Pancreatic endocrine tumors (PETs) are a group of predominantly well-differentiated neuroendocrine tumors that arise in the pancreas and surrounding tissues. They demonstrate diverse clinical presentations depending on the hormone secreted but share common imaging features of appearing as hypervascular masses. Larger PETs tend to be heterogeneous while smaller ones are often homogeneous. Imaging plays a key role in diagnosis, staging, and treatment planning. While prognosis depends on factors like size and metastasis, PETs generally have an indolent course amenable to various palliative options.

1. Pancreatic Endocrine Tumors:
imaging
PRESENTER:Dr.Vishwanath Patil
Moderator:Dr.Shilpa P R

2. • Pancreatic endocrine tumors (PETs) are predominantly well-differentiated
pancreatic or peripancreatic tumors that demonstrate endocrine
differentiation.
• They may manifest at any age, but they most often occur in the 4th– 6th
decades of life.

3. General Imaging Features
• US Studies:
• Heterogeneous or homogeneous, and when contrast material is
administered, they demonstrate a hypervascular pattern.
• Evidence of malignancy includes enlarged peripancreatic lymph nodes and
liver metastases.
• Liver lesions typically are hyperechoic, although they may be hypoechoic
or have a target like appearance.

4. • CT Studies:
• PETs appear as circumscribed solid
masses that tend to displace
surrounding structures.
• They typically are hyperattenuating
on arterial and venous phase images,
a finding due to their rich capillary
network.
• Smaller lesions tend to be more
homogeneous, and larger lesions are
more likely to demonstrate
heterogeneous enhancement, a
finding due to areas of cystic
degeneration, necrosis, fibrosis, and
calcification.

5. • Lymph node and liver metastases also are hypervascular and therefore
more conspicuous on arterial phase images.
• Hepatic metastases often demonstrate ring like enhancement.
• Arterial involvement, a characteristic important for staging and treatment,
may be evaluated with the use of multiplanar reformation of arterial
phase images.
• Venous encasement and invasion are better depicted on images obtained
in the portal venous phase.

6. MR Imaging Studies
• A normal pancreas demonstrates high signal intensity on T1-weighted
images.
• PETs appear as relatively hypointense, round or oval, circumscribed
masses on T1-weighted images, both with and without fat saturationS,
and most PETs demonstrate signal intensity much higher than that of a
normal pancreas on T2-weighted images.
• They may demonstrate ringlike and heterogeneous enhancement typically
are seen in larger lesions with cystic or necrotic areas.

7. • Liver metastases usually are hypointense on T1-weighted images and
hyperintense on T2- weighted images, and they often are well seen on T2-
weighted images obtained with fat suppression.
• They demonstrate moderate to intense early ringlike enhancement.
Involved peripancreatic lymph nodes also demonstrate prominent
enhancement.

8. Nuclear Medicine Studies
• Nuclear medicine imaging may be used to localize a known functioning PET in a
patient with a specific clinical syndrome, narrow the differential diagnosis of a
pancreatic mass, evaluate for metastatic disease or recurrence, and assess
receptor status for possible radionuclide-based treatment.
• However, for most of these techniques, the PET must be well-differentiated and
contain somatostatin receptors.
• Out of the five known types of somatostatin receptors, type 2 is the most
common.
• The most frequently used technique is somatostatin-receptor scintigraphy with
indium-diethylenetriaminepentaacetic acid-octreotide 111 (111In-octreotide).
• Overall, the sensitivity of this method is at least 80%, although it varies depending
on the specific hormone produced by the tumor.

