Three-Dimensional Total Body Photography, Digital Dermoscopy, and in vivo Reflectance Confocal Microscopy for Follow-Up Assessments of High-Risk Patients for Melanoma: A Prospective, Controlled Study

Abstract

Introduction

The combination of total body photography (TBP) and digital dermoscopy (DD) for monitoring patients with a high risk for melanoma can allow early detection of melanoma. This study aimed to examine if the use of three-dimensional (3D)-TBP, DD, and reflectance confocal microscopy (RCM) for regular monitoring of patients at high risk for melanoma was beneficial in comparison to monitoring using dermoscopy alone.

Methods

The intervention group (IG) underwent 3D-TBP examinations at every visit, along with DD and/or RCM for diagnosis and/or monitoring of pigmented lesions if necessary. The control group (CG) underwent dermoscopy examinations alone.

Results

A total of 600 patients (324 male and 276 female) were followed up over a median period of 23 months (mean, 2.85 visits) in the IG and 22 months (mean, 2.74 visits) in the CG (p = 0.009). DD and RCM monitoring were performed for 166 and 105 lesions, respectively. The number needed to treat (NNT) to diagnose melanoma with RCM was 2.83. The IG included more second primary melanomas (22 vs. 1, p = 0.022) and more excised nevi (186 vs. 10, p < 0.001), which consisted of more dysplastic nevi (137 vs. 2, p < 0.001). Among the melanomas diagnosed in the IG, three were diagnosed directly with RCM, nine with a combination of 3D-TBP and RCM, and 10 with dermoscopy alone.

Conclusion

Follow-up assessments with a combination of 3D-TBP, DD, and RCM led to the detection of more melanomas in comparison to the CG. The use of RCM reduced the NNT for melanocytic lesions.

Plain Language Summary

The combination of total body photography (TBP) and digital dermoscopy (DD) for the monitoring of patients with high risk for melanoma leads to early detection of melanoma. The aim of the present study was to examine if regular monitoring of patients with high risk for melanoma with 3D-TBP, DD, and confocal microscopy (RCM) leads to a benefit in comparison to a control group (CG). The intervention group (IG) was examined with 3D-TBP at every visit. If necessary, DD and/or RCM were used for diagnosis and/or monitoring of pigmented lesions. The CG was examined clinically with dermoscopy only. A total of 600 patients (324 male and 276 female) were followed up between April 21, 2021, and January 8, 2024. Lesions (n = 166) were monitored with DD and 105 lesions were examined with RCM. The number of lesions that the dermatologists had to cut out to find a melanoma was 2.83, when RCM was used. There were more melanomas (22 vs. 1, p = 0.022) and more nevi excised in the IG (186 vs. 10, p < 0.001), among them more dysplastic nevi (137 vs. 2, p < 0.001). Out of the melanomas diagnosed in the IG, three melanomas were diagnosed with RCM directly, nine melanomas with the combination of 3D-TBP and RCM, and 10 melanomas were diagnosed clinically with dermoscopy only. The follow-up with the combination of 3D-TBP, DD and RCM led to detection of more melanomas in comparison to a CG. RCM led to a reduced NNT for melanocytic lesions.

