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{{Malignant peripheral nerve sheath tumor}}
{{Malignant peripheral nerve sheath tumor}}
{{CMG}}; {{AE}} {{SC}}
{{CMG}}; {{AE}} {{Marjan}}
==Overview==
==Overview==
==Causes==
On gross pathology, a large firm [[mass]] with [[necrosis]] and [[hemorrhage]] is the characteristic finding of malignant peripheral nerve sheath tumor. On microscopic histopathological analysis, [[spindle cells]], nuclear atypia, [[mitoses]], and a herring bone pattern are characteristic findings of malignant peripheral nerve sheath tumor.<ref name=libre>Malignant peripheral nerve sheath tumor. Librepathology 2015. http://librepathology.org/wiki/index.php/Malignant_peripheral_nerve_sheath_tumour</ref> The [[neurofibromatosis type I]] (NF1) gene is involved in the pathogenesis of malignant peripheral nerve sheath tumor.<ref>{{cite journal|last=Ferrari|first=Andrea|author2=Gianni Bisogno |author3=Modesto Carli |title=Management Of Childhood Malignant Peripheral Nerve Sheath Tumor | journal=Pediatric Drugs | date=2007|volume=9|issue=4|pages=239–48|accessdate=5 Mar 2014 | pmid=17705563 | doi=10.2165/00148581-200709040-00005}}</ref>
Soft tissue sarcomas have been linked within families, so it is hypothesized that neurofibrosarcoma may be genetic, although researchers still do not know the exact cause of the disease. Evidence supporting this hypothesis includes loss of [[heterozygosity]] on the 17p chromosome. The [[p53]] (a tumor suppressor gene in the normal population) genome on 17p in neurofibrosarcoma patients is mutated, increasing the probability of cancerThe normal p53 gene will regulate cell growth and inhibit any uncontrollable cell growth in the healthy population; since p53 is inactivated in neurofibrosarcoma patients, they are much more susceptible to developing tumors.


===Genetics===
==Pathogenesis==
A malignant peripheral nerve sheath tumor is rare, but is one of the most common frequent soft tissue sarcoma in the pediatrics population. About half of these cases also happen to occur along with NF1, which is a genetic mutation on the 17th chromosome which causes tumors along the nervous system. The lifetime risk of having both of these conditions is at 8–13% while those with only MPNST have a 0.001% in the general population.<ref>{{cite journal|last=Ferrari|first=Andrea|author2=Gianni Bisogno |author3=Modesto Carli  |title=Management Of Childhood Malignant Peripheral Nerve Sheath Tumor | journal=Pediatric Drugs | date=2007|volume=9|issue=4|pages=239–48|accessdate=5 Mar 2014 | pmid=17705563 | doi=10.2165/00148581-200709040-00005}}</ref>
* Malignant peripheral nerve sheath tumors are a rare type of cancer that arise from the [[soft tissue]] that surrounds [[nerves]]. They are a type of [[sarcoma]]. Most malignant peripheral nerve sheath tumors arise from the [[nerve plexus]]es that distribute nerves into the limbs&mdash;the [[brachial plexus|brachial]] and [[lumbar plexus|lumbar]] plexuses&mdash;or from nerves as they arise from the trunk.<ref name="Panigrahi">{{Cite journal | pmid = 24174807| doi = 10.4103/0976-3147.116480| title = Primary malignant peripheral nerve sheath tumor at unusual location| journal = Journal of Neurosciences in Rural Practice| volume = 4| issue = 5| pages = 83| year = 2013| last1 = Panigrahi | first1 = S. | last2 = Mishra | first2 = S. | last3 = Das | first3 = S. | last4 = Dhir | first4 = M. | pmc=3808069}}</ref>
NF1 and MPNST are categorized as autosomal dominant disorders. This means when one receives an abnormal gene from one of their parents, they will ultimately have that disorder. That person has a 50/50 chance of passing on that gene to their offspring. The pedigree to the right describes this genetic pattern.
 
==Genetics==
*The genotypic hallmark of NF1 involves mutations to or other loss of the 350 kilobase gene NF1 on the long arm of chromosome 17, which encodes the tumor suppressor protein neurofibromin.
*NF1 inactivation leads to ras hyperactivity and consequent activation of multiple downstream survival and proliferative pathways, including the mitogen-activated protein kinase (MAPK), mammalian target of rapamycin (mTOR), and AKT (Mouse breed AK thymoma, also termed protein kinase B, or PKB) pathways.
*Molecular pathways from neurofibroma to MPNST in NF1 syndrome remains uncertain, although NF1 deficiency in and of itself is clearly insufficient, given that only approximately 10% of all NF1 patients eventually develop MPNST.
 
* About half of the cases of malignant peripheral nerve sheath tumor (MPNST) occur along with [[NF1]]. The lifetime risk of having both of these conditions is at 8–13% while those with only MPNST have a 0.001% in the general population.<ref>{{cite journal|last=Ferrari|first=Andrea|author2=Gianni Bisogno |author3=Modesto Carli  |title=Management Of Childhood Malignant Peripheral Nerve Sheath Tumor | journal=Pediatric Drugs | date=2007|volume=9|issue=4|pages=239–48|accessdate=5 Mar 2014 | pmid=17705563 | doi=10.2165/00148581-200709040-00005}}</ref>
 
*A recent study in a genetically engineered mouse model showed that EGFR overexpression was sufficient to transform neurofibroma into MPNST via Janus kinase 2/signal transducer and activator of transcription 3 (STAT3) activation.


==Pathogenesis==
*Recent studies have demonstrated that there is an overall downregulation of genes in MPNST as compared with neurofibromas
Malignant peripheral nerve sheath tumors are a rare type of cancer that arise from the soft tissue that surrounds nerves. They are a type of sarcoma. Most malignant peripheral nerve sheath tumors arise from the [[nerve plexus]]es that distribute nerves into the limbs&mdash;the [[brachial plexus|brachial]] and [[lumbar plexus|lumbar]] plexuses&mdash;or from nerves as they arise from the trunk.<ref name="Panigrahi">{{Cite journal | pmid = 24174807| doi = 10.4103/0976-3147.116480| title = Primary malignant peripheral nerve sheath tumor at unusual location| journal = Journal of Neurosciences in Rural Practice| volume = 4| issue = 5| pages = 83| year = 2013| last1 = Panigrahi | first1 = S. | last2 = Mishra | first2 = S. | last3 = Das | first3 = S. | last4 = Dhir | first4 = M. | pmc=3808069}}</ref>
 
* The [[NF1]] gene locus is on chromosome 17q11.2 and the gene product is [[neurofibromin]], acts as a tumour suppressor; inactivation of the gene thus predisposes to [[tumour]] development.<ref>{{cite book | last = Albright | first = A | title = Principles and practice of pediatric neurosurgery | publisher = Thieme | location = New York | year = 2008 | isbn = 1588903958 }}</ref
 
*MPNSTs are known to have complex karyotypes, with an average of 18 aberrations per tumor based on metaphase comparative genomic hybridization analysis.
 
*Common karyotypic changes include gains from chromosome arms 7p, 8q, and 17q, and losses from 9p, 11q, 13q, and 17p
 
==Gross Pathology==
* Large and firm [[mass]]<ref name="pmid16327434">{{cite journal| author=Fetsch JF, Laskin WB, Miettinen M| title=Nerve sheath myxoma: a clinicopathologic and immunohistochemical analysis of 57 morphologically distinctive, S-100 protein- and GFAP-positive, myxoid peripheral nerve sheath tumors with a predilection for the extremities and a high local recurrence rate. | journal=Am J Surg Pathol | year= 2005 | volume= 29 | issue= 12 | pages= 1615-24 | pmid=16327434 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16327434  }} </ref>
* [[Necrosis]]
* [[Hemorrhage]]
 
==Microscopic Pathology==
*Histologic features of MPNST are rather nonspecific.
*tumors are composed of monotonous spindle cells arranged in intersecting fascicles.
*Hypercellular and hypocellular areas may be present often with hypercellular areas localized in close proximity to blood vessels.
*Malignant peripheral nerve sheath tumors demonstrate a marked increase in tumor cellularity, pleomorphism, and mitotic activity and show a more organized cellular growth pattern, with less extracellular matrix material when compared with benign neurofibromas.
*Malignant peripheral nerve sheath tumors demonstrating skeletal muscle differentiation are particularly aggressive and associated with poor prognosis.
*There is no pathognomonic molecular or immunohistochemical study for malignant peripheral nerve sheath tumors.
*S100 protein is weakly and patchily present in <50% of cases.
*The most reliable method of diagnosis remains electron microscopy, which can identify ultrastructural features of Schwann cells.
<gallery>
Image:
Malignant_peripheral_nerve_sheath_tumour.jpg|Malignant peripheral nerve sheath tumor<ref name=libre>Malignant peripheral nerve sheath tumor. Librepathology 2015. http://librepathology.org/wiki/index.php/Malignant_peripheral_nerve_sheath_tumour</ref>
</gallery>


