The diagnosis of pancreatic endocrine neoplasm (PEN) is often straightforward; however, cytomorphologic variants may impose a diagnostic challenge, particularly in small biopsies such as fine-needle aspiration (FNA). Here we describe prominent fine cytoplasmic vacuoles in three cases of PENs which were initially evaluated by endoscopic ultrasound-guided FNA. The clinicopathologic features and diagnostic pitfalls of this cytomorphologic variant were discussed. Awareness of this rare cytomorphologic feature with application of immunocytochemical studies is crucial for rendering an accurate diagnosis and avoiding diagnostic pitfalls.
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