title: Skin Cancer Diagnosis With Reflectance Confocal Microscopy: Reproducibility of Feature Recognition and Accuracy of Diagnosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Farnetani
authors.affiliation: 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.
authors.forename: Alon
authors.initials: A
authors.lastname: Scope
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Braun
authors.affiliation: Internal Medicine Department, Alcala University, Madrid, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Gonzalez
authors.affiliation: Melanoma Institute Australia, The University of Sydney, Sydney7Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Pascale
authors.initials: P
authors.lastname: Guitera
authors.affiliation: 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.
authors.forename: Josep
authors.initials: J
authors.lastname: Malvehy
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Manfredini
authors.affiliation: Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Ashfaq A
authors.initials: AA
authors.lastname: Marghoob
authors.affiliation: Dermatology and Skin Cancer Unit, Arcispedale S. Maria Nuova-Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Moscarella
authors.affiliation: Department of Dermatology and Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida.
authors.forename: Margaret
authors.initials: M
authors.lastname: Oliviero
authors.affiliation: 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.
authors.forename: Susana
authors.initials: S
authors.lastname: Puig
authors.affiliation: Department of Dermatology and Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida.
authors.forename: Harold S
authors.initials: HS
authors.lastname: Rabinovitz
authors.affiliation: 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.
authors.forename: Ignazio
authors.initials: I
authors.lastname: Stanganelli
authors.affiliation: Dermatology and Skin Cancer Unit, Arcispedale S. Maria Nuova-Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Longo
authors.affiliation: Center for Environmental, Genetic, and Nutritional Epidemiology, Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Malagoli
authors.affiliation: Center for Environmental, Genetic, and Nutritional Epidemiology, Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Vinceti
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pellacani
mesh_terms: D000046:Academic Medical Centers; D002280:Basal Cell Carcinoma / Q000175:diagnosis* / Q000473:pathology; D003880:Dermatology / Q000379:methods*; D006801:Humans; D055623:Keratosis, Actinic / Q000175:diagnosis / Q000473:pathology; D008545:Melanoma / Q000175:diagnosis* / Q000473:pathology; D018613:Microscopy, Confocal / Q000379:methods*; D009508:Nevus, Pigmented / Q000175:diagnosis / Q000473:pathology; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000473:pathology