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


  • Other participants in the study are listed on page 599.

Correspondence: Dr M. Preti, Department of Obstetrics and Gynaecology, University of Turin, Via Don Grioli 6–10137 Turin, Italy.


Objective To evaluate the inter-observer variability of vulvar intraepithelial neoplasia diagnosis and grading system.

Design Prospective study.

Sample Histological sections of 66 vulvar biopsies.

Methods Six consultant pathologists working at different European institutions independently reviewed 66 vulvar biopsies. The following variables were investigated: specimen adequacy, gross categorisation into benign or neoplastic changes, presence of atypical cytological pattern, presence of neoplastic architectural pattern, grade of vulvar intraepithelial neoplasia, presence of histopathologic associated findings for human papillomavirus infection.

Main outcome measures The degree of inter-observer variation for each histopathologic parameter was assessed by Kappa (κ) statistics. The frequency and the degree of disagreement were calculated by a symmetrical agreement matrix showing the number paired classifications.

Results A good agreement (overall weighted κ= 0.65, unweighted κ= 0.46) was observed for grading vulvar intraepithelial neoplasia. Human papillomavirus infection associated findings and specimen adequacy were the variables with less inter-observer agreement (overall weighted κ 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 intraepithelial neoplasia 2 and 3 as a single class. Conversely, only 5.0% of vulvar intraepithelial 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 intraepithelial neoplasia (vulvar intraepithelial neoplasia 2 and 3) there is good agreement, the diagnostic category of vulvar intraepithelial neoplasia 1 is not reproducible.