Introduction

The incidence of malignant melanoma has been steadily increasing over the previous decades [1]. This increase has been accompanied by an increase in the incidence of subsequent primary melanomas in patients with previous melanoma, which is associated with worsened survival [2]. The use of total body photography (TBP) with digital dermoscopy (DD), which has been described by Malvehy and Puig [3] as a “two-step method for digital follow-up” [4], allows early detection of melanoma in high-risk patients [3–21]. The European interdisciplinary guideline for melanoma recommends the use of TBP for the monitoring of patients with a high risk for melanoma [6]. In comparison with two-dimensional (2D)-TBP, image acquisition in three-dimensional (3D)-TBP requires only a few seconds since the process is performed in only one body position [22]. In 3D-TBP, the position vectors of the body surface are acquired in addition to the image information so that skin changes can be precisely and automatically assigned over time. In addition, lesions can be displayed side-by-side and changes in size or color can be visualized. In vivo reflectance confocal microscopy (RCM) is a noninvasive imaging technique that visualizes the skin at a cellular level up to a depth of at least 200 μm [23]. RCM leads to a reduced number needed to treat (NNT) in cases of doubtful melanocytic lesions and allows early diagnosis of melanoma [6, 24–26]. In the present study, the authors used 3D-TBP to examine patients at a high risk for developing melanoma, and used DD and RCM, if necessary, for examining individual lesions over a period of 33 months. The aim of the present study was to examine if regular monitoring using 3D-TBP, DD, and RCM for patients with a high risk for melanoma was beneficial in comparison with regular monitoring using dermoscopy alone.

Methods

This prospective study was conducted with 600 patients who were treated between April 21, 2021, and January 8, 2024, at the Department of Dermatology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. The study protocol adhered to the Declaration of Helsinki and was approved by the Local Ethics Committee (Ethikkommission an der TU Dresden, BO-EK-97022021).

Patients’ written informed consent was obtained during their clinical visits to assess their medical records, including images. This study included patients at a high risk for melanoma. Inclusion criteria were the presence of previous melanoma, dysplastic nevi (diagnosed clinically and/or histologically), congenital nevi (>5 cm, medium, giant), multiple nevi (>50, >100), gene defects that increased the risk for developing melanoma (xeroderma pigmentosum, 1q-deletion-syndrome, familial atypical multiple mole melanoma syndrome), and immunosuppression. Patients interested in the study who showed at least one of the above risk factors were included in the intervention group (IG). Patients from our tumor follow-up consultation who met the inclusion criteria were included in the control group (CG). No randomization was performed. In the IG, the nevi count in 3D-TBP was recorded, while the nevi count in the CG was estimated by the physician.

Patients were monitored at intervals of three, six, or 12 months depending on their risk status as recommended by the German guideline for melanoma [27]. Each patient underwent a clinical examination (skin check) with dermoscopy at every visit. The IG consisted of patients who underwent additional evaluation with 3D-TBP, and, if necessary, DD (for follow-up) and/or RCM (for noninvasive diagnosis) for assessment of changed or unclear lesions. The CG consisted of patients who underwent only clinical examination with dermoscopy, consistent with our clinical routine.

Since the study was conducted in the university hospital, most patients underwent additional dermatologist examinations in the outpatient setting alternating with the clinical examinations, consistent with our clinical routine for patients with a high risk for melanoma. The dermatologists in the outpatient setting and the university hospital independently performed skin examinations and provided indications for excision of suspicious lesions.

For diagnostics and image acquisition, we used Vectra^® WB360 (Canfield Scientific GmbH, Parsippany, USA) for 3D-TBP, DermaGraphix^® (Canfield Scientific GmbH, Parsippany, USA) for DD, and Vivascope^® 3000 (VivaScope GmbH, Munich, Germany) for RCM. The clinician noted if the pigmented lesions changed between the visits and, if present, the changes in 3D-TBP and DD, the dermoscopy and RCM findings as well as the diagnoses obtained with each technique. At each visit, patients in both the IG and CG underwent clinical examinations with dermoscopy. In the CG, the diagnosis was based on the clinical examination and dermoscopy findings (Fig. 1). In the IG, 3D-TBP was performed at every visit (Fig. 1). Subsequently, images were compared between the visits. New or changed pigmented lesions were examined individually with dermoscopy. If dermoscopy indicated that the lesion was benign, no further imaging assessment was performed. If the lesion was diagnosed as benign but required monitoring, DD was performed (Fig. 1). For diagnosis of melanoma, the Algorithm of Pellacani et al. [28] (at least 3 points) was used. If the lesion was diagnosed as malignant or unclear (low confidence), RCM was performed (Fig. 1). If RCM indicated that the lesion was benign with high confidence, no further diagnostic assessment was performed. If the lesion was diagnosed as benign but required monitoring, DD was performed. If the lesion was diagnosed as malignant or unclear (low confidence), excision or biopsy was planned (Fig. 1, 2).

