title: Grading epithelial atypia in endoscopic ultrasound-guided fine-needle aspiration of intraductal papillary mucinous neoplasms: an international interobserver concordance study.
abstract: 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.
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Martha B
authors.initials: MB
authors.lastname: Pitman
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Centeno
authors.forename: Muriel
authors.initials: M
authors.lastname: Genevay
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fonseca
authors.forename: Mari
authors.initials: M
authors.lastname: Mino-Kenudson
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000473:pathology* / Q000601:surgery; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology* / Q000601:surgery; D015331:Cohort Studies; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D060787:Neoplasm Grading / Q000379:methods; D015588:Observer Variation; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000601:surgery; D011300:Preoperative Care / Q000379:methods; D012494:Sampling Studies; D012680:Sensitivity and Specificity
keywords: cytology; endoscopic ultrasound; epithelial atypia; fine-needle aspiration; interobserver; intraductal papillary mucinous neoplasm; pancreas; variability