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Distinctive features of pancreatic neuroendocrine neoplasms exhibiting an increment in proliferative activity during the course of the disease

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Abstract

Purpose

Neuroendocrine neoplasms (NENs) differ in their biological behavior and growth potential in a way that can be predicted using histological classification and grading systems. A subset of pancreatic NENs (pNENs) may develop a more aggressive phenotype during the course of the disease, associated with an increase in the Ki-67 proliferation index (PI). The purpose of the study was to present the clinical characteristics of these patients.

Methods

Using re-biopsy of growing lesions, we investigated the increase in Ki-67 PI sufficient to change initial grading (G).

Results

Of 264 patients with well differentiated (WD) pNENs who showed progressive disease during follow-up, 15 (6%) exhibited an increase in Ki-67 PI at a median time 36.8 (9.3–255.8) months. All neoplasms had WD-morphology: five had G1 (Ki-67 median value 1%), nine G2 (median value 5%), one G3 (25%) grades. Upon change of Ki-67 PI, 3 patients had G2 (8%) and 12 G3 (57.5%) NENs, while all retained their WD-morphology. At last follow-up, eight patients were alive with a median overall survival (OS) of 52.5 (9.5–264.3) months. Μedian OS was shorter in patients who had a change in Ki-67 PI before 36 months compared to those who had a change of Ki-67 PI at a later stage (27.5 95%CI: 11.88–43.06 vs. 120.87 95%CI: 96.05–145.69; log-rank p = 0.018).

Conclusions

During the course of their disease, 6% patients with progressive pNENs develop an increase in Ki-67 PI resulting in an increase in grading status while maintaining their morphology. This process is associated with worse OS when it occurs at an early stage.

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Author information

Authors and Affiliations

  1. ENETS Center of Excellence, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

    Krystallenia I. Alexandraki, Maria Kaltsatou, Georgios Kyriakopoulos, Stamatios Theocharis & Gregory A. Kaltsas

  2. 2nd Department of Surgery, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Krystallenia I. Alexandraki

  3. Department of Pathology, Evaggelismos Hospital, Athens, Greece

    Georgios Kyriakopoulos

  4. Endocrine Unit, 1st Department of Propaedeutic Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

    Vasiliki Mavroeidi & Gregory A. Kaltsas

  5. Department of Pathology, “G. Gennimatas” General Hospital, Athens, Greece

    Akrivi Kostopoulou

  6. Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    Karine Atlan

  7. First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Stamatios Theocharis

  8. Anatomic Pathology Section, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italy

    Guido Rindi

  9. Anatomic Pathology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy

    Guido Rindi

  10. ENETS Center of Excellence, Roma, Italy

    Guido Rindi

  11. Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

    Ashley B. Grossman

  12. University of Oxford, Oxford, UK

    Ashley B. Grossman

  13. Green Templeton College, Oxford, UK

    Ashley B. Grossman

  14. ENETS Center of Excellence, Royal Free London, London, UK

    Ashley B. Grossman

  15. Neuroendocrine Tumor Unit, ENETS Center of Excellence, Department of Endocrinology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    Simona Grozinsky-Glasberg

Authors
  1. Krystallenia I. Alexandraki
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  2. Maria Kaltsatou
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  9. Ashley B. Grossman
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  11. Gregory A. Kaltsas
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Contributions

Conceptualization, K.I.A., G.A.K.; Design/methodology, K.I.A., S.G.-G., G.R., G.A.K.; Analysis, K.I.A. M.K., G.K., V.M., A.K., K.A., S.T.; Investigation, K.I.A. G.K., S.T.; Data curation, K.I.A. M.K., G.K., V.M., A.K., K.A., S.T., G.R., S.G.-G.; Writing—original draft preparation, K.I.A.; Writing—review and editing, K.I.A., S.G.-G., and G.A.K.; Visualization, G.K., S.T.; Validation, S.T., G.R., A.B.G.; Supervision, S.G.-G., A.B.G., G.A.K.; Project administration, K.I.A.

Corresponding author

Correspondence to Krystallenia I. Alexandraki.

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Alexandraki, K.I., Kaltsatou, M., Kyriakopoulos, G. et al. Distinctive features of pancreatic neuroendocrine neoplasms exhibiting an increment in proliferative activity during the course of the disease. Endocrine 72, 279–286 (2021). https://doi.org/10.1007/s12020-020-02540-w

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  • DOI: https://doi.org/10.1007/s12020-020-02540-w

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