Pancreatic neuroendocrine tumors (PanNETs) are the second most common primary pancreatic neoplasms. Tumors in their classical state are characterized by monotonous plasmacytoid epithelial cells featuring moderate amounts of eosinophilic cytoplasm and eccentrically placed round to oval nuclei with stippled “salt-and-pepper” chromatin. Tumors may exhibit diverse architectural patterns such as nests, pseudorosettes, and trabeculae. Nontraditional morphologic patterns have been described, but their prognostic and clinical relevance and molecular correlations have not been explored.
To elucidate the morphologic spectrum of PanNETs, emphasizing the various subtypes that may mimic other neoplasms, highlighting their unique diagnostic challenges, and exploring the clinical significance of these variants.
The review synthesizes findings from a thorough literature review of published studies and incorporates the authors’ own research.
PanNETs represent a group of neoplasms with significant histologic and cytologic variability that may complicate and confound diagnosis. Accurate recognition of these variants is crucial for effective diagnosis and in some cases carries important prognostic implications, particularly for more aggressive tumor forms (oncocytic, hepatoid, lipid rich, rhabdoid/plasmacytoid, and papillary). Additionally, certain morphologic variants or adjacent precursors may be linked to syndromic diseases or specific hormone expressions. Integrating detailed morphologic analysis with advanced molecular techniques is essential for diagnosis, predicting patient outcome, and improving patient management.
Author notes
Presented in part at the Companion Meeting of the Pancreatobiliary Pathology Society at the 113th United States and Canadian Academy of Pathology Annual Meeting; March 24, 2024; Baltimore, Maryland.
The authors have no relevant financial interest in the products or companies described in this article.