09 - Pancreatic Endocrine Neoplasia

Question 1

(Pancreatic Endocrine Neoplasia)

1. Background: The endocrine pancreas is comprised of several different cell types, which are normally arranged in the pancreatic islets. Each of the endocrine cell types secretes one or more hormones. Cell types include

(say what each secretes)

β-cells

α-cells

δ-cells

PP-cells

In addition, the fetal pancreas contains cells that produce gastrin. Tumors of the endocrine pancreas may synthesize any of these hormones.

Answer 1

insulin and IAPP

glucagon

somatostatin

pancreatic polypeptide

Question 2

(Pancreatic Endocrine Neoplasia)

((Pancreatic Endocrine Neoplasia occurence))

(Dogs)

1. how common?
2. sex?
3. age?
4. carcinomas or adenomas more common?

(ferrets)

1. relatively common tumor which is often assocated with adrenal cortical adenomas/carcinomas
2. rarely reported in other species

Answer 2

1. rare in all (irish setters and boxers slightly higher)
2. no sex predilection
3. middle - elderly (peak at 9-10)
4. Carcinomas are more common than adenomas, with approximately half or more of canine pancreatic endocrine tumors exhibiting malignant behavior in the form of metastasis to regional lymph nodes or liver, or both.

Question 3

(Pancreatic Endocrine Neoplasia)

(Pathology)

1. macroscopically both carcinoma and adenoma appear how?
2. which are well delineated… adenomas or carcinomas?
3. –Microscopically tumors are typically composed of polyhedral cells that closely resemble normal cells of the pancreatic islets and are typically arranged in a solid (lobular) pattern in which broad columns of closely packed cells are separated by fibrovascular septa.
4. do most tumors secrete one hormone?

which is the most frequently detected hormone?

5. Tumors consisting predominantly of IAPP, PP, glucagon, or gastrin-immunoreactive cells also occur in dogs and ferrets.

Answer 3

1. gray-white to dull red, have a firm consistency, and may have a dense fibrous texture when cut
2. adenomas (well delineated from surrounding exocrine pancreas and are well enapsulated)

–Carcinomas are poorly delineated and show extensive invasion of the surrounding tissues.

4. secrete more than one

insulin (in a minority of cases is the only homrone demonstrable in primary tumors)

Question 4

(Pancreatic Endocrine Neoplasia)

4. Clinicopathologic Syndromes
   Despite the polyhormonal nature of most canine pancreatic endocrine tumors, the majority of these tumors present with a clinical syndrome primarily related to the overproduction or inappropriate secretion of one hormone. This feature gives rise to the clinical designations of insulinoma, glucagonoma, gastrinoma, etc.

(insulinomas)

1. typically presented with complaints attributable to hypoglycemia due to what?
2. clinical signs include what?

(glucagonomas)

1. rare in dogs but have been associated with what?

(Gastrinomas)

1. rare in dogs but have been associated with gastrin hypersecretion, causing gastric acid hypersecretion (Zollinger-Ellison syndrome) which includes diarrhea, vomiting, and esophageal, gastric, and/or duodenal ulceration, and hypertrophic gastritis
2. gastrinomas appear to be unique among canine pancreatic endocrine tumors in that they appear to be what?

Answer 4

1. inaapropriate/episodic insulin secretion
2. episodic muscle tremors and fasciculation, seizures, and coma
3. clinical syndrome of superficial necrolytic dermatitis (SND)
4. monohormonal

Question 5

(Pheochromocytoma)

1. These are neoplasms arising from the chromaffin cells of the what?

therefore functional pheochromocytoma can do what?

(occurence)

1. most common in what?
2. age?

(Clinical features)

1. –Signs referable to increased and episodic catecholamine release and include tachycardia, edema, cardiac hypertrophy, and hypertension.

what is the principle hormone released?

Answer 5

1. adrenal medulla

secrete catecholamines

1. dogs and cattle
2. dogs 6 years or older (higher in Boxer)
3. NE

Question 6

(Pheochromocytoma)

(Pathologic Features)

1. most often unitlateral
2. in dogs, what % show evidence of malignancy?
3. malignant tumors frequently invade what and extend into what?
4. metastates most often found where?
5. microscopically appear similar to what?
6. Tumor cells typically express neuroendocrine markers such as synaptophysin and chromogranin-A (as do pancreatic endocrine tumors and parathyroid tumors)
7. Catecholamines cannot be directly demonstrated by immunohistochemistry and therefore diagnosis is based upon location, histologic features (neuroendocrine tumor pattern) and expression of synaptophysin and/or chromogranin-A (which are not expressed in adrenal cortical tumors).

Answer 6

2. 50
3. adrenal vein and extend into the caudal vena cava
4. regional lymph nodes, liver, spleen, and lungs
5. pancreatic endocrine tumor and parathyroid tumors

Question 7

(Hypoadrenocorticism (Addison’s disease))

1. occurence?

