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==Overview==
==Overview==
''Glucagonoma'' is a tumor of the [[alpha cells]] of the [[pancreas]] characterized by the excessive secretion of [[glucagon]] and [[necrolytic migratory erythema]]. Glucagonoma causes hyperglucagonemia, [[zinc deficiency]], [[fatty acid]] deficiency, [[Aminoacid|hypoaminoacidemia]] that may cause [[necrolytic migratory erythema]]. Glucagonoma may be a part of [[MEN1 syndrome|type 1 multiple endocrine neoplasia]]. It is an autosomal dominant syndrome that is usually caused by mutations in the [[MEN1 syndrome|''MEN1'' gene]]. [[MEN1 syndrome|''MEN1'' gene]] is a [[tumor suppressor gene]] and causes [[MEN1 syndrome|type 1 multiple endocrine neoplasia]] by [[Knudson hypothesis|Knudson's "two hits" model]] for [[tumor]] development. All glucagonomas are located in the pancreas, 50–80% occur in the pancreatic tail, 32.2% in the body and 21.9% in the head. Glucagonoma can metastasize mainly to the liver. Glucagonomas consist of [[Pleomorphism|pleomorphic]] cells containing granules that stain for other peptides, most frequently [[pancreatic polypeptide]]. [[Immunoperoxidase|Immunoperoxidase staining]] can detect glucagon within the tumor cells and [[Glucagon|glucagon.]]


==Pathophysiology==
==Pathogenesis==
*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.<ref>Glucagonoma. Wikipedia. https://en.wikipedia.org/wiki/Glucagonoma. Accessed on October 13, 2015.</ref>
* Glucagonoma is a rare tumor of the [[alpha cells]] of the [[pancreas]] that results in the overproduction of the hormone [[glucagon]]. Glucagonomas are [[neuroendocrine tumors]] derived from [[Stem cells|multipotential stem cells]].<ref name="pmid9113318">{{cite journal| author=Frankton S, Bloom SR| title=Gastrointestinal endocrine tumours. Glucagonomas. | journal=Baillieres Clin Gastroenterol | year= 1996 | volume= 10 | issue= 4 | pages= 697-705 | pmid=9113318 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9113318  }}</ref><ref name="pmid6127984">{{cite journal| author=Braverman IM| title="Cutaneous manifestations of internal malignant tumors" by Becker, Kahn and Rothman, June 1942. Commentary: Migratory necrolytic erythema. | journal=Arch Dermatol | year= 1982 | volume= 118 | issue= 10 | pages= 784-98 | pmid=6127984 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6127984  }}</ref><ref>Necrolytic migratory erythema. Wikipedia. https://en.wikipedia.org/wiki/Necrolytic_migratory_erythema. Accessed on October 13, 2015.</ref><ref name="pmid9591806">{{cite journal| author=Mullans EA, Cohen PR| title=Iatrogenic necrolytic migratory erythema: a case report and review of nonglucagonoma-associated necrolytic migratory erythema. | journal=J Am Acad Dermatol | year= 1998 | volume= 38 | issue= 5 Pt 2 | pages= 866-73 | pmid=9591806 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9591806  }} </ref><ref name="pmid13978995">{{cite journal| author=STURZBECHER M| title=[8 letters of Ferdinand von HEBRAS on his contributin to Virchow's Handbuch der Speziellen Pathologie and Therapie]. | journal=Z Haut Geschlechtskr | year= 1963 | volume= 34 | issue=  | pages= 281-6 | pmid=13978995 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13978995  }}</ref><ref name="pmid14356022">{{cite journal| author=Wilson LA, Kuhn JA, Corbisiero RM, Smith M, Beatty JD, Williams LE et al.| title=A technical analysis of an intraoperative radiation detection probe. | journal=Med Phys | year= 1992 | volume= 19 | issue= 5 | pages= 1219-23 | pmid=1435602 | doi=10.1118/1.596754 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1435602 }}</ref>
*The primary [[physiology|physiological]] effect of glucagonoma is an overproduction of the [[peptide]] hormone [[glucagon]], which enhances [[blood glucose]] levels through the activation of [[catabolism|catabolic]] processes including [[gluconeogenesis]] and [[lipolysis]]. Gluconeogenesis produces [[glucose]] from [[protein]] and [[amino acid]] materials; lipolysis is the breakdown of [[adipose tissue|fat]].
** [[Glucagon]] increases [[glycogenolysis]], [[gluconeogenesis]] from amino acid substrates and inhibits [[glycolysis]]. This causes weight loss due to the [[Catabolism|catabolic]] action of [[glucagon]].
*[[Diabetes mellitus]] also frequently results from the [[insulin]] and [[glucagon]] imbalance that occurs in glucagonoma.<ref>{{cite journal |author=Koike N, Hatori T, Imaizumi T, ''et al'' |title=Malignant glucagonoma of the pancreas diagnoses through anemia and diabetes mellitus |journal=Journal of hepato-biliary-pancreatic surgery |volume=10 |issue=1 |pages=101-5 |year=2003 |pmid=12918465 |doi=}}</ref>
** When [[glucagon]] is secreted by a tumor, it becomes independent and is no longer influenced by feedback control mechanisms.
*Pathogenesis of necrolytic migratory erythema is ill defined. Postulated mechanism for necrolytic migratory erythema involves combined effect of hyperglucagonemia, zinc deficiency, fatty acid deficiency, hypoaminoacidemia, and liver disease, that leads to excessive inflammation in the epidermis in response to trauma and to the necrolysis observed in necrolytic migratory erythema.<ref>Necrolytic migratory erythema. Wikipedia. https://en.wikipedia.org/wiki/Necrolytic_migratory_erythema. Accessed on October 13, 2015.</ref><ref name="pmid9591806">{{cite journal| author=Mullans EA, Cohen PR| title=Iatrogenic necrolytic migratory erythema: a case report and review of nonglucagonoma-associated necrolytic migratory erythema. | journal=J Am Acad Dermatol | year= 1998 | volume= 38 | issue= 5 Pt 2 | pages= 866-73 | pmid=9591806 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9591806  }} </ref>
** Glucagonoma causes hyperglucagonemia, [[zinc deficiency]], [[fatty acid]] deficiency, [[Aminoacid|hypoaminoacidemia]] that may cause [[necrolytic migratory erythema]].
==Microscopic Pathology==
** The mechanism for [[necrolytic migratory erythema]] involves excessive inflammation in the epidermis in response to trauma and to the necrolysis.
On microscopic histopathological analysis, findings of glucagonoma are:<ref name="pmid3014912">{{cite journal| author=Kheir SM, Omura EF, Grizzle WE, Herrera GA, Lee I| title=Histologic variation in the skin lesions of the glucagonoma syndrome. | journal=Am J Surg Pathol | year= 1986 | volume= 10 | issue= 7 | pages= 445-53 | pmid=3014912 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3014912 }} </ref>
** [[Necrolytic migratory erythema]] (NME) probably results from hyponutrition and [[amino acid]] deficiency. It can be caused by the loss of [[tryptophan]] in cutaneous tissues as a result of the excess circulating [[glucagon]]. [[Tryptophan]] is responsible for [[niacin]] function, which regulates cell turnover and the maturation of the epidermis and mucosal epithelia.
** [[Diarrhea]] may result from the secretion of [[gastrin]] which occurs with glucagonoma.


