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Cerebellar astrocytoma
- Updated 08.15.2024
- Released 02.07.1994
- Expires For CME 08.15.2027
Cerebellar astrocytoma
Introduction
Overview
Cerebellar astrocytomas are the most common benign brain tumor of childhood. The majority would now be classified in the 2021 WHO classification of CNS tumors under circumscribed astrocytic gliomas as pilocytic astrocytomas. Less frequently, pediatric-type diffuse low-grade gliomas will occur in the cerebellum (40). Most tumors are pilocytic astrocytomas and are amenable to gross total resections. After such treatment, 95% or more of patients will be cured of disease. For those tumors that cannot be grossly totally resected, including occasional midline pilocytic astrocytomas and other variants of low-grade glioma, attempts at re-resection or, in infrequent situations, radiation therapy or chemotherapy may be indicated. New biological insights suggest that molecular-targeted therapy may be available soon to treat subtotally resected and/or progressive lesions. This clinical article updates the reader in the new concepts of the molecular pathogenesis of the tumor and the possible important role of BRAF fusion abnormalities in prognosis of subtotally resected pilocytic astrocytomas. The RAS intracellular signaling pathway is an intriguing target, especially utilizing agents that target BRAF and MEK. Increasing information concerning other molecular targets is included.
Key points
• Cerebellar astrocytomas are the most common form of childhood low-grade primary intracranial tumors. | |
• After total resection, over 95% of children with cerebellar astrocytomas are cured. | |
• Post-surgical adjuvant chemotherapy or radiotherapy is not needed for the vast majority of patients with cerebellar astrocytomas. |
Historical note and terminology
Since the mid-1920s, low-grade glial tumors of the cerebellum have been identified as having a more favorable prognosis than other astrocytomas of the central nervous system (03). As early as 1931, in a report of 76 cases of cerebellar astrocytoma, Cushing stressed their favorable postoperative outcome and how they differed from cerebral astrocytomas (11). In fact, as late as 1937, Bergstrand suggested that many cerebellar astrocytomas were so histologically benign that they should be considered congenital malformations of the cerebellar leptomeninges, "gliocytoma embryonals," rather than a true malignancy (48). This concept has been rejected by other pathologists.
Within the categorization of childhood cerebellar low-grade gliomas, a second subvariety has been identified. Gilles and colleagues, and Gjerris and Klinken, pointed out the differences between the more common classical juvenile or pilocytic cerebellar astrocytoma and the diffuse or Gilles type B lesion (22; 23). The majority of childhood cerebellar astrocytomas are pilocytic astrocytomas (38).
The 2017 revised WHO classification of tumors of the central nervous system recognizes pilocytic astrocytomas as a distinct entity, but does not subdivide tumors further on molecular findings or tumor location (39).
Clinical manifestations
Presentation and course
The classical, or juvenile, pilocytic cerebellar astrocytoma tends to be a slow-growing lesion arising in the lateral cerebellar hemispheres (44). The tumor may cause lateralized appendicular symptoms for weeks to months before extending to the midline and obstructing the fourth ventricle. When cerebrospinal fluid flow is obstructed, the more nonspecific and nonlocalizing signs of increased intracranial pressure, including headache and vomiting, become preeminent. In addition, midline cerebellar deficits, such as truncal unsteadiness, become more frequent. As the tumor enlarges, the child may become apathetic and irritable and develop neck stiffness. Head tilt may occur, secondary to herniation of the cerebellar tonsil ipsilateral to the side of the tumor. Flexion of the neck will cause meningeal signs. Laterally placed cerebellar astrocytoma will infrequently cause cranial nerve palsies, except for abducens involvement due to hydrocephalus. Similarly, corticospinal tract dysfunction usually only occurs late in the course of illness with longstanding hydrocephalus.
Patients with diffuse or nonpilocytic cerebellar astrocytomas tend to be young children and, more commonly, adults. The majority of cerebellar astrocytomas that arise in adults are of the diffuse type. The duration of symptoms prior to diagnosis is usually shorter with diffuse tumors, and patients are more likely to present with midline cerebellar deficits, such as truncal unsteadiness, followed by, or concomitant with, signs of increased intracranial pressure (23). Because the tumor is frequently abutting, or even attached to, the brainstem, cranial nerve palsies are more frequent. Similarly, the cerebellar peduncles may be compressed or infiltrated, and cerebellar outflow abnormalities, including unilateral dysmetria and severe nystagmus, may be present. At times, it may be essentially impossible to distinguish between a diffuse cerebellar astrocytoma invading the brainstem and a large exophytic brainstem glioma extending from the brainstem. In these cases, multiple cranial nerve palsies are frequent, as are cerebellar and long-tract signs and symptoms.
