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==Overview== | ==Overview== | ||
==Pathogenesis== | ==Pathogenesis== | ||
* A glucagonoma is a rare tumor of the alpha cells of the pancreas that results in the overproduction of the hormone [[glucagon]]. | * A glucagonoma is a rare tumor of the [[alpha cells]] of the [[pancreas]] that results in the overproduction of the hormone [[glucagon]]. | ||
* It causes hyperglucagonemia, [[zinc deficiency]], [[fatty acid]] deficiency, hypoaminoacidemia that may cause necrolytic migratory erythema. | * It causes hyperglucagonemia, [[zinc deficiency]], [[fatty acid]] deficiency, [[Aminoacid|hypoaminoacidemia]] that may cause [[necrolytic migratory erythema]]. | ||
* The postulated mechanism for necrolytic migratory erythema involves | * The postulated mechanism for [[necrolytic migratory erythema]] involves excessive inflammation in the epidermis in response to trauma and to the necrolysis.<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> | ||
* Glucagon increases gluconeogenesis from amino acid substrates. This causes weight loss due to the catabolic action of glucagon.<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> | * Glucagon increases gluconeogenesis from amino acid substrates. This causes weight loss due to the [[Catabolism|catabolic]] action of glucagon.<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> | ||
* Necrolytic migratory erythema probably results from hyponutrition and amino acid deficiency.<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> | * [[Necrolytic migratory erythema]] probably results from hyponutrition and amino acid deficiency.<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> | ||
* Diarrhea may result from the secretion of gastrin occurs with | * [[Diarrhea]] may result from the secretion of [[gastrin]] occurs with hyperglucagonoma. | ||
== Genetics == | == Genetics == | ||
Glucagonoma may be part of multiple endocrine neoplasia type1 (MEN1). It is an autosomal dominant syndrome that is usually caused by mutations in the ''MEN1'' gene. | Glucagonoma may be part of multiple endocrine neoplasia type1 (MEN1). It is an autosomal dominant syndrome that is usually caused by mutations in the [[MEN1 syndrome|''MEN1'' gene]]. | ||
* It is characterized by the development of the following tumors:<sup>[[Multiple endocrine neoplasia type 1 pathophysiology#cite note-wikipedia-1|[1]]]</sup> | * It is characterized by the development of the following tumors:<sup>[[Multiple endocrine neoplasia type 1 pathophysiology#cite note-wikipedia-1|[1]]]</sup> | ||
* [[Pituitary adenoma|Pituitary adenomas]] | * [[Pituitary adenoma|Pituitary adenomas]] | ||
* [[Islet cell tumor|Islet cell tumors]] of the [[pancreas]] (commonly [[gastrinoma]] and glucagonoma) | * [[Islet cell tumor|Islet cell tumors]] of the [[pancreas]] (commonly [[gastrinoma]] and glucagonoma) | ||
* [[Parathyroid]] [[hyperplasia]] with resulting [[hyperparathyroidism]] | * [[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.<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>''MEN1'', spans about 10 Kb and consists of ten exons encoding a 610 [[amino acid]] nuclear protein, named menin.<sup>[[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid17014705-2|[2]]]</sup> | * 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.<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>''MEN1'', spans about 10 Kb and consists of ten exons encoding a 610 [[amino acid]] nuclear protein, named menin.<sup>[[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid17014705-2|[2]]]</sup> | ||
* ''MEN1'' [[gene]] is a putative [[tumor suppressor gene]] and causes type 1 multiple endocrine neoplasia by Knudson's "two hits" model for [[tumor]] development.<sup>[[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid7902574-7|[7]]]</sup> | * ''MEN1'' [[gene]] is a putative [[tumor suppressor gene]] and causes type 1 multiple endocrine neoplasia by Knudson's "two hits" model for [[tumor]] development.<sup>[[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid7902574-7|[7]]]</sup> | ||
* 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. | * 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. | ||
== Gross Pathology == | == Gross Pathology == | ||
* Glucagonomas are neuroendocrine tumors derived from multipotential stem cells. | * Glucagonomas are [[neuroendocrine tumors]] derived from [[Stem cells|multipotential stem cells]]. | ||
* Glucagonomas are generally large tumors at diagnosis with a mean diameter of 5 cm, From 50 to 82% have evidence of metastatic spread at presentation. | * Glucagonomas are generally large tumors at diagnosis with a mean diameter of 5 cm, From 50 to 82% have evidence of [[Metastasis|metastatic]] spread at presentation. | ||
