Cytologic Criteria for Well Differentiated Adenocarcinoma of the Pancreas in Fine-needle Aspiration Biopsy Specimens

Background: Fine-needle aspiration biopsy (FNAB) of pancreatic lesions has become popular to establish a tissue diagnosis before chemotherapy and/or surgery. The diagnostic sensitivity and specificity of FNAB have improved as a result of several articles regarding cytologic criteria for pancreatic adenocarcinoma. However, false-negative and "suspicious for malignancy" rates remain relatively high, in part because of the underdiagnosis of well differentiated adenocarcinoma (WDA). Existing cytologic criteria do not specifically focus on WDA. In this study, the authors attempt to add to, redefine, and test cytologic criteria for WDA of the pancreas in FNAB specimens.

Methods: The authors retrospectively reviewed the specimens of 291 consecutive computed tomography-guided FNABs of pancreatic lesions performed at the study institution between 1995 and 1999. The original cytologic diagnoses were confirmed by cell blocks (131), surgical tissue (84), or clinical follow-up. The FNAB specimens were evaluated for the presence of 10 cytologic criteria: 1) anisonucleosis, 2) nuclear membrane irregularity, 3) nuclear crowding/overlapping/three-dimensionality, 4) nuclear enlargement (if there are more than two red blood cells), 5) gap versus confluent cell spacing, 6) hyperchromasia, 7) macronucleoli, 8) mitosis, 9) chromatin clearing, and 10) necrosis.

Results: The original cytologic diagnoses were nondiagnostic in 24 cases, benign in 27, suspicious for malignancy in 15, and malignant in 225. Among the 225 malignant lesions, 74 cases were diagnosed as WDA. Cytologic criteria 1-4 were observed in 92-99% of WDA cases, whereas criteria 5-10 were present in only 7-38% of WDA cases. Six of 15 suspicious and 4 of 27 negative cases were of low cellularity but retrospectively met the cytologic criteria 1-4 for WDA (the diagnosis was confirmed on clinical follow-up).

Conclusions: The diagnosis of pancreatic WDA can be made in FNAB specimens by the observance of anisonucleosis, nuclear membrane irregularity, nuclear crowding/overlapping/three-dimensionality, and nuclear enlargement. Necrosis, chromatin clearing, mitosis, macronucleoli, and hyperchromasia are of limited diagnostic significance because they are commonly absent in pancreatic WDA.