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The Pathology of Neuroendocrine Tumors: Diagnosis, Grading and Staging

The Pathology of Neuroendocrine Tumors: Diagnosis, Grading and Staging. Wendy L. Frankel, MD Vice Chair and Director of AP The Ohio State University Columbus, OH. Overview GI and Pan NET. Diagnosis Typical H&E, immunohistochemical stains Variants and mixed tumors Differential diagnosis

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The Pathology of Neuroendocrine Tumors: Diagnosis, Grading and Staging

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  1. The Pathology of Neuroendocrine Tumors: Diagnosis, Grading and Staging Wendy L. Frankel, MD Vice Chair and Director of AP The Ohio State University Columbus, OH

  2. Overview GI and Pan NET • Diagnosis • Typical H&E, immunohistochemical stains • Variants and mixed tumors • Differential diagnosis • Tumor Grading (WHO 2010) • Tumor Staging (AJCC TNM, 7th ed)

  3. NET Terminology • Neuroendocrine rather than endocrine • Tumor rather than neoplasm • Neuroendocrine tumor (well differentiated) rather than carcinoid • Neuroendocrine carcinoma (poorly differentiated, high grade) rather than small/large cell endocrine carcinoma

  4. Diagnosis • Histology • Gross • Yellow • Pink/red • Solid • Rarely cystic • Microscopic • Acinar, nested • Solid • Trabecular

  5. Histology- Nested

  6. Acinar Trabecular Solid

  7. Histology Necrosis

  8. Immunohistochemistry • Typical NE markers • Synaptophysin and chromogranin • CD 56 less specific • Hormone markers • Gastrin, insulin, PP, etc. • Not typically done • Serology and symptoms/syndrome • Proliferation marker- Ki67

  9. Immunohistochemistry Neuroendocrine Markers (Chromogranin, Synaptophysin)

  10. NET Variants Rhabdoid Cystic or microcystic Angiomatoid Oncocytic Fusiform Clear cell Rhabdoid

  11. Fusiform Oncocytic Clear Cell

  12. Mixed Adenoneuroendocrine Carcinoma- MANEC Adenocarcinoma, NET, acinar Usually adenocarcinoma element predominates Must be distinct population May need IHC to diagnose Intimately admixed Arbitrarily set at 30% Usually acts more like adenocarcinoma

  13. Mixed AdenoNEC Chromogranin

  14. Mixed AdenoNEC Neuroendocrine Adenocarcinoma

  15. Appendix NET (Typical Carcinoid) Goblet Cell Carcinoid

  16. Goblet Cell Carcinoid • NET and mucin production • Old term- crypt cell carcinoid • Prognosis intermediate NET and adenocarcinoma

  17. AppendixMixed Adenoneuroendocrine Carcinoma • Poor prognosis • Conventional goblet cell carcinoid and either glandular or signet cell carcinoma or pools of mucin • Arise from pre-existing goblet cell carcinoid

  18. NET- Differential Diagnosis • Adenocarcinoma • Adenocarcinoma with focal neuroendocrine differentiation • For PanNET • Neuroendocrine aggregation in chronic pancreatitis • Acinar cell carcinoma • Solid pseudopapillary tumor

  19. Adenocarcinoma

  20. Chronic Pancreatitis

  21. Solid Pseudopapillary Tumor Young Women- Fibrovascular stalks

  22. Immunohistochemistry *Includes ductal adeno, MCN and IPMN **CD10+, nuclear beta-Catenin, loss E-Cadherin

  23. WHO Classification

  24. Grade- NETUse Hot Spot Count 50 HPF Count 2000 cells

  25. 2010 WHO Grade NET 1 NET 2 NET/C 3 (carcinoma) Lower grade morphology but ↑ mitotic rate or proliferative rate High grade morphology Small cell Large cell NET 1

  26. NEC 3- Mixed Group?? Small Cell Carcinoma Increased Mitotic Count/ Prolif

  27. Proliferation- Ki67High Power Field < 2% 15-20%

  28. Stage- Site Specific AJCC Cancer Staging Manual, 7th ed GI NET Appendix NEC 3 and goblet cell carcinoid staged like adenocarcinoma NET 1, 2 Stomach and intestines NEC 3 staged like adenocarcinoma NET 1,2 similar but size criteria added Pancreas NET Staged the same as adenocarcinoma

  29. Pan NET- Stage

  30. Synoptic Reports • Site • Size • Margins • Mitoses per 10 high power fields • Ki67- proliferative index • Grade • TNM Stage

  31. Pathologic Challenges and Controversies • NEC (G3)- 2 types • Grading-Use whichever is higher • Mitosis counting • Ki67 counting: Eyeballing, true count (static picture or microscope, automated) • Staging ENETS or AJCC (pancreas)

  32. Pathology NET Summary • Typical H&E appearance but variants • Immunohistochemistry is useful • 2010 WHO- NET 1, NET 2, NEC 3 • Grading – Based on mitotic figures and proliferation rate • Staging – TNM AJCC or ENETS

  33. QUESTIONS 33 33

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