* 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. | * 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, the location was extrapancreatic, such as in kidney, duodenum, lung, accessory pancreatic tissue. | * In few patients, the location was extrapancreatic, such as in [[Kidney|kidney,]] [[duodenum]], [[lung]], [[Accessory pancreatic|accessory pancreatic tissue]]. | ||
* Metastasis usually occurs to the liver. The most common site for distal metastases is the liver | * Metastasis usually occurs to the liver. The most common site for distal metastases is the liver. | ||
* Other sites are lymph nodes, bone, mesentery, lung, and adrenals.<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> | * Other sites are [[Lymph node|lymph nodes]], [[bone]], [[mesentery]], [[lung]], and [[Adrenal gland|adrenals]].<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> | ||
*Tumors below 2 cm in diameter are associated with a very low chance of malignancy. | *Tumors below 2 cm in diameter are associated with a very low chance of malignancy. | ||
==Microscopic Pathology== | ==Microscopic Pathology== | ||
* Many glucagonomas are | * Many glucagonomas are [[Pleomorphism|pleomorphic]]<ref name="pmid62956222">{{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> with cells containing granules that stain for other peptides, most frequently [[pancreatic polypeptide]].<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> | ||
* Glucagon is usually detectable within the tumor cells by immunoperoxidase staining, and glucagon mRNA may be detected. | * Glucagon is usually detectable within the tumor cells by [[Immunoperoxidase|immunoperoxidase staining]], and glucagon [[mRNA]] may be detected. | ||
* Electron microscopy reveals a variable number of secretory granules, indicative of their alpha cell origin. | * [[Electron|Electron microscopy]] reveals a variable number of secretory granules, indicative of their [[alpha cell]] origin. | ||
* Benign tumors are usually fully granulated, whereas malignant cells have fewer granules.<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> | * Benign tumors are usually fully granulated, whereas malignant cells have fewer granules.<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> | ||
Revision as of 16:39, 2 August 2017
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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
Pathogenesis
- A glucagonoma is a rare tumor of the alpha cells of the pancreas that results in the overproduction of the hormone glucagon.
- It causes hyperglucagonemia, zinc deficiency, fatty acid deficiency, hypoaminoacidemia that may cause necrolytic migratory erythema.
- The postulated mechanism for necrolytic migratory erythema involves excessive inflammation in the epidermis in response to trauma and to the necrolysis.[1][2]
- Glucagon increases gluconeogenesis from amino acid substrates. This causes weight loss due to the catabolic action of glucagon.[3]
- Necrolytic migratory erythema probably results from hyponutrition and amino acid deficiency.[4]
- Diarrhea may result from the secretion of gastrin occurs with hyperglucagonoma.
Genetics
Glucagonoma may be part of multiple endocrine neoplasia type1 (MEN1). It is an autosomal dominant syndrome that is usually caused by mutations in the MEN1 gene.
- It is characterized by the development of the following tumors:[1]
- Pituitary adenomas
- 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 tumors and by linkage analysis in multiple endocrine neoplasia type 1 families.[2][3][4][5][6]MEN1, spans about 10 Kb and consists of ten exons encoding a 610 amino acid nuclear protein, named menin.[2]
- MEN1 gene is a putative tumor suppressor gene and causes type 1 multiple endocrine neoplasia by Knudson's "two hits" model for tumor development.[7]
- two hits model for tumor development suggests that there is a germline mutation present in all 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 cells the survival advantage needed for tumor development.
Gross Pathology
- Glucagonomas are neuroendocrine tumors derived from multipotential stem cells.
- Glucagonomas are generally large tumors at diagnosis with a mean diameter of 5 cm, From 50 to 82% have evidence of metastatic spread at presentation.
- 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, the location was extrapancreatic, such as in kidney, duodenum, lung, accessory pancreatic tissue.
- Metastasis usually occurs to the liver. The most common site for distal metastases is the liver.
- Other sites are lymph nodes, bone, mesentery, lung, and adrenals.[5]
- Tumors below 2 cm in diameter are associated with a very low chance of malignancy.
