247 0,079 0,769 0,016 0,686 0,409 1,150 0,153 1,238 0,343 4,464 0,744 ODDS RATIO P-VALUE LOWER LIMIT UPPER LIMIT ODDS RATIO AND 95% CI GURGEN AND GATTI, 2012 DIKA ET AL., 2017 SHIN ET AL, 2020 LITAIEM ET AL, 2020 SUZUKI ET AL., 2014 STUDY NAME 0,6 0,2 0,0 0,4 studies reported a recurrence rate of 3% in BCCs treated with dermoscopy-guided MMS and of 5.2% in those treated with curettage-guided MMS (P = 0.48; Fisher exact test) af- ter a follow-up period of 82.6 and 62.5 months respectively [9]. In the second study, both study groups showed no recur- rence after a mean follow-up period of 10 ± 5 months [4]. Conclusions In the present study, we aimed to assess the effectiveness of dermoscopy as an ancillary tool for MMS. Six studies were included: 2 RCTs [6,7], and 4 observational studies [4,8- 10]. The total number of evaluated BCCs was 508. Three studies specified the subtypes of evaluated BCCs [6,7,9]. Three studies excluded recurrent BCC [4,6,7], while one study included only recurrent BCC following ablative laser [10]. Of the included studies, pooling of the data was fea- sible for 3 evaluated outcomes. There was no statistically significant difference in the proportion of total margin clear- ance on the first MMS stage between BCCs removed using dermoscopy-guided MMS and those that had curettage or vi- sual inspection. However, lateral margin involvement was sig- nificantly lower in BCCs that had dermoscopy-guided MMS. To the best of our knowledge, no systematic review ad- dressed the question of whether dermoscopy is useful for delineating BCC margins for MMS. Que published a com- prehensive narrative review on noninvasive imaging tech- nologies used for the delineation of BCC in the setting of Review | Dermatol Pract Concept. 2022;12(4):e2022176 9 FUNNEL PLOT OF STANDARD ERROR BY STD DIFF IN MEANS ST A N D A R D E R R O R STD DIFF IN MEANS -2,0 0,4 0,3 0,2 0,1 0,0 -1,5 -1,0 -0,5 0,0 0,5 1,0 1,5 2,0 META ANALYSIS (OUTCOME: NUMBER OF MOHS SESSIONS) (Q TEST) P=0,034 -I2: 70,3% STANDARD OR CURETTAGE-GUIDED MMSDERMOSCOPY-GUIDED MMS STUDY NAME STATISTICS FOR EACH STUDY STANDARD ERROR UPPER LIMIT LOWER LIMIT P-VALUE STD DIFF IN MEANS STD DIFF IN MEANS AND 95% CI ASILIAN MOMENI 2012 GURGEN GATTI 2012 LITAIEM 2020 0,200 0,191 -0,130 -0,739 0,317 0,317 0,323 0,281 0,317 0,317 0,323 -2,00 -1,00 0,00 1,00 2,00 0,281 -0,421 -0,430 -0,764 -1,290 0,821 0,812 -0,503 -0,187 Figure 3. Comparison of the number of Mohs stages using dermoscopy-guided vs. standard or curettage MMS for BCC treatment STATISTICS FOR EACH STUDY ODDS RATIO AND 95% CISTUDY NAME LITAIEM 2020 SHIN 2020 ODDS RATIO P-VALUE 0,001 0,012 0,000 0,429 0,703 0,385 0,034 0,061 0,066 0,120 0,206 0,159 LOWER LIMIT UPPER LIMIT STANDARD AND CURETTAGE-GUIDED MMSDERMOSCOPY-GUIDED MMS 0,01 0,1 1 10 100 META ANALYSIS (OUTCOME: POSITIVE LATERAL MARGINS AFTER THE FIRST MOHS SESSIONS) (Q TEST) P=0,550 - I 2 : 0% Figure 4. Comparison of the proportion of positive lateral margins after the first Mohs stage using dermoscopy-guided vs. standard or curettage guided MMS for BCC treatment 10 Review | Dermatol Pract Concept. 2022;12(4):e2022176 not indicated in all included studies. This may hinder the interpretation of findings and undermine their accuracy. Fi- nally, both dermoscopy and MMS are operator-dependent procedures [4]. Thus, controlled, consistent and reproducible results are not readily attainable. Despite these limitations, this systematic review is a com- prehensive summary on the reported use of dermoscopy for BCC delineation in MMS to date. Overall, our data suggest that dermoscopy could improve lateral margin assessment within the first Mohs stage. Future randomized clinical trials are required to develop an evidence-based recommendation regarding the utility of dermoscopy in MMS. References 1. Cameron MC, Lee E, Hibler BP, et al. Basal cell carcinoma: Con- temporary approaches to diagnosis, treatment, and prevention. J Am Acad Dermatol. 2019;80(2):321-339. DOI:10.1016/j. jaad.2018.02.083. PMID: 29782901. 2. Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (kerati- nocyte carcinomas) in the us population, 2012. JAMA Derma- tology. 