title: Diagnostic accuracy of confocal microscopy imaging vs. punch biopsy for diagnosing and subtyping basal cell carcinoma.
abstract: BACKGROUND
  In vivo reflectance confocal microscopy (RCM) is a promising non-invasive skin imaging technique that could facilitate early diagnosis of basal cell carcinoma (BCC) instead of routine punch biopsies. However, the clinical value and utility of RCM vs. a punch biopsy in diagnosing and subtyping BCC is unknown.
  
  
  OBJECTIVE
  To assess diagnostic accuracy of RCM vs. punch biopsy for diagnosing and subtyping clinically suspected primary BCC.
  
  
  METHODS
  A prospective, consecutive cohort of 100 patients with clinically suspected BCC were included at two tertiary hospitals in Amsterdam, the Netherlands, between 3 February 2015 and 2 October 2015. Patients were randomized between two test-treatment pathways: diagnosing and subtyping using RCM imaging followed by direct surgical excision (RCM one-stop-shop) or planned excision based upon the histological diagnosis and subtype of punch biopsy (standard care). The primary outcome was the agreement between the index tests (RCM vs. punch biopsy) and reference standard (excision specimen) in correctly diagnosing BCC. The secondary outcome was the agreement between the index tests and reference standard in correctly identifying the most aggressive BCC subtypes.
  
  
  RESULTS
  Sensitivity to detect BCC was similar for RCM and punch biopsy (100% vs. 93.94%), but a punch biopsy was more specific than RCM (79% vs. 38%). RCM expert evaluation for diagnosing BCC had a sensitivity of 100% and a specificity of 75%. The agreement between RCM and excision specimen in identifying the most aggressive BCC subtype ranged from 50% to 85% vs. 77% by a punch biopsy.
  
  
  CONCLUSIONS
  Reflectance confocal microscopy and punch biopsy have comparable diagnostic accuracy to diagnose and subtype BCC depending on RCM experience. Although experienced RCM users could accurately diagnose BCC at a distance, we found an important difference in subtyping BCC. Future RCM studies need to focus on diagnostic accuracy, reliability and specific criteria to improve BCC subtype differentiation.
authors.affiliation: Department of Dermatology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: D J
authors.initials: DJ
authors.lastname: Kadouch
authors.affiliation: Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: M M
authors.initials: MM
authors.lastname: Leeflang
authors.affiliation: Department of Dermatology, Academic Medical Centre, Amsterdam, The Netherlands.|Department of Dermatology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Y S
authors.initials: YS
authors.lastname: Elshot
authors.affiliation: Dermatology and Skin Cancer Unit, Arcispedale Santa Maria Nuova - IRCCS/University of Modena and Reggio Emilia, Reggio Emilia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Longo
authors.affiliation: Private Dermatology Office/CMB Collegium Medicum Berlin, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ulrich
authors.affiliation: Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: A C
authors.initials: AC
authors.lastname: van der Wal
authors.affiliation: Department of Dermatology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Wolkerstorfer
authors.affiliation: Department of Dermatology, Academic Medical Centre, Amsterdam, The Netherlands.|Department of Dermatology, VU Medical Centre, Amsterdam, The Netherlands.
authors.forename: M W
authors.initials: MW
authors.lastname: Bekkenk
authors.affiliation: Department of Dermatology, Academic Medical Centre, Amsterdam, The Netherlands.|Department of Dermatology, VU Medical Centre, Amsterdam, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: de Rie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy / Q000592:standards*; D002280:Basal Cell Carcinoma / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D008853:Microscopy / Q000592:standards*; D008875:Middle Aged; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery