Pheochromocytoma pathophysiology: Difference between revisions
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==Overview== | ==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|microscopic histopathological]] analysis, nesting (Zellballen) pattern composed of well-defined clusters of tumor cells separated by fibrovascular stroma is a characteristic finding. It may be benign or malignant, | Pheochromocytoma arises from chromaffin cells of the adrenal medulla.On [[gross pathology]], pheochromocytoma has a multinodular and a multicentric pattern of growth. On [[microscopic|microscopic histopathological]] analysis, nesting (Zellballen) pattern composed of well-defined clusters of tumor cells separated by fibrovascular stroma is a characteristic finding. It may be benign or malignant, familial origin([[multiple endocrine neoplasia]] type 2) or sporadic one. Both of them have genetic origin depends on a large number of genes: [[Von Hippel-Lindau tumor suppressor|VHL]], [[SDH|SDH,]] [[NF1]], [[RET proto-oncogene|RET]]. | ||
==Pathophysiology== | ==Pathophysiology== | ||
Pheochromocytoma arises from chromaffin cells of the adrenal medulla and sympathetic ganglia. | 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 the ability to spread locally and distant. <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> | ||
Malignant and benign pheochromocytomas share the same biochemical and histological features, the only difference is the ability to spread locally and distant. <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> | |||
==Genetics== | ==Genetics== | ||
* Pheochromocytomas can be familial and occur in patients with [[multiple endocrine neoplasia]]<nowiki/>s (MEN 2 and MEN 3). | * Pheochromocytomas can be familial and occur in patients with [[multiple endocrine neoplasia]]<nowiki/>s (MEN 2 and MEN 3). | ||
* Patients with Von Hippel Lindau ([[VHL]]) may also develop pheochromocytoma.<ref name="pmid24642075">{{cite journal| author=Shuch B, Ricketts CJ, Metwalli AR, Pacak K, Linehan WM| title=The genetic basis of pheochromocytoma and paraganglioma: implications for management. | journal=Urology | year= 2014 | volume= 83 | issue= 6 | pages= 1225-32 | pmid=24642075 | doi=10.1016/j.urology.2014.01.007 | pmc=4572836 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24642075 }}</ref> | * Patients with Von Hippel Lindau ([[VHL]]) may also develop pheochromocytoma.<ref name="pmid24642075">{{cite journal| author=Shuch B, Ricketts CJ, Metwalli AR, Pacak K, Linehan WM| title=The genetic basis of pheochromocytoma and paraganglioma: implications for management. | journal=Urology | year= 2014 | volume= 83 | issue= 6 | pages= 1225-32 | pmid=24642075 | doi=10.1016/j.urology.2014.01.007 | pmc=4572836 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24642075 }}</ref> | ||
* It is autosomal dominant inheritance and has two pathways of tumor pathogenesis. Cluster 1 tumors are noradrenergic. Cluster 2 tumors are adrenergic.<ref name="pmid23933153">{{cite journal| author=King KS, Pacak K| title=Familial pheochromocytomas and paragangliomas. | journal=Mol Cell Endocrinol | year= 2014 | volume= 386 | issue= 1-2 | pages= 92-100 | pmid=23933153 | doi=10.1016/j.mce.2013.07.032 | pmc=3917973 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23933153 }}</ref> | * It is [[Autosomal dominant inheritance|autosomal dominant]] inheritance and has two pathways of tumor pathogenesis. Cluster 1 tumors are [[noradrenergic]]. Cluster 2 tumors are [[adrenergic]].<ref name="pmid23933153">{{cite journal| author=King KS, Pacak K| title=Familial pheochromocytomas and paragangliomas. | journal=Mol Cell Endocrinol | year= 2014 | volume= 386 | issue= 1-2 | pages= 92-100 | pmid=23933153 | doi=10.1016/j.mce.2013.07.032 | pmc=3917973 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23933153 }}</ref> | ||
{| class="wikitable" | {| class="wikitable" | ||
!Cluster 1 | !Cluster 1 | ||
| Line 24: | Line 17: | ||
|- | |- | ||
! | ! | ||
* Succinate dehydrogenase (SDH) subunit genes | * [[Succinate dehydrogenase]] (SDH) subunit genes | ||
* Von Hippel-Lindau (VHL) disease | * [[Von Hippel-Lindau Disease|Von Hippel-Lindau]] (VHL) disease | ||
