Research ArticlesLymphoid Enhancer Binding Factor 1 (LEF1) and Paired Box Gene 8 (PAX8): A Limited Immunohistochemistry Panel to Distinguish Solid Pseudopapillary Neoplasms and Pancreatic Neuroendocrine TumorsLu, Haiyan MD, PhD*; Allende, Daniela MD*; Liu, Xiuli MD, PhD†; Zhang, Yaxia MD, PhD*,‡Author Information *Department of Pathology, Cleveland Clinic Foundation, Cleveland, OH †Department of Pathology, University of Florida, Gainesville, FL ‡Department of Pathology and Laboratory Medicine, Hospital for Special Surgery, New York The authors declare no conflict of interest. Reprints: Yaxia Zhang, MD, PhD, Department of Pathology, Hospital for Special Surgery, 535 E 70th Street, New York, NY 10021 (e-mail: [email protected]). Applied Immunohistochemistry & Molecular Morphology: November/December 2020 - Volume 28 - Issue 10 - p 776-780 doi: 10.1097/PAI.0000000000000830 Buy Metrics Abstract Solid pseudopapillary neoplasms (SPNs) and pancreatic neuroendocrine tumors (PanNETs) are distinctive entities. However, due to overlapping morphologies, distinguishing them remains a diagnostic challenge. Our study investigates the utility of immunohistochemistry for nuclear lymphoid enhancer binding factor 1 (LEF1) and paired box gene 8 (PAX8) in differentiating these 2 entities. LEF1 and PAX8 immunohistochemistry were performed on fine-needle aspiration cell blocks and surgical resection specimens diagnosed as SPN or PanNET at our institution from January 2007 to August 2016. Eight SPN and 25 PanNET cell blocks and 17 SPN and 34 PanNET surgical resection specimens were examined. On cell blocks, positive staining for LEF1 had high frequency, sensitivity, and specificity for SPN (88%, 88%, and 88%) as did positive staining for PAX8 for PanNET (76%, 76%, and 75%). The findings on surgical resection specimens were consistent with those from cell blocks (LEF1+ in SPN: 100%, 100%, and 97%; PAX8+ in PanNET: 59%, 59%, and 100%). A combined LEF1+/PAX8− phenotype showed high sensitivity and specificity for SPN (cell block: 63% and 100%; surgical specimen: 100% and 98%) as did a LEF1−/PAX8+ phenotype for PanNET (cell block: 64% and 100%; surgical specimen: 59% and 100%). SPN and PanNET exhibit opposite immunophenotypic profiles with LEF1+/PAX8− in SPN and LEF1−/PAX8+ in PanNET. The combination of these 2 stains provides an effective means of distinguishing these 2 entities. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.