Microscopic Pathology
- Many glucagonomas are pleomorphic[6] with cells containing granules that stain for other peptides, most frequently pancreatic polypeptide.[7]
- Glucagon is usually detectable within the tumor cells by immunoperoxidase staining, and glucagon mRNA may be detected.
- Electron microscopy reveals a variable number of secretory granules, indicative of their alpha cell origin.
- Benign tumors are usually fully granulated, whereas malignant cells have fewer granules.[8]
Images
-
![Confluent epidermal necrosis (high mag)[9]](/images/2/2d/800px-Confluent_epidermal_necrosis_-_high_mag.jpg)
Confluent epidermal necrosis (high mag)[9]
-
![Confluent epidermal necrosis (very high mag)[9]](/images/f/ff/1024px-Confluent_epidermal_necrosis_-_very_high_mag.jpg)
Confluent epidermal necrosis (very high mag)[9]
-
![Confluent epidermal necrosis (intermed mag)[9]](/images/7/70/1024px-Confluent_epidermal_necrosis_-_intermed_mag.jpg)
Confluent epidermal necrosis (intermed mag)[9]
-
![Confluent epidermal necrosis (low mag)[9]](/images/d/db/800px-Confluent_epidermal_necrosis_-_low_mag.jpg)
Confluent epidermal necrosis (low mag)[9]
-
![(A) Skin lesions affecting pretibial area. (B) Skin biopsy in necrolytic migratory erythema showing a zone of necrolysis and vacuolated keratinocytes[10]](/images/3/3b/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[10]
-
![Skin biopsy in necrolytic migratory erythema showing a large zone of necrolysis in the upper epidermis (arrow)[11]](/images/9/9a/NEM111.jpg)
Skin biopsy in necrolytic migratory erythema showing a large zone of necrolysis in the upper epidermis (arrow)[11]
-
![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).[12]](/images/3/3a/Glucagonoma%27.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).[12]
-
![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.[12]](/images/4/4d/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.[12]
-
![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)[12]](/images/7/7b/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)[12]
![Confluent epidermal necrosis (high mag)[9]](/index.php/File:800px-Confluent_epidermal_necrosis_-_high_mag.jpg)
![Confluent epidermal necrosis (very high mag)[9]](/index.php/File:1024px-Confluent_epidermal_necrosis_-_very_high_mag.jpg)
![Confluent epidermal necrosis (intermed mag)[9]](/index.php/File:1024px-Confluent_epidermal_necrosis_-_intermed_mag.jpg)
![Confluent epidermal necrosis (low mag)[9]](/index.php/File:800px-Confluent_epidermal_necrosis_-_low_mag.jpg)
![(A) Skin lesions affecting pretibial area. (B) Skin biopsy in necrolytic migratory erythema showing a zone of necrolysis and vacuolated keratinocytes[10]](/index.php/File:1752-1947-5-402-1.jpg){kind=small}
![Skin biopsy in necrolytic migratory erythema showing a large zone of necrolysis in the upper epidermis (arrow)[11]](/index.php/File:NEM111.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).[12]](/index.php/File:Glucagonoma%27.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.[12]](/index.php/File:Gross1.jpg){kind=small}
![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)[12]](/index.php/File:Histo.jpg){kind=small}
References
- ↑ Necrolytic migratory erythema. Wikipedia. https://en.wikipedia.org/wiki/Necrolytic_migratory_erythema. Accessed on October 13, 2015.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Warner TF, Block M, Hafez GR, Mack E, Lloyd RV, Bloom SR (1983). "Glucagonomas. Ultrastructure and immunocytochemistry". Cancer. 51 (6): 1091–6. PMID 6295622.
- ↑ Warner TF, Block M, Hafez GR, Mack E, Lloyd RV, Bloom SR (1983). "Glucagonomas. Ultrastructure and immunocytochemistry". Cancer. 51 (6): 1091–6. PMID 6295622.
- ↑ 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.
- ↑ 9.0 9.1 9.2 9.3 Glucagonoma. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Confluent_epidermal_necrosis_-_high_mag.jpg
- ↑ 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.
- ↑ 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.
- ↑ 12.0 12.1 12.2 Erdas E, Aste N, Pilloni L, Nicolosi A, Licheri S, Cappai A; et al. (2012). "Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?". BMC Cancer. 12: 614. doi:10.1186/1471-2407-12-614. PMC 3543729. PMID 23259638.
