Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2022; 28(34): 5047-5057
Published online Sep 14, 2022. doi: 10.3748/wjg.v28.i34.5047
Analysis of invasiveness and tumor-associated macrophages infiltration in solid pseudopapillary tumors of pancreas
Jie Yang, Chun-Lu Tan, Dan Long, Yan Liang, Li Zhou, Xu-Bao Liu, Yong-Hua Chen
Jie Yang, Chun-Lu Tan, Xu-Bao Liu, Yong-Hua Chen, Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Dan Long, Key Laboratory of Transplant Engineering and Immunology of the Ministry of Health, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Yan Liang, Li Zhou, Core Facilities, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Yang J, Tan CL, Long D, Liang Y, Zhou Li, Liu XB, and Chen YH designed the research study; Yang J, Tan CL, Liu XB, and Chen YH performed the research; Yang J, Long D, Liang Y, Zhou Li, and Chen YH analyzed the data and wrote the manuscript; all authors have read and approved the final manuscript.
Supported by Natural Science Foundation of China, No. 82071746; Key Research and Development Projects in Sichuan Province, No. 2019YFS0043; and 1·3·5 Project for Disciplines of Excellence–Clinical Research Incubation Project, West China Hospital, Sichuan University, No. ZY2017302.
Institutional review board statement: The study was reviewed and approved by the Medical Ethics Committee of West China Hospital at Sichuan University (2014 Trial No. 37).
Informed consent statement: All study participants or their legal guardians provided informed written consent about personal and medical data collection prior to study enrollment.
Conflict-of-interest statement: All authors report no relevant conflict of interest for this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Yong-Hua Chen, MD, Professor, Department of Pancreatic Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu 610041, Sichuan Province, China.
Received: May 17, 2022
Peer-review started: May 17, 2022
First decision: August 1, 2022
Revised: August 5, 2022
Accepted: August 25, 2022
Article in press: August 25, 2022
Published online: September 14, 2022
Research background

Solid pseudopapillary tumor (SPT) has been classified as a low-grade malignant tumor, and indeed only 9.2% patients 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. One of the most frequently mentioned predictive factors is whether the tumor had a capsule or incomplete capsule as assessed by computed tomography imaging. However, assessing the integrity of the capsule and growth pattern of tumor cells, especially on SPT margins, using a microscope might reflect the real biological behavior of SPT. Tumor-associated macrophages (TAMs), especially the M2-like macrophages subtype, could enhance tumor invasion and metastasis; however, only limited studies are available regarding the role of the TAMs in the SPT microenvironment and their relationship with malignant behaviors of SPT.

Research motivation

The present study suggests that an invasiveness feature, as determined using a microscope is a good predictive factor for the malignant behavior of an SPT and illustrates the macrophage infiltration in the tumor microenvironment of an SPT.

Research objectives

Instead of assessing the integrity of the capsule on computed tomographic imaging, we divided SPT patients into two groups, either with invasion or capsule, based on the integrity of capsule and growth pattern of the tumor cells, especially on the tumor margins, under the microscope; we then investigated differences in the malignant behavior and TAM infiltration between these two groups.

Research methods

Hematoxylin-eosin-stained sections of SPT patients were used to assess the integrity of the capsule and growth pattern of tumor cells, especially on tumor margins. Immunohistochemical staining was used to evaluate the intratumoral and peritumoral presence of TAMs (CD68-positive) and M2-like macrophages (CD163-positive).

Research results

Malignant behavior was present more frequently in the invasion group, including in 2 patients with peripheral organ invasion, 3 with liver metastasis, and 1 with both lymph node and spleen metastases. Immunohistochemical analysis found that the invasion group had a significant increase of CD68-positive TAMs and CD163-positive M2-like macrophages in intratumoral and peritumoral sites in comparison with the capsule group.

Research conclusions

SPT patients with invasion detected using a microscope were more likely to have a tumor that demonstrated malignant behavior and TAM infiltration, especially of M2-like macrophages.

Research perspectives

This study may provide a histopathological basis for identification of malignant SPT. The phenomenon of increased infiltration of TAMs, especially M2-like macrophages in the invasion feature, might help us to investigate the underlying mechanism of TAM-mediated SPT malignant behavior, as well as to potentially treat recurrent and metastatic SPT by targeting TAMs.