*Epidermal necrosis
== Genetics ==
Glucagonoma may be part of [[MEN1 syndrome|type 1 multiple endocrine neoplasia]]. It is an autosomal dominant syndrome that is usually caused by mutations in the [[MEN1 syndrome|''MEN1'' gene]].<sup>[[Multiple endocrine neoplasia type 1 pathophysiology#cite note-wikipedia-1|[1]]]</sup><sup>[[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid17014705-2|[2]]][[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid2894610-3|[3]]][[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid2568587-4|[4]]][[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid2568586-5|[5]]][[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid1968641-6|[6]]]</sup><sup>[[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid7902574-7|[7]]]</sup>
* It is characterized by the development of the following tumors:
** [[Pituitary adenoma|Pituitary adenomas]]
** [[Islet cell tumor|Islet cell tumors]] of the [[pancreas]] (commonly [[gastrinoma]] and glucagonoma)
**[[Parathyroid]] [[hyperplasia]] with resulting [[hyperparathyroidism]]
* The [[gene]] [[locus]] causing [[multiple endocrine neoplasia type 1]] has been localized to [[chromosome]] 11q13 by studies of [[loss of heterozygosity]] on [[multiple endocrine neoplasia type 1]]-associated [[Tumor|tumors]] and by linkage analysis in [[multiple endocrine neoplasia type 1]] families. ''MEN1'', spans about 10 Kb and consists of ten exons encoding a 610 [[amino acid]] nuclear protein, named menin.
* ''MEN1'' [[gene]] is a [[tumor suppressor gene]] and causes type 1 multiple endocrine neoplasia by Knudson's "two hits" model for [[tumor]] development.
* Two hits model for [[tumor]] development suggests that there is a [[germline mutation]] present in all [[Cell|cells]] at birth and the second [[mutation]] is a somatic [[mutation]] that occurs in the predisposed [[endocrine]] [[cell]] and leads to loss of the remaining wild type [[allele]]. This "two hits" model gives [[Cell|cells]] the survival advantage needed for [[tumor]] development.


