Dermatologic Manifestations of Glucagonoma Syndrome Workup
- Author: Nathalie C Zeitouni, MD, CM, FRCPC; Chief Editor: William D James, MD more...
Laboratory Studies
Since glucagonoma may arise in the context of a polyfunctional endocrine tumor, assessing serum glucagon, in addition to serum insulin, corticotropin, PP, 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 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.
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.[5]
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.
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. The epidermis shows focal exocytosis of lymphocytes, slight spongiosis, and occasional dyskeratotic keratinocytes. Later, changes include a lymphohistiocytic infiltrate with some neutrophils and eosinophils. The epidermis shows mild acanthosis, mild spongiosis, parakeratosis, and loss of the granular cell layer (note the image below). Dyskeratosis and necrosis in the superficial layers result in a characteristic cleftlike detachment from the deeper epidermis. 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 patient with necrolytic migratory erythema and glucagonoma syndrome. Note prominent intracellular edema and loss of granular cell layer (X10). Nakashima H, Komine M, Sasaki K, Mitsui H, Fujimoto M, Ihn H, et al. Necrolytic migratory erythema without glucagonoma in a patient with short bowel syndrome. J Dermatol. Aug 2006;33(8):557-62. [Medline].
Doyle JA, Schroeter AL, Rogers RS 3rd. Hyperglucagonaemia and necrolytic migratory erythema in cirrhosis--possible pseudoglucagonoma syndrome. Br J Dermatol. Nov 1979;101(5):581-7. [Medline].
Echenique-Elizondo M, Tuneu Valls A, Elorza Orúe JL, Martinez de Lizarduy I, Ibáñez Aguirre J. Glucagonoma and pseudoglucagonoma syndrome. JOP. Jul 2004;5(4):179-85. [Medline].
Chao SC, Lee JY. Brittle nails and dyspareunia as first clues to recurrences of malignant glucagonoma. Br J Dermatol. Jun 2002;146(6):1071-4. [Medline].
Lewis RB, Lattin GE Jr, Paal E. Pancreatic endocrine tumors: radiologic-clinicopathologic correlation. Radiographics. Oct 2010;30(6):1445-64. [Medline].
van der Loos TL, Lambrecht ER, Lambers JC. Successful treatment of glucagonoma-related necrolytic migratory erythema with dacarbazine. J Am Acad Dermatol. Feb 1987;16(2 Pt 2):468-72. [Medline].
Nitta N, Ohta S, Tanaka T, Takazakura R, Toyama T, Sonoda A, et al. An initial clinical study on the efficacy of cisplatin-releasing gelatin microspheres for metastatic liver tumors. Eur J Radiol. Sep 2009;71(3):519-26. [Medline].
Melen-Mucha G, Lawnicka H, Kierszniewska-Stepien D, Komorowski J, Stepien H. The place of somatostatin analogs in the diagnosis and treatment of the neuoroendocrine glands tumors. Recent Pat Anticancer Drug Discov. Jun 2006;1(2):237-54. [Medline].
Mir O, Coriat R, Goldwasser F. Advances in pancreatic neuroendocrine tumor treatment. N Engl J Med. May 12 2011;364(19):1871; author reply 1873-4. [Medline].
Poggi G, Villani L, Bernardo G. Multimodality treatment of unresectable hepatic metastases from pancreatic glucagonoma. Rare Tumors. Jul 22 2009;1(1):e6. [Medline]. [Full Text].
Blackford S, Wright S, Roberts DL. Necrolytic migratory erythema without glucagonoma: the role of dietary essential fatty acids. Br J Dermatol. Nov 1991;125(5):460-2. [Medline].
Print
