Cystic neoplasm and Endocrine tumors of

pancreas

Presenter : Dr. Fuzail Ahmad

Guide : Dr. Ravishankar N.

Dr. Benak S.
 Pancreas
• It is a retroperitoneal organ just anterior to first lumbar vertebra
that lies in an oblique position, sloping upward from the C-loop
of the duodenum to the splenic hilum.
• Weighs around 75-125g and measures 10-20cm.
• Anatomically divided into five parts – head, uncinate, neck,
body and tail.
• The exocrine pancreas accounts for about 85% of the pancreatic
mass; 10% of the gland is accounted for by extracellular matrix, and
4% by blood vessels and the major ducts, whereas only 2% of the
gland is comprised of endocrine tissue.
Relations of pancreas
Blood supply
Lymphatic drainage
Cystic Neoplasm of Pancreas
Cystic neoplasms have become a well defined radiographic entity.
With increasing use of cross sectional imaging, nearly 2.6 % cystic
lesion of pancreas are encountered per year.

Differential includes non-neoplastic pancreatic pseudocysts and

cystic neoplasms.
 Serous Cystadenoma
• Mean year of presentation – 60s, F:M 7:3
• These are essentially considered benign tumors with extremely
rare malignant potential (<1 %).
• 50% of these cases remain asymptomatic. Most symptomatic
patients have mid upper abdominal pain, epigastric fullness or
moderate weight loss.
• SCA present with variable size, when >10cm may cause
symptoms from local compression. Can be seen at all regions
of pancreas.
• Gross appearance : variable size, spongy appearance, multiple
small cysts
• Imaging characteristics : microcystic characteristic honey-comb
pattern, stellate scars
• Histological features : Clear cytoplasm, well-defined borders
with uniform nuclei. Glycogen-rich cells.
• Cyst fluid analysis : Low viscosity, low CEA and Amylase levels.
 Mucinous Cystic Neoplasm
• Mean age of presentation : 45-55. F:M : >10:1
• MCNs are mucin-producing cystic tumors that lack
communication with the pancreatic duct and contains mucin
producing columnar epithelium.
• Encompasses spectrum of range from benign to potentially
malignant to carcinoma with aggressive behaviour.
• Pancreatic MCNs are most commonly found in the body and tail
and ranges in size from small 2cm to large 25cm.
• Any macrocystic lesion in the distal pancreas of a female
should be considered highly suspicious of MCN.
• Gross appearance : Large size, multilocular, thick walled. May
have nodules or calcifications within the wall of cysts.
• Imaging characteristics : Macrocystic, doesn’t communicate
with duct and peripheral “eggshell” calcification. Malignancy
associated features are – presence of septations, larger size,
and mural nodularity.
• Histological features : Tall columnar mucin producing
epithelium. Ovarian type stroma(spindle cells with elongated
nuclei) is key pathologic feature.
• Cyst fluid analysis : High viscosity, elevated CEA, low amylase.
Variable cellularity with columnar cells with/out atypia.
 Intraductal papillary mucinous neoplasm
• IPMNs are epithelial tumors that arise from the main or branch
pancreatic ducts causing ductal dilatation from mucin
production.
• Mean year of presentation : 65-75, F:M 1:1
• IPMNs represent 15-30% of all the cystic neoplastic lesions of
pancreas.
• Usually seen at the head of pancreas.
• Presenting features are pain abdomen or recurrent
pancreatitis(due to obstruction of pancreatic duct by mucin).
• Some IPMNs primarily involve main pancreatic duct, while
others are known as branch-duct IPMN and mixed variant (both
main and branch ducts).
• Radiographic classification of IPMN into – 1) MD-IPMN 2)BD-
IPMN 3) MIXED VARIANT has formed backbone of
management paradigm as this subtype is the strongest
predictor of high-grade dysplasia.
• As many as 60% of MD-IPMNs are malignant (in-situ and
invasive malignancy).
• Genetics : GNAS mutation have been noted in as many as 66%
of the cases. KRAS, loss of p16 and TP53 are frequently
observed mutation as well.
• Histologically, the mucosa of IPMNs can express a range of
dysplasia (low, moderate and high grade dysplasia and
carcinoma).
• Gross appearance : Variable size, multilocular, involving main
or branch ducts of pancreas.
• Imaging characteristics : Macrocystic, ductal involvement.
• ERCP finding : mucin can be seen extruding from ampulla of
Vater giving a fish-eye appearance.
• Histological features : Papillary projections of columnar-lined
epithelium with varying dysplasia.
• Cyst fluid analysis : High viscosity, elevated CEA, high
Amylase.
 Solid Pseudopapillary
tumors
• Mean age of presentation 25. F:M – 9:1.
• Usually situated at Tail > Head of pancreas.
• Gross appearance : Irregular cystic cavities with hemorrhage.
• Imaging characteristics : Macrocystic, well-circumscribed with
irregular areas of hypodensity secondary to necrosis or
hemorrhage.
• Histological features : Solid sheets of variable cells. Hyaline
globules. Neuroendocrine features however do not stain
positive for markers such as chromogranin.
• Cyst fluid analysis : Bloody necrotic debris
 Management of pancreatic
cystic neoplasm
1) Serous Cystadenoma: Resection should be reserved for young patients
with lesions that have experienced significant growth or when lesion is clearly
symptomatic.

