Successful implementation of handheld reflectance confocal microscopy as the standard of care in the (surgical) management of lentigo maligna (melanoma).

BACKGROUND: Reflectance confocal microscopy (RCM) has shown promise in predicting surgical outcomes by non-invasively detecting subclinical lentigo maligna (melanoma) (LM/LMM). OBJECTIVES: To assess the effects of presurgical mapping using handheld RCM (HH-RCM) on surgical treatment, follow-up outcomes and management decisions. METHODS: A total of 117 consecutive LM/LMM cases (2015-2023) were included. The diagnostic accuracy of HH-RCM in detecting subclinical LM and invasive components was evaluated. The primary endpoints included histological margin status and changes in management based on the outcomes of the HH-RCM mapping procedure. Margin and follow-up outcomes were compared to a historical cohort before HH-RCM was introduced in our center (n = 94) (2003-2014). RESULTS: HH-RCM detected subclinical LM in 60% (n = 60) of cases. The median mapping duration was 14 min (range 4-50). In 27% (n = 33), the mapping procedure resulted in modified management, the majority consisting of limited surgery with adjuvant imiquimod (n = 15) or imiquimod monotherapy (n = 14). The remaining cases (n = 84) underwent HH-RCM-assisted surgery. Histological margins were cleared in 96.5% of the patients with a median histological margin of 3.0 mm, significantly higher than 81% in the historical cohort (median 2.0 mm) (p = 0.001). The sensitivity and specificity for detecting the extent of subclinical LM were 94% (95% CI 80.4-99.3) and 84% (95% CI 70.3-92.7), respectively. The negative predictive value for the detection of LMM was 94% (95% CI 84.4-97.7), and 75% of the initially missed LMM (n = 12) were identified during the HH-RCM mapping procedure. The study cohort had a 1.6% local recurrence rate compared with 25% in the historical cohort. CONCLUSIONS: Integrating HH-RCM as the standard of care could lead to more personalized treatment strategies for LM/LMM and allows for the selection of patients suitable for nonsurgical treatment.

Lentigo maligna (melanoma): A systematic review and meta-analysis on surgical techniques and presurgical mapping by reflectance confocal microscopy.

Because of an increased risk of local recurrence following surgical treatment of lentigo maligna (melanoma) (LM/LMM), the optimal surgical technique is still a matter of debate. We aimed to evaluate the effect of different surgical techniques and reflectance confocal microscopy (RCM) on local recurrence and survival outcomes. We searched MEDLINE, Embase and PubMed databases through 20 May 2022. Randomized and observational studies with ≥10 lesions were eligible for inclusion. Bias assessment was performed using the Methodological Index for Non-Randomized Studies instrument. Meta-analysis was performed for local recurrence, as there were insufficient events for the other clinical outcomes. We included 41 studies with 5059 LM and 1271 LMM. Surgical techniques included wide local excision (WLE) (n = 1355), staged excision (n = 2442) and Mohs' micrographic surgery (MMS) (n = 2909). Six studies included RCM. The guideline-recommended margin was insufficient in 21.6%-44.6% of LM/LMM. Local recurrence rate was lowest for patients treated by MMS combined with immunohistochemistry (<1%; 95% CI, 0.3%-1.9%), and highest for WLE (13%; 95% CI, 7.2%-21.6%). The mean follow-up varied from 27 to 63 months depending on surgical technique with moderate to high heterogeneity for MMS and WLE. Handheld-RCM decreased both the rate of positive histological margins (p < 0.0001) and necessary surgical stages (p < 0.0001). The majority of regional (17/25) and distant (34/43) recurrences occurred in patients treated by WLE. Melanoma-associated mortality was low (1.5%; 32/2107), and more patients died due to unrelated causes (6.7%; 107/1608). This systematic review shows a clear reduction in local recurrences using microscopically controlled surgical techniques over WLE. The use of HH-RCM showed a trend in the reduction in incomplete resections and local recurrences even when used with WLE. Due to selection bias, heterogeneity, low prevalence of stage III/IV disease and limited survival data, it was not possible to determine the effect of the different surgical techniques on survival outcomes.

Biopsy outperforms reflectance confocal microscopy in diagnosing and subtyping basal cell carcinoma: results and experiences from a randomized controlled multicentre trial.

BACKGROUND: Reflectance confocal microscopy (RCM) is a noninvasive method for skin assessment, allowing entire lesion evaluation up to the papillary dermis. RCM is a potentially attractive alternative to punch biopsy (PB) in basal cell carcinoma (BCC). OBJECTIVES: To determine the diagnostic accuracy of RCM vs. PB in diagnosing and subtyping BCC, and to study patient satisfaction and preferences. METHODS: Patients with a clinically suspected primary BCC were randomized between RCM and biopsy. Conventional surgical excision or follow-up were used as reference. Sensitivity and specificity for BCC diagnosis and subtyping were calculated for both methods. BCC subtype was stratified based on clinical relevance: aggressive (infiltrative/micronodular) vs. nonaggressive (superficial/nodular) histopathological subtype and superficial vs. nonsuperficial BCC. Data on patient satisfaction and preferences were collected using a questionnaire and a contingent valuation method. RESULTS: Sensitivity for BCC diagnosis was high and similar for both methods (RCM 99·0% vs. biopsy 99·0%; P = 1·0). Specificity for BCC diagnosis was lower for RCM (59·1% vs. 100·0%; P < 0·001). Sensitivity for aggressive BCC subtypes was lower for RCM (33·3% vs. 77·3%; P = 0·003). Sensitivity for nonsuperficial BCC was not significantly different (RCM 88·9% vs. biopsy 91·0%; P = 0·724). Patient satisfaction and preferences were good and highly comparable for both methods. CONCLUSIONS: Biopsy outperforms RCM in diagnosing and subtyping clinically suspected primary BCC. This outcome does not support routine clinical implementation of RCM, as a replacement for PBs in this patient group.