Distinction is primarily between cerebellar astrocytomas and other childhood posterior fossa tumors (44). The other common types of childhood posterior fossa tumors include medulloblastoma or primitive neuroectodermal tumors, brainstem gliomas, and ependymomas. These tumors have different clinical and neuroradiographic features. Medulloblastomas or primitive neuroectodermal tumors tend to have a more explosive presentation. Midline cerebellar deficits and symptoms of increased intracranial pressure occur early in the course of illness. Laterally placed medulloblastomas are even more difficult to clinically distinguish from classical cerebellar astrocytomas. Brainstem gliomas present with the insidious onset of multiple cranial nerve findings, long-tract signs, and cerebellar symptoms. Clinical distinction between an intrinsic brainstem tumor and a laterally placed cerebellar astrocytoma is usually not difficult; however, there may be clinical overlap between exophytic brainstem gliomas and the cerebellar astrocytomas. Similarly, diffuse cerebellar astrocytomas may have associated cranial nerve deficits and can be difficult to distinguish from more exophytic brainstem gliomas. Ependymomas, especially when laterally placed, can be difficult to distinguish from cerebellar astrocytomas. Posterior fossa ependymomas tend to have a somewhat shorter duration of symptoms before diagnosis and result in more cranial nerve deficits.
Other lesions of the posterior fossa may mimic cerebellar astrocytomas. Lhermitte-Duclos or dysplastic gangliocytoma of the cerebellum is a condition wherein there are cerebellar hamartomas that can cause cerebellar deficits (49). This condition is much less likely to cause hydrocephalus and, although considered a nontumorous condition, can apparently cause an increased mass effect over time. In these cases, clinical differentiation of Lhermitte-Duclos and cerebellar astrocytomas is virtually impossible. Other processes that may occur in the cerebellum include acute demyelinating lesions, cerebellar abscesses, and vascular malformations. Cerebellar hemangioblastomas occur with increased frequency in von Hippel-Lindau disease.
Prognosis and complications
The overall prognosis for the majority of patients with cerebellar astrocytomas is excellent. For children with the more common classical juvenile or pilocytic astrocytomas, the 5-year progression-free survival rate after total surgical resection ranges between 90% and 95% (17; 26; 28; 19; 54; 56; 24). The vast majority of such patients can be considered to be cured of their disease. Prognosis for patients subtotally resected is somewhat less favorable in juvenile astrocytomas; however, those patients with subtotally resected pilocytic astrocytomas with a BRAF-KIAA1549 fusion abnormality in their tumors did well (27). The addition of radiotherapy does not improve survival for patients with totally resected pilocytic astrocytomas (36; 17).
In contradistinction, survival rates for patients with diffuse cerebellar astrocytomas are much less favorable. Five-year and 10-year survivals ranging between 7% and 30% have been reported (22; 28). In a series of primarily older patients, a 5- and 10-year survival rate of 7% was documented. In these patients, duration of survival may be somewhat lengthened after the addition of radiotherapy. The rare high-grade cerebellar glioma carries a poor prognosis, possibly worse than those for children with cortical high-grade gliomas (33).
The majority of survivors of low-grade astrocytomas of the cerebellum have good qualities of life. There has been no documentation of deterioration in intelligence over time in such patients treated with surgery alone. They often have minor neurologic abnormalities such as mild residual ataxia, dysmetria, or nystagmus. Postural sway, which relies on vestibular input for equilibrium control, is often present in long-term survivors and has been related to damage of the fastigial and interposed nuclei (34). More subtle findings, such as apraxia and motor neglect, as well as language executive function and memory deficits may be present (01). In addition, more complex neuropsychologic deficits and even epilepsy has been seen after surgery, although there is no clear-cut causation (52; 59; 13). Vermian tumors have been associated with poorer long-term functional outcome (13).
