Clinicopathological and molecular features of solid pseudopapillary neoplasms: a retrospective series including a small subset of aggressive cases

Solid pseudopapillary neoplasms (SPNs) are rare pancreatic tumors that are indolent but occasionally present with metastatic or locally invasive disease. Although recurrent CTNNB1 exon 3 mutations define their molecular background, the clinicopathological and molecular features associated with these less common presentations remain incompletely characterized. This retrospective study included 62 patients diagnosed with SPN between 2000 and 2025. Clinicopathological and immunohistochemical features, including β-catenin, progesterone receptor (PR), androgen receptor (AR), and BAP1, were evaluated. Targeted sequencing was performed in a subset of cases with metastatic or locally invasive disease (n = 5). Patients showed a wide age range (8–71 years), female predominance (54/62, 87.1%), and a mean tumor size of 7.2 cm. Lymphovascular invasion was rare (1/59, 1.7%). Metastatic or locally invasive SPNs (n = 8) more frequently showed higher Ki-67 values (median, 5%; range, 1%–15%), increased mitotic activity (2/8, 25%), and capsular/parenchymal invasion (6/8, 75%), while perineural invasion was absent. All tumors demonstrated nuclear β-catenin expression, with PR and AR positivity (50/59, 84.7% and 47/57, 82.5%, respectively). PR expression was higher in AR-positive cases (43/47, 91.5% vs. 6/10, 60%). BAP1 loss was identified in 13/57 cases (22.8%). Targeted sequencing consistently identified CTNNB1 exon 3 mutations. Additional low-frequency molecular alterations affecting genes involved in cell cycle regulation, chromatin remodeling, and signaling pathways, including CDKN2A and BAP1 , were observed. During a mean follow-up of 97.2 months, distant metastasis occurred in 4/62 patients (6.5%) and locally invasive disease in 4/62 (6.5%), with an overall survival rate of 95%. Overall, these findings highlight the biological heterogeneity of SPNs and indicate that, despite a shared molecular background, aggressive behavior is not defined by a single reproducible pathological or molecular feature.