Pathological differential diagnosis of solid-pseudopapillary neoplasm and endocrine tumors of the pancreas

Abstract

Aim: To investigate differential points of solid-pseudopapillary neoplasm (SPN) of the pancreas and pancreatic endocrine tumor (PET).

Methods: Ten cases of SPN and fourteen cases of PET were studied in this retrospective study. Clinical and pathologic features, immunostaining reactions and beta-catenin gene mutations were analyzed.

Results: The mean age of SPN patients was 25.6 years and these patients had no specific symptoms. The mean diameter of the tumors was 11.0 cm, 9/10 cases were cystic or a mixture of solid and cystic structures, and there was hemorrhage and necrosis on the cut surface in 8/10 (80%) cases. Characteristic pseudopapillary structure and discohesive appearance of the neoplastic cells were observed in all 10 (100%) cases. The results of immunostaining showed that nuclear expression of beta-catenin and loss of E-cadherin in all the cases, was only seen in SPN. Molecular studies discovered that 9/10 (90%) cases harbored a point mutation of exon 3 in beta-catenin gene. On the other hand, the mean age of PET patients was 43.1 years. Eight of 14 cases presented with symptoms caused by hypoglycemia, and the other 6 cases presented with symptoms similar to those of SPN. The mean size of the tumors was 2.9 cm, most of the tumors were solid, only 3/14 (21%) were a mixture of solid and cystic structures, and macroscopic hemorrhage and necrosis were much less common (3/14, 21%). Histologically, tumor cells were arranged in trabecular, acinar or solid patterns and demonstrated no pseudopapillary structure and discohesive appearance in all 14 (100%) cases. The results of immunostaining and mutation detection were completely different with SPN that membrane and cytoplastic expression of beta-catenin without loss of E-cadherin, as well as no mutation in beta-catenin gene in all the cases.

Conclusion: Both macroscopic and microscopic features of SPN are quite characteristic. It is not difficult to distinguish it from PET. If necessary, immunostaining of beta-catenin and E-cadherin is quite helpful to make the differential diagnosis.

Figure 1

Histopathological and immunohistochemical features of solid-pseudopapillary neoplasm (SPN) and pancreatic endocrine tumor (PET). A: SPN arranged in solid areas, patternless sheets of uniform epithelial cells with numerous small blood vessels (hematoxylin-eosin, original magnification × 200); B: SPN formed characteristic pseudopapillary changes due to the degenerative and discohesive nature of the tumor cells (hematoxylin-eosin, original magnification × 200); C: PET arranged in acinar-like pattern; the tumor cells are small and round with granular eosinophilic or clear cytoplasm (hematoxylin-eosin, original magnification × 200); D: β-catenin immunostaining of SPN: Nuclear translocation and accumulation of β-catenin protein (arrow) is seen in neoplastic epithelial cells (original magnification × 200); E: β-catenin immunostaining of PET: Membrane and cytoplasmic positive expression of β-catenin protein without nuclear stain (arrow) (original magnification × 200).

Figure 2

β-catenin oncogene mutations in SPN. Representative DNA sequencing chromatograms demonstrate. A: A GAC→TAC mutation in codon 32 of case 5; B: A TCT→TAT mutation in codon 37 of case 2; C: A GAC→GTC mutation in codon 32 of case 9. Three samples of PET cases were randomly selected to be sequenced and the results confirmed that there was not any mutation on amplified PCR fragments of β-catenin gene exon 3.