Cytological features contributing to the misclassification of pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors are a diverse group of malignant neoplasms of varying biological behavior, with outcomes predicted by tumor differentiation and grade. Initial diagnosis is often made by fine-needle aspiration cytology via endoscopic ultrasound of the pancreas primary. We retrospectively reviewed our institutional experience with pancreatic neuroendocrine cytology diagnosis and evaluated for tumor typing accuracy and causes of misdiagnosis.

We searched our institutional database (1994-2012) for all pancreas fine-needle aspirations with corresponding pancreatic histology and a neuroendocrine diagnosis. Cases with discrepant cytology and histology diagnoses were reviewed for factors contributing to misclassification.

143 patients were identified with a neuroendocrine diagnosis either by cytology or histology. In the 129 cytology cases classified as positive/neoplastic/suspicious, tumor type was diagnosed correctly in 101 (78%) cases, incorrectly in 17 (13%), and unclassified (epithelioid neoplasm) in 11 (9%). The most common tumor classification error (7 cases) was misclassifying a neuroendocrine tumor as adenocarcinoma on cytology, which in one case led to inappropriate neoadjuvant chemotherapy. Features of neuroendocrine cytology misdiagnosed as adenocarcinoma included cell clustering and anisonucleosis. Features of non-neuroendocrine cytology misclassified as neuroendocrine included abundant acinar cells or problematic interpretation of immunohistochemical stains.

Cytology can accurately identify neuroendocrine differentiation in the majority of cases; nevertheless, there are potential serious pitfalls. Misclassification of a neuroendocrine tumor as adenocarcinoma or vice versa can have significant clinical impact. Clinical and radiological correlation is essential.