Git endocrine tumors

1. By / Marwa Mahmoud Khalifa
Hematology resident
Internal medicine department

3. BACKGROUND
1969 (Pearse) described APUD cells (amine precursor
uptake and decarboxylation) cells that make polypeptides
and biogenic amines
Also called Kulchinsky or enterochromaffin cells
These cells have dense core secretory granules which
store and release hormones in response to external
stimuli
Are part of the diffuse endocrine system (DES)
Endocrine tumors of the gut and pancreas originate from
DES cells

5. Incidence
Incidence 1-2 in 100,000 population
Account for <2% of GI malignancies
Neuroendocrine tumors have a higher incidence
in patients >50 years old
Carcinoid of the appendix have a higher
incidence in patients age <30 years old

7. GENERAL CLASSIFICATION
1- Carcinoid Tumors
 25% foregut
 40-60% midgut (distal ileum and jejunum) (includes
carcinoid syndrome)
 15-35%hindgut (colon, rectum)
2-Endocrine Pancreatic Tumors
 60% Functioning (Zollinger Ellison, insulinoma,
glucagonomas, VIPomas, etc)
 Non-functioning (usually large and metastatic at the
time of diagnosis

8. 1-Endocrine Pancreatic Tumors
a-INSULINOMAS
Islet cell tumors
Most common type of NET
Usually present at age 40-50
More common in women
Secrete excess of predominantly insulin or less
commonly proinsulin
lead to the clinical syndrome of hypoglycemic
symptoms, low blood glucose, and relief with
administration of glucose, referred to as Whipple’s
triad. These symptoms are often exacerbated with
fasting and relieved by food consumption.

9. Clinical symptoms include sweating, tremors,
tachycardia, confusion, weakness
The majority of insulinomas are small (< 2cm),
solitary, benign (>90%) and uniformly distributed
throughout the pancreas.
CT, transabdominal ultrasound, and MRI have a
<50% sensitivity.
Endoscopic ultrasound has reported sensitivities up
to 80%. Arteriography with portal venous sampling
has sensitivity in the 80-90% range but is an invasive
procedure.

10. The most sensitive imaging technique is
intraoperative ultrasound, which localizes over 90%
of insulinomas.
10% of patients develop metastasis
Complete resection cures most patients

11. (CT) scan image with
oral and intravenous
contrast in a patient
with biochemical
evidence of
insulinoma. The 3-cm
contrast-enhancing
neoplasm (arrow) is
seen in the tail of the
pancreas (P) posterior
to the stomach (S)

12. Endoscopic
ultrasonogram in a
patient with an
insulinoma. The
hypoechoic neoplasm
(arrows) is seen in the
body of the pancreas
anterior to the splenic
vein (SV).

13. b-GASTRINOMAS
Over secretion of gastrin
Age at diagnosis ~50
More common in males (~60%)
About 75% occur sporadically while 25% are
associated with the MEN-1 syndrome.
Zollinger-Ellison Syndrome: atypical peptic ulcer
disease, gastric hyperacidity and hypersecretion,
associated with islet cell pancreatic tumors

14. The diagnosis of gastrinoma is confirmed by a basal serum
gastrin level >1000 pg/ml off proton-pump inhibitors.
A basal gastrin levels >250 pg/ml is suggestive and can be
confirmed with a secretion stimulation test and calcium
infusion test

16. CT, transabdominal ultrasound, and MRI only
detect <50% of lesions. Octreotide scanning has a
reported sensitivity of 80-90%
Metastasis in 60% of patients
Complete resection results in 10 year survival of
90%; less likely if large primary

17. (CT) scan of the
pancreas in a patient
with multiple endocrine
neoplasia syndrome
type 1 (MEN1) and a
gastrinoma. This image
shows a pancreatic
head mass (large,
white arrow), as well as
a low-attenuating lesion
in the liver (small, black
arrowhead) that
indicates metastases

18. c-GLUCAGONOMAS
Present in the fifth decade of life with an even gender
distribution.
~70% are malignant
Metastasis in >60% patients
Glucagonomas tend to be solitary and are more
commonly occur in the body and tail of the pancreas.
cause the “4D syndrome”: diabetes, dermatitis, deep
vein thrombosis, and depression.
Others :cheilitis, anemia, weight loss,
hypoaminoacidemia, and other neuropsychiatric
symptoms

19. •A characteristic rash called
necrolytic migratory erythema
seen in the face, lower
abdomen, perineum, and
lower extremities.

21. The diagnosis is made by a serum glucagon level
of > 500 pg/ml
very large at the time of presentation (>5 cm)
CT or MRI often detects the lesion. Octreotide
scanning has a sensitivity exceeding 75%.
 A distal pancreatectomy is usually the operation of
choice for these tumors without evidence for
metastatic disease

22. d-VIPOMAS
Over secretion of VIP( Vasoactive Intestinal
Peptide)
also called pancreatic cholera or Verner-Morrison
syndrome
Causes the “WDHA syndrome”: watery (secretory)
diarrhea, hypokalemia, and achlorhydria.
Others : abdominal pain, flushing, muscle weakness,
and weight loss
80% are associated with the pancreas
Metastasis occurs in ~70% of patients
The diagnosis is made by a serum VIP level > 200
pg/ml.

