CNS tumor

Other astrocytic tumors

Pilocytic astrocytoma

Authors: Rebecca Yoda, M.D., P.J. Cimino, M.D., Ph.D.

Deputy Editor-in-Chief: Chunyu "Hunter" Cai, M.D., Ph.D.

Minor changes: 9 September 2021

Copyright: 2002-2021, PathologyOutlines.com, Inc.

PubMed Search: Pilocytic astrocytoma[TI] CNS tumor "free full text"[sb]

See Also: Pilomyxoid astrocytoma

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Table of Contents

Cite this page: Yoda R, Cimino PJ. Pilocytic astrocytoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumorpilocyticastrocytoma.html. Accessed September 21st, 2021.

Definition / general

Circumscribed, well differentiated astrocytic neoplasm with piloid (hair-like) processes, most commonly occurring in children and young adults, WHO grade 1 (Acta Neuropathol 2016;131:803)

Essential features

Most common glioma in children (Neuro Oncol 2020;22:iv1)
Radiologic appearance often cystic with an enhancing mural nodule (Radiographics 2004;24:1693)
Generally circumscribed, biphasic, astrocytic neoplasm with piloid processes, Rosenthal fibers and eosinophilic granular bodies (EGBs)
Activating genetic alterations in components of MAPK pathway (most frequently BRAF fusions) (Nat Genet 2013;45:927, Nat Genet 2013;45:602)
WHO grade 1 (Acta Neuropathol 2016;131:803)

Terminology

Pilocytic astrocytoma
Juvenile pilocytic astrocytoma (not recommended)
Spongioblastoma (not recommended)
Pilomyxoid astrocytoma (subtype)
Optic nerve glioma

ICD coding

ICD-O: 9421/1 - pilocytic astrocytoma
ICD-11: 2A00.0Y - other specified gliomas of brain
ICD-11: XH29Q5 - pilomyxoid astrocytoma

Epidemiology

M = F (Neuro Oncol 2014;16:iv1)
5.4% of all gliomas (J Neuropathol Exp Neurol 2005;64:479)
Most common glioma in children (Neuro Oncol 2014;16:iv1)
Most common glioma during first 2 decades of life (Neuro Oncol 2014;16:iv1)

Sites

Found throughout neuraxis
Most common sites: cerebellum (42%), supratentorial (36%), optic pathway / hypothalamus (9%), brainstem (9%), spinal cord (2%) (J Neurosurg 2003;98:1170)
Infratentorial location most common in childhood (J Neurooncol 2017;131:163)

Pathophysiology

Mutation in MAPK pathway component → pathway activation → transcription factor activation → increased cell growth and proliferation
Biallelic inactivation of NF1 in the setting of neurofibromatosis type 1 (Genome Res 2013;23:431)

Etiology

Most cases are sporadic
Germline mutations in MAPK pathway genes, including FGFR1, NF1, PTPN11 and RAF1

Diagrams / tables

Images hosted on other servers:

MAPK pathway mutations

Clinical features

Neurological deficits depending on tumor location
Nonlocalizing signs
- Macrocephaly
- Headache
- Endocrinopathy
- Increased intracranial pressure
Optic pathway tumors in 15% of patients with neurofibromatosis type 1 (Ophthalmology 1984;91:929)

Diagnosis

Diagnosis may be made on histologic features alone (Acta Neuropathol 2015;129:775)
When microscopic findings are limited / ambiguous, molecular testing may be necessary to assess for gene fusions and other alterations

Radiology description

Well demarcated enhancing mass (Insights Imaging 2014;5:387)
Cystic mass with enhancing mural nodule (~66% of cases), solid or heterogeneous mixed solid - cystic
Fusiform mass in optic pathway

Radiology images

Contributed by P.J. Cimino, M.D., Ph.D.

T1 postcontrast MRI

Prognostic factors

10 year survival > 95% after surgical intervention alone (J Neurosurg 2003;98:1170)
Optic nerve tumors in NF1 patients: favorable (Ann Neurol 2007;61:189)
Deep, midline location: high rates of incomplete resection, recurrence, shorter survival (Neuropathol Appl Neurobiol 2013;39:693)
Supratentorial: poor (Cancer 1993;72:1335)
Partial resection: poor (Neurosurgery 2003;53:544)
Age > 40: poor (J Neurooncol 2020;148:187)
Anaplastic features in adults: poor, no definitive WHO grade (Am J Surg Pathol 2010;34:147, Acta Neuropathol 2020;139:287, Acta Neuropathol 2016;131:803)
Pilomyxoid astrocytoma variant: unclear prognosis, no definitive WHO grade (Acta Neuropathol 2016;131:803)

