Inter-observer variation in histopathological diagnosis and grading of vulvar intraepithelial neoplasia: results of an European collaborative study

Objective To evaluate the inter-observer variability of vulvar intraepithel ial neoplasia diagnosis and grading system. Design Prospective study. Sample Histological sections of 66 vulvar biopsies. Methods Six consultant pathologists working at different European instituti ons independently reviewed 66 vulvar biopsies. The following variables were investigated: specimen adequacy, gross categorisation into benign or neopl astic changes, presence of atypical cytological pattern, presence of neopla stic architectural pattern, grade of vulvar intraepithelial neoplasia, pres ence of histopathologic associated findings for human papillomavirus infect ion. Main outcome measures The degree of inter-observer variation for each histo pathologic parameter was assessed by Kappa (kappa) statistics. The frequenc y and the degree of disagreement were calculated by a symmetrical agreement matrix showing the number paired classifications. Results A good agreement (overall weighted kappa = 0.65, unweighted kappa = 0.46) was observed for grading vulvar intraepithelial neoplasia. Human pap illomavirus infection associated findings and specimen adequacy were the va riables with less inter-observer agreement (overall weighted kappa 0.26 and 0.22, respectively). Exact agreement between two pathologists for grade of vulvar intraepithelial neoplasia was observed in 63.6% of paired readings; the rate of paired agreement reached 73.9% considering vulvar intraepithel ial neoplasia 2 and 3 as a single class. Conversely, only 5.0% of vulvar in traepithelial neoplasia 1 diagnoses were concordant in paired analysis. Conclusions Current terminology offers a reproducible tool in the hands of expert pathologists. While on the diagnosis of 'high grade' vulvar intraepi thelial neoplasia (vulvar intraepithelial neoplasia 2 and 3) there is good agreement, the diagnostic category of vulvar intraepithelial neoplasia 1 is not reproducible.