Fig. 1.

Distribution of patients in the study arms and workflow for melanocytic lesions.

Fig. 2.

a 3D-TBP: brown and greyish macule of the left lower leg with progression in size at the lower leg of a 36-year-old woman. b DD: thickened reticulated pattern with greyish area and blurred pattern. c In vivo RCM: dendritic cells (yellow arrow) and pagetoid cells (red arrow) with non-edged papillae (blue star) and an atypical, broadened, meshwork pattern at the dermoepidermal junction. d histopathology (HE-staining) of a malignant melanoma with atypic melanocytes in the superficial epithelium and upper dermis with a Breslow thickness of 0.5 mm with infiltration into the papillary layer of the dermis.

In the CG, excision or biopsy was planned for unclear or malignant lesions (Fig. 1). The diagnostic categories were melanoma, nevi, and “other.” Surgery, local treatment, or follow-up was planned based on the findings obtained during each examination. The physician noted if the excision, biopsy, or local treatment was initiated by the university hospital or the dermatologist in the outpatient setting.

Statistical analysis was performed using SPSS (Version 28, IBM Corporation, Armonk, NY). Tests were two-sided, with a threshold of p < 0.05 for statistical significance. Chi-square test and Fisher’s exact test were used to explore intergroup differences in sex, skin type, presence of immunosuppression, previous melanoma, nevi count (<50, >50, >100), dysplastic nevi, gene defects, lesion localization, number of excisions, biopsies, and number of lesions that received local treatment. Fisher’s exact test was used in groups with less than five lesions. The Mann-Whitney U test was used to evaluate age differences and differences in the number of months of monitoring.

Results

Patient Characteristics at Baseline

A total of 600 patients (324 male and 276 female patients) were included in our clinical examination, including 410 patients in the IG and 190 in the CG. The median age in the IG was lower than that in the CG (52 vs. 68 years; p < 0.001; Table 1). Sex distribution was similar between the groups (p = 0.669; Table 1). The two groups showed significant differences in the distribution of Fitzpatrick skin type, hair color, and eye color (p < 0.001). Fourteen patients in the IG and 21 in the CG were immunocompromised due to rheumatic diseases, transplants, multiple sclerosis, immune defect syndrome, Crohn disease, or autoimmune hepatitis (p < 0.001; Table 1). Immunosuppression was caused by mycophenolate mofetil, prednisolone, mesalazine, azathioprine, methotrexate, cyclosporine, tacrolimus, everolimus, methylprednisolone, infliximab, interferon beta, tocilizumab, and leukemia or lymphoma. The risk factors for the development of melanoma differed significantly between the two groups: the IG included a higher nevi count than the CG (p < 0.001; Table 1), while the CG included fewer patients with previous primary melanomas (IG vs. CG: 286 [70%] vs. 169 [88%], p < 0.001), ≥2 previous primary melanomas (IG vs. CG: 43 [10%] vs. 5 [3%], p < 0.001), ≥3 primary melanomas (IG vs. CG: 11 [3%] vs. 0, p = 0.020), and previous dysplastic nevi (IG vs. CG: 128 [30%] vs. 3 [2%], p < 0.001). The mean number of primary tumors per patient was 0.885 in the IG, ranging between 0 and 11, and 0.91 in the CG, ranging between zero and two (p < 0.001). In the IG, 1 patient each had xeroderma pigmentosum, 1q-deletion-syndrome, and familial atypical multiple mole melanoma syndrome.

Table 1.

