Multidisciplinary GI Conference
10.25.07
Case Presentation
• 62 yo wf with two major acute GI bleeds
• PMH history notable for:
– Hodgkin’s lymphoma treated with mantle radiation
– Breast cancer, s/p mastectomy
– S/p AoV replacement, MV repair, CABG 1 year ago
– S/p appendectomy and tubal ligation
– Smoker
Case Presentation
Upper endoscopy and colonoscopy negative
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Capsule
Mass in the jejunum
Intraoperative Endoscopy (sort of)
Path Summary in the Case
• Two foci of carcinoid tumor (0.8 cm and 0.5 cm)
• Both tumors involve submucosa
• No angiolymphatic invasion
• 4 mesenteric lymph nodes negative
GI Carcinoid Tumors:
Overview
True or False:
Carcinoid tumors are so called
because they are responsible for
“carcinoid syndrome”
True or False:
Carcinoid syndrome is caused by
overproduction of serotonin
“Carcinoid”
It’s like a carcinoma,
….but it’s NOT a carcinoma
Carcinoid
Pathologic Definition: well-differentiated
neuroendocrine tumor of the dispersed endocrine
system (i.e., outside of endocrine organs)
Neuroendocrine Tumors
Neuroendocrine tumors come in two varieties:
a) tumors of the endocrine organs (pancreas, adrenal)
b) tumors of the dispersed endocrine cells
( GI tract, bronchopulmonary, C cells of
the thyroid)
“Carcinoid” refers to neuroendocrine tumors of the dispersed
endocrine system ONLY
Classification of NE Tumors
• Well-differentiated NE tumors = Carcinoids
Benign behavior or uncertain malignant potential
• Well-differentiated NE carcinomas (atypical
carcinoids)
Low-grade malignancy
• Poorly differentiated NE carcinomas (usually
small cell)
High-grade malignancy
GI Carcinoids
• Well-differentiated NE tumors = Carcinoids
Benign behavior or uncertain malignant potential
• Poorly differentiated NE carcinomas (small cell)
High-grade endocrine neoplasm
Classification of NE Tumors
GI TRACT
• Well-differentiated NE tumors = Carcinoids
Benign behavior or uncertain malignant potential
• Poorly differentiated NE carcinomas (small cell)
High-grade endocrine neoplasm
GI Carcinoids
• Easily recognized, well-defined shared morphologic
features
• Tumor’s cell type corresponds to distribution in the GI
tract of its normal counterpart
• Morphology, hormone production, and behavior can be
predicted by tumor’s location
• Many are associated with known risk factors
GI Carcinoids
Morphology
• Located in mucosa and submucosa
• Arise at the base of the crypts
• Nested growth pattern (insular, acinar, trabecular)
• Small uniform cells
• Round regular nuclei
• Finely stippled “salt & pepper” chromatin
• Lack of prominent nucleoli and mitotic activity
• Stain with neuroendocrine markers
GI Carcinoids
IHC
Shared Neuroendocrine Markers
Chromogranin
Synaptophysin
Specific Neuroendocrine Hormones
Gastrin (G cells)
Somatostatin (D cells)
Serotonin (EC cells)
Glucagon (L cells)
GI Carcinoids
Prediction of Behavior
Size is the best indicator
Smaller than 1 cm unlikely to spread
Larger than 2 cm usually aggressive
Other
Brisk mitotic rate
Necrosis
Deep invasion
Site (small bowel)
GI Neuroendocrine Cells
Distribution
Gastric body: ECL (enterochromaffin-like) cells
Histamine
Antrum and Duodenum: G cells
Gastrin
Duodenum: D cells
Somatostatin
Bowel: EC (enterochromaffin) cells
Serotonin
Stomach and bowel: L cells
Enteroglucagon
GI Carcinoid as:
distinct individuals
• Foregut carcinoids
Gastric, duodenal
• Midgut carcinoids
Ileal/Jejunal
Appendiceal
• Hindgut carcinoids
Rectal
Behavior of GI Carcinoids by Site
• Foregut carcinoids
Gastric (10%), duodenal (<5%). Generally low malignant
potential
• Midgut carcinoids
Ileal/Jejunal (25%). 60% malignant
Appendiceal (40%). 1% malignant
• Hindgut carcinoids
Rectal (20%), 15% malignant
Foregut Carcinoids:
Gastric
• Type I High Gastrin State
• Type II High Gastrin State
• Type III
What are the causes of high gastrin levels?
• Type I Atrophic Gastritis, Autoimmune Gastritis
• Type II ZE, MEN (type 1)
ECL cells develop into carcinoids after chronic stimulation
by high gastrin levels
Clinical course is usually indolent (if <1 cm)
Type I Carcinoids
Small, multiple, polypoid;
QuickTime™ and a
May have central ulceration
TIFF (Uncompressed) decompressor
are needed to see this picture.
Foregut Carcinoids, cont.:
• Type III. Gastrin-independent
Sporadic
Account for 20% of gastric carcinoids
Most aggressive
Metastatic in 60% at resection
May produce 5-HT and cause carcinoid syndrome
Appendiceal Carcinoids
• Typically benign course
• 1/300 appendices contains a carcinoid tumor
• Often found incidentally
• Goblet cell carcinoid variety makes serotonin and is more aggressive
Small Bowel Carcinoids
• Most aggressive
• May present with obstruction or abdominal pain due to
intussusception, mechanical effect of the tumor, or mesenteric
ischemia due to local fibrosis or angiopathy
• Carcinoid syndrome present in up to 10% patients
• Multiple tumors in up to 30% of patients (worse prognosis)
Colon Carcinoids
• Usually right colon, particularly cecum
• Carcinoid syndrome is rare
Rectal Carcinoids
• Size correlates with metastases: <1 cm - rare; > 2 cm (>70%)
• Carcinoid syndrome is rare
• Local excision of small carcinoids
• Extensive excision of larger (similar to adenocarcinoma)
• Controversial for > 1 cm, < 2 cm
Carcinoid Syndrome
•Diversion of tryptophan to serotonin can
result in tryptophan and nicotinic acid
deficiency (pellagra)
•Serotonin causes diarrhea
•Serotonin stimulates fibroblast growth
and fibrogenesis
QuickTime™ and a •Serotonin does NOT cause flushing
TIFF (Uncompressed) decompressor
are needed to see this picture. •Flushing may be caused by histamine
and kallikrein
•Liver inactivates bioactive products;
thus carcinoid syndrome does not happen
in absence of liver mets (or non-GI
carcinoids)
•Most useful initial test is 24-hour urine
5-HIAA excretion