Optic nerve glioma pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
Simrat Sarai (talk | contribs)
CMEUser, nocaptcha
5,683 edits
Created page with "__NOTOC__ {{Optic nerve glioma}} {{CMG}}{{AE}}{{Simrat}} ==Overview== ==Pathophysiology== Gross pathology of resected tumors reveals a smooth, fusiform intradural lesion. Macr..."
 
Aditya Ganti (talk | contribs)
Bureaucrats, bureaucrats, nocaptcha, Administrators
11,402 edits
 
(43 intermediate revisions by 3 users not shown)
Line 3: Line 3:
{{CMG}}{{AE}}{{Simrat}}
{{CMG}}{{AE}}{{Simrat}}
==Overview==
==Overview==
==Pathophysiology==
[[Genes]] involved in the pathogenesis of optic nerve glioma include ''BRAF-KIAA'', [[tumor suppressor genes]] and [[chromosomes]] 7q34 and 17q. On gross [[pathology]], smooth and [[fusiform]] intradural [[lesions]] are  characteristic findings of optic nerve glioma. On microscopic [[histopathological]] analysis, low grade [[spindle]] shaped [[pilocytic]] [[astrocytes]] & glial filaments, with the presence of numerous Rosenthal’s fibers are characteristic findings of optic nerve gliomas.
Gross pathology of resected tumors reveals a smooth, fusiform intradural lesion. Macroscopically, these tumors may be solid, gelatinous or cystic. Although having certain gross similarities with oligodendrocytes, closer microscopic, ultrastructural and immunostaining techniques have confirmed their low grade spindle shaped pilocytic (hair like) astrocytes & glial filaments, with the presence of numerous Rosenthal’s fibers. Other histologic findings include arachnoid hyperplasia & mucus-substance. The tumor may start in the anterior end of the optic nerve and proceed backwards intracranially or may arise originally from the optic nerve-chiasmal junction. Occasionally, a glioma from the optic tract or the anterior third ventricle region may involve the chiasma and the optic nerve secondarily. About 40% of optic pathway astrocytomas are fibrillary and 60% are pilocytic. Hypothalamic tumors which have invaded the optic chiasm behave differently, showing evidence of local invasion and histologically are not pilocytic in nature but are similar to other cerebral hemisphere gliomas.
OPGs are generally classified as low-grade astrocytomas, although they have a range of growth rates [1]. For this reason, it had been suggested that some OPGs may be hamartomas [11].
Tumors are composed of:


Immature astrocytes, the nuclei of which are regular without mitoses
==Pathogenesis==
Rosenthal fibers are common
Microcystic degeneration seen
Focal calcification sometimes present
 
Several histological patterns of these tumors have been described:
 
Astrocytic and oligodendroglial proliferation
Reticular pattern, involves microcystic foci with mucous-like fluid
Leptomeningeal invasion, involves fibrillated cells in bundles
 
Occasionally pathology is positive for grade II fibrillary astrocytoma.
 
These tumors are slow growing and are not generally associated with metastatic deposits.
 
High grade lesions are very rare in children.
 
The suggested precursor cell is the 02A cell, a glial precursor present in the optic pathway.  This precursor can differentiate into both astrocytes and oligodendrolia, which could account for the presence of these cells within the tumor.
 
Because of the location of these tumors, biopsies are not always performed.
 
Tumors tend to be more aggressive in adult patients.  Tumor de-differentiation is rarely seen in younger children with optic pathway tumors, but may be observed in older children and adults.  The tumor may become an anaplastic astocytoma or glioblastoma multiforme.
 
 
 
 
However, most evidence supports their designation as true, slow-growing neoplasms:


●OPGs are virtually identical histologically to pilocytic astrocytomas seen elsewhere in the nervous system [12]. Sporadic pilocytic astrocytomas often have a tandem duplication of chromosome 7q34 and associated BRAF-KIAA fusion gene, which may eventually provide opportunities for targeted therapy [13,14]. (See "Diagnosis and classification of low-grade gliomas", section on 'Pilocytic astrocytomas'.)
* Optic nerve gliomas are classified as low-grade astrocytomas.  
●Their clinical behavior may be aggressive; this is never observed with hamartomas.
* The majority of cases of optic nerve glioma are pilocytic.  
●Allelic chromosomal loss occurs in some pilocytic astrocytomas, suggesting that they are clonal lesions arising from inactivation of a tumor suppressor gene. As an example, loss of chromosome 17q (the location of the NF1 gene) is demonstrable in some cases, even in patients without NFI or NF2, suggesting some link between this gene and tumor development [15].
* Tumor de-differentiation is rarely seen in younger children with optic nerve gliomas but may be observed in older children and adults.
●OPGs in patients with NF1 exhibit a characteristic loss of neurofibromin (which functions as a negative growth regulator for astrocytes) and increased RAS activation [16,17].
* In rare cases, tumor may become an [[anaplastic]] astrocytoma or [[glioblastoma]].
* About 60% of optic pathway astrocytomas are pilocytic and 40% are fibrillary.
* [[Hypothalamic]] tumors which invade the optic chiasm, show evidence of local invasion and histologically are not pilocytic in nature but they are very similar to [[cerebral]] hemisphere gliomas.  
* Pilomyxoid astrocytomas are a new subgroup of optic pathway gliomas that has been defined.
* Pilomyxiod astrocytomas have different histological features and have been shown to behave more aggressively than pilocytic astrocytomas.


