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ENDOCRINE CELLS OF THE GASTROENTROPANCREATIC TRACT

ENDOCRINE CELLS OF THE GASTROENTROPANCREATIC TRACT. Stomach Small Large Cell Main Product Pa CF An D J I Ap C R P/D 1 Ghrelin f + r r EC 5HT r + + + + + + + + D Somatostatin + + + + r r + r + L GLI/PYY r + + + + + A Glucagon + f PP PP + f

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ENDOCRINE CELLS OF THE GASTROENTROPANCREATIC TRACT

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  1. ENDOCRINE CELLS OF THE GASTROENTROPANCREATIC TRACT Stomach Small Large Cell Main Product Pa CF An D J I Ap C R P/D1 Ghrelin f + r r EC 5HT r + + + + + + + + D Somatostatin + + + + r r + r + L GLI/PYY r + + + + + A Glucagon + f PP PP + f B Insulin + ECL Histamine + G Gastrin + + CCK CCK + + r S Secretin + + GIP GIP + + r M Motilin + + r N Neurotensin r + + Intestine Rindi et al., Digestion 2000, 62(S1):19

  2. GASTROENTERPANCREATIC ENDOCRINE TUMORScell type, site and possible hyperfunctional syndromes Tumor Main Stomach Small LargePossible Type Cell Type Pa CF An D J I Ap C R Syndrome Well B + PHH Differentiated A + glucagonoma PP + - (?) + + WDHA D + + + somatostatinoma EC + + + + + + + + + “carcinoid” ECL + “atypical carcinoid” G + + + + ZES L + + + + + - Poorly + + + + + + + + - Differentiated Intestine Rindi et al., Digestion 2000, 62(S1):19

  3. DES TUMORSGENERAL CATEGORIES WELL DIFFERENTIATED endocrine neoplasia 1 - tumor (carcinoid) 2 - carcinoma (malignant carcinoid) POORLY DIFFERENTIATED endocrine carcinoma 3 - Small or large cell carcinoma

  4. DES TUMORSWell Differentiated • Structural features • Nests / solid islets • Trabeculae /cords • Acini • Mixed • Cytological features • Monomorphism • Mild to moderate atypia • Occasional mitosis

  5. Solid nests Pseudoglandular Well differentiated tumors - Structural patterns Trabecular

  6. MARKER EXPRESSION IN TUMORS OF THE DIFFUSE ENDOCRINE SYSTEM Well differentiated endocrin neoplasm General Markers CgA INTENSE AND DIFFUSE Syn “ “ NSE “ “ PGP9.5 “ “ Specific Markers variousVARIABLE CgA PP

  7. WELL DIFFERENTIATED ENDOCRINE TUMORS OF THE GASTROENTEROPANCREATIC TRACT HISTOPATHOLOGICAL PARAMETERS WITH POTENTIAL PROGNOSTIC IMPACT • CYTOLOGIC ATYPIA • MITOSES • Ki67 INDEX • P53 EXPRESSION • PLOIDYSTATUS

  8. SIZE INFILTRATION ANGIOINVASION PERINEURAL SPACE INVASION WELL DIFFERENTIATED ENDOCRINE TUMORS OF THE GASTROENTEROPANCREATIC TRACT HISTOPATHOLOGICAL PARAMETERS WITH POTENTIAL PROGNOSTIC IMPACT CD31

  9. GASTRIC ECL CELL TUMORSDIAGNOSTIC CATEGORIES • Well Differentiated CAG-associated (type I) • Well Differentiated ZES / MEN1-associated (type II) • Well Differentiated Sporadic (type III) • Poorly differentiated WHO Histological Typing of Endocrine Tumours, 2000

  10. Diffuse hyperplasia Gastric ECL cells

  11. Dysplasia Micronodular hyperplasia

  12. Gastric ECL carcinoid

  13. Carcinoma endocrino poco differenziato

  14. MARKER EXPRESSION IN TUMORS OF THE DIFFUSE ENDOCRINE SYSTEM Poorly differentiated (small cell) endocrine carcinoma General markers CgA SCANT OR ABSENT Syn DIFFUSEAND VARIABLE NSE “ “ PGP9.5 “ “ Specific markers Various ABSENT Syn PGP9.5

  15. Clinicopathologic classification of gastric endocrine tumours 1. Well differentiated endocrine tumour Confined to mucosa-submucosa, with moderate cellular atypia a) Lower risk: Nonangioinvasive, <1 cm, nonfunctioning. Mostly ECL cell tumors with hypergastrinemia and A- type cron.atr.gastr. or MEN1 syndrome; occasional EC cell carcinoid or gastrin cell tumour. b) Higher risk: Angioinvasive, >1 cm or functioning. ECL cell tumors, sporadic or with MEN1 or A-CAG; occasional EC cell carcinoid or gastrin cell tumour. 2. Well differentiated endocrine carcinoma Low grade malignant, deeply invasive (muscolaris propria or beyond) ormetastatic ECL cell, mostly sporadic, sometimes with atypical carcinoid syndrome; EC cell, serotonin producin, occasionally with typical carcinoid syndrome; rare gastrin, ghrelin or ACTH producing tumors, with or without syndrome. 3. Poorly differentiated endocrine carcinoma High grade malignant, small to large cell; reactive with some neuroendocrine markers but usually nonfunctioning; occasionally with inappropriate hormonal syndrome.

  16. Poorly differentiated : 3 cases

  17. Argentaffin EC cell tumors (carcinoids) • Site: 1/4 multiple tumors ileum, appendix, Merkel’s diverticulum, jejunum, caecum • rare in duodenum, stomach, distal colon and rectum. • Histology: • well differentiated, solid nests • peripheral palisading of serotonin rich, highly granular tumor cells • deep infiltration of muscular wall and mesenteric fibroblastic reaction • argyrophilic, argentaffin, diazonium, formalehyde induced fluorescence, chromogranin+, serotonin+, substance P+ • pleomorphic/osmiophilic granules. • Metastases: 2% (<1cm), 50% (1-2 cm), 80% (>2 cm) • Behavior: low grade malignant • Most of symptomatic cases are metastatic • Symptoms:obstruction (mesenteric retraction) • Carcinoid syndrome (7%), all with liver metatases

  18. Endocrine tumor of small bowel. Panoramic view showing submucosal nodule

  19. Panoramic view of ileal endocrine tumor showing full thickness involvement with a largely preserved mucosa

  20. 5-HT

  21. WHO Histological Typing of Endocrine Tumours, 2000

  22. Size increase Mets presence ENETS STAGING PROPOSALPANCREAS

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