Biopsy Outperforms Reflectance Confocal Microscopy in Diagnosing and Subtyping Basal Cell Carcinoma

Results and Experiences From a Randomized Controlled Multicentre Trial

W. Woliner–van der Weg; M. Peppelman; Y.S. Elshot; M.B. Visch; M.B. Crijns; H.A.C. Alkemade; E.M. Bronkhorst; E. Adang; A. Amir; M.J.P. Gerritsen; P.E.J. van Erp; S.F.K. Lubeek


The British Journal of Dermatology. 2021;184(4):663-671. 

In This Article

Abstract and Introduction


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.


Since the 1990s, reflectance confocal microscopy (RCM) – also called confocal imaging – became known for its noninvasive skin imaging potential. Preliminary studies of RCM used for basal cell carcinoma (BCC) focused on the correlation of histopathological and RCM features.[1–3] The high and increasing incidence of BCC,[4–6] accompanied by a persistent increasing pressure on our already heavily overloaded healthcare systems, justify the interest in this field. Ultimately, RCM could be a quick, patient-friendly and economically interesting alternative to the current standard punch biopsy (PB) diagnosis. A PB is an invasive procedure, with risks of pain, scar formation and sampling error.[7–11] The latter might lead to undertreatment followed by a recurrent tumour requiring additional (costly) therapy. Furthermore, PB does not give an immediate result owing to the time needed for tissue processing and assessment.

In contrast, RCM provides a noninvasive cellular-level view and facilitates direct diagnosing with the possibility of complete lesion assessment, minimizing the risk of sampling error. Therefore, replacing PB with RCM would potentially save time, patient discomfort and money. Also, it might facilitate diagnosis and treatment in one visit ('one-stop shop').[12]

As recently concluded, clinical evidence on the implementation of RCM for regular BCC diagnostics is currently too premature. Furthermore, most work was performed by experts,[13] and cost-effectiveness has yet to be evaluated. Ideally, RCM should at least have similar diagnostic accuracy in diagnosing BCC as the currently used biopsies. Furthermore, the BCC subtype should be identified correctly, to select the most appropriate treatment. Also, costs of RCM preferably should not exceed costs of PB, and implementation should be feasible. Furthermore, the patient's experience should, ideally, be superior with RCM or at least similar to PB. All of these outcomes were assessed in this randomized controlled trial (RCT).

The primary objective was to investigate whether a correct diagnosis and subtype could be determined with RCM in patients with a clinically suspected primary BCC, in a real-world setting. The secondary objectives were to study patient satisfaction and patient preferences.