==Genetics==


* Optic nerve gliomas are classified as low-grade astrocytomas.<ref name="pmid3275755">{{cite journal| author=Alvord EC, Lofton S| title=Gliomas of the optic nerve or chiasm. Outcome by patients' age, tumor site, and treatment. | journal=J Neurosurg | year= 1988 | volume= 68 | issue= 1 | pages= 85-98 | pmid=3275755 | doi=10.3171/jns.1988.68.1.0085 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3275755  }} </ref>
* Sporadic pilocytic astrocytomas usually  have a tandem duplication of chromosome 7q34 and associated ''BRAF-KIAA'' fusion gene.<ref name="pmid19603027">{{cite journal| author=Jacob K, Albrecht S, Sollier C, Faury D, Sader E, Montpetit A et al.| title=Duplication of 7q34 is specific to juvenile pilocytic astrocytomas and a hallmark of cerebellar and optic pathway tumours. | journal=Br J Cancer | year= 2009 | volume= 101 | issue= 4 | pages= 722-33 | pmid=19603027 | doi=10.1038/sj.bjc.6605179 | pmc=PMC2736806 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19603027  }} </ref><ref name="pmid19794125">{{cite journal| author=Yu J, Deshmukh H, Gutmann RJ, Emnett RJ, Rodriguez FJ, Watson MA et al.| title=Alterations of BRAF and HIPK2 loci predominate in sporadic pilocytic astrocytoma. | journal=Neurology | year= 2009 | volume= 73 | issue= 19 | pages= 1526-31 | pmid=19794125 | doi=10.1212/WNL.0b013e3181c0664a | pmc=PMC2777068 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19794125  }} </ref>
* Pilocytic astrocytomas associated with [[neurofibromatosis]] type 1 lack this fusion gene.
* There is characteristic loss of neurofibromin (which is a negative growth regulator for astrocytes), and increased RAS activation in patients with optic nerve gliomas associated with NF1.<ref name="pmid11005256 [">{{cite journal| author=Lau N, Feldkamp MM, Roncari L, Loehr AH, Shannon P, Gutmann DH et al.| title=Loss of neurofibromin is associated with activation of RAS/MAPK and PI3-K/AKT signaling in a neurofibromatosis 1 astrocytoma. | journal=J Neuropathol Exp Neurol | year= 2000 | volume= 59 | issue= 9 | pages= 759-67 | pmid=11005256 [ | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11005256  }} </ref>
* In some pilocytic astrocytomas there is loss of allelic chromosome, suggesting that they are clonal lesions that arise from inactivation of a [[tumor suppressor gene]].
* There is  link between [[NF-1]] [[gene]] and [[tumor]] development in optic nerve glioma, as loss of chromosome 17q (the location of NF-1 gene) has been demonstrated in some cases, even in patients without NF1 or NF2.


Tumors are composed of:
==Gross pathology==
On tumor resection, gross pathology reveals a smooth, [[fusiform]] intradural lesion. Macroscopically, these [[tumors]] may be [[cystic]], [[solid]] or gelatinous.


Immature astrocytes, the nuclei of which are regular without mitoses
==Microscopic pathology==
Rosenthal fibers are common
Histologically, optic nerve gliomas are identical to [[pilocytic]] [[astrocytomas]]. Typical histology of pilocytic astrocytoma consists of:
Microcystic degeneration seen
*Densely [[cellular]] areas alternating with loose cystic regions
Focal calcification sometimes present
*Immature [[spindle]] shaped pilocytic astrocytes and glial filaments
*Rosenthal fibers are common  
*[[Eosinophilic]] granular bodies are seen
*Microcystic degeneration is seen
*[[Mitotic]] figures usually cannot be identified
*Microcalcifications can be seen in 50% of these tumors
Several other histological patterns of optic pathway gliomas that have been described are:
*Oligodendroglial and [[astrocytic]] proliferation
*[[Leptomeningeal]] invasion
*[[Reticular]] pattern that involves microcystic foci with mucous-like fluid
*[[Arachnoid]] hyperplasia & mucus-substance
   