Case reports

13 year old girl with left cerebellar cystic mass (NMC Case Rep J 2019;6:95)
33 year old woman with mesial temporal lobe mass (Case Rep Pathol 2020;2020:5903863)
39 year old woman with optic nerve glioma (Brain Tumor Pathol 2021;38:59)

Treatment

Gross total surgical resection
Radiation or chemotherapy may be considered for subtotally resected or recurrent cases
Variable success reported for MAPK pathway targeted therapies (Proc Natl Acad Sci U S A 2013;110:5957, Nat Med 2013;19:1401)

Clinical images

Images hosted on other servers:

Intraoperative surgical image

Exophthalmos - optic nerve glioma

Orbital pilocytic astrocytoma

Gross description

Usually well circumscribed (Acta Neuropathol 2015;129:775)
Commonly cystic
May have myxoid or mucoid appearance
May contain calcifications or hemosiderin staining

Gross images

Images hosted on other servers:

Intraocular pilocytic astrocytoma

Cerebellar tumor

Optic nerve tumor

Frozen section images

Contributed by P.J. Cimino, M.D., Ph.D.

Atypical piloid glial cells

Microscopic (histologic) description

Growth pattern
- Predominantly solid / circumscribed; often limited peripheral infiltration
- Frequent extension into subarachnoid space
Biphasic appearance
- Compact fibrillar portions: elongated nuclei, bipolar piloid processes, Rosenthal fibers
- Loose microcystic portions: round to oval nuclei, cobweb-like processes, eosinophilic granular bodies
Occasional "pennies on a plate" multinucleated cells
Oligodendroglioma-like areas may be present
Glomeruloid vessels
Regressive / degenerative changes
- Degenerative atypia
- Vascular hyalinization
- Infarct-like necrosis
- Calcification
- Perivascular lymphocytes
Anaplasia in a minority of cases
- Increased mitotic activity (> 4 mitoses/10 high power fields) with or without necrosis (Am J Surg Pathol 2010;34:147)
Pilomyxoid astrocytoma subtype
- Variant with angiocentric arrangement of monophasic bipolar tumor cells in a myxoid background

Microscopic (histologic) images

Contributed by P.J. Cimino, M.D., Ph.D.

Biphasic appearance

Compact fibrillary area

Cystic area

Rosenthal fibers

Eosinophilic granular bodies

Microvascular proliferation

Multinucleated cells

Hyalinized vessels

Extensive regressive features

Oligodendroglial-like
cytomorphology

Mitosis

GFAP piloid processes

Rosenthal fiber - GFAP

ATRX retained nuclear immunoreactivity

Increased Ki67 with anaplasia

Masson trichrome - EGBs

Virtual slides

Images hosted on other servers:

Pilocytic astrocytoma (grade I)

Cytology description

Smear preparation (alcohol fixed, H&E stained) (Cancer Cytopathol 2015;123:331)
- Mildly atypical glial cells with long piloid processes
- Ovoid nuclei with delicate chromatin
- Rosenthal fibers
- Eosinophilic granular bodies

Cytology images

Contributed by P.J. Cimino, M.D., Ph.D.

Smear (squash) preparation

Positive stains

Tumor cells:
- GFAP (Am J Surg Pathol 2012;36:43)
- Olig2 (J Neurooncol 2011;104:423)
- S100 (Am J Surg Pathol 2012;36:43)
- SOX10 (J Neuropathol Exp Neurol 2016;75:295)
- ATRX (retained nuclear staining) (Surg Neurol Int 2018;9:29, Acta Neuropathol 2020;139:287)
- Ki67 (generally low but increased with anaplasia) (J Neuropathol Exp Neurol 1999;58:46, Hum Pathol 1998;29:1511, J Clin Oncol 2003;21:2968, Am J Surg Pathol 2010;34:147)
Eosinophilic granular bodies (EGBs) (Hum Pathol 1998;29:1511):
Rosenthal fibers (Hum Pathol 1998;29:1511, Acta Neuropathol 1985;66:155):
- LFB (bright blue)
- Alpha B crystallin
- GFAP (limited to periphery)

Negative stains

IDH1 R132H (Brain Pathol 2010;20:245)
p53 (weak / low to absent) (Histopathology 1998;33:446)
BRAF V600E (~5% of cases) (Brain Behav 2017;7:e00641)

Electron microscopy description

Rosenthal fibers: amorphous, electron dense elements surrounded by intermediate filaments within astrocytic processes (J Pathol Transl Med 2015;49:427)
Eosinophilic granular bodies: round body, electron dense homogeneous material

