Multihormonal Pancreatic Endocrine Tumor in a Dog with Duodenal Ulcers and Hypertrophic Gastropathy

Abstract

Pancreatic endocrine tumors in dogs are usually associated with hyperinsulinism and hypoglycemia.5 Gastrin-secreting tumors have been reported in a few dogs with a ZollingerEllison-like syndrome.' Multiple polypeptide hormones have been reported in a majority of human pancreatic endocrine tumors and recently in canine pancreatic endocrine tumors.8. 10 We report a pancreatic endocrine tumor with immunoreactivity for pancreatic polypeptide and insulin in a dog with a hypertrophic gastropathy and multiple duodenal ulcers.A 7-year-old7 spayed female cocker spaniel dog was presented with a history of frequent vomiting, inappetence, and severe weight loss. Clinicopathologic studies revealed hypoproteinemia (total protein, 3.2 g/dl), leukocytosis (44,400 celldpl), hypoglycemia (74 mg/dl), and metabolic alkalosis (pH 7.53, HCO, 27 mEq/liter). At necropsy, six round to oval, well-encapsulated nodules ranging in size from 0.5 to 2.0 cm were in the cranial lobe of the pancreas. Cut surface was white, firm, and partially lobulated. Mucosa of the pyloric region of the stomach contained numerous small raised nodules from 2 to 3 mm in diameter. Nineteen round to oval ulcers that eroded deep into the muscle layers were in the duodenum and were from 5 to 10 mm in diameter. Ulcers extended from the pylorus to the distal duodenum. In the liver there were multiple, round, white, circumscribed nodules scattered randomly throughout the parenchyma.Tissues for light microscopy were fixed in 10% neutral buffered formalin, embedded in paraffin, sectioned at 5 pm, and stained with hematoxylin and eosin (HE). Tissues selected for transmission electron microscopy were fixed in 3% glutaraldehyde, washed with phosphate buffer, and transferred to 1.0% osmium tetroxide, dehydrated in a graded series of alcohol solutions, and embedded in plastic blocks. Ultrathin sections were cut with a diamond knife, stained with uranyl acetate and lead citrate, and examined electron microscopically.Immunohistochemical analysis was done on formalin-fixed, paraffin-embedded tissues. Five-micron sections were placed on glass microslides with 15% white casein glue and dried overnight. Sections were deparaffinized with two changes of xylene followed by 100% ethanol and repeated for 2 minutes each, followed by a 2-minute rinse in distilled water and 30 minutes in 3% hydrogen peroxide-methanol to block endogenous peroxidase activity. Sections were rinsed three times with 0.0 1 M phosphate buffer solution (PBS) containing 0.15 M NaCl, pH 7.4 and placed overnight at 4 C in 10% normal serum-PBS derived from the same species as the bridge (secondary) antibody to reduce nonimmunologic binding of antiserum.For detection of polypeptides, sections were flooded with primary rabbit antiserum for 30 minutes at room temperature in a humidity chamber followed by immunoperoxidase staining utilizing the peroxidase-anti-peroxidase method. For detection of chromogranin, sections were flooded with primary mouse antiserum followed by reagents in the avidinbiotin peroxidase complex me...

CASE REPORT: Metastatic pancreatic polypeptide-secreting islet cell tumor in a dog

“…Gastrointestinal Helicobacter-like organisms may have been the underlying cause of the gastritis, but a cause and effect relationship between these bacteria and clinical signs is arguable. 11 Although gastrointestinal ulceration was not detected, unlike in the previously described case, 12,13 the possibility that PP contributed to the vomiting cannot be excluded. Hormone levels were not evaluated in this patient owing to lack of an appropriate specimen.…”

“…18 However, retrospective staining of the primary mass in this case with Congo red was negative for amyloid. Pancreatic islet cell tumors that only secretes PP are rare [12][13]15 ; to our knowledge, this is the third report in dogs. This case is unique in that the dog had signs that mimicked the presentation occasionally seen in human cases.…”

“…25 Electron microscopic examination of a canine islet cell tumor that secreted both PP and insulin demonstrated cytoplasmic granules that were membrane bound. 13 The granules observed may be secretory product. Amyloid was also considered as some human and canine neuroendocrine tumors stain positively for this material.…”

“…15 A tumor that secreted significant amounts of both PP and insulin, but with metastatic masses that produced solely PP, was described in 2 separate articles. 12,13 It is well known that islet cell neoplasms may produce hormones not normally secreted by these cells, including VIP, gastrin, adrenocorticotropic hormone, and chromogranins A and B. 4,12,16 Of the pancreatic islet cell tumors diagnosed in people and dogs, a considerable number are thought to produce more than 1 hormone.…”

“…4,12,16 Of the pancreatic islet cell tumors diagnosed in people and dogs, a considerable number are thought to produce more than 1 hormone. 12,13,[15][16][17][18] One retrospective study of canine islet cell tumors revealed that 28 of 31 pancreatic endocrine tumors produced more than 1 hormone, and, whereas most tumors predominantly produced insulin, PP was the second most common hormone present with 26 out of 31 tumors staining positively for PP. 18 Another study showed 4 of 18 multihormonal islet cell tumors with positive immunolabeling for PP.…”