Central Nervous System Tumors - Brain Tumors

Central nervous system (CNS) tumors are abnormal collections of benign or malignant cells. Integrated phenotypic and genotypic CNS tumor classification parameters are the hallmark of the 2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System.

Tabs Content

Clinical Overview

Diagnosis

Indications for Testing

Central nervous system (CNS) tumors cause either focal or generalized neurologic symptoms
- Focal neurological deficits
  - Seizures
  - Changes in vision and/or papilledema
  - Changes in hearing
  - Changes in speech or swallowing
  - Change in cognition/executive function and/or personality
  - Other motor weakness
- Generalized neurological symptoms
  - Severe headaches – either new onset or change in previous headache characteristics
Nonspecific symptoms
- Nausea
- Vomiting
- Fatigue

Laboratory Testing

Nonspecific testing to rule out other disease processes (eg, meningitis)
- CBC, chemistry profile, C-reactive protein (CRP)
- Lumbar puncture with collection of cerebrospinal fluid (CSF) may be indicated – do not perform before imaging studies due to risk of increased intracranial pressure and herniation
  - Protein
  - Glucose
  - Culture and Gram stain
  - Cell count and differential
  - Oligoclonal bands
  - Cytology

Histology

Diagnosis is based on a combination of histology (phenotyping) and molecular findings (genotyping) which direct therapy and provide prognostic information
- See Classification in Background and table in Pediatrics
Immunohistochemical staining – determine tumor cell origin
Genotyping – assist with classification (National Comprehensive Cancer Network [NCCN], 2017)
- 1p/19q deletion status by fluorescent in situ hybridization (FISH) or polymerase chain reaction (PCR)
  - Codeletion, uni-deletion, or no deletion
- IDH1 and IDH2 by PCR or pyrosequencing
- IDH1 R1324 by immunohistochemistry

Imaging Studies

Magnetic resonance imaging (MRI)/contrast-enhanced computed tomography (CT) – diagnosis and possible classification of tumor
- Perform prior to lumbar puncture
Magnetic resonance (MR) spectroscopy, MR perfusion – specialized circumstances
CT myelogram – evaluate spinal lesions
CT chest, abdomen, pelvis – tumor staging
Bone scan – suspected bone metastases
Positron emission tomography (PET) – may aid in diagnosis, grading gliomas, and differentiating between tumor recurrence and radiation necrosiss

Familial Genetic Testing

Indications for genetic testing are fairly rare and fully outlined in American College of Medical Genetics (ACMG) guidelines (Hampel, ACMG, 2015).

Prognosis

Differentiation of astrocytomas from oligodendrogliomas has prognostic and therapeutic importance
Mutations
- 1p/19q codeletion (FISH or PCR)
  - Better prognosis than those with a single or no deletion
  - Mutually exclusive for TP53 and ATRX mutations and EGFR amplification
  - Frequently associated with IDH1 or IDH2 mutations
  - Loss of 1p may identify treatment-sensitive malignant glioma in particular subtypes of anaplastic oligodendroglioma
    - Prognostic relevance in low-grade tumors less well characterized
- IDH1/IDH2 mutations (PCR)
  - Favorable outcomes in World Health Organization (WHO) gliomas
  - SNP rs11554137 associated with unfavorable prognosis
- MGMT promoter methylation (PCR)
  - Prognostic in glioma
  - Associated with significantly increased overall and progression-free survival – improved survival in those treated with alkylating agents
- Markers may affect prognosis if present together – methylation is associated with better prognosis in the absence of IDH1/IDH2 mutations
- Promising mutations – TERT may co-occur with IDH1/IDH2 and 1p19q deletion (triple-positive tumor)

Differential Diagnosis

Metastatic cancer
Infections
- Meningitis
- Encephalitis
- Brain abscess
- Parasites
  - Toxoplasma gondii
  - Toxocara spp
Seizure disorder
Migraine headache
Stroke
Vasculitis
Autoimmune CNS syndrome (eg, systemic lupus erythematosus cerebritis, multiple sclerosis, sarcoidosis, autoimmune encephalitis, neuromyelitis optica)
Progressive multifocal leukoencephalopathy (see JC Virus topic)
Subacute sclerosing panencephalitis (see Rubeola topic)

Background

Epidemiology

Incidence
- New brain tumor – 6.4/100,000 (Perkins, 2016)
- ~50% are benign
Prevalence
- Malignant – ~23,380 cases in U.S. in 2014 (Perkins, 2016; National Comprehensive Cancer Network [NCCN], 2017)
- Small percentage are hereditary
- Metastatic malignant CNS tumors are 10 times more frequent than primary tumors (NCCN, 2017)
Sex
- All CNS tumors – M<F, minimal
- Meningioma – M<F
Age – peak 55-64 years (Perkins, 2016)

Risk Factors

Viral infection – HIV infection associated with CNS lymphoma
High dose ionizing radiation
Genetic syndromes (see table in Genetics)

Classification

For a list of the classification for various CNS tumors, see the 2016 WHO summary.