2) Mucinous Cystic Neoplasm : Due to the malignant potential of MCNs,

resection is recommended. MCNs are most often located in distal pancreas
and therefore distal pancreatectomy.
Patients with mucinous cystadenocarcinoma should undergo pancreatectomy
and post-operative surveillance.
3) Main duct and combined type IPMN : Operative resection is
recommended since these lesions have high risk of harbouring high-grade
dysplasia or invasive disease.
Resection of IPMN containing pancreas viz., pancreaticoduodenctomy for
head of pancreas and distal pancreatectomy for body and tail of pancreas
should be performed.

Post-operative surveillance is required in all cases. In absence of invasive

disease, radiological studies should be obtained every 6-12 months (low grade
vs high grade dysplasia).
Completion pancreatectomy is indicated for treatment of any undetected
recurrence thought to be representative of high grade dysplasia or invasive
disease.
4) Branch duct-IPMN : Resection is reserved when lesion includes a solid
component, mural nodule, septations, increasing size or size >3cm.

If the decision is made for non-operative management, protocol is to follow-up

with MDCT or MRI every 6 months for 2 years, after 2 years of demonstrable
stability, to be followed up annually.

5) Solid pseudopapillary tumors : Resection is indicated and patients are

generally cured by complete surgical extirpation. However, metastasis has
been reported in as many as 15% of patients.
 Pancreatic Neuroendocrine tumors
• PNETs are a group of rare, heterogenous neoplasms that were
earlier referred as islet cell tumors.
• It accounts for about 7% of all NETs and 1-2% of pancreatic
tumors.
• Their cellular origin is debated but it is likely to be from
pluripotent stem cells in pancreatic ductal/acinar system rather
than the islets themselves.
• Classified as – functional(if they cause a specific hormonal
syndrome) and non functional.
• Males and females are equally affected.
• Most patients are diagnosed between age of 60-80 years.
• Approximately 5% of patients have an underlying familial
syndrome predisposing to PNET development viz., MEN-1,
VHL, TS, NF-I and these patients present at younger age.
• In well differentiated PNETs, the most commonly mutated
genes are MEN1, DAXX/ATRX and mTOR.
• Poorly differentiated PNETs are clinically and genetically distinct
from well differentiated counterparts. Most common genes in
this group are p53 and Rb.
 Functional Tumors
1) Insulinoma : represent 1-2 % of all pancreatic tumors. It is the
most common functional pancreatic NET.
• They are typically small <2cm, solitary (except in MEN-1),
intrapancreatic, and cause symptoms of hypoglycemia.
• Whipple’s triad : Plasma glucose <40mg/dl, symptoms of
hypoglycemia, and resolution of symptoms with a meal.
• Diagnosis is made by drawing plasma glucose, insulin, C-
peptide and proinsulin levels during a 72 hour fast.
• Usually localised with CT and EUS.
• Evenly distributed throughout head, body and tail of pancreas.
• 90% of insulinomas are solitary and benign.
• 90% of insulinomas are sporadic, rest 10 % are associated with
MEN-1 syndrome and these are more likely to be multifocal
with higher rate of recurrence.
• They are typically cured by simple enucleation. However,
tumors located close to MPD and large >2cm may require a
distal pancreatectomy or pancreaticoduodenectomy.
2) Gastrinoma : Gastrin-secreting PNET is the second most
common functional endocrine tumors.
• Mean age of diagnosis is 50 years. Slightly more common in
males(60%), and are associated with MEN1 in 25% of cases.
• Patients with Gastrinoma or Zollinger-Ellison syndrome have a
fulminant peptic ulcer disease, acid hypersecretion, non-beta
islet cells tumors of pancreas.
• Hypergastrinemia results in peptic acid hypersecretion and
refractory peptic ulcer disease.
• Duodenal ulcers are most common, but jejunal ulcers may also
occur.
• 75% of patients present with abdominal pain, almost 2/3rd of
these individuals have diarrhoea, and in 10-20% diarrhoea is
the only symptom.
• This acid induced diarrhoea is stopped by nasogastric
aspiration of gastric secretions, differentiating it from other
secretory diarrhoeas.
• 1/3rd of the patients have signs and symptoms of GERD.
• These are usually solitary tumors unless seen in MEN-1, in
which case they are small, multiple and likely to be in
duodenum.
• Regardless of etiology, these are found to be in Gastrinoma
(Passaro’s triangle).
• Diagnosis : Fasting serum gastrin levels 10 times the normal
level(100pg/ml) coupled with a gastric pH <2 confirms the
diagnosis.
• If diagnosis remains in doubt, a secretin stimulation test is
done, wherein fasting gastrin levels are measured before
secretin (2IU/kg) is administered IV, and subsequently samples
obtained at 2, 5, 10 and 20 minutes after secretin
administration.
• Gastrin levels higher than 200pg/ml after administration are
noted in 87% of the patients.