==References==
==References==
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Latest revision as of 13:18, 23 August 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Marjan Khan M.B.B.S.[2]

Overview

On gross pathology, a large firm mass with necrosis and hemorrhage is the characteristic finding of malignant peripheral nerve sheath tumor. On microscopic histopathological analysis, spindle cells, nuclear atypia, mitoses, and a herring bone pattern are characteristic findings of malignant peripheral nerve sheath tumor.[1] The neurofibromatosis type I (NF1) gene is involved in the pathogenesis of malignant peripheral nerve sheath tumor.[2]

Pathogenesis

  • Malignant peripheral nerve sheath tumors are a rare type of cancer that arise from the soft tissue that surrounds nerves. They are a type of sarcoma. Most malignant peripheral nerve sheath tumors arise from the nerve plexuses that distribute nerves into the limbs—the brachial and lumbar plexuses—or from nerves as they arise from the trunk.[3]

Genetics

  • The genotypic hallmark of NF1 involves mutations to or other loss of the 350 kilobase gene NF1 on the long arm of chromosome 17, which encodes the tumor suppressor protein neurofibromin.
  • NF1 inactivation leads to ras hyperactivity and consequent activation of multiple downstream survival and proliferative pathways, including the mitogen-activated protein kinase (MAPK), mammalian target of rapamycin (mTOR), and AKT (Mouse breed AK thymoma, also termed protein kinase B, or PKB) pathways.
  • Molecular pathways from neurofibroma to MPNST in NF1 syndrome remains uncertain, although NF1 deficiency in and of itself is clearly insufficient, given that only approximately 10% of all NF1 patients eventually develop MPNST.
  • About half of the cases of malignant peripheral nerve sheath tumor (MPNST) occur along with NF1. The lifetime risk of having both of these conditions is at 8–13% while those with only MPNST have a 0.001% in the general population.[4]
  • A recent study in a genetically engineered mouse model showed that EGFR overexpression was sufficient to transform neurofibroma into MPNST via Janus kinase 2/signal transducer and activator of transcription 3 (STAT3) activation.
  • Recent studies have demonstrated that there is an overall downregulation of genes in MPNST as compared with neurofibromas

Microscopic Pathology

  • Histologic features of MPNST are rather nonspecific.
  • tumors are composed of monotonous spindle cells arranged in intersecting fascicles.
  • Hypercellular and hypocellular areas may be present often with hypercellular areas localized in close proximity to blood vessels.
  • Malignant peripheral nerve sheath tumors demonstrate a marked increase in tumor cellularity, pleomorphism, and mitotic activity and show a more organized cellular growth pattern, with less extracellular matrix material when compared with benign neurofibromas.
  • Malignant peripheral nerve sheath tumors demonstrating skeletal muscle differentiation are particularly aggressive and associated with poor prognosis.
  • There is no pathognomonic molecular or immunohistochemical study for malignant peripheral nerve sheath tumors.
  • S100 protein is weakly and patchily present in <50% of cases.
  • The most reliable method of diagnosis remains electron microscopy, which can identify ultrastructural features of Schwann cells.

References

  1. 1.0 1.1 Malignant peripheral nerve sheath tumor. Librepathology 2015. http://librepathology.org/wiki/index.php/Malignant_peripheral_nerve_sheath_tumour
  2. Ferrari, Andrea; Gianni Bisogno; Modesto Carli (2007). "Management Of Childhood Malignant Peripheral Nerve Sheath Tumor". Pediatric Drugs. 9 (4): 239–48. doi:10.2165/00148581-200709040-00005. PMID 17705563. |access-date= requires |url= (help)
  3. Panigrahi, S.; Mishra, S.; Das, S.; Dhir, M. (2013). "Primary malignant peripheral nerve sheath tumor at unusual location". Journal of Neurosciences in Rural Practice. 4 (5): 83. doi:10.4103/0976-3147.116480. PMC 3808069. PMID 24174807.
  4. Ferrari, Andrea; Gianni Bisogno; Modesto Carli (2007). "Management Of Childhood Malignant Peripheral Nerve Sheath Tumor". Pediatric Drugs. 9 (4): 239–48. doi:10.2165/00148581-200709040-00005. PMID 17705563. |access-date= requires |url= (help)

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