Pathophysiology

CNS tumors are classified as glioma or nonglioma through histology and genetic testing – classification of not otherwise specified (NOS) is possible if genetic testing is unavailable
- Gliomas (~50% of primary brain tumors) – most common
  - Astrocytomas – includes glioblastoma
    - Glioblastoma – 50% of gliomas; ~15% of all CNS tumors
    - Low-grade astrocytoma can transform into glioblastoma within 5-10 years
  - Oligodendrogliomas
  - Ependymomas – occur more often in spinal canal
  - Other astrocytic tumors and gliomas
- Nongliomas
  - Region specific tumors (pineal region, choroid plexus, sellar region, cranial and paraspinal nerves) and glioneuronal tumors
    - Pituitary adenomas – usually benign
  - Meningiomas – usually benign but can be atypical meningiomas (WHO grade II) or anaplastic (WHO Grade III)
    - Atypical graded based on the following characteristics (WHO, 2016)
      - Brain invasion or
      - >4 mitoses or
      - 3 of 5 histological features (spontaneous necrosis, sheeting, prominent nucleoli, high cellularity, and small cell change)
  - Mesenchymal tumors – solitary fibrous tumors
    - Characterized by inversions at 12q13 with NAB2-STAT6 fusion
    - Graded I-III with cellularity, “staghorn” vasculature, and mitoses as key features
  - Melanocytic tumors
  - Embryonal tumors – see Pediatrics
- Primary spinal cord tumors – extradural, intradural-extramedullary, and intradural-intramedullary
  - Extradural tumors are usually metastatic
- Metastases
  - Leptomeningeal metastases – 50% of patients with cancer
  - Spinal metastases – arise most commonly from breast, lung, prostate, and renal cancers
  - Brain metastases – arise most commonly from lung and breast cancers, and melanoma
- Hematopoietic/lymphoid tumors
  - B-cell lymphomas
  - T-cell/NK-cell lymphomas

Genetics

Associated CNS tumors/syndromes by gene

Gene Symbol	Associated CNS Tumors/Syndromes
ALK	Neuroblastoma, ganglioneuroblastoma, ganglioneuroma (typically infancy to early childhood)
APC	CNS medulloblastoma
ATRX	CNS glioma
BAP1	Meningioma
BRAF	Pilocytic astrocytoma, pleomorphic xanthoastrocytoma, leptomeningeal glioneuronal tumors, epithelioid glioblastoma
BRCA2	Medulloblastoma
C19MC	Embryonal tumor with multilayered rosettes
H3F3A	Diffuse midline glioma, H3K27M-mutant
HIST1H3B	Diffuse midline glioma, H3K27M-mutant
IDH	Astrocytic tumors
LZTR1	Schwannoma
MEN1	MEN1 syndrome (pituitary adenoma)
MLH1	CNS glioblastoma, medulloblastoma, Turcot syndrome, constitutional mismatch repair-deficiency syndrome
MSH2	CNS glioblastoma, medulloblastoma, Turcot syndrome, constitutional mismatch repair-deficiency syndrome
MSH6	CNS glioblastoma, medulloblastoma, Turcot syndrome, constitutional mismatch repair-deficiency syndrome
NAB2	Solitary fibrous tumor/hemangiopericytoma with inversion at 12q13 and NAB2-STAT6 fusion
NF1	CNS glioma
NF2	Bilateral vestibular schwannoma, meningioma, ependymoma, glioma, rarely astrocytoma
PHOX2B	Neuroblastoma, ganglioma
PMS2	Glioblastoma
PRKAR1A	Carney complex (pituitary adenoma, melanotic schwannoma)
PTCH1	Nevoid basal cell carcinoma syndrome (Gorlin syndrome), medulloblastoma
PTCH2	Medulloblastoma
PTEN	Occasionally brain tumor, Lhermitte-Duclos syndrome, Cowden syndrome type I (cerebellar dysplastic gangliocytoma)
RB1	Pinealoblastoma, retinoblastoma
RELA	Ependymoma, RELA-fusion positive
SHH	Medulloblastoma, SHH-activated and TP53-mutant; medulloblastoma, SHH-activated and TP53-WT
SMARCB1	Choroid plexus carcinoma, medulloblastoma, central primitive neuroectodermal, schwannomatosis, meningioma, malignant rhabdoid tumor predisposition
STAT6	Solitary fibrous tumor/hemangiopericytoma with inversion at 12q13 and NAB2-STAT6 fusion
STK11	Occasional brain tumor
SUFU	Desmoplastic medulloblastoma, meningioma
SWNTS1	Schwannomatosis (spinal schwannomas, meningioma)
TP53	Tuberous sclerosis complex (astrocytoma, glioma), brain, Li-Fraumeni syndrome (medulloblastoma)
TSC1	Tuberous sclerosis type I (astrocytoma)
VHL	Retinal, spinal, cerebellar, hemangioblastoma, CNS
WNT	Medulloblastoma, WNT-activated
CNS = central nervous system; MEN1 = multiple endocrine neoplasia type 1