• Having biochemically confirmed, CT and MRI is done for
localising the gastrinoma.
• The imaging test of choice is Octreotide scintigraphy in
combination with CT.
• EUS is another modality that helps in preoperative localisation
of gastrinomas, it is particularly helpful in localising tumors in
pancreatic head or duodenal wall, wherein gastrinomas are
usually <1cm in size.
• Serum calcium levels are checked to rule out MEN-1.
• Approximately, 50% of gastrinomas metastasize to lymph
nodes and are therefore considered malignant.
• Operative approach is indicated when curative resection
appears possible based on pre-op imaging or for palliative
cytoreduction for symptom control.
• The presence or absence of malignant disease is the most
important prognostic indicator. Liver metastasis being the best
predictor.
• Most gastrinomas require segmental resection, including distal
pancreatectomy or pancreaticoduodencectomy. Detailed
inspection of peripancreatic, periduodenal, portohepatic LNs
should be performed because resection of these positive LNs
increases disease free survival.
• More than 50% of cases present with metastatic disease – for
unresectable, symptomatic metastatic disease, treatment
should be focused on symptom control.
• Symptoms are controlled in more than 90% patients with high
dose of PPI (eg 60-80mg of Pantoprazole). PPI dose should be
titrated to keep basal acid output <10meQ/hr.
• Gastrectomy may be indicated for patients who are unable to
tolerate PPIs and cannot achieve acid secretion control through
other means.
3) Vasoactive intestinal peptide secreting NETs : Usually arise
from the pancreatic islet D2 cells and release high levels of VIP.
• The classic syndrome associated with this PNET consists of
severe intermittent watery diarrhoea, hypokalemia, achlorhydria
(WDHA) syndrome or pancreatic cholera.
• More than two-thirds are malignant and at the time of
presentation over 70% patients have metastatic disease.
• 90% of lesions are found in pancreas, rest 10% in the colon,
bronchus, liver, adrenal gland and sympathetic ganglia.
• Tumors are generally solitary, >3cm at diagnosis, usually found
at pancreatic body and tail.
• 95% are sporadic, rest 5 % are associated with MEN-1.
• Profuse, watery iso-osomotic diarrhoea is most common
presenting feature and it may exceed a volume of 3-5L/day.
• The diarrhoea persists despite fasting, which qualifies it as
secretory diarrhoea, and despite nasogastric aspiration which
differentiates it from ZES.
• Weight loss, crampy abdominal pain, dehydration, electrolyte
abnormalities and metabolic acidosis is common with VIPomas.
• The diagnosis is confirmed by VIP levels. Normal levels
<200pg/ml; VIPomas patient have levels 225-2000pg/mL.
• Treatment begins with aggressive pre-operative hydration and
correction of electrolyte abnormalities and acid base
disturbances.
• Formal anatomic resection with negative margins including
lymphadenectomy is needed in the setting of resectable
disease.
4) Glucagon secreting PNET – Two to threefold more common in
women. These tend to be larger, averaging 5-10cm at the time of
diagnosis.
• These tumors almost always arise in pancreas, 65-75% located
in tail or body of pancreas, corresponding to the normal
distribution of alpha cells in pancreas.
• Glucagonomas are malignant in 50-80% of cases.
• Most cases are sporadic, with only 5-17% being associated
with MEN-1.
• Classic presentation of the 4Ds : diabetes, dermatitis, deep vein
thrombosis and depression.
• Also characterised by a severe catabolic state with weight loss,
depletion of fat and protein stores, and associated with vitamin
deficiencies.
• The characteristic skin lesion, a necrolytic migrating erythema
often appears before other symptoms and is seen in 2/3rd of the
cases.
• Diabetes develops in 76-94% of patients but is usually mild.
• Diagnosis is established by measuring glucagon levels; normal
fasting glucagon levels <100pg/mL. A fasting glucagon level
>1000pg/mL is considered diagnostic.
• Treatment begins with medical therapy to improve nutritional
status with supplemental enteral nutrition.
• Octreotide is often needed alongwith basic caloric needs to
reverse the catabolic state. IV infusions of amino acids are
required to combat symptoms and improve dermatitis.
• Prophylaxis against thromboembolism is started early to
prevent DVT and PE.
• Complete anatomic resection is warranted for resectable
disease.
5) Somatostatin secreting PNET – These are exceedingly rare
with less than 100 cases reported so far.
• Patients present with steatorrhea, diabetes mellitus,
hypochlorhydria, and gallstones.
• In patients with diabetes, gallstones, and steatorrhea, with or
without finding of pancreatic mass on imaging, a fasting plasma
somatostatin level should be measured.
• >160pg/mL is diagnostic.
• These are usually solitary, >2cm. More than 60% are found in
pancreas, rest in duodenum or elsewhere in SI. 90% cases are
malignant and have metastasis at time of diagnosis.