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Enhancing NEC Diagnosis Through WHO 2010 Guideline Implementation

Investigating the impact of WHO 2010 guidance on extra-pulmonary large cell NEC diagnosis for improved treatment decisions. Study evaluates pathology reports and survival rates to enhance neuroendocrine carcinoma management.

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Enhancing NEC Diagnosis Through WHO 2010 Guideline Implementation

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  1. Pertinence of the WHO 2010 guideline on NEC diagnosisReliable pathology reporting of extra-pulmonary large cell NEC JM van der Zwan Ph.D., IACR, Vancouver 2019

  2. Conflict of Interest Disclosure Formin accordance with the rules of the Health Care Inspectorate (IGZ) name: Jan Maarten van der Zwan affiliation: Netherlands Comprehensive Cancer Organisation I have no potential conflict of interest to report 

  3. Background Extra pulmonary neuroendocrine carcinomas (EP-NEC) are rare tumors, therefore many publications concern small cohorts only. • A correct diagnosis and grading is of great importance for the treatment of choice. Population based Cancer Registry data gives the opportunity to study these poor surviving patients.

  4. Background (cont.) Classification of neuroendocrineneoplasms (NEN) changedthrough time. Embryonal origin Morphology (well vs poorly differentiated) (year 2000) Proliferative activity (year 2010)

  5. Background (cont.) Classification of neuroendocrineneoplasms (NEN) Proliferative activity (2010) NET G2 2-20 mitoses / 10hpf OR 3%-20% Ki67 index NEC G3 >20 mitoses / 10hpf OR >20% Ki67 index NET G1 <2 mitoses / 10hpf AND <3% Ki67 index Klimstra et al., Pancreas Volume 39, number 6, August 2010

  6. Aim of the study Demonstrate a change in pathology reporting after the implementation of the WHO 2010 guideline.  Did the implementation of the WHO 2010 result in a more uniform diagnostic pattern?

  7. The NCR The Netherlands Cancer Registry (NCR) receives their notification from the National pathology archive (PALGA) Information is mainly retrieved from the pathology report and patient files.

  8. Methods Selection: • EP-NEC • NEC with unknown primary localization • M8013 & M8246 • Years 2008 – 2012 Pathology reviewed on: • Morphology • Immunohistochemistry • Grading Compare: • 2008-2010 (baseline) • 2011-2012

  9. Review pathology reports

  10. Review: Flow chart Period 2008-2012 The NCR included 591 EP-NEC cases.

  11. Review: Flow chart Carcinomas with neuroendocrine characteristics and NET G1 & G2

  12. Review: Flow chart Carcinomas with neuroendocrine characteristics and NET G1 & G2 Negative staining for NET/NEC

  13. Review: Flow chart Carcinomas with neuroendocrine characteristics and NET G1 & G2 Negative staining for NET/NEC • 93 cases no Grading

  14. Review: Flow chart Carcinomas with neuroendocrine characteristics and NET G1 & G2 Negative staining for NET/NEC • 93 cases no Grading • 58 cases low Grade

  15. Review: Flow chart Carcinomas with neuroendocrine characteristics and NET G1 & G2 Negative staining for NET/NEC • 93 cases no Grading • 58 cases low Grade • 196 cases confirmed NEC

  16. Results

  17. Completeness pathology • 2008: 50% of thereportsincluded IHC andGrading • 2012: 69% of thereportsincluded IHC andGrading Completeness of pathology reports of neuroendocrine carcinomas from 2008 to 2012 (percentage) Any neuroendocrine IHC: either synaptophysin or chromogranin was reported

  18. Completeness pathology • 2008: 50% of the reports included IHC and Grading • 2012: 69% of the reports included IHC and Grading • Mainly the result of reporting Grade (63% vs 74%) Completeness of pathology reports of neuroendocrine carcinomas from 2008 to 2012 (percentage) Any neuroendocrine IHC: either synaptophysin or chromogranin was reported

  19. Overall survival Overall survival patterns are in accordance with the histopathological classification. • Low grade NET: Mean survival of 2.2yrs • Small cell NEC: • Mean survival of • 1.1 yrs Kaplan-Meier analysis of overall survival (p=0.02)

  20. Take home message • EP-NECs are difficultmalignanciesto diagnose  Expert pathologistsmightimprovequality diagnoses • There are discrepancies in thepathologyreports • Expert datamanagers mightimprove data-quality • Reporting neuroendocrine markers andgrade are important as prognostic factors andto select the treatment of choice  Considertheinvolvement of Expert Centres.

  21. Conclusion • Although publication of guidelines improves the use of essential parameters, the implementation may require a considerable period of time (sometimes even years).  Synoptic reporting might give an important boost to meet requirements more quickly.

  22. Acknowledgements • Wouter ZandeePh.D. MD • Wouter de Herder Ph.D. MD • Marie-Louise van VelthuysenPh.D. MD

  23. Questions

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