   
Typical histology of pilomyxoid astrocytoma consists of:
*Pilomyxoid astrocytomas classically show a markedly myxoid [[matrix]], with small, compact, piloid and highly monomorphous cells.
*[[Tumor]] cells are often arranged radially around vessels in a pattern that simulates the perivascular pseudorosettes seen in [[ependymomas]].
*Tumor samples appear solid without the presence of Rosenthal fibers and [[eosinophilic]] granular bodies.
*Satellitosis of the tumor cells in the surrounding [[neuropil]] can be seen,
*[[Mitotic]] figures can be seen occasionally.
*14% of patients with pilomyxoid astrocytomas had cerebrospinal fluid dissemination of their disease which was not recognized in patients with the pilocytic variant.
The growth pattern of tumor can be either perineural or intraneural in nature. Patients with NF1 tend to have a perineural growth pattern, whereas sporadic optic pathway glioma patients tend to have an intraneural growth pattern.


Several histological patterns of these tumors have been described:
==References==
 
{{reflist|2}}
Astrocytic and oligodendroglial proliferation
{{WikiDoc Help Menu}}
Reticular pattern, involves microcystic foci with mucous-like fluid
{{WikiDoc Sources}}
Leptomeningeal invasion, involves fibrillated cells in bundles
 
Occasionally pathology is positive for grade II fibrillary astrocytoma.
 
These tumors are slow growing and are not generally associated with metastatic deposits.
 
High grade lesions are very rare in children.
 
The suggested precursor cell is the 02A cell, a glial precursor present in the optic pathway.  This precursor can differentiate into both astrocytes and oligodendrolia, which could account for the presence of these cells within the tumor.
 
Because of the location of these tumors, biopsies are not always performed.
 
Tumors tend to be more aggressive in adult patients.  Tumor de-differentiation is rarely seen in younger children with optic pathway tumors, but may be observed in older children and adults.  The tumor may become an anaplastic astocytoma or glioblastoma multiforme.


Histologically, OPGs are generally low-grade astrocytic tumors that can be placed within the World Health Organization Grade I and can be further categorized as either pilocytic and or fibrillary in nature. The majority of cases are pilocytic.
[[Category:Neurology]]
Typical pilocytic histology consists of compact and biphasic architecture with densely cellular areas alternating with loose cystic regions with characteristic Rosenthal fibers and eosinophilic granular bodies. Mitotic figures usually cannot be identified in most samples, and microcalcifications can be seen in 50% of these tumors.
[[Category:Ophthalmology]]
Recently, however, a new subgroup of OPGs has been defined which has yet to be categorized within the WHO system: pilomyxoid astrocytomas. Pilomyxoid astrocytomas classically show a markedly myxoid matrix with small compact piloid and highly monomorphous cells. Tumor cells are often arranged radially around vessels in a pattern that mimics the perivascular pseudorosettes seen in other pathological samples such as ependymoma. Tumor samples appear solid without the presence of Rosenthal fibers and eosinophilic granular bodies. Satellitosis of the tumor cells in the surrounding neuropil can be seen, as can the presence of mitotic figures, giving these tumors a more aggressive histology. These tumors were once classified along with their pilocytic counterparts, but, as more cases were identified and a more aggressive natural history was observed, these are now recognized as a separate entity. Kotomar et al. reported a series of patients and noted that there was a marked difference in natural history in patients with pilomyxoid histology, where 14% of patients with this variant had cerebrospinal fluid dissemination of their disease, which was not recognized in patients with the pilocytic variant.
[[Category:Up-To-Date]]
The pattern of growth can be either perineural or intraneural in nature. Those patients with NF1 tend to have a perineural growth pattern, whereas those patients who have sporadic OPG tend to have an intraneural growth pattern.
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Ophthalmology]]
[[Category:Neurosurgery]]

Latest revision as of 05:38, 19 September 2019

Optic nerve glioma Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Optic nerve glioma from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Echocardiography or 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

Optic nerve glioma pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Optic nerve glioma pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Optic nerve glioma pathophysiology

CDC on Optic nerve glioma pathophysiology

Optic nerve glioma pathophysiology in the news

Blogs on Optic nerve glioma pathophysiology

Directions to Hospitals Treating Optic nerve glioma

Risk calculators and risk factors for Optic nerve glioma pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Simrat Sarai, M.D. [2]

Overview

Genes involved in the pathogenesis of optic nerve glioma include BRAF-KIAA, tumor suppressor genes and chromosomes 7q34 and 17q. On gross pathology, smooth and fusiform intradural lesions are characteristic findings of optic nerve glioma. On microscopic histopathological analysis, low grade spindle shaped pilocytic astrocytes & glial filaments, with the presence of numerous Rosenthal’s fibers are characteristic findings of optic nerve gliomas.