(causes)

a. Idiopathic: The most frequently observed histopathological change in dogs with hypoadrenocorticism is bilateral idiopathic adrenocortical atrophy, in which all layers of the adrenal cortex are markedly reduced in thickness. The pathogenesis is unknown, but it has been proposed that the process is immune-mediated.
b. Adrenalitis: Bacterial and parasitic agents frequently localize in the adrenal glands and produce varying degrees of inflammation and necrosis.
c. Adrenocortical hemorrhage (Waterhouse-Friderichsen Syndrome): Massive diffuse often bilateral adrenal cortical hemorrhage can be a sequel to sepsis (usually endotoxin) or less often due to Gram positive organisms or anticoagulant poisoning.

Answer 7

1. common in dogs (esp young adult), can occur in any species

Question 8

(Hypoadrenocorticism (Addison’s disease))

(Pathogenesis)

1. less potassium is excreted by the kidneys… resulting in what?
2. Less sodium and chloride are reabsorbed from renal tubules… leading to what?

(Clinical Signs)

4. Clinical signs: Clinical signs are a result of deficient production of any or all classes of corticosteroids (mineralocorticoids {primarily aldosterone}, gluococorticoids, and adrenal sex steroids). There are often marked alterations of serum potassium, sodium, and chloride concentrations. Clinical signs are often non-specific and can range from lethargy and bradycardia to gastrointestinal disturbances. May also see acute circulatory collapse, hypotension, emesis, diarrhea, anorexia, weight loss, dehydration, and hemoconcentration.

Answer 8

1. severe hyperkalemia ((frequently produces cardiovascular disturbances such as bradycardia – predisposing to weakness and circulatory collapse)
2. hypernaturia and hyperchloriduria and a corresponding decline in blood concentrations of these ions.

Question 9

J. Diabetes Insipidus (DI)

“diabetes” = Greek for passing water like a siphon or to pass through (polyuria)

“mellitus” = Latin for pertaining to honey/sweet (glucosuria)

“insipidus” = Latin for without taste (low sodium and no glucose in the dilute urine)

1. Diabetes insipidus results from when what or what occurs?
2. The hypophyseal form results from compression and destruction of the pars nervosa, infundibular stalk, or supraoptic nucleus in the hypothalamus (eg: large pituitary tumor, inflammation of pituitary, trauma). These causes interrupt the non-myelinated axons that do what?

Answer 9

1. inadequate antidiuretic hormone (ADH = vasopressin) is produced (hypophyseal or central form), OR, when target cells in the kidney fail to respond to normal or increased concentrations of ADH (nephrogenic form).
2. transport ADH from its site of production (including supraoptic nucleus of hypothalamus) to its site of release (capillary plexus of pars nervosa).

Question 10

J. Diabetes Insipidus (DI)

(cont)

1. In the nephrogenic form of DI, blood levels of ADH are normal or elevated, but target cells in the distal nephron are unable to respond due to a lack of what in the PM?
2. There are a number of causes of nephrogenic DI: these include hereditary causes as well as acquired causes (eg: lithium toxicity in humans, amyloidosis, chronic kidney disorders).

Animals with diabetes insipidus produce large volumes of hypotonic/dilute urine (specific gravity <1.005), which necessitates the ingestion of large quantities of water to prevent dehydration. In response to water deprivation, urine concentration remains low (however, in cases of diabetes insipidus, water deprivation tests are extremely dangerous). Urine concentration will increase following exogenous administration of ADH in the hypophyseal form, but not in the nephrogenic form. Patients affected with DI are also hypernatremic (serum sodium and osmolality are increased as a result of excessive renal loss of free water, resulting in an increased thirst and polydipsia).

Answer 10

1. adenylate cyclase

Question 11

(K. Pitutiary Dwarfism (Panhypopituitarism))

1. Pituitary dwarfism in dogs is usually the result of what?

the result is what?

2. Juvenile panhypopituitarism is most frequent in what breed?

The dwarf pups appear normal at birth to about 2 months of age. Subsequently, the slower growth, retention of puppy hair coat and lack of primary guard hairs eventually become apparent. Also, there can be bilaterally symmetrical alopecia and hyperpigmentation of the skin. Affected dogs have a fox or coyote appearance (small size and soft woolly coat). Permanent dentition is delayed or completely absent and the closure of epiphyses is delayed.

3. mode of inheritance thought to be what?
4. pathogenesis related to low activity of what?

Answer 11

1. a failure of the oropharyngeal ectoderm of Rathke’s pouch to differentiate into trophic hormone secreting cells of the pars distalis

a progressively enlarging, multiloculated cyst and an absence of adenohypophysis

2. German shephard
3. autosomal recessive.
4. somatomedin (insulin like growth factor; IGF-1)