Grading epithelial atypia in endoscopic ultrasound-guided fine-needle aspiration of intraductal papillary mucinous neoplasms: an international interobserver concordance study

Cancer Cytopathol. 2013 Dec;121(12):729-36. doi: 10.1002/cncy.21334. Epub 2013 Jul 23.


Background: Preoperative cytological analysis of cyst fluid from intraductal papillary mucinous neoplasms (IPMN) contributes to risk stratification for malignancy. To the authors' knowledge, agreement among pathologists in grading epithelial atypia in IPMN cyst fluids has not been studied to date.

Methods: Blinded to the histological grade, 4 observers independently graded 60 cell groups from endoscopic ultrasound-guided fine-needle aspiration samples of 24 IPMNs of various grades as either 0 (nonlesional), 1 (low-grade dysplasia), 2 (intermediate-grade dysplasia [IGD]), 3 (high-grade dysplasia), or 4 (invasive adenocarcinoma). The percentage of agreement and the kappa (k) coefficient were calculated for these 5 tiers and a reduced 2-tier grouping (low-grade [LG] [0-1 and 0-2] vs high-grade [HG] [2-4 and 3-4]). Agreement between the 2 most experienced reviewers established a consensus diagnosis that was compared with the histological grade.

Results: Among the 4 reviewers there was poor agreement using a 5-tiered system and fair agreement with the 2-tiered system. LG and HG grouping of IGD did not appear to greatly affect agreement, with 54% agreement for grouping 0 to 2 and 3 to 4 (k = 0.45) and 52% agreement for grouping 0 to 1 and 2 to 4 (k = 0.44). The 2 most experienced reviewers had 87% agreement for the 0 to 2 and 3 to 4 grouping (k = 0.74) and 88% for the 0 to 1 and 2 to 4 grouping (k = 0.71). HG atypia on cytology with IGD grouped as LG yielded a sensitivity of 82%, with a specificity of 70% for detecting a cyst with HG morphology.

Conclusions: Grading cellular atypia in cyst fluids requires experience, which results in very good interobserver agreement and good correlation with histology using a 2-tiered LG and HG grading system and IGD classified as LG.

Keywords: cytology; endoscopic ultrasound; epithelial atypia; fine-needle aspiration; interobserver; intraductal papillary mucinous neoplasm; pancreas; variability.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma, Mucinous / pathology*
  • Adenocarcinoma, Mucinous / surgery
  • Carcinoma, Pancreatic Ductal / pathology*
  • Carcinoma, Pancreatic Ductal / surgery
  • Cohort Studies
  • Endoscopic Ultrasound-Guided Fine Needle Aspiration / methods*
  • Female
  • Humans
  • Male
  • Neoplasm Grading / methods
  • Observer Variation
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / surgery
  • Preoperative Care / methods
  • Sampling Studies
  • Sensitivity and Specificity