Francesca Farnetani1, Alon Scope2, Ralph P Braun3, Salvador Gonzalez4, Pascale Guitera5, Josep Malvehy6, Marco Manfredini1, Ashfaq A Marghoob7, Elvira Moscarella8, Margaret Oliviero9, Susana Puig6, Harold S Rabinovitz9, Ignazio Stanganelli10, Caterina Longo8, Carlotta Malagoli11, Marco Vinceti11, Giovanni Pellacani1. 1. Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy. 2. Sheba Medical Center, Department of Dermatology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel3Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, New York. 3. Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. 4. Internal Medicine Department, Alcala University, Madrid, Spain. 5. Melanoma Institute Australia, The University of Sydney, Sydney7Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, Sydney, Australia. 6. Melanoma Unit, Dermatology Department, Hospital Clinic and University of Barcelona, Institut de Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Spain9Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III. 7. Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, New York. 8. Dermatology and Skin Cancer Unit, Arcispedale S. Maria Nuova-Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy. 9. Department of Dermatology and Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida. 10. Skin Cancer Unit-Istituto di Ricovero e Cura a Carattere Scientifico Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Forlì-Cesena, Italy. 11. Center for Environmental, Genetic, and Nutritional Epidemiology, Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy.
Abstract
IMPORTANCE: Reflectance confocal microscopy (RCM) studies have been performed to identify criteria for diagnosis of skin neoplasms. However, RCM-based diagnosis is operator dependent. Hence, reproducibility of RCM criteria needs to be tested. OBJECTIVE: To test interobserver reproducibility of recognition of previously published RCM descriptors and accuracy of RCM-based skin cancer diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Observational retrospective web-based study of a set of RCM images collected at a tertiary academic medical center. Nine dermatologists (6 of whom had ≥3 years of RCM experience) from 6 countries evaluated an RCM study set from 100 biopsy-proven lesions, including 55 melanocytic nevi, 20 melanomas, 15 basal cell carcinomas, 7 solar lentigines or seborrheic keratoses, and 3 actinic keratoses. Between June 15, 2010, and October 21, 2010, participanting dermatologists, blinded to histopathological diagnosis, evaluated 3 RCM mosaic images per lesion for the presence of predefined RCM descriptors. MAIN OUTCOMES AND MEASURES: The main outcome was identification of RCM descriptors with fair to good interrater agreement (κ statistic, ≥0.3) and independent correlation with malignant vs benign diagnosis on discriminant analysis. Additional measures included sensitivity and specificity for diagnosis of malignant vs benign for each evaluator, for majority diagnosis (rendered by ≥5 of 9 evaluators), and for experienced vs recent RCM users. RESULTS: Eight RCM descriptors showed fair to good reproducibility and were independently associated with a specific diagnosis. Of these, the presence of pagetoid cells, atypical cells at the dermal-epidermal junction, and irregular epidermal architecture were associated with melanoma. Aspecific junctional pattern, basaloid cords, and ulceration were associated with basal cell carcinomas. Ringed junctional pattern and dermal nests were associated with nevi. The mean sensitivity for the group of evaluators was 88.9% (range, 82.9%-100%), and the mean specificity was 79.3% (range, 69.2%-90.8%). Majority diagnosis showed sensitivity of 100% and specificity of 80.0%. Sensitivity was higher for experienced vs recent RCM users (91.0% vs. 84.8%), but specificity was similar (80.0% vs. 77.9%). CONCLUSIONS AND RELEVANCE: The study highlights key RCM diagnostic criteria for melanoma and basal cell carcinoma that are reproducibly recognized among RCM users. Diagnostic accuracy increases with experience. The higher accuracy of majority diagnosis suggests that there is intrinsically more diagnostic information in RCM images than is currently used by individual evaluators.
IMPORTANCE: Reflectance confocal microscopy (RCM) studies have been performed to identify criteria for diagnosis of skin neoplasms. However, RCM-based diagnosis is operator dependent. Hence, reproducibility of RCM criteria needs to be tested. OBJECTIVE: To test interobserver reproducibility of recognition of previously published RCM descriptors and accuracy of RCM-based skin cancer diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Observational retrospective web-based study of a set of RCM images collected at a tertiary academic medical center. Nine dermatologists (6 of whom had ≥3 years of RCM experience) from 6 countries evaluated an RCM study set from 100 biopsy-proven lesions, including 55 melanocytic nevi, 20 melanomas, 15 basal cell carcinomas, 7 solar lentigines or seborrheic keratoses, and 3 actinic keratoses. Between June 15, 2010, and October 21, 2010, participanting dermatologists, blinded to histopathological diagnosis, evaluated 3 RCM mosaic images per lesion for the presence of predefined RCM descriptors. MAIN OUTCOMES AND MEASURES: The main outcome was identification of RCM descriptors with fair to good interrater agreement (κ statistic, ≥0.3) and independent correlation with malignant vs benign diagnosis on discriminant analysis. Additional measures included sensitivity and specificity for diagnosis of malignant vs benign for each evaluator, for majority diagnosis (rendered by ≥5 of 9 evaluators), and for experienced vs recent RCM users. RESULTS: Eight RCM descriptors showed fair to good reproducibility and were independently associated with a specific diagnosis. Of these, the presence of pagetoid cells, atypical cells at the dermal-epidermal junction, and irregular epidermal architecture were associated with melanoma. Aspecific junctional pattern, basaloid cords, and ulceration were associated with basal cell carcinomas. Ringed junctional pattern and dermal nests were associated with nevi. The mean sensitivity for the group of evaluators was 88.9% (range, 82.9%-100%), and the mean specificity was 79.3% (range, 69.2%-90.8%). Majority diagnosis showed sensitivity of 100% and specificity of 80.0%. Sensitivity was higher for experienced vs recent RCM users (91.0% vs. 84.8%), but specificity was similar (80.0% vs. 77.9%). CONCLUSIONS AND RELEVANCE: The study highlights key RCM diagnostic criteria for melanoma and basal cell carcinoma that are reproducibly recognized among RCM users. Diagnostic accuracy increases with experience. The higher accuracy of majority diagnosis suggests that there is intrinsically more diagnostic information in RCM images than is currently used by individual evaluators.
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