FOLLOW-UP

Three weeks after the surgery, the dog's clinical condition improved. The skin lesions resolved, and the dog's appetite and attitude returned to normal. However, seven months after the surgery, the dog returned to Purdue for reevaluation because of anemia, anorexia, and vomiting. Because of the owner's financial constraints and the dog's poor clinical condition, the owner elected euthanasia.

A blood sample was obtained before euthanasia, and the dog's plasma glucagon concentration was 216 ng/L. Necropsy results showed no gross evidence of glucagonoma metastases or other primary neoplasia. A histologic examination of tissues from necropsy (pancreas, liver, kidney, spleen, adrenal glands, gastrointestinal tract, heart, lung, bone marrow) revealed splenic extramedullary hematopoiesis, mild and multifocal hepatocellular vacuolar degeneration, and cholestasis. The gross necropsy results and histologic findings did not provide an explanation for the clinical signs or elevated glucagon concentration.

Islet cell tumors, uncommon neoplasms of neuroendocrine cells within the pancreas, are classified as insulinomas, glucagonomas, gastrinomas, or somatostatinomas, depending on the predominant hormone secreted by the neoplasm.² About 200 cases in people have been reported.^2-4 A few cases of glucagonomas in dogs have been reported, but the cytologic and histologic examination results have not been reported together.^5-11

About 50% of the islet cell tumors in people are immunohistochemically reactive for multiple hormones. These tumors can secrete any of the hormones known to be present in the pancreatic islets, including insulin, glucagon, somatostatin, pancreatic polypeptide, and gastrin, either singly or in any combination.¹² However, a single cell type and pancreatic hormone generally predominate and usually result in the corresponding metabolic syndrome.¹² This ability to produce multiple hormones is also found in canine islet cell tumors.^6,12,13

In people, glucagonomas are neoplasms of alpha cells that result in a paraneoplastic disease characterized by necrolytic migratory erythema, diabetes mellitus, weight loss, anemia, glossitis, stomatitis, thromboembolism, and gastrointestinal and neuropsychiatric disturbances. These clinical findings along with hyperglucagonemia and a pancreatic islet cell tumor establish the diagnosis.

Superficial necrolytic dermatitis

The hallmark clinical finding in people with a glucagonoma is necrolytic migratory erythema. The skin lesions have a predilection for the perioral region, perineum, lower abdomen, thighs, buttocks, and distal extremities. In all the reported cases of glucagonomas in dogs, skin lesions were also a primary complaint.^5,8

In dogs, the skin lesions are most commonly identified on the footpads, elbows, hocks, face, ventral abdomen, and perineum. The terms superficial necrolytic dermatitis, metabolic epidermal necrosis, diabetic dermatosis, hepatocutaneous syndrome, and necrolytic migratory erythema have been used to describe the skin lesions in dogs.^5,6,8-11,14 Unlike necrolytic migratory erythema in people, superficial necrolytic dermatitis in dogs appears to occur most commonly with a hepatopathy (hepatocutaneous syndrome) and less commonly with a glucagon-secreting tumor.¹⁵

Histologic features. In people, the skin lesions include parakeratotic hyperkeratosis and moderate epidermal hyperplasia associated with intracellular edema of the upper portion of the stratum spinosum. The lesions create distinctive layers: intensely eosinophilic, keratinous cellular debris superficially; pale-staining edematous keratinocytes in a middle layer; and a deep zone of basophilic hyperplastic basal cells. Similar histologic changes have been identified in dogs with glucagon-secreting neoplasms or hepatic disease (hepatocutaneous syndrome). Because the characteristic lesions are not seen in every punch biopsy sample from an affected patient, three to five biopsies are recommended.