Clinical vignette
A 7-year-old girl was referred to the neurologist because of unsteadiness. Over the previous 3 months, the child had increasing difficulties with balance and, eventually, with the use of her right arm. The week prior to evaluation, she had developed severe morning headaches associated with nausea and vomiting. In retrospect, she may have had some mild headaches over the past 2 months.
On examination, the child was awake and alert. Her pupils were equal and reactive. She had bilateral papilledema. Cranial nerve examination disclosed bilateral mild sixth nerve palsies. Her upgaze was intact and she had good downgaze. Her face moved symmetrically and the remainder of her cranial nerves was normal. On motor and coordination testing, there was marked dysmetria with the right hand; she was a bit unsteady with the left hand. Her gait was wide-based, and she tended to fall to the right.
A CT scan disclosed a cystic mass within the right cerebellum that extended to the midline and caused blockage of the fourth ventricle. There was associated hydrocephalus. After contrast enhancement, a small nodule was found within the cystic-like structure. MRI scan disclosed a similar picture with a large cystic mass. The small nodule (mural nodule) also enhanced readily with contrast on MRI scan.
Biological basis
The etiology in the vast majority of patients with cerebellar astrocytomas is unknown. There is a higher incidence of tumors in children with neurofibromatosis type 1 (10).
Etiology and pathogenesis
The more common classical juvenile pilocytic astrocytoma accounts for 80% to 85% of tumors. The 2021 WHO Classification of Tumors of the Central Nervous System classifies these tumors under the subgroup of circumscribed astrocytic astrocytomas as pilocytic astrocytomas (40). They are composed of fusiform astrocytes loosely interwoven in a fine fibrillary background.
Pilocytic astrocytoma: Rosenthal fibers and bipolar stellate astrocytes
Pilocytic astrocytoma is characterized by bipolar cells with long delicate processes (hair cell), nuclear hyperchromasia, and moderate pleomorphism. Several Rosenthal fibers are also seen. (Contributed by Drs. Julio H Garcia and E...
Mitoses are rare in such lesions. The pilocytic tumor frequently has a microcystic component, and Rosenthal fibers, believed to represent the degenerated astrocytes, are commonly seen.
The tumor tends to have a large macrocystic structure, filled with proteinaceous fluid and is often associated with a mural nodule. Nuclear atypia and focal leptomeningeal invasion are often seen, but despite the presence of such more aggressive features, the pilocytic tumor tends to behave in a benign fashion. Rarely, a possibly more virulent variant, the pilomyxoid pilocytic astrocytoma, can occur in the cerebellum (37).
In contradistinction, the diffuse or fibrillary astrocytomas are more histologically similar to low-grade astrocytomas of the cerebral hemisphere. In the newest WHO classification they are considered “pediatric-type diffuse low-grade gliomas” and are then further subclassified based on molecular finding, with the majority being “diffuse low-grade glioma, MAPK pathway-altered” (40).
This tumor is more cellular and infiltrative. Prognosis for the diffuse cerebellar astrocytoma is much less favorable, and these tumors are often either associated with more malignant-appearing glial regions or are more likely to transform into a more aggressive lesion. Molecular features can be useful in separating pilocytic astrocytomas with atypical features from malignant gliomas, as BRAF fusion mutations, as described below, are characteristic of the pilocytic astrocytomas. TP53 mutations suggest a more aggressive clinical course (12).
In Gilles separation, tumors that contain microcysts, leptomeningeal deposits, Rosenthal fibers, or oligodendrial glial features can be grossly grouped into a cluster, or type A classification, which carries a benign prognosis. The Gilles type B tumor contains perivascular pseudorosettes and 1 or more of the following features: high cell density, necrosis, mitosis, or calcification. Gilles and colleagues have outlined a schema to determine the prognostic significance of individual factors in these clusters (22). For example, patients with only 1 factor suggesting poorer prognosis tend to fare better than those patients with more factors. Other investigators have also stressed that histological features, usually related to poorer outcome, such as pleomorphism, endothelial proliferation, and hypervascularity, do not predict poorer outcome for patients with cerebellar astrocytomas (28).