*Subcorneal pustules, either isolated or associated with necrosis of the epidermis
== Gross Pathology ==
The gross pathology of glucagonoma may show:<ref name="pmid21859461">{{cite journal| author=Castro PG, de León AM, Trancón JG, Martínez PA, Alvarez Pérez JA, Fernández Fernández JC et al.| title=Glucagonoma syndrome: a case report. | journal=J Med Case Rep | year= 2011 | volume= 5 | issue=  | pages= 402 | pmid=21859461 | doi=10.1186/1752-1947-5-402 | pmc=PMC3171381 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21859461  }} </ref><ref name="pmid9880781">{{cite journal| author=Soga J, Yakuwa Y| title=Glucagonomas/diabetico-dermatogenic syndrome (DDS): a statistical evaluation of 407 reported cases. | journal=J Hepatobiliary Pancreat Surg | year= 1998 | volume= 5 | issue= 3 | pages= 312-9 | pmid=9880781 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9880781  }}</ref><ref name="pmid25152626">{{cite journal| author=Fang S, Li S, Cai T| title=Glucagonoma syndrome: a case report with focus on skin disorders. | journal=Onco Targets Ther | year= 2014 | volume= 7 | issue=  | pages= 1449-53 | pmid=25152626 | doi=10.2147/OTT.S66285 | pmc=PMC4140234 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25152626  }} </ref>


*Confluent parakeratosis
* Large tumors at diagnosis with a mean diameter of 5 cm. About 50 to 82% have evidence of [[Metastasis|metastatic]] spread at presentation.


*Epidermal hyperplasia, and marked papillary dermal angioplasia
* Nearly all glucagonomas are located in the [[pancreas]], 50–80% occur in the pancreatic tail, 32.2% in the body and 21.9% in the head.
* In few patients, location can be [[extrapancreatic]], such as in [[Kidney|kidney,]] [[duodenum]], [[lung]], [[Accessory pancreas|accessory pancreatic tissue]].


*Suppurative folliculitis
* Metastasis usually occurs to [[Liver|the liver]]. Other sites are [[Lymph node|lymph nodes]], [[bone]], [[lung]], and [[Adrenal gland|adrenals]].
===Images===
<gallery>Image:800px-Confluent epidermal necrosis - high mag.jpg|Confluent epidermal necrosis(high mag)<ref name=picture>Glucagonoma. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Confluent_epidermal_necrosis_-_high_mag.jpg</ref>


*Tumors smaller than 2 cm in diameter are associated with a very low chance of [[malignancy]].


Image:1024px-Confluent epidermal necrosis - very high mag.jpg|Confluent epidermal necrosis(very high mag)<ref name=picture>Glucagonoma. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Confluent_epidermal_necrosis_-_high_mag.jpg</ref>
==Microscopic Pathology==
The microscopic pathology of glucagonoma tumors in [[pancreas]] usually show intense staining for [[glucagon]].<ref name="pmid6295622">{{cite journal| author=Warner TF, Block M, Hafez GR, Mack E, Lloyd RV, Bloom SR| title=Glucagonomas. Ultrastructure and immunocytochemistry. | journal=Cancer | year= 1983 | volume= 51 | issue= 6 | pages= 1091-6 | pmid=6295622 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6295622  }}</ref><ref name="pmid1973365">{{cite journal| author=Mozell E, Stenzel P, Woltering EA, Rösch J, O'Dorisio TM| title=Functional endocrine tumors of the pancreas: clinical presentation, diagnosis, and treatment. | journal=Curr Probl Surg | year= 1990 | volume= 27 | issue= 6 | pages= 301-86 | pmid=1973365 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1973365  }}</ref>
* Many glucagonomas are [[Pleomorphism|pleomorphic]] with cells containing [[granules]] that stain for other [[peptides]], most frequently [[pancreatic polypeptide]].
* [[Immunoperoxidase|Immunoperoxidase staining]] can detect glucagon within the tumor cells and glucagon [[mRNA]] also may be detected.
* [[Electron|Electron microscopy]] shows secretory granules indicating the origin of glucagonoma from [[alpha cells]].
* Benign tumors are usually fully granulated and [[malignant]] cells have fewer granules.
*[[Skin biopsy]] may depict [[Epidermal|epidermal necrosis]].


