Beta cell tumors (insulinomas) are the most common type of PanNET and elaborate sufficient insulin to induce attacks of hypoglycemia when blood glucose levels fall below 50 mg/dL. These attacks manifest as confusion, stupor, and loss of consciousness. They are precipitated by fasting or exercise and are promptly relieved by feeding or parenteral administration of glucose. Most insulinomas are cured by surgical resection.
MORPHOLOGYThemajorityofinsulinomasareidentifiedwhiletheyaresmall(<2cmindiameter)andlocalizedtothepancreas.Mostaresolitarylesions,althoughmultifocaltumorsortumorsectopictothepancreasmaybeencountered.Malignancyininsulinomasoccursinlessthan10%ofcases,andisdiagnosedonthebasisoflocalinvasionormetastases.Onhistologicexamination,thebenigntumorslookremarkablylikegiantislets,withpreservationoftheregularcordsofmonotonouscellsandtheirorientationtothevasculature.Malignantlesionsalsotendtobewell-differentiatedandmaybedeceptivelyencapsulated.Depositionofamyloidisacharacteristicfeatureofmanyinsulinomas(
Fig.20.33 ).Undertheelectronmicroscope,neoplasticbetacells,liketheirnormalcounterparts,displaydistinctiveroundgranules.
Fig.20.33Pancreaticneuroendocrinetumor(PanNET),alsocalledislet cell tumor. Theneoplasticcellsaremonotonousinappearanceanddemonstrateminimalpleomorphismormitoticactivity.Thereisabundantamyloiddeposition,characteristicofaninsulinoma.
Marked hypersecretion of gastrin usually has its origin in gastrin-producing tumors (gastrinomas), which are just as likely to arise in the duodenum and peripancreatic soft tissues as in the pancreas (the so-called “gastrinoma triangle”). The Zollinger-Ellison syndrome refers to the association of pancreatic islet cell lesions with hypersecretion of gastric acid and severe peptic ulceration, present in 90% to 95% of patients with gastrinomas. Hypergastrinemia from a pancreatic or duodenal tumor stimulates extreme gastric acid secretion, which, in turn, causes peptic ulceration. The duodenal and gastric ulcers often are multiple; although they are identical to those found in the general population, they often are unresponsive to usual therapy. In addition, ulcers may occur in unusual locations such as the jejunum; when intractable jejunal ulcers are found, Zollinger-Ellison syndrome should be considered. More than one-half of affected patients have diarrhea; in 30%, it is the presenting manifestation.
MORPHOLOGYGastrinomasmayariseinthepancreas,theperipancreaticregion,orthewalloftheduodenum.Overone-halfofgastrin-producingtumorsarelocallyinvasiveorhavealreadymetastasizedatthetimeofdiagnosis.Inapproximately25%ofpatients,gastrinomasariseinconjunctionwithotherendocrinetumors,thusconformingtotheMEN-1syndrome(discussedlater);MEN-1–associatedgastrinomasfrequentlyaremultifocal,whilesporadicgastrinomasusuallyaresingle.Aswithinsulin-secretingtumorsofthepancreas,gastrin-producingtumorsarehistologicallyblandandrarelyexhibitmarkedanaplasia.
The adrenal glands are paired endocrine organs consist-consists of three layers of distinct cell types. Beneath the ing of two regions, the cortex and medulla, which differ capsule of the adrenal gland is the narrow layer of zona in their development, structure, and function. The cortex glomerulosa. An equally narrow zona reticularis abuts the http://ebooksmedicine.net