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Necrosis is an independent predictor of disease-free and overall survival in pancreatic well-differentiated neuroendocrine tumours (NETs): a proposal to include it in grading systems

  • Talia L. Fuchs
    Correspondence
    Address for correspondence: Department of Anatomical Pathology, Royal North Shore Hospital, Pacific Highway, St Leonards, NSW, 2065, Australia.
    Affiliations
    Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, Australia

    Douglass Hanly Moir, Macquarie Park, NSW, Australia

    Sydney Medical School, University of Sydney, Sydney, NSW, Australia
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  • Angela Chou
    Affiliations
    Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, Australia

    Sydney Medical School, University of Sydney, Sydney, NSW, Australia

    NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia
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  • Mahsa Ahadi
    Affiliations
    Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, Australia

    Sydney Medical School, University of Sydney, Sydney, NSW, Australia

    NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia
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  • Amy Sheen
    Affiliations
    Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, Australia
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  • Loretta Sioson
    Affiliations
    Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, Australia
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  • Anubhav Mittal
    Affiliations
    Sydney Medical School, University of Sydney, Sydney, NSW, Australia

    Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, St Leonards, NSW, Australia

    Australian Pancreatic Centre, St Leonards, NSW, Australia

    University of Notre Dame, Darlinghurst, NSW, Australia
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  • Jaswinder Samra
    Affiliations
    Sydney Medical School, University of Sydney, Sydney, NSW, Australia

    Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, St Leonards, NSW, Australia

    Australian Pancreatic Centre, St Leonards, NSW, Australia
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  • Anthony J. Gill
    Affiliations
    Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, Australia

    Sydney Medical School, University of Sydney, Sydney, NSW, Australia

    NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia
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      Summary

      Pancreatic neuroendocrine tumours (NETs) are currently graded using the World Health Organization (WHO) 2019 system, which is based solely on mitotic count and Ki-67 proliferative index. Although necrosis is a well recognised adverse prognostic feature that is included in the grading systems of NETs of certain types such as pulmonary carcinoid and medullary thyroid carcinoma, there is currently insufficient evidence to support its inclusion in the grading of pancreatic NETs. Therefore, we sought to investigate the prognostic significance of tumour necrosis in our cohort of resected pancreatic NETs, with a view to providing evidence to support its incorporation into the WHO grading scheme.
      Under our proposal, pancreatic NETs without necrosis would continue to be graded based solely on mitotic count and Ki-67 index using the established WHO cut-offs, while NETs with tumour necrosis would be classified as grade 3, irrespective of proliferative activity.
      Using this system in our cohort of 110 resected pancreatic NETs, overall survival (OS) was 250, 198, and 151 months (p=0.039) and disease-free survival (DFS) was 180 months, 117 months, and 38 months (p<0.0001) for grades 1, 2, and 3, respectively. In contrast, there was no significant difference in OS (p=0.231) or DFS (p=0.058) between low grade (grade 1) and intermediate-high grade (grade 2/3) tumours using the current WHO system which does not consider necrosis. Interobserver concordance for assessment of necrosis was excellent.
      In conclusion, necrosis is an independent predictor of OS and DFS for pancreatic NETs, and our findings strongly support its addition to the grading scheme for this tumour.

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