23. e-SOMATOSTATINOMAS
Cholelithiasis, DM, diarrhea, weight loss, steatorrhea
An elevated somatostatin level (>10 ng/ml) confirms
the diagnosis
The median age at diagnosis is 50, and gender
distribution is equal
65-70% of these tumors are located in the pancreas
(two-thirds in the head )
extrapancreatic tumors are located in the duodenum,
ampulla, or remaining small bowel

24. very large (> 5cm) at the time of presentation
localized with CT or MRI. Octreotide scanning is also
highly sensitive
Metastasis in ~50% patients
Complete resection with 5 year survival of 95% and if
has metastasis the 5 year survival decreases to 60%

25. f- Pancreatic Polypeptide-Secreting Tumor
(Ppoma)
The function of pancreatic polypeptide is not
completely understood. Patients present with weight
loss, jaundice, and abdominal pain.
The diagnosis is confirmed by pancreatic polypeptide
levels > 300 pg/ml.
very large at the time of presentation seen in CT or
MRI.
Octreotide scanning is also sensitive
 Surgical resection is the only chance for cure

26. g-Non-Functional Islet Cell Tumors
Histologically resemble other NETs but do not
secrete biologically active substances that result in a
detectable clinical syndrome
Most of these tumors, however, secrete chromogranin
A which can be detected in the serum and thus
confirm the diagnosis.
 Most patients present with abdominal pain or other
vague symptoms
diagnosed by CT or MRI
very large at the time of presentation (>6cm)
>50% are malignant.

27. SOMATOSTATIN ANALOGS
Used since 1980’s
Hormone blocking agents that are synthetic
somatostatin derivatives (ex: octreotide and
lanreotide)
First line of treatment for neuroendocrine
gastroenteropancreatic tumors
2nd
-3rd
line for insulinomas and gastrinomas
Side effects: development of gallstones secondary
to inhibition of cholecystokinin release, pain at
site, hypo or hyperglycemia, rash, alopecia, fluid
retention

29. 2-Carcinoid Tumours
arise in the thymus, bronchi and throughout the
gastrointestinal tract,
most commonly observed in the small bowel.
derived from Kulchinsky or enterochromaffin cells,
present due to local mass effects, e.g. small bowel
obstruction, appendicitis, pain from hepatic
metastases, or because of symptoms related to
hormone excess.

30. This includes ectopic secretion of ACTH, causing
Cushing's syndrome , or 5-HT, causing 'carcinoid
syndrome'.
 Carcinoid syndrome only occurs when the
vasoactive hormones reach the systemic circulation.
 In the case of gastrointestinal carcinoids, this
invariably means that the tumour has metastasised to
the liver, as hormones secreted by the primary
tumour into the portal vein are metabolised by the
liver

31. CLINICAL FEATURES OF THE
CARCINOID SYNDROME
Flushing
Wheezing
Diarrhoea
Facial telangiectasia
Cardiac involvement (tricuspid regurgitation,
pulmonary stenosis, right ventricular endocardial
plaques leading to heart failure

35. Gastric Carcinoid Tumors

36. Small Intestinal Carcinoid Tumors
The most common location 29%, with over half being in
the distal ileum.
 Patients typically present with symptoms of abdominal
pain or intestinal obstruction.
can create a characteristic fibrotic reaction in the
mesentery that may cause kinking of the bowel leading
to intermittent obstruction or intestinal ischemia.
slow growing ,prolonged disease course.
classic carcinoid syndrome is present in only 5% of
patients.
 spread to the lymph nodes (39%) or have distant
metastases (31%)

37. Appendiceal Carcinoid Tumors
The majority of appendiceal carcinoids are diagnosed
incidentally during surgery.
Over half of patients with appendiceal carcinoids
present with signs and symptoms suggestive of acute
appendicitis.
The prognosis of appendiceal carcinoids is very good.
The 5-year survival is 94% for local disease, 85% for
regional metastasis, and 34% when distant metastases
are present.

38. Colonic Carcinoid Tumors
 rare
typically present during the seventh decade of life.
more frequent in women
present with abdominal pain being the most common
complaint.
 large and are most commonly located in the right
colon.
 At the time of diagnosis, approximately 44 % have
spread to the lymph nodes and 38% have spread to
distant locations.
 The overall 5 year survival of these lesions is 25-41%.

39. Rectal Carcinoid Tumors
50% of these tumors are diagnosed incidentally on
routine endoscopy.
The size of these tumors is closely correlated to their
risk of metastasis as well as their survival.
 The five year survival rates for these patients is 81% if
there is only local disease, 47% if regional metastasis
are present, and 18% if distant metastases are found.

40. DIAGNOSTIC PROCEDURE
Biopsy  Immunohistochemistry
Stain for serotonin if suspect carcinoid

41. Anatomic Imaging: CT
Std
Venous Delayed
Arterial
Imaging studies property of James Yao, MD. CT: computed tomography.

45. MRI = magnetic resonance imaging
Imaging studies property of James Yao, MD.

46. Imaging studies property of James Yao, MD.

47. THERAPY
Endoscpic surgery for small tumors.
Surgery
Hormonal therapy
Distant metastases :palliative