Image:1024px-Confluent epidermal necrosis - intermed mag.jpg|Confluent epidermal necrosis(intermed mag)<ref name=picture>Glucagonoma. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Confluent_epidermal_necrosis_-_high_mag.jpg</ref>
===Images===
<gallery>Image:800px-Confluent epidermal necrosis - high mag.jpg|'''Histology of confluent epidermal necrosis''' '''(high mag)''',<small>Source:By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=16874054</small><ref name=picture>Glucagonoma. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Confluent_epidermal_necrosis_-_high_mag.jpg</ref>


Image:800px-Confluent epidermal necrosis - low mag.jpg|Confluent epidermal necrosis(low mag)<ref name=picture>Glucagonoma. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Confluent_epidermal_necrosis_-_high_mag.jpg</ref>
Image:1752-1947-5-402-1.jpg|(A) Skin lesions affecting pretibial area. (B) Skin biopsy in necrolytic migratory erythema showing a zone of necrolysis and vacuolated keratinocytes<ref name="pmid21859461">{{cite journal| author=Castro PG, de León AM, Trancón JG, Martínez PA, Alvarez Pérez JA, Fernández Fernández JC et al.| title=Glucagonoma syndrome: a case report. | journal=J Med Case Rep | year= 2011 | volume= 5 | issue=  | pages= 402 | pmid=21859461 | doi=10.1186/1752-1947-5-402 | pmc=PMC3171381 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21859461  }} </ref>
Image:NEM111.jpg|Skin biopsy in necrolytic migratory erythema showing a large zone of necrolysis in the upper epidermis (arrow)<ref name="pmid25152626">{{cite journal| author=Fang S, Li S, Cai T| title=Glucagonoma syndrome: a case report with focus on skin disorders. | journal=Onco Targets Ther | year= 2014 | volume= 7 | issue=  | pages= 1449-53 | pmid=25152626 | doi=10.2147/OTT.S66285 | pmc=PMC4140234 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25152626  }} </ref>


Image:Glucagonoma'.jpg|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).<ref name="pmid23259638">{{cite journal| author=Erdas E, Aste N, Pilloni L, Nicolosi A, Licheri S, Cappai A et al.| title=Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association? | journal=BMC Cancer | year= 2012 | volume= 12 | issue=  | pages= 614 | pmid=23259638 | doi=10.1186/1471-2407-12-614 | pmc=PMC3543729 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23259638  }} </ref>
Image:1024px-Confluent epidermal necrosis - very high mag.jpg|'''Histology of confluent epidermal necrosis (very high mag)'''<small>Source:By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=16874054</small><ref name=picture>Glucagonoma. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Confluent_epidermal_necrosis_-_high_mag.jpg</ref>
Image:Gross1.jpg|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.<ref name="pmid23259638">{{cite journal| author=Erdas E, Aste N, Pilloni L, Nicolosi A, Licheri S, Cappai A et al.| title=Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association? | journal=BMC Cancer | year= 2012 | volume= 12 | issue=  | pages= 614 | pmid=23259638 | doi=10.1186/1471-2407-12-614 | pmc=PMC3543729 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23259638  }} </ref>
 
Image:Histo.jpg|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)<ref name="pmid23259638">{{cite journal| author=Erdas E, Aste N, Pilloni L, Nicolosi A, Licheri S, Cappai A et al.| title=Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association? | journal=BMC Cancer | year= 2012 | volume= 12 | issue=  | pages= 614 | pmid=23259638 | doi=10.1186/1471-2407-12-614 | pmc=PMC3543729 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23259638  }} </ref>
Image:1024px-Confluent epidermal necrosis - intermed mag.jpg|'''Histology of confluent epidermal necrosis''' '''(intermed mag)'''<small>Source:By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=16874054</small><ref name=picture>Glucagonoma. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Confluent_epidermal_necrosis_-_high_mag.jpg</ref>


</gallery>
</gallery>
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Latest revision as of 22:28, 30 May 2019

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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] Mohammed Abdelwahed M.D[3]

