Glucagonoma pathophysiology: Difference between revisions

Jump to navigation Jump to search
mNo edit summary
 
(3 intermediate revisions by 3 users not shown)
Line 13: Line 13:
** The mechanism for [[necrolytic migratory erythema]] involves excessive inflammation in the epidermis in response to trauma and to the necrolysis.
** The mechanism for [[necrolytic migratory erythema]] involves excessive inflammation in the epidermis in response to trauma and to the necrolysis.
** [[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.
** [[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]] occurs with glucagonoma.
** [[Diarrhea]] may result from the secretion of [[gastrin]] which occurs with glucagonoma.


== Genetics ==
== Genetics ==
Line 28: Line 28:
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>
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>


* Large tumors at diagnosis with a mean diameter of 5 cm, From 50 to 82% have evidence of [[Metastasis|metastatic]] spread at presentation.
* Large tumors at diagnosis with a mean diameter of 5 cm. About 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|kidney,]] [[duodenum]], [[lung]], [[Accessory pancreas|accessory pancreatic tissue]].
* In few patients, location can be [[extrapancreatic]], such as in [[Kidney|kidney,]] [[duodenum]], [[lung]], [[Accessory pancreas|accessory pancreatic tissue]].


* Metastasis usually occurs to [[Liver|the liver]]. Other sites are [[Lymph node|lymph nodes]], [[bone]], [[lung]], and [[Adrenal gland|adrenals]].
* Metastasis usually occurs to [[Liver|the liver]]. Other sites are [[Lymph node|lymph nodes]], [[bone]], [[lung]], and [[Adrenal gland|adrenals]].


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


==Microscopic Pathology==
==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>
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]].
* 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.
* [[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]].
* [[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.
* Benign tumors are usually fully granulated and [[malignant]] cells have fewer granules.
*Skin biopsy may depict epidermal necrosis.
*[[Skin biopsy]] may depict [[Epidermal|epidermal necrosis]].


===Images===
===Images===
Line 52: Line 52:


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>
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>
Image:800px-Confluent epidermal necrosis - low mag.jpg|'''Histology of confluent epidermal necrosis (low 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: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: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>


</gallery>
</gallery>
Line 70: Line 62:
[[Category:Medicine]]
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Endocrinology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Gastroenterology]]
[[Category:Surgery]]

Latest revision as of 22:28, 30 May 2019

Glucagonoma Microchapters

Home

Patient Information

Overview

Historical Perspective

Pathophysiology

Causes

Differentiating Glucagonoma from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Staging

History and Symptoms

Physical Examination

Laboratory Findings

Chest X Ray

CT

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Glucagonoma pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Glucagonoma pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Glucagonoma pathophysiology

CDC on Glucagonoma pathophysiology

Glucagonoma pathophysiology in the news

Blogs on Glucagonoma pathophysiology

Directions to Hospitals Treating Glucagonoma

Risk calculators and risk factors for Glucagonoma pathophysiology

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

Template:WH Template:WS