Optic nerve glioma pathophysiology
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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:
- 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.
References
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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
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