Histopathological and Immunophenotypic Changes of Pancreatic Neuroendocrine Tumors after Neoadjuvant Peptide Receptor Radionuclide Therapy (PRRT): Endocrine Pathology

M. Schiavo Lena, S. Partelli, P. Castelli, V. Andreasi, C.E. Smart, E. Pisa, M. Bartolomei, E. Bertani, G. Zamboni, M. Falconi, C. Doglioni

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Peptide Receptor Radionuclide Therapy (PRRT) is an emerging therapeutic option for pancreatic neuroendocrine tumors (PanNETs). A possible role for PRRT as a neoadjuvant agent is still largely undetermined, explored only in case reports or small case series. Likewise, the histopathological and immunophenotypic changes induced by PRRT are poorly characterized. In the present study, 24 patients who underwent neoadjuvant PRRT on the basis of their disease’s characteristics were retrospectively matched with 24 patients who underwent upfront surgery. A comprehensive morphological and immunohistochemical evaluation was conducted to identify the differences in the two groups. The most significant findings were that the total percentage of stroma increased significantly in patients who underwent PRRT (p < 0.0001) and the characteristics of the stroma were different in the two groups. The somatostatin receptors type 2A (SSTR2A) were retained in most patients (87%) after PRRT. The density of CD163+ M2-polarized macrophages was greater in the PRRT group (p = 0.022), and M2-polarized macrophages tended to assume an epithelioid morphology (p = 0.043). In the neoadjuvant PRRT group, none of the histological parameters considered were associated with progression-free survival (PFS). Neoadjuvant PRRT in PanNETs is associated with reduced tumor diameter, an increased percentage of stroma, preserved SSTR2A expression in most of the cases, and an increased CD163+ M2-polarized macrophages density. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
Original languageEnglish
Pages (from-to)119-131
Number of pages13
JournalEndocr. Pathol.
Issue number2
Publication statusPublished - 2020


  • Immunohistochemistry
  • M2-polarized macrophages
  • Pancreatic neuroendocrine tumor
  • Peptide Receptor Radionuclide Therapy
  • Response to neoadjuvant therapy
  • antineoplastic agent
  • CD163 antigen
  • peptide receptor radionuclide
  • somatostatin receptor
  • somatostatin receptor type 2A
  • unclassified drug
  • adult
  • aged
  • Article
  • cancer radiotherapy
  • cancer surgery
  • cell density
  • clinical article
  • controlled study
  • female
  • histopathology
  • human
  • immunophenotyping
  • macrophage
  • male
  • neoadjuvant therapy
  • pancreas islet cell tumor
  • peptide receptor radionuclide therapy
  • priority journal
  • progression free survival
  • protein expression
  • retrospective study
  • tumor volume


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