• Highly cellular aspirate with papillary-like formations comprising delicate vascular cores covered by loosely adhered neoplastic epithelial cells ("spinning" off)
• Small clusters and scattered dispersed epithelial cells in the background
• Epithelial cells contain eccentric reniform nuclei with mild nuclear pleomorphism
• Nuclear grooves may be seen
• Small nucleoli may be present
• Finely distributed chromatin
• Some nuclei exhibit nuclear inclusions 
• Abundant finely vacuolated cytoplasm with perinuclear vacuoles

The following differential diagnoses show a degree of cytomorphologic overlap and the key distinguishing features include

• Solid pseudopapillary neoplasm
  • Low-power: Papillary-like structures with delicate to hyalinised vascular stalks (important diagnostic feature) and relative cellular discohesion
  • High power: Reniform nuclei with nuclear grooves and perinuclear vacuoles
• Neuroendocrine tumour
  • Low-power: Loosely cohesive groups, pseudorosettes and single plasmacytoid cells
  • High-power: Round to plump oval nuclei, stippled chromatin and inconspicuous nucleoli
• Acinar cell carcinoma
  • Low-power: Acinar architecture with scattered bare nuclei
  • High-power: Fragile cytoplasm with spilled zymogen granules and single prominent nucleolus

The non-discriminating features which may be shared by these tumours include:

• Low-power pattern of small cell clusters and scattered single cells which appear relatively uniform
• Plasmacytoid neoplastic cells with eccentric, round to oval shaped nuclei
• Delicate cytoplasm with microvacuoles

There is diffuse nuclear expression of beta-catenin and LEF1 by the tumour cells. Synaptophysin is also focally positive; this is a potential pitfall where the tumour may be mistaken as a neuroendocrine tumour, although the latter is likely to show diffuse positivity. Identification of pseudopapillae with hyalinised vascular stalks and nuclear expression of beta-catenin is key to the diagnosis.

Solid pseudopapillary neoplasm

• Uncommon tumour (1 to 2% of pancreatic exocrine neoplasms) of low malignant potential
• Predominantly in adolescent girls and young women
• Slight preference for pancreatic tail
• Histogenesis unclear – possible genital ridge origin
• Somatic mutation in exon 3 of CTNNB1 gene
• A rare subset of cases may be associated with familial adenomatous polyposis
• Well-demarcated tumours with solid areas, pseudocystic spaces and haemorrhagic necrosis
• The presence of hyalinised vascular stalk with clinging neoplastic cells is a key morphologic feature
• Highly divergent immunohistochemical profile
  • Positive: Beta-catenin (nuclear), cyclin D1, alpha-1 antitrypsin, CD56, CD10, PR receptor, synaptophysin (focal and a pitfall)
  • Recent studies show high rate of diffuse nuclear expression of LEF1, AR and TFE3 (1)

1. Kim, E. K., Jang, M., Park, M., & Kim, H. (2017). LEF1, TFE3, and AR are putative diagnostic markers of solid pseudopapillary neoplasms. Oncotarget, 8(55), 93404–93413. https://doi.org/10.18632/oncotarget.21854

Remaining information cited from: Klöppel, G., Klimstra, D. S., Basturk, O., Notohara, K. Solid pseudopapillary neoplasm. (2019). In: WHO Classification of Tumours: Digestive system tumours (5th edn). Lyon; IARC.