9. • Sensitivity of this technique is highest for
gastrinomas,and it is lowest (50%–70%) for
primary insulinomas,although metastatic
lesions often demonstrate uptake.
• When octreotide is conjugated with the chelator
tetraazacyclododecanetetraacetic acid (DOTA), it
may be labeled with various radionuclides for
imaging and therapy.
• DOTA-octreotide may be modified with the
addition of tyrosine to form DOTA-tyrosine-3-
octreotide (DOTATOC), which demonstrates a
higher affinity for somatostatin receptor subtype
2.
• Sodium iodide may be added to form DOTA-1-
NaI-octreotide (DOTA-NOC), which
demonstrates a higher affinity for subtypes 2, 3,
and 5

11. Specific Clinical and Imaging Feature

12. Insulinoma
• Insulinomas are the most common functioning PET, accounting for just over 40% of
all functioning PETs.
• They tend to manifest earlier and have a smaller size(90% of tumors being smaller
than 2 cm). So insulinomas have the best prognosis.
• Insulinomas usually are sporadic, but they account for 10%–30% of functioning
PETs in patients with MEN1 and they have been reported in patients with
neurofibromatosis type 1.
• They have a slight female predominance (female-to male ratio, 1.4:1), and the
mean age at presentation is 47 years.
• A low fasting serum glucose level in conjunction with a high serum insulin level
and an elevated serum C-peptide level, which excludes an exogenous source
of insulin, may confirm the diagnosis.

13. CT and MR imaging, insulinomas
• Typically are homogeneous and
hyperenhancing.
• The use of coronal images may
help differentiate these small
hyperenhancing lesions from
nearby vasculature.
• Heterogeneous enhancement
from cystic change or necrosis is
rare and usually is seen in lesions
that are larger than 2 cm .
• Large lesions (those >3 cm) may
demonstrate malignant behavior,
with metastases most often seen
in peripancreatic lymph nodes.

14. • The advantages of CT over
endoscopic US include a lack of
invasiveness, less operator
dependence, and improved
detection of liver metastasis.

15. Gastrinoma
• Zollinger and Ellison reported a triad of peptic ulcers in unusual locations (such as
the postbulbar duodenum and jejunum) in the presence of gastric acid
hypersecretion and a PET.
• Gastrinomas are the second most common functioning PET.
• The peak incidence is in the 5th decade of life and there is a slight male
predominance.
• Most common functioning PET in patients with MEN1.
• Around 60% of gastrinomas demonstrate malignant behavior.
• Serum gastrin levels often are markedly elevated at over 1000 pg/mL (normal
level, <100).
• When a gastrinoma is present, it stimulates the release of gastrin from gastrinoma
cells. A rise of 200 pg/mL from baseline is 90% sensitive and specific for
gastrinoma.

16. • Gastrinomas often arise in the gastrinoma
triangle.
• They are more common in the duodenum than in
the pancreas; around 80% of sporadic lesions
and 90% of lesions associated with MEN1
originate from the duodenum.
• Pancreatic gastrinomas have an average
diameter of 3–4 cm, and most are located in the
pancreatic head.

17. • Homogeneous or ringlike
enhancement, common findings of
gastrinoma.
• Gastrinomas have a high
concentration of somatostatin
receptors, a characteristic that
enables localization of small.
• Duodenal gastrinomas usually are
less than 1 cm in diameter, and they
often are multicentric, especially in
patients with MEN1.
• Endoscopic US is useful in evaluating
small lesions in the duodenal wall
and peripancreatic lymph nodes.

18. Glucagonoma:
• Glucagonomas are the third most common functioning PET and they are rare, with
an incidence of one in 20 million people per year.
• Glucagonoma usually occurs in those who are between 40 and 60 years of age
(range, 19–84 years), and it has an equal sex distribution.
• Most glucagonomas demonstrate malignant behavior, and about three-quarters
ultimately are fatal.
• Although they have been reported in the duodenum, most glucagonomas
originate from the pancreas, usually the body or tail.
• The diagnosis often is delayed, and most primary tumors have a diameter larger
than 5–6 cm.

19. Glucagonoma
• At CT and MR imaging, they may
demonstrate homogeneous or
heterogeneous enhancement with
areas of hypoattenuation or
hypointensity .
• As many as 80% of glucagonomas
larger than 5 cm demonstrate
malignant behavior, and 50%–60% of
patients have liver metastases at the
time of presentation.

