The mesenchymal tumors of the pancreas account for approximately 1–2% of all pancreatic neoplasms and they are not commonly encountered in our daily practice. When these rare entities are seen during endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) with rapid onsite evaluation (ROSE) or EUS-guided fine-needle biopsy (FNB) specimens sampled from the pancreas, it is usually difficult to establish a diagnosis solely based on cytohistology due to the significant overlapping cytomorphological features among these neoplasms. Ancillary studies including immunohistochemical stains and molecular testing are critical to reach the correct final diagnosis. Here, we reviewed the pancreatic mesenchymal neoplasms diagnosed with EUS-FNA cytology specimens or EUS-FNB small biopsy specimens. Gastrointestinal stromal tumors (GIST), solitary fibrous tumors (SFT), paraganglioma, perivascular epithelioid cell tumor (PEComa), and Granular cell tumor were discussed in detail each with a representative case from our practice collections. The characteristic cytohistological features and immunostaining markers for each entity are highlighted for differential diagnosis. In summary, cytopathologists need to be vigilant for these rare entities and perform necessary immunostaining to establish an accurate diagnosis.
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