Patient characteristics and univariate analysis of the characteristics in the intervention and CG

Patient characteristics	Intervention group (410 patients)	CG (190 patients)	p value
Age at inclusion, median (range), years	52 (18–84)	68 (34–90)	<0.001
Sex, n (%)
Male	224 (55)	100 (53)	0.647
Female	186 (45)	90 (47)
Fitzpatrick skin type, n (%)
I	115 (28)	73 (38)	<0.001
II	202 (49)	111 (58)
III	93 (23)	6 (3)
Hair color, n (%)
Red	20 (5)	5 (3)	<0.001
Blonde	181 (44)	108 (57)
Brown	203 (50)	59 (31)
Black	6 (1)	16 (8)
Unknown	20 (5)	1 (1)
Eye color, n (%)
Blue	177 (43)	58 (31)	<0.001
Green	68 (10)	43 (23)
Brown	103 (25)	31 (16)
Gray	60 (15)	57 (30)
Unknown	2	1
Nevi count, n (%)
<50	36 (9)	133 (70)	<0.001
50–100	70 (17)	25 (13)
>100	304 (74)	31 (16)
Unknown		1 (1)
Previous primary melanoma, n (%)	286 (70)	169 (89)	<0.001
Previous ≥2 primary melanomas, n (%)	43 (10)	5 (3)	<0.001
Previous ≥3 primary melanomas, n (%)	11 (3)	0	0.020
Previous dysplastic nevi, n (%)	128 (30)	3 (2)	<0.001
Immunocompromised, n (%)	14 (3)	22 (12)	<0.001
Congenital nevus, n
Small size	0	3
Medium size	0	1
Giant size	2	0
Xeroderma pigmentosum, n	1	0
FAMMM-PC, n	1	0
1q-deletion-syndrome, n	1	0

FAMMMM-PC, familial atypical multiple mole melanoma syndrome.

A total of 23 patients dropped out of the study (IG vs. CG: 13 vs. 10, p = 0.282), including 3 patients who died due to metastatic melanoma, three who died as a result of a second tumor, 3 transplant patients who died due to the primary disease, 1 patient who died as the result of an accident, 1 patient with an unknown cause of death, 8 patients who showed noncompliance, 2 patients who had relocated, and two patients who opted out of the study. The data of the patients who dropped out were included in the analyses.

Excisions at Baseline

The CG included a larger proportion of patients were already undergoing close dermatological skin screening before inclusion in the study, while several patients in the IG were not undergoing dermatological follow-up before inclusion in the study. Therefore, excisions were recommended at the baseline visit in 35 cases in the IG and none in the CG. The lesions for which excisions were recommended included four melanomas (three stage IA melanomas and one melanoma in situ), 20 dysplastic nevi, a granuloma pyogenicum, an acral nevus, two irritated nevi and a nodular basal cell carcinoma (BCC). Three lesions highly suspicious for melanoma in 1 patient were not excised because of an acute palliative situation due to the appearance of a second tumor after inclusion in the study. Among the excised lesions, nine were also examined with RCM, including two melanomas and seven dysplastic nevi.

Management of the Lesions in the Follow-Up Assessments

The median follow-up duration was 23 months in the IG (mean, 20.92 months; range, 3–33 months) and 22 months in the CG (mean, 19.46 months; range, 7–31 months, p = 0.009). The mean number of visits per patient was 2.85 (range, 1–8 visits) in the IG and 2.74 (range, 1–10) in the CG.

Among the 374 lesions examined in the study, 313 (mean, 0.52 per patient), underwent primary excision (IG vs. CG: 265 vs. 49, p < 0.001), three were evaluated by punch biopsy (IG vs. CG: 1 vs. 2; p = 0.131), and 55 received initial local treatment (IG vs. CG: 23 vs. 32, p < 0.001; Table 2). A total of 316 lesions were examined histologically.

Table 2.