2015;151(10):1081-1086. DOI:10.1001/jamadermatol .2015.1187. PMID: 25928283. 3. Danesh MJ, Menge TD, Helliwell L, Mahalingam M, Waldman A. Adherence to the National Comprehensive Cancer Network Criteria of Complete Circumferential Peripheral and Deep Margin Assessment in Treatment of High-Risk Basal and Squa- mous Cell Carcinoma. Dermatol Surg. 2020;46(12):1473-1480. DOI:10.1097/DSS.0000000000002354. PMID: 32149872. 4. Litaiem N, Karray M, Jones M, Rammeh S, Zeglaoui F. Effectiveness of dermoscopy in the demarcation of surgi- cal margins in slow Mohs surgery. Dermatol Ther. Published online 2020;33(6):e14196. DOIi:10.1111/dth.14196. PMID: 32798257. 5. Rosendahl C, Marozava A, eds. Dermatoscopy and Skin Cancer: A Handbook for Hunters of Skin Cancer and Melanoma. 1st edition. Scion Publishing; 2019:276-284. 6. Asilian A, Momeni I. Comparison between examination with naked eye, curretage and dermoscopy in determining tumor extension before Mohs micrographic surgery. Adv Biomed Res. 2013;2:2. DOI: 10.4103/2277-9175.107961. PMID: 23930247. PMCID: PMC3732882. 7. Gurgen J, Gatti M. Epiluminescence microscopy (Dermoscopy) versus visual inspection during mohs microscopic surgery of infiltrative basal cell carcinoma. Dermatologic Surg. 2012;38 (7 PART 1):1066-1069. DOI:10.1111/j.1524-4725.2012.02424 .x. PMID: 22676346. 8. Suzuki HS, Serafini SZ, Sato MS. Utility of dermoscopy for de- marcation of surgical margins in Mohs micrographic surgery. An Bras Dermatol. 2014;89(1):38-43. DOI:10.1590/abd1806- 4841.20142400. PMID: 24626646. PMCID: PMC3938352. 9. Dika E, Fanti PA, Christman H, Ravaioli GM, Patrizi A. Video- dermoscopy and curettage: The value of simple procedures during Mohs surgery. Dermatologic Surg. 2017;43(12):1411-1417. DOI:10.1097/DSS.0000000000001247. PMID: 28858922. MMS [22]. Three technologies were discussed: dermoscopy, confocal microscopy, and optical coherence tomography. Only the number of Mohs stages was evaluated as an out- come measure in relation to dermoscopy. Que stated that dermoscopy did not prove to decrease the number of Mohs stages. In our systematic review, there was no statistically significant difference in the number of Mohs stages between the use of dermoscopy or visual inspection for MMS (the standardized mean difference -0.17, 95% CI -0.51 to 0.17; three studies [4,6,7]). A hypothesis to explain this finding is that dermoscopy utility is limited to the first Mohs stage. Subsequent stages would only rely on the surgeon’s skills and experience. In the present systematic review, there was no significant association between the use of dermoscopy and the propor- tion of total margin clearance on the first MMS stage. Surgi- cal margin assessment includes both deep and lateral margin evaluation. A dermoscope is a magnifying instrument that enables visualization of pigmented structures and vessels up to 1mm into the dermis and therefore would not allow for deep margin evaluation [5]. Hence, it is rational to use it for lateral margin evaluation [4,10]. There are several potential implications for both practice and research. Relapsing BCCs and BCCs bearing aggressive histopathological features may exhibit a subclinical exten- sion of their lateral margins [23]. This could result in recur- rences and incomplete surgical excision [23]. Further studies assessing lateral margin involvement are needed. In addition, future research is warranted to investigate the utility of der- moscopy for tumor delineation in high‐risk BCC. Combining two imaging techniques is beyond the scope of the present systematic review. Recently, Lupu et al evalu- ated whether BCC lateral excision margins could be precisely evaluated preoperatively through the use of dermoscopy and reflectance confocal microscopy [23]. In this study, 18 pa- tients (20 BCCs, mostly were nodular: 12/20) were included. The authors concluded that dermoscopy served as an ac- curate guide during reflectance confocal microscopy [23]. The global accuracy of the procedure was 93.1% (95% CI 0.77–0.99) [23]. The present systematic