Glucagonoma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Parminder Dhingra, M.D. [2]

Overview

A glucagonoma is a rare tumor of the alpha cells of the pancreas that results in the overproduction of the hormone glucagon. On microscopic histopathological analysis, findings of glucagonoma are epidermal necrosis, subcorneal pustules, confluent parakeratosis, epidermal hyperplasia and marked papillary dermal angioplasia, and suppurative folliculitis.

Pathophysiology

A glucagonoma is a rare tumor of the alpha cells of the pancreas that results in the overproduction of the hormone glucagon. Alpha cell tumors are commonly associated with glucagonoma syndrome, though similar symptoms are present in cases of pseudoglucagonoma syndrome in the absence of a glucagon-secreting tumor.^[1]
The primary physiological effect of glucagonoma is an overproduction of the peptide hormone glucagon, which enhances blood glucose levels through the activation of catabolic processes including gluconeogenesis and lipolysis.
Gluconeogenesis produces glucose from protein and amino acid materials. Lipolysis is the breakdown of fat.
Diabetes mellitus also frequently results from the insulin and glucagon imbalance that occurs in glucagonoma.^[2]
Pathogenesis of necrolytic migratory erythema is ill defined. The postulated mechanism for necrolytic migratory erythema involves the combined effect of hyperglucagonemia, zinc deficiency, fatty acid deficiency, hypoaminoacidemia, and liver disease, that lead to excessive inflammation in the epidermis in response to trauma and to the necrolysis.^[3]^[4]

Microscopic Pathology

On microscopic histopathological analysis, findings of glucagonoma are:^[5]

Epidermal necrosis

Subcorneal pustules, either isolated or associated with necrosis of the epidermis

Confluent parakeratosis

Epidermal hyperplasia, and marked papillary dermal angioplasia

Suppurative folliculitis

Images

Confluent epidermal necrosis (high mag)^[6]
Confluent epidermal necrosis (very high mag)^[6]
Confluent epidermal necrosis (intermed mag)^[6]
Confluent epidermal necrosis (low mag)^[6]
(A) Skin lesions affecting pretibial area. (B) Skin biopsy in necrolytic migratory erythema showing a zone of necrolysis and vacuolated keratinocytes^[7]
Skin biopsy in necrolytic migratory erythema showing a large zone of necrolysis in the upper epidermis (arrow)^[8]
A) Psoriasiform hyperplasia of the epidermis with overlying parakeratosis and mild perivascular infiltrate of lymphocytes in the upper dermis (HE 5 X). B) Vascular dilatation (HE 20 X).^[9]
Specimen from distal splenopancreatectomy.A) The neoplasia is located in the inferior border of the pancreas (arrow); it shows an exophytic growth but appears well circumscribed. B) The cut surface is whitish-yellow in color with focal areas of hemorrhage.^[9]
Histopathological examination of the pancreatic tumor.A) The tumor appears encapsulated and composed of polygonal cells with trabecular or ribbon-like proliferation (HE 5 X). B) At immunohistochemistry, neoplastic cells showed an intense diffuse staining for glucagon (Anti-glucagon antibody 5 X)^[9]