1. GENERAL ENDOCRINE TUMORS CATEGORIES WHO classification 1.Well differentiated endocrine tumor 2.Well differentiated endocrine carcinoma 3. Poorly differentiated endocrine (small cell) carcinoma 4. Mixed exocrine - endocrine tumor 5.Tumor - like lesion WHO Histological Typing of Endocrine Tumours, 2000/2004

2. PURE ENDOCRINE TUMORS The Differentiation Concept Well differentiated endocrine neoplasm 1 - tumor (carcinoid) 2 - carcinoma (malignant / atypical carcinoid) Poorly differentiated endocrine carcinoma 3 - small / intermediate cell carcinoma

3. GUT ENDOCRINE TUMORS TUMOR GRADING AND CLASSIFICATION ENETS GRADING PROPOSAL

4. ENETS TNM WORKING PROPOSAL PANCREAS Size increase

5. ENETS STAGING PROPOSAL PANCREAS Size increase Mets presence

6. GENERAL NEUROENDOCRINE TUMORS CATEGORIES lung Well differentiated neuroendocrine neoplasm 1 - tumor (carcinoid) 2 - carcinoma (malignant / atypical carcinoid) Poorly differentiated endocrine carcinoma 3 - large cell neuroendocrine carcinoma 4 - small / intermediate cell carcinoma

7. THE SPECTRUM OF NEUROENDOCRINE PROLIFERATIONS lung 1.NEUROENDOCRINE CELL HYPERPLASIA AND TUMORLETS 2.TUMORS WITH NEUROENDOCRINE MORPHOLOGY 3.NON-SCLC WITH NEUROENDOCRINE DIFFERENTIATION 4.OTHER TUMORS WITH NEUROENDOCRINE PROPERTIES Travis et al. WHO Classification of Tumours, 2004

8. REQUIRED THE SPECTRUM OF LUNG NEUROENDOCRINE PROLIFERATIONS IMMUNOHISTOCHEMISTRY TC/AC CD56 N-CAM + CgA + Syn + Ki67 low LCNEC CD56 N-CAM + CgA +/- Syn + Ki67 high SCLC CD56 N-CAM + CgA +/- Syn + Ki67 very high HMWCK - LMWCK CAM5.2 + P63/Desmocollin - TTF1 usually - HMWCK - LMWCK CAM5.2 + P63/Desmocollin - TTF1 usually +/- HMWCK - LMWCK CAM5.2 + P63/Desmocollin - TTF1 usually +

9. marker expected positivity LDCV antigens WDET/WDEC/PDEC SSV antigens WDET/WDEC/PDEC cytosol antigens WDET/WDEC/PDEC Ki67 indexWDET/WDEC/PDEC P53 WDET/WDEC/PDEC hormonesWDET/WDEC/PDEC membrane antigens WDET/WDEC/PDEC FAL/AI/CINWDET/WDEC/PDEC MARKER EXPRESSION IN ENDOCRINE TUMORS CD56 n-CAM SST2 (e.g. chromogranin A) (e.g. synaptophysin) (e.g. NSE, PGP9.5)

10. Well differentiated Poorly differentiated (NEURO)ENDOCRINE TUMORS TUMOR GRADING AND CLASSIFICATION SUMMARY DifferentiationTumor definition Carcinoid / TC / WDET Atypical carcinoid / AC / WDEC SCNEC / PDEC / LCNEC / SCLC WHO1/G1 WHO2/G2 WHO3/G3 Grading