The biological underpinnings of pediatric low-grade gliomas are being increasingly understood. Cytogenetic studies have disclosed that the majority of tumors have no cytogenetic abnormalities (25). BRAF oncogenic activating mutations have been shown to be associated with cerebellar pilocytic astrocytomas (31; 46; 20; 29). The majority of cerebellar pilocytic astrocytomas are fusion protein abnormalities, primarily BRAF-KIAA1549 duplication-fusions, but other activating-fusion protein abnormalities have been noted, as well as much less frequent point mutations (30; 47; 06; 43; 50). In addition, transcriptional profiles of cerebellar astrocytomas demonstrate genes upregulated that are crucial in early brain regionalization, as well as those essential in later stages of cerebellar morphogenesis and differentiation (57).
The diffuse low-grade gliomas MAPK pathway-altered are usually driven by BRAF mutations or FGFR1 alterations (40). Diffuse astrocytoma MYB or MYB1-altered circumscribed astrocytic glioma may also occur (40).
Epidemiology
Cerebellar astrocytomas account for 10% to 20% of all childhood brain tumors (44). They are the second most common tumor of the posterior fossa and comprise 30% to 40% of all posterior fossa tumors in childhood (44). The tumor rarely occurs in adulthood; when such low-grade tumors occur in the adult years, they are more commonly of the nonpilocytic or diffuse type. Diffuse cerebellar astrocytomas also more frequently occur in infants. The peak incidence for cerebellar astrocytomas is in the latter half of the first decade of life, with the second peak in the first half of the second decade.
Prevention
The risk factors for cerebellar astrocytomas are essentially unknown except for the relationship of such tumors and neurofibromatosis type 1.
Diagnostic workup
The diagnostic workup of patients with cerebellar astrocytoma has been remarkably simplified since the advent of CT and MRI (05).
On CT, low-grade cerebellar astrocytomas usually display a homogenous low-density pattern associated with a macrocystic component. Within the macrocystic component, there is frequently a nodule (the mural nodule) that shows marked contrast enhancement. Hydrocephalus is present in the majority of patients at the time of diagnosis. CT findings of the diffuse cerebellar astrocytoma usually disclose an isodense or hypotense lesion, which enhances in a variable fashion after contrast (58). The laterally placed cerebellar astrocytoma most commonly arises in the cerebellar hemisphere and often upwardly displaces the fourth ventricle. The diffuse cerebellar astrocytoma more commonly arises in the midline, compressing the fourth ventricle. On MRI, the tumor's noncystic components are commonly isointense or hypointense in comparison with adjacent normal cerebellum on T1-weighted images, and hypertense compared with normal tissue on T2-weighted images.
The cyst may have intermediate signal intensities depending on the protein content. Hemorrhage within the cyst may occur, but it is uncommon. After gadolinium, the mural nodule of the pilocytic astrocytoma usually enhances. Cyst wall enhancement is infrequent, and enhancement suggests tumor within the wall of the cyst. In patients with diffuse cerebellar astrocytomas, MRI often displays the diffuse infiltrating nature of such lesions, including apparent involvement of the brainstem or cerebellar peduncles.
Usually CT or MRI is all that is needed to confirm the presence of a cerebellar astrocytoma. The classical pilocytic cerebellar astrocytoma rarely, if ever, disseminates the neuraxis, and staging of the tumor with studies such as cerebrospinal fluid cytology and MRI of the spine are not indicated. In contradistinction, dissemination has been more frequently reported in diffuse midline cerebellar astrocytomas, especially in tumors that may display associated anaplastic features (51; 45). In these cases, evaluation of the extent of disease is indicated. Multiple cerebellar astrocytomas have been noted in patients with neurofibromatosis type 1 (14).
The combination of MRI, spectroscopy, and computer-based multifactorial analysis may increase preoperative prediction of tumor type (02).
Management
The treatment of the pilocytic astrocytoma is surgical resection (26; 28; 18). Complete tumor excision is associated with improved long-term survival and cure in the majority of patients. Perioperative cerebrospinal fluid diversion is required in the majority of patients; however, probably less than one third of patients will require internalization of spinal fluid diversion and a ventriculoperitoneal shunt for persistent hydrocephalus. Children less than 3 years old with cerebellar gliomas are somewhat more likely to have higher-grade (malignant) lesions (55).
