ORIGINAL ARTICLE Grading keratinocyte atypia in actinic keratosis: a correlation of reflectance confocal microscopy and histopathology G. Pellacani, 1,†, * M. Ulrich, 2,† A. Casari, 1 T.W. Prow, 3 F. Cannillo, 4 E. Benati, 1 A. Losi, 1 A.M. Cesinaro, 5 C. Longo, 6 G. Argenziano, 6 H.P. Soyer 3 1 Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy 2 Dermatologie am Regierungsviertel, Berlin, Germany 3 Dermatology Research Centre, School of Medicine, Translational Research Institute, The University of Queensland, Brisbane, Queensland, Australia 4 Karmaweb S.r.l., Modena, Italy 5 Department of Pathology, University of Modena and Reggio Emilia, Modena, Italy 6 Skin Cancer Unit, IRCCS Santa Maria Nuova, Reggio Emilia, Italy *Correspondence: G. Pellacani. E-mail: pellacani.giovanni@unimore.it Abstract Background Actinic Keratosis (AK) is the clinical manifestation of cutaneous dysplasia of epidermal keratinocytes, with progressive trend towards squamous cell carcinoma. Objective To evaluate the strength of the correlation between keratinocyte atypia, as detected by Reflectance Confo- cal Microscopy (RCM) and histopathology, and to develop a more objective atypia grading scale for RCM quantification, through a discrete ranking. Methods A total of 48 AKs and two control areas (photodamaged and non-photodamaged skin) were selected for this study. All these areas were documented by RCM and biopsied for histopathology. One representative image of the epi- dermis was selected for RCM and for histopathology and used for side-by-side comparison with purpose written soft- ware. The assessor chose which of two images displayed more keratinocyte atypia, and an ordered list from the image showing the least to the most keratinocyte atypia was generated. Three evaluations were obtained for RCM and two for histopathology. Results Good interobserver correlation was obtained for RCM and histopathology grading, with high concordance between RCM and histopathology grading. Conclusions Expert rater scan consistently distinguish different grades of cytological atypia. Non-invasive RCM data from in vivo imaging can be graded for keratinocyte atypia, comparable to histopathological grading. Received: 25 January 2015; Accepted: 22 May 2015 Funding sources None. Financial disclosure None reported. Conflicts of interest The authors declare no conflict of interests. Introduction Actinic keratosis (AK) represents the most common sun-in- duced preneoplastic lesion, commonly presenting as a scaly or keratotic red papule or plaque with tendency to become thicker progressively over time, and may evolve into a squamous cell carcinoma. 1,2 Upon histopathology, AK is the clinical manifesta- tion of cutaneous dysplasia of epidermal keratinocytes that are altered in size, shape and organization. 3,4 Due to its similarity in biological behaviour and progression rates with cervical intrae- pithelial neoplasia, the concept of AKs as keratinocytic † Equally contributed to the manuscript. © 2015 European Academy of Dermatology and Venereology JEADV 2015, 29, 2216–2221 DOI: 10.1111/jdv.13215 JEADV