Improving Basal Cell Carcinoma Subtype Diagnosis with Dermoscopy and Reflectance Confocal Microscopy: A Multicenter Prospective Study

Stefania Guida; Marco Spadafora; Silvana Ciardo; Marica Mirra; Serena Magi; Laura Mazzoni; Shaniko Kaleci; Francesca Farnetani; Franco Rongioletti; Ignazio Stanganelli; Giovanni Pellacani; Caterina Longo

doi:10.1093/ced/llag037

Improving Basal Cell Carcinoma Subtype Diagnosis with Dermoscopy and Reflectance Confocal Microscopy: A Multicenter Prospective Study

Clin Exp Dermatol. 2026 Feb 13:llag037. doi: 10.1093/ced/llag037. Online ahead of print.

Authors

Stefania Guida^{1

2}, Marco Spadafora^{3

4}, Silvana Ciardo⁵, Marica Mirra⁴, Serena Magi⁶, Laura Mazzoni⁶, Shaniko Kaleci³, Francesca Farnetani⁵, Franco Rongioletti^{1

2}, Ignazio Stanganelli^{6

7}, Giovanni Pellacani⁸, Caterina Longo^{3

5}

Affiliations

¹ School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
² Dermatology Clinic, IRCCS San Raffaele Scientific Institute, Milan, Italy.
³ Department of Surgery, Medicine, Dental Medicine and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
⁴ Azienda Unità Sanitaria Locale, IRCCS di Reggio Emilia, Skin Cancer Center, Reggio Emilia, Italy.
⁵ Dermatology Department, Azienda Ospedaliero-Universitaria Policlinico di Modena, Italy.
⁶ Skin Cancer Unit, IRCCS, Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola.
⁷ Dermatology Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy.
⁸ Dermatology Clinic, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.

PMID: 41685950
DOI: 10.1093/ced/llag037

Abstract

Introduction: Basal cell carcinoma (BCC) is the most prevalent form of skin cancer. Accurate histological subtyping is essential for appropriate therapeutic planning, particularly for infiltrative variants associated with higher recurrence rates. Noninvasive imaging modalities such as dermoscopy and reflectance confocal microscopy (RCM) may enhance the diagnostic precision of BCC subtyping prior to treatment.

Methods: This was a prospective multicenter study conducted between August 2017 and June 2019 across three centers in Northern Italy. A total of 281 histologically confirmed BCCs from 256 patients were analyzed. Each lesion underwent standardized clinical, dermoscopic, and handheld RCM evaluation prior to biopsy. Subtype-specific features were recorded and correlated with histopathology. Interobserver agreement was assessed using Cohen's kappa, and diagnostic performance was evaluated via sensitivity, specificity, and area under the receiver operating characteristic curve (AUC).

Results: Among the 281 BCCs, 15% were superficial, 38% nodular, and 47% infiltrative. Dermoscopically, superficial BCCs exhibited brown globules and shiny white-red structureless areas; nodular BCCs presented blue structures, arborizing vessels, and ulceration; infiltrative BCCs showed white porcelain areas and lacked pigmentation. RCM identified streaming and cords in superficial BCCs (p=0.003; 3-fold risk), large tumor islands in nodular BCCs, and dark silhouettes in infiltrative BCCs (p=0.005; 2-3-fold risk). Diagnostic accuracy improved with combined dermoscopy and RCM. Sensitivity for superficial BCC increased from 74.4% (95% CI 60.2-85.8) to 81.4% (95% CI 68.1-91.0), specificity from 97.9% (95% CI 95.5-99.5) to 98.3% (95% CI 96.1-99.5), and AUC reached 0.899.

Conclusions: The integration of dermoscopic and RCM findings significantly enhances the noninvasive preoperative classification of BCC subtypes. This approach improves diagnostic accuracy and may inform more precise, subtype-tailored management, reducing treatment failures and supporting personalized dermatologic care.