20. Vipoma
• Vipomas are rare functioning PETs with clinical symptoms caused by the
secretion of VIP, a peptide not normally secreted by pancreatic islet cells.
• VIP was suggested as the causative agent of this syndrome. VIP acts on cyclic
adenosine monophosphate within the bowel epithelium to inhibit the
absorption of and stimulate the secretion of water and electrolytes into the
lumen.
• Vipomas usually manifest in the 5th–6th decades.
• An elevated fasting serum VIP level, usually more than 100 pg/mL, is
highly specific for vipoma.
• Commonly intrapancreatic(74%).

21. Imaging finding Vipomas
• Pancreatic vipomas most frequently
occur in the pancreatic tail.
• Their mean size at diagnosis is just
over 5 cm.
• Smaller lesions may demonstrate
homogeneous enhancement, and
cystic change and calcification may
be seen in larger masses.
• Most vipomas demonstrate
malignant behavior, with metastases
present in 60%–80% of patients at
the time of presentation.

22. Somatostatinoma.
• <2% of all well-differentiated PETs.
• The mean age at presentation is 50 years, and there is an equal sex
distribution.
• Frequently occur in the pancreas or periampullary region of the
duodenum. Duodenal somatostatinomas are more likely to be associated
with neurofibromatosis type 1.
• Somatostatin inhibits the intestinal absorption and release of insulin,
glucagon, gastrin, and pancreatic enzymes, which may lead to diabetes
mellitus, steatorrhea, diarrhea, cholelithiasis, hypochlorhydria, and weight
loss.
• Many somatostatin-secreting PETs are discovered incidentally or as a
result of symptoms of mass effect, such as abdominal pain.

23. • Somatostatinomas, just under one-
half were found in the pancreas, with
most of the remainder occurring in
the duodenum, near the ampulla of
Vater .
• Also have been reported in the rest
of the small bowel, colon, and
rectum.
• In the pancreas, most occur in the
head, and the average size is 5–6 cm.
• The imaging characteristics of the
primary tumor are similar to those of
other PETs.
• Metastases are present at diagnosis
in 50%–75% of patients, usually in
the lymph nodes or liver.

24. Nonfunctioning PETs
• According to recent studies, the number of PETs with no clinical evidence of
hormone production is greater than that of functioning tumors.
• Many of these nonfunctioning tumors secrete pancreatic polypeptide or other
hormones, without associated clinical symptoms.
• The mean age at presentation was 55 years.
• Symptoms such as abdominal pain, weight loss, an abdominal mass, and, rarely,
jaundice are a result of mass effect.
• Nonfunctioning PETs are increasingly being found incidentally at imaging.
• Elevated serum chromogranin A levels are about 70% sensitive for the diagnosis of
a PET.

25. Imaging.
• On average, nonfunctioning PETs are
larger than functioning PETs,
especially insulinomas and
gastrinomas.
• Because of their large size, most
nonfunctioning PETs demonstrate
heterogeneity with areas of cystic
degeneration and necrosis at
imaging.
• Calcification also may be present.
They have an even distribution
throughout the pancreas, and diffuse
involvement of the entire pancreas is
rare.
• The frequency of metastatic disease
at the time of diagnosis has been
reported to be as high as 60%–80%.

26. Poorly Differentiated Endocrine
Carcinomas
• Also referred to as high-grade endocrine carcinomas are rare, accounting for less
than 2%–3% of all PETs.
• These tumors usually occur in older (middle-aged to elderly) men.
• When a poorly differentiated endocrine carcinoma is present, metastatic disease
to the pancreas and direct extension from the ampullary region should be
excluded.
• Jaundice may be a presenting symptom in patients with a lesion causing common
bile duct obstruction.
• Paraneoplastic syndromes such as Cushing syndrome, hypercalcemia, and
carcinoid syndrome have been reported in association with poorly differentiated
endocrine carcinoma.
• Poorly differentiated endocrine carcinoma is rapidly fatal, usually within less than
1 year.

