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ENDOCRINE CELLS OF THE
GASTROENTROPANCREATIC TRACT
Intestine
Small
Stomach
Large
Cell
Main Product
Pa
CF
An
D
J
I
Ap
C
R
P/D1
EC
Ghrelin
5HT
f
r
+
+
r
+
r
+
+
+
+
+
+
D
Somatostatin
+
+
+
+
r
r
+
r
+
L
GLI/PYY
r
+
+
+
+
+
A
PP
B
ECL
G
CCK
S
GIP
M
N
Glucagon
PP
Insulin
Histamine
Gastrin
CCK
Secretin
GIP
Motilin
Neurotensin
+
+
+
f
f
+
+
+
+
+
+
+
r
+
+
+
+
+
r
r
r
+
Rindi et al., Digestion 2000, 62(S1):19
GASTROENTERPANCREATIC ENDOCRINE TUMORS
cell type, site and possible hyperfunctional syndromes
Intestine
Tumor
Type
Main
Cell Type
Stomach
Pa CF An
Well
Differentiated
B
A
PP
(?)
D
EC
ECL
G
L
+
+
+
+
+
+
Poorly
Differentiated
+
+
+
+
+
Small
D J
I
+
+
+
+
+
+
+
Ap
C
Large Possible
R
Syndrome
+
+
+
+
+
+
+
+
+
+
+
+
+
PHH
glucagonoma
WDHA
somatostatinoma
“carcinoid”
“atypical carcinoid”
ZES
-
+
+
+
+
-
Rindi et al., Digestion 2000, 62(S1):19
DES TUMORS
GENERAL CATEGORIES
WELL DIFFERENTIATED endocrine neoplasia
1 - tumor (carcinoid)
2 - carcinoma (malignant carcinoid)
POORLY DIFFERENTIATED endocrine carcinoma
3 - Small or large cell carcinoma
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
Well differentiated
tumors
Structural patterns
Trabecular
MARKER EXPRESSION
IN TUMORS OF THE DIFFUSE
ENDOCRINE SYSTEM
Well differentiated endocrin neoplasm
General Markers
CgA INTENSE AND DIFFUSE
Syn
“
“
NSE
“
“
PGP9.5
“
“
various
CgA
Specific Markers
VARIABLE
PP
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
Diffuse hyperplasia
Gastric ECL cells
Dysplasia
Micronodular hyperplasia
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
“
“
Syn
Specific markers
Various
ABSENT
PGP9.5
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.
Poorly differentiated : 3 cases
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
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 PROPOSAL
PANCREAS
Size increase
Mets presence