Electron microscopy images

Images hosted on other servers:

Eosinophilic granular bodies

Molecular / cytogenetics description

Activating alterations in components of MAPK pathway (Nat Genet 2013;45:927, Nat Genet 2013;45:602)
- > 70% KIAA1549-BRAF fusion due to 7q34 tandem duplication
  - ~90% cerebellar cases
  - ~50% supratentorial cases
- ~5% other BRAF fusion
- ~5% BRAF V600E
- ~8% NF1 loss
- < 5% FGFR1 mutation
- < 5% FGFR1 fusions / internal tandem duplication
- ~2% NTRK fusions
- PTPN1 mutation (rare)
- KRAS mutation (rare)
- RAF1 fusions (rare)
Chromosomal polysomies (5, 6, 7, 11, 15) detected by comparative genomic hybridization (CGH) (J Neuropathol Exp Neurol 2006;65:1049, Br J Cancer 2000;82:1218)
Infratentorial / supratentorial tumors show distinct gene expression and DNA methylation signatures (Acta Neuropathol 2013;126:291)
H3 K27M mutation (rare) (Brain Pathol 2019;29:126)
Negative for IDH1 / IDH2 exon 4 mutations
Usually negative for TP53 mutations

Molecular / cytogenetics images

Images hosted on other servers:

KIAA1549-BRAF fusion by FISH

Copy number variation plot

NTRK2 fusion by next generation sequencing

NF1 biallelic inactivation

Pilocytic astrocytoma methylation classifier

Videos

Pilocytic astrocytoma

Rosenthal fibers in pilocytic astrocytoma

Sample pathology report

Brain, cerebellum, biopsy:
- Pilocytic astrocytoma, WHO grade 1 (see comment)
- Comment: Positive for KIAA1549-BRAF fusion.

Differential diagnosis

Neoplastic
- Diffuse glioma (including oligodendroglioma, IDH mutant astrocytoma, IDH wildtype astrocytic gliomas, diffuse midline glioma, H3 K27M mutant):
  - Diffusely infiltrative
  - Eosinophilic granular bodies and Rosenthal fibers uncommon
  - Distinct molecular features
- High grade astrocytoma with piloid features:
  - High grade histological features
  - Distinct molecular features
  - Frequent loss of ATRX nuclear staining (Acta Neuropathol 2018;136:273)
- Diffuse leptomeningeal glioneuronal tumor:
  - Primary leptomeningeal location
  - Commonly not reactive for GFAP
  - Distinct molecular features
- Pleomorphic xanthoastrocytoma:
  - Most frequently in superficial cerebral cortex
  - Pleomorphic, occasionally xanthomatous cells
  - Reticulin rich foci
- Ganglioglioma:
  - Neoplastic dysmorphic ganglion cells
- Dysembryoplastic neuroepithelial tumor:
  - Predominantly cortical
  - Mucin rich nodules
  - Floating neurons in microcysts
Nonneoplastic
- Reactive piloid gliosis:
  - Hypocellular
  - Lack of genetic alterations
- Vascular malformation

Additional references

Louis: WHO Classification of Tumours of the Central Nervous System, 4th Edition, 2016, Perry: Practical Surgical Neuropathology - A Diagnostic Approach, 2nd Edition, 2017

Board review style question #1

The above tumor is from the cerebellum of a child. What is the most common underlying genetic alteration in this entity?

TP53 mutation
IDH1 R132H
BRAF V600E mutation
BRAF fusion involving KIAA1549
NF1 loss

Board review style answer #1

D. BRAF fusion involving KIAA1549. TP53 mutations (answer A) are uncommon in pilocytic astrocytoma. IDH1 R132H (answer B) is the most common mutation in IDH mutant astrocytomas and oligodendrogliomas but should be negative in pilocytic astrocytomas. BRAF V600E mutation (answer C) and NF1 loss (answer E) occur in pilocytic astrocytomas at lower frequencies.

Comment Here

Reference: Pilocytic astrocytoma

Board review style question #2

Which of the following is true of pilocytic astrocytomas?

Show diffuse p53 immunoreactivity
Most frequently occur in adults
Demonstrate reticulin rich foci
Associated with neurofibromatosis 2
Potentially curable with resection

Board review style answer #2

E. Potentially curable with resection. Pilocytic astrocytomas should not show significant p53 immunopositivity (answer A) and they usually occur in children (answer B). Reticulin rich foci are a more typical feature of pleomorphic xanthoastrocytoma or gliosarcoma (answer C). In addition, pilocytic astrocytomas are associated with NF1 (answer D).

Comment Here

Reference: Pilocytic astrocytoma