Elettra Merola1, Wouter Zandee2, Louis de Mestier3, Heinz Josef Klümpen4, Karolina Makulik5, Karen Geboes6, Marie Louise van Velthuysen7, Anne Couvelard8, Jérôme Cros8, Susanne van Eeden9, Anne Hoorens10, Timothy Stephenson11, W Zajęcki5, Wouter de Herder2, Alia Munir12. 1. Department of Gastroenterology, Azienda Provinciale Servizi Sanitari (APSS), Trento, Italy, elettra.merola@gmail.com. 2. Department of Internal Medicine, Sector of Endocrinology, Erasmus MC, Rotterdam, The Netherlands. 3. Department of Gastroenterology and Pancreatology, Beaujon Hospital (APHP) and Paris 7 University, Clichy, France. 4. Department of Medical Oncology, Academic Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands. 5. Department of Endocrinology and Neuroendocrine Tumors, Medical University of Silesia, Katowice, Poland. 6. Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium. 7. Department of Pathology, Erasmus MC, Rotterdam, The Netherlands. 8. Department of Pathology, Beaujon/Bichat Hospital (APHP) and Université de Paris, Clichy, France. 9. Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands. 10. Department of Pathology, University Hospital Ghent, Ghent, Belgium. 11. Department of Pathology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom. 12. Department of Endocrinology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.
Abstract
BACKGROUND: The correct histopathological diagnosis of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) is crucial for treatment selection and prognostication. It is also very challenging due to limited experience in nonexpert centers. Revision of pathology is standard of care for most patients who are referred to NEN expert centers. OBJECTIVES: To describe the clinical impact of histopathological revision for GEP-NEN patients referred to an expert center. METHODS: Retrospective multicenter analysis of all GEP-NENs receiving a histopathological revision in 6 European NEN expert centers (January 2016 to December 2016) to evaluate the impact on patient management. RESULTS: 175 patients were included and 14.7% referred for a second opinion. Histological samples were 69.1% biopsies, 23.4% surgical specimens, and 7.5% endoscopic resections. Histopathological changes due to revision included first assessment of Ki67 in 8.6% of cases, change in grading in 11.4% (3.4% G1 to G2; 5.7% G2 to G1; 0.6% G2 to G3; 1.7% G3 to G2), definition of tumor invasion in 10.8%, additional immunohistochemical staining in 2.3%, diagnosis of mixed adenoneuroendocrine carcinoma in 3.4%, exclusion of NEN in 3.4%, first diagnosis of NEN in 2.3%, and tumor differentiation for G3 in 1.7%. The revision had a clinical impact in 36.0% of patients, leading to a new therapeutic indication in 26.3%. The indication to then perform a new imaging test occurred in 21.1% and recommendation to follow-up with no further treatment in 6.3%. CONCLUSIONS: Histopathological revision in expert centers for NENs can change the diagnosis, with a significant clinical impact in about one third of patients.
BACKGROUND: The correct histopathological diagnosis of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) is crucial for treatment selection and prognostication. It is also very challenging due to limited experience in nonexpert centers. Revision of pathology is standard of care for most patients who are referred to NEN expert centers. OBJECTIVES: To describe the clinical impact of histopathological revision for GEP-NEN patients referred to an expert center. METHODS: Retrospective multicenter analysis of all GEP-NENs receiving a histopathological revision in 6 European NEN expert centers (January 2016 to December 2016) to evaluate the impact on patient management. RESULTS: 175 patients were included and 14.7% referred for a second opinion. Histological samples were 69.1% biopsies, 23.4% surgical specimens, and 7.5% endoscopic resections. Histopathological changes due to revision included first assessment of Ki67 in 8.6% of cases, change in grading in 11.4% (3.4% G1 to G2; 5.7% G2 to G1; 0.6% G2 to G3; 1.7% G3 to G2), definition of tumor invasion in 10.8%, additional immunohistochemical staining in 2.3%, diagnosis of mixed adenoneuroendocrine carcinoma in 3.4%, exclusion of NEN in 3.4%, first diagnosis of NEN in 2.3%, and tumor differentiation for G3 in 1.7%. The revision had a clinical impact in 36.0% of patients, leading to a new therapeutic indication in 26.3%. The indication to then perform a new imaging test occurred in 21.1% and recommendation to follow-up with no further treatment in 6.3%. CONCLUSIONS: Histopathological revision in expert centers for NENs can change the diagnosis, with a significant clinical impact in about one third of patients.