Analysis of invasiveness and tumor-associated macrophages infiltration in solid pseudopapillary tumors of pancreas

Abstract

Background: Solid pseudopapillary tumor (SPT) is a rare pancreatic tumor. Considering its malignant behaviors, SPT has been classified as a low-grade malignant tumor. Indeed, only 9.2% of all SPT patients are initially diagnosed as malignant with invasion or metastasis. Thus, one of the challenges in managing SPT patients is predicting malignant behavior.

Aim: To investigate the malignant behavior and tumor-associated macrophage (TAM) infiltration between different histopathologic features of SPT patients.

Methods: Twenty-five formalin-fixed paraffin-embedded tissue samples from 22 patients pathologically diagnosed with an SPT between 2009 and 2019 at West China Hospital were included in this retrospective study. Integrity of the capsule and growth pattern of the tumor cells was assessed microscopically in hematoxylin-eosin (HE)-stained sections. Based on the histopathological features, the SPT patients were divided into two groups: capsule or invasion. Clinical features, malignant behavior, and TAM infiltration were compared between the two groups.

Results: Among the 22 SPT patients, 11 were identified for each group, having either a capsule or invasion histopathologic feature. Malignant behavior was more frequent in the invasion group, including 2 patients who had peripheral organ invasion, 3 with liver metastasis, and 1 with both lymph node and spleen metastases (P= 0.045). Ki-67 index of more than 3% was also more frequent in the invasion group (P = 0.045). Immunohistochemical analysis showed that the invasion group had a significant increase of CD68-positive TAMs in intratumor and peritumor sites in comparison with the capsule group (all P < 0.0001). Similarly, CD163-positive M2-like macrophages were also markedly increased in the intratumor and peritumor sites in the invasion group (all P < 0.0001). At the liver metastasis site, both intratumor and peritumor tissues showed relatively high-level CD68-positive TAMs and CD163-positive M2-like macrophages infiltration. However, the differences between the intratumor, peritumor and normal hepatic tissues did not reach statistical significance (all P > 0.05).

Conclusion: SPT patients with invasion evident under microscope were more likely to exhibit malignant behavior and TAM infiltration, especially M2-like macrophages. This finding can help in future investigations of the underlying mechanism of TAM-mediated SPT malignant behavior.

Keywords: Histological labeling; Immunohistochemistry; Malignancy; Pancreatic neoplasms; Solid pseudopapillary tumors; Tumor-associated macrophages.