* Fumarate hydratase gene mutations | * [[Fumarate hydratase|Fumarate hydratase gene]] mutations | ||
| | | | ||
* '''Multiple endocrine neoplasia type 2A''' | * '''[[Multiple endocrine neoplasia, type 2|Multiple endocrine neoplasia]] type 2A''' | ||
* '''Multiple endocrine neoplasia type 2B''' | * '''[[Multiple endocrine neoplasia (MEN 2b),|Multiple endocrine neoplasia]] type 2B''' | ||
* '''Neurofibromatosis type 1 (NF1)''' | * '''[[Neurofibromatosis type I|Neurofibromatosis type 1]] (NF1)''' | ||
|} | |} | ||
. Patients with the succinate dehydrogenase B mutations are likely to develop a malignant disease.<ref name="pmid15328326">{{cite journal| author=Neumann HP, Pawlu C, Peczkowska M, Bausch B, McWhinney SR, Muresan M et al.| title=Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. | journal=JAMA | year= 2004 | volume= 292 | issue= 8 | pages= 943-51 | pmid=15328326 | doi=10.1001/jama.292.8.943 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15328326 }}</ref> | . Patients with the [[Succinate dehydrogenase|succinate dehydrogenase B]] mutations are likely to develop a malignant disease.<ref name="pmid15328326">{{cite journal| author=Neumann HP, Pawlu C, Peczkowska M, Bausch B, McWhinney SR, Muresan M et al.| title=Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. | journal=JAMA | year= 2004 | volume= 292 | issue= 8 | pages= 943-51 | pmid=15328326 | doi=10.1001/jama.292.8.943 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15328326 }}</ref> | ||
==Associated conditions== | ==Associated conditions== | ||
* Pheochromocytoma can be part of other syndromes named Multiple endocrine neoplasias (MEN2) Which are autosomal dominant syndromes controlled by RET gene. Pheochromocytoma occurs in 50% of patients with | * Pheochromocytoma can be part of other syndromes named [[Multiple endocrine neoplasia|Multiple endocrine neoplasias]] (MEN2) Which are [[Autosomal dominant inheritance|autosomal dominant]] syndromes controlled by [[RET proto-oncogene|RET gene]]. Pheochromocytoma occurs in 50% of patients with [[MEN2]] as follows: | ||
{| class="wikitable" | {| class="wikitable" | ||
!MEN1 | !MEN1 | ||
| Line 41: | Line 34: | ||
|- | |- | ||
| rowspan="3" | | | rowspan="3" | | ||
* Medullary thyroid cancer | * [[Medullary thyroid cancer]] | ||
* Pheochromocytoma | * [[Pheochromocytoma]] | ||
* Primary hyperparathyroidism | * [[Primary hyperparathyroidism]] | ||
| | | | ||
* Medullary thyroid cancer | * [[Medullary thyroid cancer]] | ||
* Pheochromocytoma | * [[Pheochromocytoma]] | ||
* Mucosal neuromas | * [[Neuroma|Mucosal neuromas]] | ||
* Marfanoid habitus | * [[Marfan's syndrome|Marfanoid habitus]] | ||
|- | |- | ||
|- | |- | ||
Revision as of 16:59, 31 July 2017
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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 composed of well-defined clusters of tumor cells separated by fibrovascular stroma is a characteristic finding. It may be benign or malignant, familial origin(multiple endocrine neoplasia type 2) or sporadic one. Both of them have genetic origin depends on a large number of genes: VHL, SDH, NF1, RET.
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 the ability to spread locally and distant. [1]
Genetics
- Pheochromocytomas can be familial and occur in patients with multiple endocrine neoplasias (MEN 2 and MEN 3).
- Patients with Von Hippel Lindau (VHL) may also develop pheochromocytoma.[2]
- It is autosomal dominant inheritance and has two pathways of tumor pathogenesis. Cluster 1 tumors are noradrenergic. Cluster 2 tumors are adrenergic.[3]
| Cluster 1 | Cluster 2 |
|---|---|
|
|
. Patients with the succinate dehydrogenase B mutations are likely to develop a malignant disease.[4]
Associated conditions
- Pheochromocytoma can be part of other syndromes named Multiple endocrine neoplasias (MEN2) 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.
-
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.
-
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.
_histopathology.jpg)
_histopathology.jpg)
_histopathology.jpg)
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.
- ↑ 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.