Pheochromocytoma pathophysiology: Difference between revisions
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==Pathophysiology== | ==Pathophysiology== | ||
Pheochromocytoma arises from [[chromaffin cells]] of the [[adrenal medulla]] and [[Sympathetic ganglion|sympathetic ganglia]]. [[Malignant]] and [[benign]] pheochromocytomas share the same [[biochemical]] and [[histological]] features, the only difference is to have a distant spread or be locally invasive. <ref name="pmid10363888">{{cite journal| author=Goldstein RE, O'Neill JA, Holcomb GW, Morgan WM, Neblett WW, Oates JA et al.| title=Clinical experience over 48 years with pheochromocytoma. | journal=Ann Surg | year= 1999 | volume= 229 | issue= 6 | pages= 755-64; discussion 764-6 | pmid=10363888 | doi= | pmc=1420821 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10363888 }}</ref> | * Pheochromocytoma arises from [[chromaffin cells]] of the [[adrenal medulla]] and [[Sympathetic ganglion|sympathetic ganglia]]. [[Malignant]] and [[benign]] pheochromocytomas share the same [[biochemical]] and [[histological]] features, the only difference is to have a distant spread or be locally invasive. <ref name="pmid10363888">{{cite journal| author=Goldstein RE, O'Neill JA, Holcomb GW, Morgan WM, Neblett WW, Oates JA et al.| title=Clinical experience over 48 years with pheochromocytoma. | journal=Ann Surg | year= 1999 | volume= 229 | issue= 6 | pages= 755-64; discussion 764-6 | pmid=10363888 | doi= | pmc=1420821 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10363888 }}</ref> | ||
* Epinephrine acts on nearly all body tissues. Its actions vary by tissue type and tissue expression of adrenergic receptors. | |||
* Epinephrine is a nonselective agonist of all adrenergic receptors, including the major subtypes α<sub>1</sub>, α<sub>2</sub>, β<sub>1</sub>, β<sub>2</sub>, and β<sub>3:</sub> | |||
* Binding to α<sub>1</sub> receptors causing vasoconstriction and to increase cardiac output via its binding to β<sub>1</sub> receptors. Binding to α-adrenergic receptors inhibits insulin secretion by the pancreas, stimulates glycogenolysis in the liver and muscle, and stimulates glycolysis and inhibits insulin-mediated glycogenesis in muscle. | |||
==Genetics== | ==Genetics== | ||
* 60-65 percent of pheochromocytomas are sporadic.<ref name="pmid6103678">{{cite journal |vauthors=Webb TA, Sheps SG, Carney JA |title=Differences between sporadic pheochromocytoma and pheochromocytoma in multiple endocrime neoplasia, type 2 |journal=Am. J. Surg. Pathol. |volume=4 |issue=2 |pages=121–6 |year=1980 |pmid=6103678 |doi= |url=}}</ref><ref name="pmid3474647">{{cite journal |vauthors=Yee JK, Moores JC, Jolly DJ, Wolff JA, Respess JG, Friedmann T |title=Gene expression from transcriptionally disabled retroviral vectors |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue=15 |pages=5197–201 |year=1987 |pmid=3474647 |pmc=298821 |doi= |url=}}</ref> | * 60-65 percent of pheochromocytomas are sporadic.<ref name="pmid6103678">{{cite journal |vauthors=Webb TA, Sheps SG, Carney JA |title=Differences between sporadic pheochromocytoma and pheochromocytoma in multiple endocrime neoplasia, type 2 |journal=Am. J. Surg. Pathol. |volume=4 |issue=2 |pages=121–6 |year=1980 |pmid=6103678 |doi= |url=}}</ref><ref name="pmid3474647">{{cite journal |vauthors=Yee JK, Moores JC, Jolly DJ, Wolff JA, Respess JG, Friedmann T |title=Gene expression from transcriptionally disabled retroviral vectors |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue=15 |pages=5197–201 |year=1987 |pmid=3474647 |pmc=298821 |doi= |url=}}</ref> | ||
Revision as of 13:57, 16 August 2017
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Pheochromocytoma Microchapters |
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Pheochromocytoma pathophysiology On the Web |
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Risk calculators and risk factors for Pheochromocytoma pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmad Al Maradni, M.D. [2] Mohammed Abdelwahed M.D[3]
Overview
Pheochromocytoma arises from chromaffin cells of the adrenal medulla.On gross pathology, pheochromocytoma has a multinodular and a multicentric pattern of growth. On microscopic histopathological analysis, nesting (Zellballen) pattern is composed of well-defined clusters of tumor cells separated by fibrovascular stroma. It may be benign, malignant, familial(multiple endocrine neoplasia 1 and type 2B) or sporadic. All of these forms have genetic origin depending on a large number of genes, for example, VHL, SDH, NF1, RET genes.