Pathogenesis

  • Optic nerve gliomas are classified as low-grade astrocytomas.
  • The majority of cases of optic nerve glioma are pilocytic.
  • Tumor de-differentiation is rarely seen in younger children with optic nerve gliomas but may be observed in older children and adults.
  • In rare cases, tumor may become an anaplastic astrocytoma or glioblastoma.
  • About 60% of optic pathway astrocytomas are pilocytic and 40% are fibrillary.
  • Hypothalamic tumors which invade the optic chiasm, show evidence of local invasion and histologically are not pilocytic in nature but they are very similar to cerebral hemisphere gliomas.
  • Pilomyxoid astrocytomas are a new subgroup of optic pathway gliomas that has been defined.
  • Pilomyxiod astrocytomas have different histological features and have been shown to behave more aggressively than pilocytic astrocytomas.

Genetics

  • Optic nerve gliomas are classified as low-grade astrocytomas.[1]
  • Sporadic pilocytic astrocytomas usually have a tandem duplication of chromosome 7q34 and associated BRAF-KIAA fusion gene.[2][3]
  • Pilocytic astrocytomas associated with neurofibromatosis type 1 lack this fusion gene.
  • There is characteristic loss of neurofibromin (which is a negative growth regulator for astrocytes), and increased RAS activation in patients with optic nerve gliomas associated with NF1.[4]
  • In some pilocytic astrocytomas there is loss of allelic chromosome, suggesting that they are clonal lesions that arise from inactivation of a tumor suppressor gene.
  • There is link between NF-1 gene and tumor development in optic nerve glioma, as loss of chromosome 17q (the location of NF-1 gene) has been demonstrated in some cases, even in patients without NF1 or NF2.

Gross pathology

On tumor resection, gross pathology reveals a smooth, fusiform intradural lesion. Macroscopically, these tumors may be cystic, solid or gelatinous.

Microscopic pathology

Histologically, optic nerve gliomas are identical to pilocytic astrocytomas. Typical histology of pilocytic astrocytoma consists of:

  • Densely cellular areas alternating with loose cystic regions
  • Immature spindle shaped pilocytic astrocytes and glial filaments
  • Rosenthal fibers are common
  • Eosinophilic granular bodies are seen
  • Microcystic degeneration is seen
  • Mitotic figures usually cannot be identified
  • Microcalcifications can be seen in 50% of these tumors

Several other histological patterns of optic pathway gliomas that have been described are:

Typical histology of pilomyxoid astrocytoma consists of:

  • Pilomyxoid astrocytomas classically show a markedly myxoid matrix, with small, compact, piloid and highly monomorphous cells.
  • Tumor cells are often arranged radially around vessels in a pattern that simulates the perivascular pseudorosettes seen in ependymomas.
  • Tumor samples appear solid without the presence of Rosenthal fibers and eosinophilic granular bodies.
  • Satellitosis of the tumor cells in the surrounding neuropil can be seen,
  • Mitotic figures can be seen occasionally.
  • 14% of patients with pilomyxoid astrocytomas had cerebrospinal fluid dissemination of their disease which was not recognized in patients with the pilocytic variant.

The growth pattern of tumor can be either perineural or intraneural in nature. Patients with NF1 tend to have a perineural growth pattern, whereas sporadic optic pathway glioma patients tend to have an intraneural growth pattern.

References

  1. ↑ Alvord EC, Lofton S (1988). "Gliomas of the optic nerve or chiasm. Outcome by patients' age, tumor site, and treatment". J Neurosurg. 68 (1): 85–98. doi:10.3171/jns.1988.68.1.0085. PMID 3275755.
  2. ↑ Jacob K, Albrecht S, Sollier C, Faury D, Sader E, Montpetit A; et al. (2009). "Duplication of 7q34 is specific to juvenile pilocytic astrocytomas and a hallmark of cerebellar and optic pathway tumours". Br J Cancer. 101 (4): 722–33. doi:10.1038/sj.bjc.6605179. PMC 2736806. PMID 19603027.
  3. ↑ Yu J, Deshmukh H, Gutmann RJ, Emnett RJ, Rodriguez FJ, Watson MA; et al. (2009). "Alterations of BRAF and HIPK2 loci predominate in sporadic pilocytic astrocytoma". Neurology. 73 (19): 1526–31. doi:10.1212/WNL.0b013e3181c0664a. PMC 2777068. PMID 19794125.
  4. ↑ Lau N, Feldkamp MM, Roncari L, Loehr AH, Shannon P, Gutmann DH; et al. (2000). "Loss of neurofibromin is associated with activation of RAS/MAPK and PI3-K/AKT signaling in a neurofibromatosis 1 astrocytoma". J Neuropathol Exp Neurol. 59 (9): 759–67. PMID [ 11005256 [ Check |pmid= value (help).

Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=Optic_nerve_glioma_pathophysiology&oldid=1582237"