Interrater and intrarater agreement of confocal microscopy imaging in diagnosing and subtyping basal cell carcinoma.

BACKGROUND: Reflectance confocal microscopy (RCM) imaging can be used to diagnose and subtype basal cell carcinoma (BCC) but relies on individual morphologic pattern recognition that might vary among users. OBJECTIVES: We assessed the inter-rater and intrarater agreement of RCM in correctly diagnosing and subtyping BCC. METHODS: In this prospective study, we evaluated the inter-rater and intrarater agreement of RCM on BCC presence and subtype among three raters with varying experience who independently assessed static images of 48 RCM cases twice with four-week interval (T1 and T2). Histopathologic confirmation of presence and subtype of BCC from surgical excision specimen was defined as the reference standard. RESULTS: The inter-rater agreement of RCM for BCC presence showed an agreement of 82% at T1 and 84% at T2. The agreements for subtyping BCC were lower (52% for T1 and 47% for T2). The intrarater agreement of RCM for BCC presence showed an observed agreement that varied from 79% to 92%. The observed agreements for subtyping varied from 56% to 71%. CONCLUSIONS: In conclusion, our results show that RCM is reliable in correctly diagnosing BCC based on the assessment of static RCM images. RCM could potentially play an important role in BCC management if accurate subtyping will be achieved. Therefore, future clinical studies on reliability and specific RCM features for BCC subtypes are required.

One-stop-shop with confocal microscopy imaging vs. standard care for surgical treatment of basal cell carcinoma: an open-label, noninferiority, randomized controlled multicentre trial.

BACKGROUND: Routine punch biopsies are considered to be standard care for diagnosing and subtyping basal cell carcinoma (BCC) when clinically suspected. OBJECTIVES: We assessed the efficacy of a one-stop-shop concept using in vivo reflectance confocal microscopy (RCM) imaging as a diagnostic tool vs. standard care for surgical treatment in patients with clinically suspected BCC. METHODS: In this open-label, parallel-group, noninferiority, randomized controlled multicentre trial we enrolled patients with clinically suspected BCC at two tertiary referral centres in Amsterdam, the Netherlands. Patients were randomly assigned to the RCM one-stop-shop (diagnosing and subtyping using RCM followed by direct surgical excision) or standard care (planned excision based on the histological diagnosis and subtype of a punch biopsy). The primary outcome was the proportion of patients with tumour-free margins after surgical excision of BCC. RESULTS: Of the 95 patients included, 73 (77%) had a BCC histologically confirmed using a surgical excision specimen. All patients (40 of 40, 100%) in the one-stop-shop group had tumour-free margins. In the standard-care group tumour-free margins were found in all but two patients (31 of 33, 94%). The difference in the proportion of patients with tumour-free margins after BCC excision between the one-stop-shop group and the standard-care group was -0·06 (90% confidence interval -0·17-0·01), establishing noninferiority. CONCLUSIONS: The proposed new treatment strategy seems suitable in facilitating early diagnosis and direct treatment for patients with BCC, depending on factors such as availability of RCM, size and site of the lesion, patient preference and whether direct surgical excision is feasible.

Diagnostic accuracy of confocal microscopy imaging vs. punch biopsy for diagnosing and subtyping basal cell carcinoma.

BACKGROUND: In vivo reflectance confocal microscopy (RCM) is a promising non-invasive skin imaging technique that could facilitate early diagnosis of basal cell carcinoma (BCC) instead of routine punch biopsies. However, the clinical value and utility of RCM vs. a punch biopsy in diagnosing and subtyping BCC is unknown. OBJECTIVE: To assess diagnostic accuracy of RCM vs. punch biopsy for diagnosing and subtyping clinically suspected primary BCC. METHODS: A prospective, consecutive cohort of 100 patients with clinically suspected BCC were included at two tertiary hospitals in Amsterdam, the Netherlands, between 3 February 2015 and 2 October 2015. Patients were randomized between two test-treatment pathways: diagnosing and subtyping using RCM imaging followed by direct surgical excision (RCM one-stop-shop) or planned excision based upon the histological diagnosis and subtype of punch biopsy (standard care). The primary outcome was the agreement between the index tests (RCM vs. punch biopsy) and reference standard (excision specimen) in correctly diagnosing BCC. The secondary outcome was the agreement between the index tests and reference standard in correctly identifying the most aggressive BCC subtypes. RESULTS: Sensitivity to detect BCC was similar for RCM and punch biopsy (100% vs. 93.94%), but a punch biopsy was more specific than RCM (79% vs. 38%). RCM expert evaluation for diagnosing BCC had a sensitivity of 100% and a specificity of 75%. The agreement between RCM and excision specimen in identifying the most aggressive BCC subtype ranged from 50% to 85% vs. 77% by a punch biopsy. CONCLUSION: Reflectance confocal microscopy and punch biopsy have comparable diagnostic accuracy to diagnose and subtype BCC depending on RCM experience. Although experienced RCM users could accurately diagnose BCC at a distance, we found an important difference in subtyping BCC. Future RCM studies need to focus on diagnostic accuracy, reliability and specific criteria to improve BCC subtype differentiation.