Pathophysiology
- Pheochromocytoma arises from chromaffin cells of the adrenal medulla and sympathetic ganglia. Malignant and benign pheochromocytomas share the same biochemical and histological features, the only difference is to have a distant spread or be locally invasive. [1]
- Epinephrine acts on nearly all body tissues. Its actions vary by tissue type and tissue expression of adrenergic receptors.
- Epinephrine is a nonselective agonist of all adrenergic receptors, including the major subtypes α1, α2, β1, β2, and β3:
- Binding to α1 receptors causing vasoconstriction and to increase cardiac output via its binding to β1 receptors. Binding to α-adrenergic receptors inhibits insulin secretion by the pancreas, stimulates glycogenolysis in the liver and muscle, and stimulates glycolysis and inhibits insulin-mediated glycogenesis in muscle.
Genetics
- Pheochromocytomas can be familial and occur in patients with multiple endocrine neoplasias (MEN1 and MEN 2B).
- Patients with Von Hippel Lindau disease (VHL) may also develop pheochromocytoma.[4]
- It has autosomal dominant inheritance and has two pathways of tumor pathogenesis. Cluster 1 tumors are noradrenergic. Cluster 2 tumors are adrenergic.[5]
| Familial pheocromocytomas | |
|---|---|
| Cluster 1 (Noradrenergic) | Cluster 2 (Adrenergic) |
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- Patients with the succinate dehydrogenase B mutations are likely to develop a malignant disease.[6]
Associated conditions
- Pheochromocytoma can be part of other syndromes named multiple endocrine neoplasias (MEN1 and MEN2B), which are autosomal dominant syndromes controlled by RET gene. Pheochromocytoma occurs in 50% of patients with MEN2 as follows:
| MEN1 | MEN2 |
|---|---|
Gross Pathology
On gross pathology, A multinodular and multicentric pattern of growth of pheochromocytoma may be seen.
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Bilateral pheochromocytoma in MEN2. Gross image.
Microscopic Pathology
On microscopic pathology, Pheochromocytoma typically demonstrates a nesting (Zellballen) pattern on microscopy. This pattern is composed of well-defined clusters of tumor cells containing eosinophilic cytoplasm separated by fibrovascular stroma.
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Micrograph of pheochromocytoma.
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Histopathology of adrenal pheochromocytoma. Adrenectomy specimen.
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Micrograph of pheochromocytoma.
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Micrograph of pheochromocytoma.
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Videos
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References
- ↑ Goldstein RE, O'Neill JA, Holcomb GW, Morgan WM, Neblett WW, Oates JA; et al. (1999). "Clinical experience over 48 years with pheochromocytoma". Ann Surg. 229 (6): 755–64, discussion 764-6. PMC 1420821. PMID 10363888.
- ↑ Webb TA, Sheps SG, Carney JA (1980). "Differences between sporadic pheochromocytoma and pheochromocytoma in multiple endocrime neoplasia, type 2". Am. J. Surg. Pathol. 4 (2): 121–6. PMID 6103678.
- ↑ Yee JK, Moores JC, Jolly DJ, Wolff JA, Respess JG, Friedmann T (1987). "Gene expression from transcriptionally disabled retroviral vectors". Proc. Natl. Acad. Sci. U.S.A. 84 (15): 5197–201. PMC 298821. PMID 3474647.
- ↑ Shuch B, Ricketts CJ, Metwalli AR, Pacak K, Linehan WM (2014). "The genetic basis of pheochromocytoma and paraganglioma: implications for management". Urology. 83 (6): 1225–32. doi:10.1016/j.urology.2014.01.007. PMC 4572836. PMID 24642075.
- ↑ King KS, Pacak K (2014). "Familial pheochromocytomas and paragangliomas". Mol Cell Endocrinol. 386 (1–2): 92–100. doi:10.1016/j.mce.2013.07.032. PMC 3917973. PMID 23933153.
- ↑ Neumann HP, Pawlu C, Peczkowska M, Bausch B, McWhinney SR, Muresan M; et al. (2004). "Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations". JAMA. 292 (8): 943–51. doi:10.1001/jama.292.8.943. PMID 15328326.