Dermatologic Manifestations of Glucagonoma Syndrome Workup

Updated: Aug 24, 2021
  • Author: Ali Alikhan, MD; Chief Editor: William D James, MD  more...
  • Print
Workup

Laboratory Studies

Since glucagonoma may arise in the context of a polyfunctional endocrine tumor, assessing serum glucagon, in addition to serum insulin, corticotropin, pancreatic polypeptide (PP), parathyroid hormone (PTH), gastrin, serotonin and vasoactive intestinal peptide levels, is important. A glucose tolerance test may help in delineating the degree of glucagon excess relative to insulin. Glucose intolerance may relate to tumor size and hepatic metastases.

A nutritional profile, consisting of amino acid, zinc, and essential fatty acid levels, is essential because necrolytic migratory erythema (NME) may respond to a correction of a nutrient deficit.

CBC count with differential is indicated to evaluate for a possible anemia.

Blood chemistry testing may help in detecting liver metastases.

Next:

Imaging Studies

Localization of the pancreatic primary tumor and metastatic disease is performed primarily with CT scanning, MRI, and ultrasonography. In selected cases, positron emission tomography scanning may be useful. Celiac axis angiography is considered the criterion standard for diagnosis and localization of the glucagonoma. Determination of metastatic spread can be achieved by imaging with a somatostatin analogue that identifies both the primary lesion and the tumor extent. [15, 16]

Previous
Next:

Procedures

Finding the glucagonoma, if one exists, is important. Depending on the radiographic workup results, either laparotomy with tumor resection or needle biopsy may be appropriate to obtain a histologic specimen.

A punch biopsy can demonstrate NME if the skin is sampled appropriately. Multiple biopsies from the edges of early lesions are most helpful in establishing a diagnosis.

Previous
Next:

Histologic Findings

Glucagonomas are tumors of the alpha cells of the pancreas. These tumors tend to arise in the tail of the pancreas, although they can be found anywhere within the organ. Many case reports describe the tumors as solid, well circumscribed, and encapsulated. The tumors show organized nests, islands, and occasional trabeculae. They are usually hypervascular, in contrast to pancreatic adenocarcinomas. Immunocytochemistry may be positive for glucagon, although the intensity of the stain may not correlate with the serum glucagon levels. If this method does not detect glucagon production, in situ hybridization to glucagon mRNA may be definitive. Electron microscopy shows neurosecretory granules and a well-developed, rough endoplasmic reticulum and Golgi complex.

The histologic findings of NME correlate with the clinical state of evolution of the lesion. NME initially manifests as a mild perivascular dermal lymphocytic infiltrate and epidermal spongiosis. It is helpful to take more than one biopsy, as early lesions may easily be mistaken for spongiotic dermatitis. In older lesions, The epidermis classically shows hyperparakeratosis, acanthosis, an absent granular layer, and pallor of keratinocytes in the upper layers of the epidermis (note the image below). Vacuolar degeneration and necrosis in the superficial layers result in a characteristic cleftlike detachment from the deeper epidermis. The infiltrate may also include neutrophils and eosinophils. In one study, keratinocytes in NME stained positive for Ki-67, K16, and K10, supporting changes in both differentiation and proliferation of keratinocytes.

Acanthosis with upper epidermal necrolysis from a Acanthosis with upper epidermal necrolysis from a patient with necrolytic migratory erythema and glucagonoma syndrome. Note prominent intracellular edema and loss of granular cell layer (X10).
Previous