review sought to summarize the existing data on the possible use of dermoscopy for tumor delineation in MMS. However, certain limitations apply to the results depicted herein. First, our sample size was limited by the scarcity of research on this subject in the literature. Only two included studies evaluated the use of dermos- copy for lateral margin assessment. Therefore, these results should be interpreted with caution. Second, some studies had missing data on outcome measures and hence were ex- cluded from the data analysis. Third, the histopathological subtype of BCC, which can act as a confounding factor, was Review | Dermatol Pract Concept. 2022;12(4):e2022176 11 17. Jawed SI, Goldberg LH, Wang SQ. Dermoscopy to identify bi- opsy sites before mohs surgery. Dermatologic Surg. 2014;40(3): 334-337. DOI:10.1111/dsu.12422. PMID: 24447179. 18. Hidalgo L, Donoso F, Guzmán M, et al. Multiple aggregated yel- low-white (MAY) globules, a dermoscopic sign to be considered in the presurgical evaluation in Mohs surgery. Dermatol Ther. 2022;35(4):e15333. DOI:10.1111/DTH.15333. PMID: 35080119. 19. Coleman AJ, Penney GP, Richardson TJ, et al. Automated regis- tration of optical coherence tomography and dermoscopy in the assessment of sub-clinical spread in basal cell carcinoma. Com- put Aided Surg. 2014;19(1-3):1-12. DOI:10.3109/10929088.20 14.885085. PMID: 24784842. PMCID: PMC4075257. 20. Jayasekera PSA, Dodd J, Oliphant T, Langtry JAA, Lawrence CM. Dermoscopy prior to Mohs micrographic surgery does not improve tumour margin assessment and leads to fewer Mohs stages. Br J Dermatol. 2018;178(2):565-566. DOI:10.1111 /bjd.15903. PMID: 28851098. 21. Cerci FB, Kubo EM, Werner B, Tolkachjov SN. Dermoscopy ac- curacy for lateral margin assessment of distinct basal cell car- cinoma subtypes treated by Mohs micrographic surgery in 368 cases. Int J Dermatol. 2022;61(4):e139-e141. DOI: 10.1111/ ijd.15655. PMID: 34013989. 22. Que SKT. Research Techniques Made Simple: Noninvasive Im- aging Technologies for the Delineation of Basal Cell Carcino- mas. J Invest Dermatol. 2016;136(4):e33-e38. DOI:10.1016/j .jid.2016.02.012. PMID: 27012561. 23. Lupu M, Voiculescu VM, Caruntu A, Tebeica T, Caruntu C. Preoperative Evaluation through Dermoscopy and Reflectance Confocal Microscopy of the Lateral Excision Margins for Pri- mary Basal Cell Carcinoma. Diagnostics. 2021;11(1):120. DOI:10.3390/diagnostics11010120. PMID: 33466602; PMCID: PMC7828674. 10. Shin K, Kim H-SH-JH, Ko H, Kim B, Kim M-B, Kim H-SH-JH. Dermoscopy-guided Mohs micrographic surgery in post-laser basal cell carcinomas: Is dermoscopy helpful for demarcation of the surgical margin? J Dermatolog Treat. 2020;0(0):1-12. DOI:1 0.1080/09546634.2020.1762839. PMID: 32345116. 11. Yeom SD, Lee SH, Ko HS, et al. Effectiveness of dermoscopy in Mohs micrographic surgery (MMS) for nonmelanoma skin cancer (NMSC). Int J Dermatol. 2017;56(6):e136-e139. DOI:10.1111 /ijd.13501. PMID: 28247925. 12. Guardiano RA, Grande DJ. A direct comparison of visual inspec- tion, curettage, and epiluminescence microscopy in determining tumor extent before the initial margins are determined for mohs micrographic surgery. Dermatologic Surg. 2010;36(8):1240-1244. DOI:10.1111/j.1524-4725.2010.01616.x. PMID: 20666811. 13. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA state- ment for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339. DOI:10.1136/bmj.b2700. PMID: 19622552. PMCID: PMC2714672. 14. Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological index for non-randomized studies (Minors): Development and validation of a new instrument. ANZ J Surg. 2003;73(9):712-716. DOI:10.1046/j.1445-2197.2003.02748.x. PMID: 12956787. 15. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Con- trol Clin Trials. 1996;17(1):1-12. DOI:10.1016/0197-2456(95) 00134-4. PMID: 8721797. 16. Terushkin V, Wang SQ. Mohs surgery for basal cell carcinoma assisted by dermoscopy: Report of two cases. Dermatologic Surg. 2009;35(12):2031-2035. DOI:10.1111/j.1524-4725.2009.01329 .x. PMID: 19758353. 12 Review | Dermatol Pract Concept. 2022;12(4):e2022176