Roadmap to Challenges in Limited Cellularity Specimens from Pancreatic Neuroendocrine Neoplasms: Diagnostic Tools for the Most Appropriate Management of Limited Material

Fine needle aspiration (FNA) and fine needle biopsy (FNB) procedures are increasingly employed in the diagnostic work-up of pancreatic masses. These procedures represent a challenge for pathologists who have to adapt to handling specimens of limited cellularity. In several cases, FNA and FNB specimens are the only available material, as many pancreatic neoplasms are surgically unresectable at the time of the initial diagnosis. In the present review paper, the diagnosis of pancreatic neuroendocrine neoplasms in limited cellularity specimens is presented using a morphology-based approach. The aim is to provide a practical guide for pathologists to select the most appropriate ancillary techniques to be used for the diagnostic work-up, while conserving precious material. The integration of morphology, immunohistochemistry, and molecular biology will be discussed to provide the reader with practical tools to solve the main differential diagnostic problems encountered in routine practice when working with cytological samples or small biopsies.