Solid pseudopapillary neoplasms occur almost exclusively in adolescent and young women and are rare in men (male-to-female ratio: 9:1). They present as a solitary, large, round, well-circumscribed mass with variable amounts of solid and cystic components. Solid pseudopapillary neoplasms show a slight propensity for the tail of the pancreas but can occur in the head and body of the organ. Delicate vessels with a myxoid or hyalinized stroma lined by neoplastic cells are a common feature. The neoplastic cells are small and monomorphic with occasional bean-shaped nuclei and nuclear grooves. They have finely vacuolated cytoplasm with perinuclear vacuoles and scattered PAS-positive, diastase resistant hyaline globules. Somatic activating mutations in CTNNB1 gene, which encodes the beta-catenin protein, have been found in a majority of solid pseudopapillary neoplasms.

LEF1 immunohistochemical staining has also shown high sensitivity (93.4%-100%) for solid pseudopapillary neoplasms, the thought being that transactivation of the LEF1 promoter with CTNNB1 may result in a positive feedback loop for Wnt/CTNNB1 signaling in these tumors.