FINAL DIAGNOSIS: Insulinoma in a cat
History: An 8-year-old castrated male
domestic shorthair cat was presented to Purdue University Veterinary Teaching
Hospital following a three week history of anorexia, weight loss, intermittent
hematuria, and urinating outside of the litter box. Physical exam findings
included muscle wasting, tachycardia (240 bpm), and hepatomegaly. Mildly
increased liver enzymes (ALT and ALP) and markedly elevated lipase levels were
noted on serum biochemistry. Complete blood count results showed a mild anemia
and lymphopenia. Radiographs demonstrated urinary calculi and an enlarged
liver with irregular margins. Several masses were identified in the liver and
pancreas on abdominal ultrasound, along with enlarged gastric lymph nodes and
mild peritoneal effusion. Cytology of liver mass aspirates was interpreted as
adenocarcinoma with hepatic lipidosis. The cat was euthanized due to poor
prognosis and submitted for necropsy examination to the Animal Disease Diagnostic
Gross examination: Subcutaneous tissue and
visceral organs were icteric. The pancreas, liver, and gastric/pancreatic
lymph nodes contained multifocal to coalescing masses, characterized by pale
tan, firm, often umbilicated, nodules measuring up to 6 cm in diameter. The
masses extended into the parenchyma of affected organs and, occasionally, had
brown, friable, central necrosis on cut section.
Histopathologic examination: Masses in the pancreas,
liver, and lymph nodes effaced normal tissue parenchyma and were composed of
solid packets or nests of neoplastic cells separated by moderate fibrovascular
stroma. The cells occasionally organized around central lumina, forming
irregular acini or ductules. Features of the tumor cells included polygonal to
columnar cell shape, moderate amphophilic cytoplasm, round to oval nuclei with
stippled chromatin, and single distinct nucleoli. Mitotic figures were common
with an index of 44 per ten high power fields (400X magnification).
Hemorrhage, necrosis, and mixed inflammation were present multifocally in the
masses. Portal veins contained tumor emboli, and micrometastases were
identified in lung and adrenal cortex.
Immunohistochemistry: Tissue of origin could not be
determined based on morphology alone in this tumor. Differential diagnoses
included carcinoma (pancreatic or biliary) or malignant neuroendocrine tumor
(pancreatic islet cell carcinoma). Immunohistochemical (IHC) tests utilized in
this case consisted of antibodies against neuron-specific enolase, PGP 9.5, and
insulin. Neuron-specific enolase and PGP 9l5 were both positive in tumor
cells, supporting a diagnosis of neuroendocrine tumor, likely of islet cell
origin. Insulin IHC was also positive, indicating the production of insulin in
tumor cells and confirming the diagnosis as beta-cell carcinoma (insulinoma).
Gross photograph depicting
the large insulinoma disrupting the pancreatic body.
Comment: Insulinoma is a tumor derived from
pancreatic beta-cells, which are the insulin-producing cells in the islets of
Langerhans. Insulinoma is rarely documented in cats, with only five reports
identified in the literature, and is uncommon in dogs. Interestingly, three of
the five cats reported with insulinoma were Siamese.
In this type of tumor, neoplastic beta-cells produce
insulin and can autonomously secrete the hormone, resulting in
hyperinsulinemia. Excess insulin causes hypoglycemia, which is the most
consistent hematologic or serum biochemical abnormality in animals with
insulinoma. The classical manifestation, best characterized in the dog, is
episodic neurological signs such as weakness, ataxia, syncope, or seizures
during fasting or exercise when hypoglycemia becomes most severe. After
eliminating other causes of hypoglycemia, demonstration of inappropriate levels
of insulin (i.e. normal or increased in the face of hypoglycemia) can help
confirm the diagnosis of insulin-secreting neoplasia. Ultrasound of the
pancreas can assist in identification of the mass, although the tumors are
commonly small (<3 cm) at the time of diagnosis, and can be difficult to
detect. Exploratory laparotomy may be warranted for definitive diagnosis
Treatment for insulinoma can include surgery,
medical management, or both. Surgery is rarely curative, and can create new
challenges by inciting pancreatitis, the most common post-operative
complication. Medical management consists of feeding frequent small meals,
supplementing with glucocorticoids to counteract the hyperinsulinemia, and
limiting excitement and exercise. The goal is to keep glucose levels from
falling dangerously low, rather than maintaining normal levels at all times.
Prognosis is poor due to challenging case management and high incidence of
metastasis of this tumor.
The interesting features in this case include the
absence of neurological signs and the inability to document hypoglycemia (cat
was euglycemic on presentation). One plausible explanation may be that ,
although the neoplastic cells produced insulin as indicated by positive insulin
IHC staining, the hormone was either non-functional or not secreted from the
tumor cells. It is also possible that hyperinsulinemia and hypoglycemia did
occur, but glycose failed to reach levels low enough to manifest as
-by Dr. Pamela Mouser, ADDL Graduate Student
Feldman EC, Nelson RW: 2004. Beta-cell neoplasia:
insulinoma. In: Canine and feline endocrinology and reproduction, 3rd
ed. Saunders, St. Louis, MO. pp 642-643.
Krajhe AC: 2003. Hypoglycemia and irreversible
neurologic complications in a cat with insulinoma. JAVMA 223:812-814.
Lurye JC, Behrend EN: 2001. Endocrine tumors.
Vet Clin North Am Small Anim Prac 31_ 1083-1110