Cytological criteria of high-grade epithelial atypia in the cyst fluid of pancreatic intraductal papillary mucinous neoplasms.
BACKGROUND
The recognition of epithelial cells with high-grade atypia (HGA) in the cyst fluid of an intraductal papillary mucinous neoplasm (IPMN) identifies a cyst at high risk of invasive carcinoma. To the best of the authors' knowledge, the cytological features of HGA have not been systematically analyzed to define diagnostic criteria.


METHODS
Cell groups from patients with histologically confirmed branch-duct IPMNs were evaluated by 2 cytopathologists with expertise in pancreatic cytology. A consensus interpretation categorized the cell groups as having either low-grade (LG) or high-grade (HG) morphology. Characteristics regarding cell size and architecture, nuclear and cytoplasmic features, and background necrosis were analyzed. Performance characteristics were assessed using the Fisher exact test at 95% confidence intervals.


RESULTS
Sixty cell groups yielded 27 LG and 25 HG morphological groups. No consensus was reached for 8 groups, which were excluded from statistical analysis. Five features that were found to be significantly different between the LG and HG groups included: 1) cell size <  a 12-μm duodenal enterocyte for HG and size equal for LG; 2) an increased nuclear-to-cytoplasmic (N/C) ratio; 3) marked nuclear membrane abnormalities; 4) abnormal chromatin pattern; and 5) background necrosis. The 3 most accurate features for the identification of HGA were background necrosis (88%), abnormal chromatin pattern (84%), and an increased N/C ratio (82%).


CONCLUSIONS
IPMN cyst fluid at high-risk of malignancy can be recognized most accurately by the presence of epithelial cells with HGA showing an increased N/C ratio, an abnormal chromatin pattern, and background necrosis.
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Martha B
MB
Pitman
Barbara A
BA
Centeno
Ebubekir S
ES
Daglilar
William R
WR
Brugge
Mari
M
Mino-Kenudson
D002288:Adenocarcinoma, Mucinous / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000000981:diagnostic imaging / Q000473:pathology*; D002291:Carcinoma, Papillary / Q000000981:diagnostic imaging / Q000473:pathology; D016001:Confidence Intervals; D003581:Cytodiagnosis / Q000379:methods; D003937:Diagnosis, Differential; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration / Q000379:methods*; D004847:Epithelial Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading / Q000379:methods; D009361:Neoplasm Invasiveness / Q000473:pathology; D010181:Pancreatic Cyst / Q000000981:diagnostic imaging / Q000473:pathology*; D015203:Reproducibility of Results; D012494:Sampling Studies; D012680:Sensitivity and Specificity
criteria; cytology; endoscopic ultrasound; fine-needle aspiration; high-grade atypia; intraductal papillary mucinous neoplasm; pancreas