27. Imaging
• FDG positron emission tomography
may be useful.
• The primary tumors were large, with
a mean diameter of 5.8 cm, and they
demonstrated minimal and
homogeneous enhancement,
mimicking pancreatic ductal
adenocarcinoma, lymphoma, and
metastatic disease.
• Associated with nodal or hepatic
metastases. In all cases, the primary
tumor had ill-defined margins, and in
the three cases that included arterial
phase imaging, heterogeneous or
rimlike hyperenhancement was seen.

28. Syndromes Associated with PETs
• Multiple Endocrine
Neoplasia Type 1:
• Typically, patients with MEN1 have
multiple microadenomas and
nonfunctioning PETs throughout the
pancreas .
• Most patients also have a functioning
tumor, most commonly a gastrinoma
(present in 60% of patients) or
insulinoma (present in 30% of
patients).

29. VHL Syndrome
• VHL syndrome are cystic lesions, with serous cystadenomas found in 17%–
56% of patients.
• PETs occur in 12%–17% of patients with VHL syndrome, usually in a subset
of patients with pheochromocytoma.
• Compared with patients with sporadic PETs, patients with VHL syndrome–
associated PETs present at a slightly younger age (mean age, 38 years).

30. Characterization and pre-therapeutic
staging
• Imaging has a major role in the staging, the diagnosis of a predisposition
syndrome.
• Grade or differentiation can be variable (G1—G3) based on Ki67 and mitotic count
and morphological architecture and represent the most important prognostic
factors.
• TNM and the extension of distant metastases especially in the liver constitute the
second most important prognostic factor.

31. Treatment and Prognosis
• In one study, the 3-year survival rate for patients with a PET was 82% for
those without hepatic metastases and 56% for those with hepatic
metastases.
• Poor prognostic factors for well-differentiated PETs include a size larger
than 2–4 cm, vascular or neural invasion, high mitotic rate, high Ki-67
index, necrosis, and chromosomal losses or gains.
• Because insulinomas usually are small with no necrosis or invasion,
patients with insulinoma have a better prognosis than those with other
PETs and an overall survival rate similar to that of the general population.
• Noninsulinoma PETs recur or metastasize in 50%–80% of patients, and
these patients have a 5-year survival rate of 50%–65%.
• Because these neoplasms often are slowly progressive, patients may
survive for many years, even after the development of metastases.

33. • Chemoembolization involves the injection of a mixture of vaso-occlusive
agents with either doxorubicin or adriamycin, a process that utilizes the
preferential hepatic arterial supply of hypervascular liver metastases.
• Radionuclide therapy may be used to treat tumors with somatostatin
receptors, the presence of which may be confirmed at 111In-octreotide
scintigraphy.
• Therapeutic agents may be administered intravenously or directly into the
hepatic artery and include a combination of octreotide, octreotate, or
lanreotide with DOTA and a radionuclide such as yttrium-90 or lutetium-
177.

34. Conclusions
• PETs are a group of neoplasms with diverse clinical findings but common imaging
features.
• Most are well-differentiated, circumscribed, and hypervascular at CT and MR
imaging, and they often demonstrate marked high signal intensity on T2-weighted
MR images.
• The use of nuclear medicine imaging such as 111In-octreotide scintigraphy and
new positron emission tomographic techniques may help confirm the presence of
somatostatin receptors and narrow the differential diagnosis.
• Use of these techniques also may enable receptor-guided treatment.
• With the exception of poorly differentiated tumors, PETs often have an indolent
course, and there are many palliative treatment options available such as medical
therapy, chemotherapy, surgical debulking, radiofrequency ablation, hepatic artery
chemoembolization, and radionuclide therapy.
• However, in patients with MEN1 or VHL syndrome, treatment is controversial
because multiple tumors often are present.

35. •Thank you