The management of patients whose tumors are initially partially resected remains unsettled. The short-term survival rate for those patients who undergo partial resections is similar to that for those patients who undergo total resections, but the relapse-free survival rates are much higher in patients undergoing partial resection (36; 17; 28; 21). Ten-year event-free survival rates are lower; those with partially resected tumors have an event-free survival rate of 50% compared to 80% to 90% for total resected lesions (24). In addition, those patients with partially resected V600E mutation tumors likely have a poorer prognosis than those with BRAF-fusion alterations (09; 32). Postoperatively, all patients require a CT scan or an MRI scan with and without contrast, to determine the extent of resection. If there is residual disease after initial tumor resection, patients should either undergo re-resection or be closely observed for tumor progression (08). Because approximately one half of the patients with partially resected tumors will remain free of progressive disease for 5 years, ongoing surveillance with sequential MRIs is required and surveillance neuroimaging will detect recurrence in asymptomatic children (53). Radiation therapy has been utilized for some patients with partially resected tumors (36; 17). Single institution studies have suggested that radiation may improve the duration of progression-free survival for patients with subtotally resected tumors, although the number of patients treated in such studies is small. If radiotherapy is to be used, conformal or other forms of more focused radiotherapy, such as gamma knife treatment, should be considered. At the present time, the consensus is to re-resect such lesions prior to making a decision to begin radiotherapy.
Patients with diffuse cerebellar astrocytomas have a worse prognosis. The tumors in such patients are often less amenable to total resection, and the tumors have a greater tendency to disseminate the neuraxis and possibly transform into more histologically malignant lesions (45). In patients with subtotally resected, diffuse cerebellar astrocytomas, postsurgical adjuvant therapy is frequently recommended.
Chemotherapy with carboplatin and vincristine or with vinblastine has been shown to be of benefit in children with progressive pilocytic astrocytomas (24; 41; 35). Biological therapy with bevacizumab and irinotecan or MEK inhibitors (04; 43; 16) has been shown to be beneficial in children with low-grade astrocytomas, and will have a future role in the management of diffuse subtotally resected cerebellar astrocytomas (42; 07; 16). For those tumors that have BRAF mutations, studies using BRAF-inhibitors, some in combination with MEK inhibitors, are nearing completions, including prospective trials comparing molecular-targeted therapy to chemotherapy for those with newly-diagnosed partially-resected disease. Focal radiotherapy can also be used. However, in many situations, a period of observation is indicated, and treatment is only started if there is progression.
Outcomes
The overall prognosis for the majority of patients with cerebellar astrocytomas is excellent. For children with the more common classical juvenile or pilocytic astrocytomas, the 5-year progression-free survival rate after total surgical resection ranges between 90% and 95% (17; 26; 28; 19; 54; 56; 24). The vast majority of such patients can be considered to be cured of their disease. Prognosis for patients subtotally resected is somewhat less favorable in juvenile astrocytomas; however, those patients with subtotally resected pilocytic astrocytomas with a BRAF-KIAA1549 fusion abnormality in their tumors did well (27).
In contradistinction, those with subtotally resected cerebellar low-grade gliomas with V600E BRAF mutations have a poorer prognosis (09; 32). In one retrospective study, low-grade diffuse gliomas, except for those with BRAF-fusion alterations, had a small, but real chance of malignant transformation (15). The addition of radiotherapy does not improve survival for patients with totally resected pilocytic astrocytomas (36; 17).
The majority of survivors of low-grade astrocytomas of the cerebellum have good qualities of life. There has been no documentation of deterioration in intelligence over time in such patients treated with surgery alone. They often have minor neurologic abnormalities such as mild residual ataxia, dysmetria, or nystagmus. Postural sway, which relies on vestibular input for equilibrium control, is often present in long-term survivors and has been related to damage of the fastigial and interposed nuclei (34). More subtle findings, such as apraxia and motor neglect, as well as language executive function and memory deficits may be present (01). In addition, more complex neuropsychologic deficits and even epilepsy has been seen after surgery, although there is no clear-cut causation (52; 59; 13). Vermian tumors have been associated with poorer long-term functional outcome (13).
Special considerations
Anesthesia
Because the majority of patients with cerebellar astrocytomas have increased intracranial pressure at the time of diagnosis, anesthesia techniques for patients with increased intracranial pressure must be utilized.
Media
References
- 01
- Aarsen FK, Van Dongen HR, Paquier PF, Van Mourik M, Catsman-Berrevoets CE. Long-term sequelae in children after cerebellar astrocytoma surgery. Neurology 2004;62:1311-6. PMID 15111667
- 02
- Arle JE, Morriss C, Wang ZJ, Zimmerman RA, Phillips PG, Sutton LN. Prediction of posterior fossa tumor type in children by means of magnetic resonance image properties, spectroscopy, and neural networks. J Neurosurg 1997;86:755-61. PMID 9126888
- 03
- Bailey P, Cushing H. A classification of the tumors of the glioma group. Philadelphia: Lippincott, 1926.
