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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 + fPP PP + fB Insulin +ECL Histamine +G Gastrin + +CCK CCK + + rS Secretin + +GIP GIP + + rM Motilin + + rN Neurotensin r + +
Rindi et al., Digestion 2000, 62(S1):19
Intestine
GASTROENTERPANCREATIC ENDOCRINE TUMORS
cell type, site and possible hyperfunctional syndromes
Tumor Main Stomach Small Large Possible
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
Rindi et al., Digestion 2000, 62(S1):19
Intestine
WELL DIFFERENTIATED endocrine neoplasia
1 - tumor (carcinoid)
2 - carcinoma (malignant carcinoid)
POORLY DIFFERENTIATED endocrine carcinoma
3 - Small or large cell carcinoma
DES TUMORS GENERAL CATEGORIES
DES TUMORS Well Differentiated
• Structural features• Nests / solid islets• Trabeculae /cords• Acini• Mixed
• Cytological features• Monomorphism• Mild to moderate atypia• Occasional mitosis
Solid nests Pseudoglandular
Trabecular
Well differentiatedtumors
-Structural patterns
MARKER EXPRESSION IN TUMORS OF THE DIFFUSE
ENDOCRINE SYSTEMWell differentiated endocrin neoplasm
General Markers
CgA INTENSE AND DIFFUSE
Syn “ “
NSE “ “
PGP9.5 “ “
Specific Markers
various VARIABLE
PP
CgA
WELL DIFFERENTIATED ENDOCRINE TUMORS OF THE
GASTROENTEROPANCREATIC TRACT
HISTOPATHOLOGICAL PARAMETERS WITH POTENTIAL PROGNOSTIC IMPACT
• CYTOLOGIC ATYPIA
• MITOSES
• Ki67 INDEX
• P53 EXPRESSION
• PLOIDY STATUS
WELL DIFFERENTIATED ENDOCRINE TUMORS OF THE
GASTROENTEROPANCREATIC TRACT
HISTOPATHOLOGICAL PARAMETERS WITH POTENTIAL PROGNOSTIC IMPACT
• SIZE
• INFILTRATION
• ANGIOINVASION
• PERINEURAL SPACE INVASION
CD31
GASTRIC ECL CELL TUMORS
DIAGNOSTIC 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
Gastric ECL cells
Diffuse hyperplasia
Micronodular hyperplasia
Dysplasia
Gastric ECL carcinoid
Carcinoma endocrino poco differenziato
MARKER EXPRESSION IN TUMORS OF THE DIFFUSE
ENDOCRINE SYSTEM
Poorly differentiated (small cell) endocrine carcinoma
General markers
CgA SCANT OR ABSENT
Syn DIFFUSE AND VARIABLE
NSE “ “
PGP9.5 “ “
Specific markers
Various ABSENT
Syn
PGP9.5
Clinicopathologic classification of gastric endocrine tumours 1. Well differentiated endocrine tumour
Confined to mucosa-submucosa, with moderate cellular atypiaa) 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.
Poorly differentiated : 3 cases
•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
Argentaffin EC cell tumors (carcinoids)
Endocrine tumor of small bowel.Panoramic view showing submucosal nodule
Panoramic view of ileal endocrine tumor showing full thickness involvement with a largely preserved mucosa
5-HT
WHO Histological Typing of Endocrine Tumours, 2000
ENETS STAGING PROPOSALPANCREAS
Size increase
Mets presence