Distinctive features of pancreatic neuroendocrine neoplasms exhibiting an increment in proliferative activity during the
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ORIGINAL ARTICLE
Distinctive features of pancreatic neuroendocrine neoplasms exhibiting an increment in proliferative activity during the course of the disease Krystallenia I. Alexandraki 1,2 Maria Kaltsatou1 Georgios Kyriakopoulos1,3 Vasiliki Mavroeidi4 Akrivi Kostopoulou5 Karine Atlan6 Stamatios Theocharis1,7 Guido Rindi8,9,10 Ashley B. Grossman11,12,13,14 Simona Grozinsky-Glasberg15 Gregory A. Kaltsas1,4 ●
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Received: 13 July 2020 / Accepted: 27 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Neuroendocrine neoplasms Change of Ki-67 PI Ki-67 p53 De-differentiation ●
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* Krystallenia I. Alexandraki [email protected]
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Anatomic Pathology Section, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italy
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ENETS Center of Excellence, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
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2nd Department of Surgery, Medical School, National and Kapodistrian University of Athens, Athens, Greece
Anatomic Pathology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
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ENETS Center of Excellence, Roma, Italy
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Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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