- 04
- Banerjee A, Jakacki RI, Onar-Thomas A, et al. A phase I trial of the MEK inhibitor selumetinib (AZD6244) in pediatric patients with recurrent or refractory low-grade glioma: a Pediatric Brain Tumor Consortium (PBTC) study. Neuro Oncol 2017;19(8):1135-44. PMID 28339824
- 05
- Barkovich AJ. Pediatric neuroimaging. In: Contemporary neuroimaging. Vol 1. New York: Raven, 1990.
- 06
- Becker AP, Scapulatempo-Neto C, Carloni AC, et al. KIAA1549: BRAF gene fusion and FGFR1 hotspot mutations are prognostic factors in pilocytic astrocytomas. J Neuropathol Exp Neurol 2015;74(7):743-54. PMID 26083571
- 07
- Bouffet E, Jakacki R, Goldmas S, et al. Phase II study of weekly vinblastine in recurrent or refractory pediatric low-grade glioma. J Clin Oncol 2012;30(12):1358-63. PMID 22393086
- 08
- Bowers DC, Krause TP, Aronson LJ, et al. Second surgery for recurrent pilocytic astrocytoma in children. Pediatr Neurosurg 2001;34:229-34. PMID 11423771
- 09
- Capper D, Jones DTW, Sill M, et al. DNA methylation-based classification of central nervous system tumours. Nature 2018;555(7697):469-74. PMID 29539639
- 10
- Cohen BH, Kaplan AM, Packer RJ. Management of intracranial neoplasms in children with neurofibromatosis type 1 and 2. Pediatr Neurosurg 1991;16:66-72. PMID 2132927
- 11
- Cushing H. Experiences with the cerebellar astrocytomas. A critical review of seventy-six cases. Surg Gynecol Obstet 1931;52:129-91.
- 12
- Cykowski MD, Allen RA, Kanaly AC, et al. The differential diagnosis of pilocytic astrocytoma with atypical features and malignant glioma: an analysis of 16 cases with emphasis on distinguishing molecular features. J Neurooncol, 2013;115(3):477-86. PMID 24057326
- 13
- Daszkiewicz P, Maryniak A, Roszkowski M, Barszca S. Long-term functional outcome of surgical treatment of juvenile pilocytic astrocytoma of the cerebellum in children. Childs Nerv Syst 2009;25:855-60. PMID 19418058
- 14
- Dunn IF, Agarwalla PK, Papanastassiou AM, et al. Multiple pilocytic astrocytomas of the cerebellum in a 17-year-old patient with neurofibromatosis type 1. Childs Nerv Sys 2007;23(10):1191-4. PMID 17457593
- 15
- Falkenstein F, Gessi M, Kandels D, et al. Prognostic impact of distinct genetic entities in pediatric diffuse glioma WHO-grade II-Report from the German/Swiss SIOP-LGG 2004 cohort. Int J Cancer 2020;147(8):2159-75. PMID 32239677
- 16
- Fangusaro J, Onar-Thomas A, Young Poussaint T, et al. Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicenter, phase 2 trial. Lancet Oncol 2019;20(7):1011-22. PMID 31151904
- 17
- Fazekas JT. Treatment of grades I and II brain astrocytomas. The role of radiotherapy. Int J Radiat Oncol Biol Phys 1977;2:661-6. PMID 893171
- 18
- Fisher BJ, Leighton CC, Vujovic O, et al. Results of a policy of surveillance alone after surgical management of pediatric low-grade gliomas. Int J Rad Oncol Biol Phys 2001;51:704-19. PMID 11597812
- 19
- Fisher PG, Tihan T, Goldthwaite PT, et al. Outcome analysis of childhood low-grade astrocytomas. Pediatr Blood Cancer 2008;51(2):245-50. PMID 18386785
- 20
- Forshew T, Tatevossian RG, Lawson AR, et al. Activation of the ERK/MAPK pathway: a signature genetic defect in posterior fossa pilocytic astrocytomas. J Pathol 2009;218:172-81. PMID 19373855
- 21
- Freeman CR, Farmer JP, Montes J. Low-grade astrocytomas in children: evolving management strategies. Int J Radiation Oncology Biol Phys 1998;41(5):979-87. PMID 9719106
- 22
- Gilles FH, Winston K, Fulchiero A, Leviton A. Histologic features and observational variation in cerebellar gliomas in children. J Natl Cancer Inst 1977;58:175-81. PMID 833867