Univariate analysis of the management of the lesions in the follow-up

	Intervention group, n = 288	CG, n = 87	p value
Lesion location, n (%)
Head/neck	48 (17)	43 (49)	<0.001
Trunk	177 (61)	25 (29)
Upper limb	23 (8)	10 (11)
Lower limb	40 (14)	9 (10)
Excision, n	265	49	<0.001
Biopsy, n	1	2	0.131
Local treatment, n	23	32	<0.001
Melanocytic lesions, n
Nevus	186	10	<0.001
Dysplastic nevus	137	2	<0.001
Malignant melanomas, n	23	1	0.022
Melanoma in situ	14	1	0.208
Invasive melanoma	9	0	0.125
Tumor thickness <1 mm	9
Stage IA	8
Stage IB	1
Actinic keratosis, n	20	33	<0.001
BCC, n	28	15	0.054
Squamous cell carcinoma, n	3	8	<0.001

The IG consisted of more second primary melanomas overall (23 vs. 1, p = 0.022, Fig. 1); these included more invasive melanomas (9 vs. 0, p = 0.125), including seven stage IA melanomas and one stage IB melanoma (Breslow thickness <1 mm) and more melanomas in situ (14 vs. 1, p = 0.208; Table 2). Furthermore, more nevi were excised in the IG (186 vs. 10, p < 0.001), which included more dysplastic nevi (137 vs. 2, p < 0.001; Table 2; Fig. 1). Excisions were initiated by our clinic and/or the dermatologist in the outpatient setting in both groups. Among the melanomas diagnosed in the IG, three were diagnosed with RCM directly, nine were diagnosed with the combination of 3D-TBP and RCM, and 10 were diagnosed clinically with dermoscopy only. In the IG, more BCCs (28 vs. 15, p = 0.054), but fewer squamous cell carcinomas (SCCs, 3 vs. 8, p < 0.001) and in situ SCCs (20 vs. 33, p < 0.001) were diagnosed (Table 2).

The IG included several other diagnoses, including six melanoma metastases, six seborrheic keratoses, three angiolipomas, one angioma, five cysts, two fibromas, two histiocytomas, a lichen-planus-like keratosis, a solar lentigo, a lipoma, a scar, and a melanosis vulvae. The other diagnoses in the CG included a recurrent melanoma, three melanoma metastases, a sebaceous carcinoma, a breast cancer, three seborrheic keratoses, a hemangioma, a fibroma, a histiocytoma, a solar lentigo, a traumatic neurinoma, a poroma, a sebaceous gland hyperplasia, and eczema.

A total of 53 lesions were not diagnosed in histopathological assessments but received immediate local treatment, including 44 in situ SCCs and nine superficial BCCs. The examined lesions were localized to the head/neck (91), trunk (202), upper limb (33), or lower limb (49); the distribution of localization sites was different between the groups (p < 0.001; Table 2).

Digital Dermoscopy

A total of 166 lesions were evaluated in 1–5 (mean, 1.98) DD examinations. DD was performed because lesions were changed (n = 23) or new (n = 5) in 3D-TBP, because lesions were not visible in 3D-TBP (localization under the hair [n = 1] or localized under underwear [n = 1]), due to an artificial change in the lesion (crust after irritation [n = 1]; shadow due to hair on the nevus [n = 1]), because the lesions were suspicious (n = 129), or because of the patient’s (n = 4) or at the dermatologist’s request in the outpatient setting (n = 1). RCM was also performed for 66 of these lesions. Of the 166 lesions evaluated with DD, follow-up DD assessments were performed for 144 lesions, and excision was performed in 22 lesions, including nine melanomas and 13 nevi (12 dysplastic nevi, one irritated nevus) (Fig. 1).

Confocal Microscopy

A total of 105 melanocytic lesions were examined with RCM. Among these, 59 lesions were diagnosed as benign but in need of monitoring, of which four lesions (three dysplastic nevi and one nevus) were excised by the dermatologist in the outpatient setting. Excision was recommended for 44 melanocytic lesions, including 12 melanomas (five stage IA melanomas and one stage IB melanoma, and six melanomas in situ) and 22 nevi (including 18 dysplastic nevi) (Fig. 1). The NNT to diagnose a melanoma was 2.83. For two lesions, excision was initially recommended, but not performed; the lesions remained stable in the follow-up.

