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Infiltrative Growth Predicts the Risk of Recurrence After Surgery in Well-Differentiated Non-Functioning Pancreatic Neuroendocrine Tumors

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Abstract

The incidence of well-differentiated non-functioning pancreatic neuroendocrine tumors (NF-PanNET) increased during the last decades. The risk of relapse after curative surgery, albeit low, is not negligible; moreover, adjuvant treatment is currently not an option and a reliable predictive model based on prognostic characteristics is urgently needed for tailoring a follow-up strategy. The histological classification of PanNET now relies only on the proliferative activity (mitosis and Ki67) and staging. In contrast to other endocrine neoplasms, the role of infiltrative growth pattern in NF-PanNET is not taken into consideration at present. In the current study, 247 consecutive patients who underwent surgical resection for a NF-PanNET were examined for the histological growth pattern of the tumor. Two distinct patterns (non-infiltrative vs. infiltrative) were described with the latter being further subclassified according to the type of structures invaded by the tumor (non-infiltrative: pattern 1; infiltration of adjacent pancreatic parenchyma and/or peripancreatic soft tissue: pattern 2; invasion of nearby organs and/or major vessels: pattern 3). The infiltrative growth resulted to be strongly associated with a poorer survival compared to a non-infiltrative growth (p < 0.001). In particular, the distinction between pancreatic parenchyma and/or peripancreatic soft tissue invasion versus adjacent organs and/or major vessels invasion was the most powerful predictor of recurrence after surgery at multivariate analysis (pattern 2 vs. pattern 1: HR 10.136, p = 0.028; pattern 3 vs. pattern 1: HR 15.775, p = 0.015). The infiltrative growth pattern could therefore provide additional prognostic information implementing the current grading and staging system.

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Any datasets used in this paper can be accessed on reasonable request to the corresponding author.

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Acknowledgements

The authors thank Luca Albarello, MD, for his support in preparing the drawings of Fig. 2.

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Authors and Affiliations

  1. Pathology Unit, Pancreas Translational and Clinical Research Center, IRCCS Ospedale San Raffaele, ENETS Center of Excellence, Via Olgettina 60, 20132, Milan, Italy

    Marco Schiavo Lena, Miriam Redegalli, Emanuela Brunetto, Beatrice Maghini, Maria Giulia Cangi & Claudio Doglioni

  2. Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS Ospedale San Raffaele, ENETS Center of Excellence, Via Olgettina 60, 20132, Milan, Italy

    Stefano Partelli, Valentina Andreasi, Francesca Muffatti & Massimo Falconi

  3. Institute of Pathology, Inselspital, University of Bern, Bern, Switzerland

    Monika Falke & Aurel Perren

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Contributions

MSL, SP, and VA performed study design, acquisition of data, analysis and interpretation of data, writing, review, and revision of the paper. FM, MGC, MF, and MR provided acquisition of data, analysis and interpretation of data, writing, review, and revision of the paper. MF, AP, and CD provided study concept and design, review, and revision of the paper. BM reviewed blindly 51 cases to evaluate the reproducibility of the growth pattern assesment. VA provided statistical analysis, prepared Figs. 1, 5, and 6 and Tables 1, 2, 3, 4, and 5. EB performed additional statistical analysis and prepared Supplementary Tables 1 and 2. MSL prepared Figs. 3 and 4. All authors read and approved the final paper.

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Correspondence to Marco Schiavo Lena.

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The study was conducted according to the criteria set by the 1964 Declaration of Helsinki and later Amendments and in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology Statement (STROBE) guidelines. Due to the retrospective nature of the study, approval by the ethical committee was waived. No identifying details of the patients were mentioned in this study, all information were anonymized, and the images included may not be identified persons.

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Schiavo Lena, M., Partelli, S., Andreasi, V. et al. Infiltrative Growth Predicts the Risk of Recurrence After Surgery in Well-Differentiated Non-Functioning Pancreatic Neuroendocrine Tumors. Endocr Pathol 34, 142–155 (2023). https://doi.org/10.1007/s12022-022-09745-x

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