- 23
- Gjerris F, Klinken L. Long-term prognosis in children with benign cerebellar astrocytoma. J Neurosurg 1978;49:179-84. PMID 671072
- 24
- Gnekow AK, Falkenstein F, von Hornstein S, et al. Long-term follow-up of the multicenter, multidisciplinary treatment study HIT-LGG-1996 for low-grade glioma in children and adolescents of the German Speaking Society of Pediatric Oncology and Hematology. Neuro-Oncology 2012;14(10):1265-84. PMID 22942186
- 25
- Griffin CA, Hawkins AL, Packer RJ, Rorke LB, Emanuel BS. Chromosome abnormalities in pediatric brain tumors. Cancer Res 1988;48:175-80. PMID 3334992
- 26
- Griffin TW, Beaufait D, Blasko JC. Cystic cerebellar astrocytomas in childhood. Cancer 1979;44:276-80. PMID 455252
- 27
- Hawkins C, Walker E, Mohamed N, et al. BRAF-KIAA 15149 fusion predicts better clinical outcome in pediatric low-grade astrocytoma. Clin Cancer Res 2011;17:4790-8. PMID 21610142
- 28
- Hayostek CJ, Shaw EG, Scheithauer B, et al. Astrocytomas of the cerebellum. Cancer 1993:856-63. PMID 8334640
- 29
- Jacob K, Albrecht S, Sollier C, et al. Duplication of 7q34 is specific to juvenile pilocytic astrocytomas and a hallmark of cerebellar and optic pathway tumours. Br J Cancer 2009;101(4):722. PMID 19603027
- 30
- Jones DT, Hutter B, Jager N, et al. Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nature Genet 2013,45(8):927-34. PMID 23817572
- 31
- Jones DT, Kocialkowski S, Liu L, et al. Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res 2008;68(21):8673. PMID 18974108
- 32
- Jones DTW, Bandopadhayay P, Jabado N. The power of human cancer genetics as revealed by low-grade gliomas. Annu Rev Genet 2019;53:483-503. PMID 31794268
- 33
- Karremann M, Rausche U, Roth D, et al. Cerebellar location may predict an unfavorable prognosis in paediatric high-grade glioma .Br J Cancer 2013;109(4):844-51. PMID 23868007
- 34
- Konczak J, Schoch B, Dimitrova A, Gizewski E, Timmann D. Functional recovery of children and adolescents after cerebellar tumour resection. Brain 2005;128(Pt 6):1428-41. PMID 15659424
- 35
- Lassaletta A, Scheinemann K, Zelcer SM, et al. Phase II weekly vinblastine for chemotherapy-naive children with progressive low-grade glioma: a Canadian Pediatric Brain Tumor Consortium Study. J Clin Oncol 2016;34(29):3537-43. PMID 27573663
- 36
- Leibel SA, Sheline GE, Wara WM, Boldrey EB, Nielsen SL. The role of radiation therapy in the treatment of astrocytomas. Cancer 1975;35:1551-7. PMID 1148989
- 37
- Linscott LL, Osborn AG, Blaser S, et al. Pilomyxoid astrocytoma: expanding the imaging spectrum. AJNR Am J Neuroradiol 2008;29(10):1861-6. PMID 18701580
- 38
- Louis DN, Ohgake H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007;114(2):97-109. PMID 17618441
- 39
- Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 2016;131(6):803-20. PMID 27157931
- 40
- Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol 2021;23(8):1231-51. PMID 34185076
- 41
- Packer RJ, Ater J, Allen J, et al. Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas. J Neurosurg 1997;86(5):747-54. PMID 9126887
- 42
- Packer RJ, Jakacki R, Horn M, et al. Objective response of multiply recurrent low-grade gliomas to bevicizumab and irinotecan. Pediatr Blood Cancer 2009;52:791-5. PMID 19165892
- 43
- Packer RJ, Pfister S, Bouffet E, et al. Pediatric low-grade gliomas: implications of the biologic era. Neuro Oncol 2017;19(6):750-61. PMID 27683733
- 44
- Packer RJ, Schut L, Sutton LN, Bruce DA. Posterior cranial fossa brain tumors in children. In: Youmans J, editor. Neurological surgery. Philadelphia: WB Saunders, 1989:3017-40.