Discussion

Previous studies reported that the combined use of TBP and DD led to improved early detection of melanomas in high-risk patients [4–21, 29]. To our knowledge, this is the first study that included 3D-TBP, DD, and RCM in the monitoring of patients with a high risk of developing melanoma and compared the findings to a CG that underwent assessments with dermoscopy alone.

The present study showed significantly more melanomas diagnosed in the IG. All detected melanomas in the IG were early melanomas, which is consistent with the findings of previous studies in which TBP and DD allowed early diagnosis of melanomas with a thinner Breslow index [9, 30–32]. Pizarro et al. [33] also found no thick, nodular melanomas in patients followed up with TBP and DD [34]. Previous studies have suggested that fast-growing melanomas may be preceded by premalignant lesions that could be detected during follow-up [33, 34]. Most of the lesions were monitored with DD because they were clinically suspicious, changed, or new in 3D-TBP assessments. The majority of the lesions remained benign in the follow-up and did not have to be excised. DD therefore led to reduced excisions of unclear lesions. Overall, only a few melanomas were found, although we monitored a high-risk population. However, Salerni et al. [5] reported a similar melanoma count per year in a 10-year-study, indicating that second primary melanomas could still be found in monitored high-risk patients after several years.

The use of RCM leads to a reduced NNT [24]. However, there were still benign nevi biopsied in the present study, even though RCM was used. In doubtful lesions in RCM, punch biopsy should still be performed to rule out melanoma.

All patients monitored in the study showed a high risk for melanoma. However, the presence of several risk factors differed significantly between the IG and CG. Patients in the IG had significantly more nevi than those in the CG. Nevertheless, the nevi count obtained in 3D-TBP was used in the IG, while the nevi count was estimated by the physicians in the CG. Cerminara et al. [35] reported a risk of overestimation in nevi counts obtained by 3D-TBP in comparison to those performed by physicians as the gold standard. The presence of more nevi overall and among these more previous dysplastic nevi in the IG may explain the more benign nevi excised in this group categorized in the clinic as well as in the outpatient setting. De Giorgi et al. [36] also reported that patients with atypical nevi had a higher risk of developing multiple primary melanomas. In addition, the IG also had a higher count of dysplastic nevi per excised nevus in comparison to the CG, which may lead to the conclusion that nevi with atypical features are more easily detected with imaging. Furthermore, the patients in the IG were younger than those in the CG. This bias is also attributable to the fact that a standardized body position is necessary for optimal image acquisition in 3D-TBP. Obtaining this posture can be difficult for older patients.

A combined follow-up regimen alternating between clinic and outpatient dermatologist assessments is common in Germany since this system can reduce the clinic’s burden of handling the rising number of melanoma patients. However, the limitation of this approach in the present study was the unnecessary excision of benign lesions because of contrasting opinions from the two dermatologists. Nevertheless, since this study included a CG that was monitored without imaging but also underwent alternate clinic and outpatient dermatologist assessments, we were able to eliminate this bias.

The IG also included more BCCs. An earlier study showed that the diagnostic accuracy of 3D-TBP is only slightly lower than that of dermoscopy for the diagnosis of nonmelanoma skin cancer (NMSC) [37]. To date, no study has examined the use of 3D-TBP in follow-up assessments of patients for the diagnosis of NMSC. However, in the present study, the NMSCs were mostly primarily detected in the clinical examination and not due to a change in 3D-TBP findings. One reason for the higher count of SCCs and in situ SCCs diagnosed in the CG may be that the CG included a significantly greater number of immunocompromised and older patients.

