Patogenesis + patofisiology

Tumours of the endocrine pancreas may produce characteristic

clinical features because of the hormones they produce:
 ●  insulinoma – psychiatric/neurological symptoms
 ●  gastrinoma – Zollinger–Ellison syndrome
 ●  glucagonoma – diabetes mellitus and skin rash
 ●  VIPoma (watery diarrhoea, hypokalaemia and
achlorhydria (WDHA) syndrome.
Histology does not reliably predict behaviour  better
indicators of potential malignancy are functionality and
established metastases – insulinoma (85% benign), gastrinoma
(60–85% malignant), size > 3 cm, site (e.g., duodenal), invasion
of vessels, nodes, adjacent organs and liver.
 PANCREATIC ENDOCRINE
TUMOUR

Pancreatic NETs may or may not cause symptoms.

Pancreatic NETs may be functional (the hormones that are released cause symptoms)
or nonfunctional (the hormones that are released do not cause symptoms) tumors :
 Functional tumors make one or more hormones, such as gastrin, insulin, and
glucagon, that cause symptoms. Most functional tumors are benign (not cancer).
 Nonfunctional tumors make substances that do not cause symptoms. Symptoms are
caused by the tumor as it spreads and grows. Most nonfunctional tumors are
malignant (cancer).
Most pancreatic NETs are functional tumors.
Multiple endocrine neoplasia type 1 (MEN1) syndrome is a risk factor for pancreatic
NETs.
 Pancreatic endocrine neoplasms, also known as "islet cell tumors," are rare in
comparison with tumors of the exocrine pancreas, accounting for only 2% of all
pancreatic neoplasms.
 They are most common in adults, may be single or multiple, and benign or malignant,
the latter metastasizing to lymph nodes and liver.
 Pancreatic endocrine neoplasms have a propensity to elaborate pancreatic hormones,
but some may be totally nonfunctional.
 Like any other endocrine neoplasms, it is difficult to predict the biologic behavior of
a pancreatic endocrine neoplasm purely on the basis of light microscopic criteria.
 In general, tumors less than 2 cm in size tend to behave in an indolent manner, but
there are significant exceptions to this rule.
 The functional status of the tumor may have some important features on prognosis,
since approximately 90% of insulinomas are benign, while 60% to 90% of other
functioning and nonfunctioning pancreatic endocrine neoplasms tend to be malignant.
 Fortunately, insulinomas are also the most common subtype of pancreatic endocrine
noplasms.
 Insulinomas
 β-cell tumors (insulinomas) are the most common of
pancreatic endocrine neoplasms and may be responsible for
the elaboration of sufficient insulin to induce clinically
significant hypoglycemia.
 There is a characteristic clinical triad resulting from these
pancreatic lesions:
(1) attacks of hypoglycemia occur with blood glucose
amounts below 50 mg/dL of serum;
(2) the attacks consist principally of such central nervous
system manifestations as confusion, stupor, and loss of
consciousness; and
(3) the attacks are precipitated by fasting or exercise and are
promptly relieved by feeding or parenteral administration of
glucose.  reversible
True hypoglicemia with increased serum insulin and C-Peptide
 Insulinomas con’t ….
 Insulinomas are most often found within the
pancreas and are generally benign.
 Most are solitary lesions, although multiple
tumors or tumors ectopic to the pancreas may be
encountered.
 Bona fide carcinomas, making up only about 10%
of cases, are diagnosed on the basis of criteria for
malignancy listed above.
 Solitary tumors are usually small (often <2 cm in
diameter) and are encapsulated, pale to red-
brown nodules located anywhere in the pancreas.
 Histologically, these benign tumors look remarkably like
giant islets, with preservation of the regular cords of
monotonous cells and their orientation to the vasculature.
 Not even the malignant lesions present much evidence of
anaplasia, and they may be deceptively encapsulated. By
immunocytochemistry, insulin can be localized in the tumor
cells.
 Under the electron microscope, neoplastic β cells, like their
normal counterparts, display distinctive round granules that
contain polygonal or rectangular dense crystals separated
from the enclosing membrane by a distinct halo. It should
be cautioned that granules may be present in the absence
of clinically significant hormone activity.
 INSULINOMA

 Insulinomas are rare neuroendocrine tumours with an incidence estimated at 1 to

4 new cases per million persons per year. Insulinoma is one of the most common
types of tumor arising from the islets of Langerhans cells (pancreatic endocrine
tumors).
 Patients with insulinomas usually develop neuroglycopenic symptoms. These
include recurrent headache, lethargy, diplopia, and blurred vision, particularly
with exercise or fasting. Severe hypoglycemia may result in seizures, coma, and
permanent neurological damage. Symptoms resulting from the catecholaminergic
response to hypoglycemia (i.e. tremulousness, palpitations, tachycardia,
sweating, hunger, anxiety, nausea) are not as common. Sudden weight gain (the
patient can become massively obese) is sometimes seen.
INSULINOMA

Suppression tests
 Normally, endogenous insulin production is suppressed in the setting of
hypoglycemia. A 72-hour fast, usually supervised in a hospital setting, can be
done to see if insulin levels fail to suppress, which is a strong indicator of the
presence of an insulin-secreting tumour.
 During the test, the patient may have calorie-free and caffeine-free liquids.
Capillary blood glucose is measured every 4 hours using a reflectance meter,
until values < 60 mg/dL (3.3 mmol/L) are obtained. Then, the frequency of
blood glucose measurement is increased to every hour until values are < 49
mg/dL (2.7 mmol/L). At that point, or when the patient has symptoms of
hypoglycemia, a blood test is drawn for serum glucose, insulin, proinsulin, and
C-peptide levels. The fast is then stopped at that point, and the hypoglycemia
treated with intravenous dextrose or calorie-containing food or drink.
DIABETES MELLITUS

 Type 1 and type 2 DM

 Pancreas pathology : number and size reduction of islets
of Langerhans (type 1); amyloid deposition in islets of
Langerhans (type 2)
Basic pancreas

1. The pancreas is an endocrine and exocrine gland. Its

exocrine function is the production of the digestive
enzymes
2. The pancreas is divided into lobules that contain
acini. The acini connect to a duct system the
eventually forms the pancreatic duct, which empties
into duodenum
3. Secretin stimulates the release of a watery
bicarbonate solution that neutralize acidic chyme
4. Cholecystokinin and vagus nerve stimulate the
release of digestive enzymes
Water (H2O) and carbon dioxide
(CO2) combine under the
influence of carbon anhydrase
(CA) to form carbonic acid
Carbonic acid (H2CO3) dissociates
to form hydrogen ions (H+) and
bicarbonate ions (HCO3-)