Overview

Glucagonoma is a tumor of the alpha cells of the pancreas characterized by the excessive secretion of glucagon and necrolytic migratory erythema. Glucagonoma causes hyperglucagonemia, zinc deficiency, fatty acid deficiency, hypoaminoacidemia that may cause necrolytic migratory erythema. Glucagonoma may be a part of type 1 multiple endocrine neoplasia. It is an autosomal dominant syndrome that is usually caused by mutations in the MEN1 gene. MEN1 gene is a tumor suppressor gene and causes type 1 multiple endocrine neoplasia by Knudson's "two hits" model for tumor development. All glucagonomas are located in the pancreas, 50–80% occur in the pancreatic tail, 32.2% in the body and 21.9% in the head. Glucagonoma can metastasize mainly to the liver. Glucagonomas consist of pleomorphic cells containing granules that stain for other peptides, most frequently pancreatic polypeptide. Immunoperoxidase staining can detect glucagon within the tumor cells and glucagon.

Pathogenesis

Genetics

Glucagonoma may be part of type 1 multiple endocrine neoplasia. It is an autosomal dominant syndrome that is usually caused by mutations in the MEN1 gene.[1][2][3][4][5][6][7]

Gross Pathology

The gross pathology of glucagonoma may show:[7][8][9]

  • Large tumors at diagnosis with a mean diameter of 5 cm. About 50 to 82% have evidence of metastatic spread at presentation.
  • Tumors smaller than 2 cm in diameter are associated with a very low chance of malignancy.

Microscopic Pathology

The microscopic pathology of glucagonoma tumors in pancreas usually show intense staining for glucagon.[10][11]

Images

References

  1. ↑ Frankton S, Bloom SR (1996). "Gastrointestinal endocrine tumours. Glucagonomas". Baillieres Clin Gastroenterol. 10 (4): 697–705. PMID 9113318.
  2. ↑ Braverman IM (1982). ""Cutaneous manifestations of internal malignant tumors" by Becker, Kahn and Rothman, June 1942. Commentary: Migratory necrolytic erythema". Arch Dermatol. 118 (10): 784–98. PMID 6127984.
  3. ↑ Necrolytic migratory erythema. Wikipedia. https://en.wikipedia.org/wiki/Necrolytic_migratory_erythema. Accessed on October 13, 2015.
  4. ↑ Mullans EA, Cohen PR (1998). "Iatrogenic necrolytic migratory erythema: a case report and review of nonglucagonoma-associated necrolytic migratory erythema". J Am Acad Dermatol. 38 (5 Pt 2): 866–73. PMID 9591806.
  5. ↑ STURZBECHER M (1963). "[8 letters of Ferdinand von HEBRAS on his contributin to Virchow's Handbuch der Speziellen Pathologie and Therapie]". Z Haut Geschlechtskr. 34: 281–6. PMID 13978995.
  6. ↑ Wilson LA, Kuhn JA, Corbisiero RM, Smith M, Beatty JD, Williams LE; et al. (1992). "A technical analysis of an intraoperative radiation detection probe". Med Phys. 19 (5): 1219–23. doi:10.1118/1.596754. PMID 1435602.
  7. ↑ Castro PG, de León AM, Trancón JG, Martínez PA, Alvarez Pérez JA, Fernández Fernández JC; et al. (2011). "Glucagonoma syndrome: a case report". J Med Case Rep. 5: 402. doi:10.1186/1752-1947-5-402. PMC 3171381. PMID 21859461.
  8. ↑ Soga J, Yakuwa Y (1998). "Glucagonomas/diabetico-dermatogenic syndrome (DDS): a statistical evaluation of 407 reported cases". J Hepatobiliary Pancreat Surg. 5 (3): 312–9. PMID 9880781.
  9. ↑ Fang S, Li S, Cai T (2014). "Glucagonoma syndrome: a case report with focus on skin disorders". Onco Targets Ther. 7: 1449–53. doi:10.2147/OTT.S66285. PMC 4140234. PMID 25152626.
  10. ↑ Warner TF, Block M, Hafez GR, Mack E, Lloyd RV, Bloom SR (1983). "Glucagonomas. Ultrastructure and immunocytochemistry". Cancer. 51 (6): 1091–6. PMID 6295622.
  11. ↑ Mozell E, Stenzel P, Woltering EA, Rösch J, O'Dorisio TM (1990). "Functional endocrine tumors of the pancreas: clinical presentation, diagnosis, and treatment". Curr Probl Surg. 27 (6): 301–86. PMID 1973365.
  12. ↑ 12.0 12.1 12.2 Glucagonoma. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Confluent_epidermal_necrosis_-_high_mag.jpg

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