Multidisciplinary GI Conference 10'25'07

1
Multidisciplinary GI Conference10.25.07
2
Case Presentation

• 62 yo wf with two major acute GI bleeds
• PMH history notable for
• Hodgkins 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

3
Case Presentation

• Upper endoscopy and colonoscopy negative

4
(No Transcript)
5
Capsule
Mass in the jejunum
6
Intraoperative Endoscopy (sort of)
7
(No Transcript)
8
(No Transcript)
9
(No Transcript)
10
(No Transcript)
11
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

12
GI Carcinoid Tumors Overview
13
True or False Carcinoid tumors are so called
because they are responsible for carcinoid
syndrome
14
True or False Carcinoid syndrome is caused by
overproduction of serotonin
15
Carcinoid

• Its like a carcinoma,
• .but its NOT a carcinoma

16
Carcinoid

• Pathologic Definition well-differentiated
  neuroendocrine tumor of the dispersed endocrine
  system (i.e., outside of endocrine organs)

17
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

18
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

19
GI Carcinoids

• Well-differentiated NE tumors Carcinoids
• Benign behavior or uncertain malignant potential
• Poorly differentiated NE carcinomas (small cell)
• High-grade endocrine neoplasm

20
Classification of NE TumorsGI TRACT

• Well-differentiated NE tumors Carcinoids
• Benign behavior or uncertain malignant potential
• Poorly differentiated NE carcinomas (small cell)
• High-grade endocrine neoplasm

21
GI Carcinoids

• Easily recognized, well-defined shared
  morphologic features
• Tumors cell type corresponds to distribution in
  the GI tract of its normal counterpart
• Morphology, hormone production, and behavior can
  be predicted by tumors location
• Many are associated with known risk factors

22
GI CarcinoidsMorphology

• 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

23
GI CarcinoidsIHC

• Shared Neuroendocrine Markers
• Chromogranin
• Synaptophysin
• Specific Neuroendocrine Hormones
• Gastrin (G cells)
• Somatostatin (D cells)
• Serotonin (EC cells)
• Glucagon (L cells)

24
GI CarcinoidsPrediction 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)

25
GI Neuroendocrine CellsDistribution

• 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

26
GI Carcinoid asdistinct individuals

• Foregut carcinoids
• Gastric, duodenal
• Midgut carcinoids
• Ileal/Jejunal
• Appendiceal
• Hindgut carcinoids
• Rectal

27
Behavior of GI Carcinoids by Site

• Foregut carcinoids
• Gastric (10), duodenal (lt5). Generally low
  malignant potential
• Midgut carcinoids
• Ileal/Jejunal (25). 60 malignant
• Appendiceal (40). 1 malignant
• Hindgut carcinoids
• Rectal (20), 15 malignant

28
Foregut CarcinoidsGastric

• Type I High Gastrin State
• Type II High Gastrin State
• Type III

29
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 lt1 cm)

30
Type I Carcinoids
Small, multiple, polypoid May have central
ulceration
31
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

32
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

33
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)

34
Colon Carcinoids

• Usually right colon, particularly cecum
• Carcinoid syndrome is rare

35
Rectal Carcinoids

• Size correlates with metastases lt1 cm - rare gt
  2 cm (gt70)
• Carcinoid syndrome is rare
• Local excision of small carcinoids
• Extensive excision of larger (similar to
  adenocarcinoma)
• Controversial for gt 1 cm, lt 2 cm

36
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
• Serotonin does NOT cause flushing
• 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