- 45
- Packer RJ, Seigel KR, Sutton LN, Litmann P, Bruce DA, Schut L. Leptomeningeal dissemination of primary central nervous system tumors of childhood. Ann Neurol 1985;18:217-22. PMID 4037762
- 46
- Pfister S, Janzarik WG, Remke M, et al. BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas. J Clin Invest 2008;118:1739-49. PMID 18398503
- 47
- Ramkissoon LA, Horowitz PM, Craig JM, et al. Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1. Proc Natl Acad Sci U S A 2013;110(20):8188-93. PMID 23633565
- 48
- Ringertz N, Nordenstam H. Cerebellar astrocytoma. J Neuropathol Exp Neurol 1951;10:343-67. PMID 14874138
- 49
- Roessmann U, Wongmongkolrit T. Dysplastic gangliocytoma of the cerebellum in a newborn. J Neurosurg 1984;60:845-50. PMID 6707754
- 50
- Ryall S, Tabori U, Hawkins C. A comprehensive review of paediatric low-grade diffuse glioma: pathology, molecular genetics and treatment. Brain Tumor Pathol 2017;24(2):51-61. PMID 28342104
- 51
- Shapiro K, Shulman K. Spinal cord seeding from cerebellar astrocytomas. Childs Brain 1976;2:177-86. PMID 971637
- 52
- Strazzer S, Zucca C, Fiocchi E. et al. Epilepsy and neuropsychologic deficit in a child with cerebellar astrocytoma. J Child Neurol 2006; 21(9):817-20. PMID 16970895
- 53
- Udaka YT, Yeh-Nayre LA, Amene CS, VandenBerg SR, Levy ML, Crawford JR. Recurrent pediatric central nervous system low-grade gliomas: the role of surveillance neuroimaging in asymptomatic children. J Neurosurg Pediatrics 2013;11:119-26. PMID 23157391
- 54
- Villarejo F, de Diego MB, de la Riva AG. Prognosis of cerebellar astrocytomas in children. Childs Nerv Syst 2008;24:203-10. PMID 17710415
- 55
- Vinchon M, Ruchoux MM, Soto-Ares G, Nicolas R, Dhellemmes P. Cerebellar gliomas in infants: specificity, pathology, and outcome. Child Nerv Syst 2001;17:31-6. PMID 11219620
- 56
- Wisoff JH, Sanford RA, Heier LA, et al. Primary neurosurgery for pediatric low-grade gliomas: a prospective multi-institutional study from the Children’s Oncology Group. Neurosurgery 2011 68(6):1548-54. PMID 21368693
- 57
- Zakrzewski K, Jarzab M, Pfeifer A, et al. Transcriptional profiles of pilocytic astrocytoma are related to their three different locations, but not to radiological tumor features. BMC Cancer 2015;15:778. PMID 26497896
- 58
- Zimmerman RA, Bilaniuk LT, Bruno L, Rosenstock J. Computed tomography of cerebellar astrocytoma. AJR Am J Roentgenol 1978;130:929-33. PMID 417594
- 59
- Zuzak TJ, Poretti A, Drexel B, et al. Outcome of children with low-grade cerebellar astrocytoma: long-term complications and quality of life. Childs Nerv Syst 2008;24:1447-55. PMID 18690461
Contributors
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Author
-
Roger J Packer MD
Dr. Packer of Children’s National Medical Center and George Washington University has no relevant financial relationships to disclose.
See Profile
Patient Profile
- Age range of presentation
-
- 0 month to 65+ years
- Sex preponderance
-
- male=female
- Heredity
-
- heredity may be a factor
- Population groups selectively affected
-
- none selectively affected
- Occupation groups selectively affected
-
- none selectively affected
ICD & OMIM codes
- ICD-9
-
- Malignant neoplasm of the cerebellum: 191.6
- ICD-10
-
- Malignant neoplasm of the cerebellum: C71.6
- ICD-0
-
- Astrocytoma, NOS: 9400/3
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