The use of 3D-TBP is associated with some limitations. Some regions cannot be fully visualized with 3D-TBP [15]. One resolution for this problem could be DD monitoring for the lesions identified in regions not visible in 3D-TBP to ensure that every pigmented lesion can be assessed in the follow-up imaging assessments. In the present study, patients could decide if they were imaged with or without underwear on. Approximately half of the patients decided to undergo imaging without underwear on to ensure better monitoring. Horsham et al. [14] examined concerns regarding privacy in TBP and found out that most patients would share identifiable images for their personal medical file [7, 13, 14]. Overall, the dropout rate in the present study was very small, and patients reported that they felt safer being also monitored with imaging devices. Moye et al. [11] also showed that patients with atypical mole syndrome had decreased cancer worry when monitored with TBP.

The combination of 3D-TBP, DD, and RCM in the follow-up of high-risk patients led to improved early detection of melanoma. However, these imaging devices are expensive, require physician training and take more time to acquire than regular dermoscopy. Therefore, this enhanced follow-up is recommended especially for patients at very high risk of developing melanoma. To date, 3D-TBP is not yet available in many skin tumor centers. However, Gassenmeier et al. [34] reported that regular follow-up total body skin examinations in patients with previous melanoma can facilitate early detection of subsequent melanomas in comparison to primary melanomas. De Giorgi also reported that cases with careful adherence to follow-up showed second primary melanomas with lower Breslow thickness [36].

Limitations

The primary limitations of the present study were that the CG was smaller than the IG and that patients were not randomized between the groups. Furthermore, the groups were not totally matched. However, all patients were at high risk for developing melanoma. In the CG, a larger proportion of patients were already undergoing close dermatological skin screening. We addressed this bias by analyzing melanoma diagnoses at first presentation separately within the IG. A more balanced distribution between the groups (on the basis of risk factors) may have yielded a clearer difference between the groups. Several high-risk patients had already undergone 3D-TBP monitoring before the initiation of the study; therefore, we did not perform randomization and included them in the study. However, previous studies had no CG at all [4, 5]. Furthermore, dermatologists in the outpatient setting also examined the patients in between the visits in our clinic. Therefore, decisions to perform excision or punch biopsy were not always based on the results of 3D-TBP, DD, and/or RCM in the IG or clinical examinations at our clinic in the CG. However, this bias was present in both groups, since all high-risk patients underwent additional dermatological examinations in the outpatient setting. RCM is not the gold standard for the diagnosis of melanocytic lesions and in unclear lesions, a punch biopsy should still be performed. The use of RCM for the diagnosis of melanocytic lesions requires additional training and the physicians have a learning curve. Furthermore, the use of RCM in the follow-up of high-risk patients increases significantly the length of the consultation. Hence, a follow-up with the combination of 3D-TBP, DD and RCM should be recommended for patients with high-risk of melanoma.

Conclusion

The combination of 3D-TBP, DD, and RCM for follow-up assessments of patients with high risk of developing melanoma led to greater detection of melanomas in comparison with dermoscopy examinations alone in the CG. Furthermore, examinations with RCM led to a reduced NNT.

Statement of Ethics

This study protocol was reviewed and approved by the Local Ethics Committee (Ethikkommission an der TU Dresden), Approval No. BO-EK-97022021. All patients in this manuscript have given written informed consent for participation in the study and the use of their de-identified, anonymized, aggregated data and their case details for publication.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This work was funded by “Stiftung zur Förderung der Hochschulmedizin in Dresden.” The funder had no role in the design, data collection, data analysis, and reporting of this study.

Author Contributions

S.H. and F.G. performed the research. S.H, F.G., J.S., F.M., and S.B. designed the research study. S.H. and F.G. analyzed the data and wrote the article.

Funding Statement

This work was funded by “Stiftung zur Förderung der Hochschulmedizin in Dresden.” The funder had no role in the design, data collection, data analysis, and reporting of this study.

Data Availability Statement

The data supporting the findings of this study are available on reasonable request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Further inquiries can be directed to the corresponding author.