Pediatrics

Clinical Background

Epidemiology

Incidence – 2-5/100,000

Risk Factors

Irradiation
Familial syndromes (refer to Background)

Indications

See Indications for Testing in Diagnosis
Nausea, emesis, and headaches are more common in the pediatric population

Specific tumors

Gliomas
- Incidence
  - 6/100,000
  - 60% of childhood central nervous system (CNS) tumors
- Age – 5-10 years; peak 6 years
- Clinical presentation – seizures
- Do not routinely possess IDH mutations
- Have 1p/19q codeletions like adult counterparts
- Pilocytic astrocytoma (World Health Organization [WHO] grade I)
  - Most common glioma of children and adolescents
  - Cerebellum, midline (optic nerve/chiasm, hypothalamus, thalamus, basal ganglia, brain stem, and spinal cord), and intraventricular locations
  - BRAF fusions (KIAA1549-BRAF) found in 90% of cerebellar and 50% of supratentorial cases
  - BRAF V600E in 5% of cases but in other CNS tumors as well
  - Absence of BRAF mutation has no diagnostic significance, but a positive result is confirmatory
  - Pilomyxoid variant has similar distribution but worse overall prognosis
- Diffuse midline glioma, H3K27-mutant (WHO grade IV)

Embryonal tumors

Incidence
- <1/100,000 (National Comprehensive Cancer Network [NCCN], 2017)
- Most common childhood malignant CNS tumor
Age – peak 6 years
Sex – M>F; 1.6:1
Ethnicity – more common in Caucasians
Nonmedulloblastoma (supratentorial) tumors
- Cerebral neuroblastoma
- Pineoblastoma
- Olfactory neuroblastoma

Medulloblastoma tumors

The most common childhood malignant CNS tumor

Diagnosis is now histologically and genetically modular

Medulloblastoma Classification
Medulloblastoma	Histology	Prevalence	Risk
WNT activated	Classic		Low
WNT activated	Large cell/anaplastic	Very rare	Uncertain significance
SHH activated, TP53 mutant	Classic		High (uncommon)
	Large cell/anaplastic	Children 7-17 yrs	High
	Desmoplastic/nodular	Very rare	Uncertain significance
SHH activated, TP53 wildtype	Classic		Standard
	Large cell/anaplastic		Uncertain significance
	Desmoplastic/nodular	Infants and adults	Low (in infants)
	Extensive nodularity	Infants	Low
Non-WNT/non-SHH, group 3	Classic		Standard
Non-WNT/non-SHH, group 3	Large cell/anaplastic		High
Non-WNT/non-SHH, group 4	Classic		Standard
Non-WNT/non-SHH, group 4	Large cell/anaplastic	Rare	Uncertain significance
Adapted from Louis, 2016

Ependymomas
- Incidence – 10% of childhood tumors
- Clinical presentation – predilection for sixth and seventh nerve palsies, loss of hearing, and swallowing difficulties
Craniopharyngiomas (WHO grade I)
- Incidence – 5-10% of all childhood CNS tumors
- Age – 6-15 years
- Clinical presentation – visual defects and endocrine abnormalities
- Adamantinomatous craniopharyngiomas show CTNNB1 mutations and aberrant nuclear beta-catenin expression in 95% of cases
- Papillary craniopharyngiomas show BRAF V600E mutations in 81-95% of cases
Teratomas
- Incidence – rare (1-3/million live births)
- Age – neonate (usually <1 year)
- Includes components of astrocytoma, primitive neuroectodermal, and choroid plexus papillomas
- Clinical presentation
  - Often diagnosed prenatally by ultrasound
  - Bulging fontanelle, failure to thrive, apnea, emesis, abnormal head circumference
  - Benign tumors often exhibit malignant behavior in this age group
Diffuse leptomeningeal glioneuronal tumor (no WHO grade assigned)
- Commonly harbor BRAF fusions
- Deletions of 1p and occasionally 19q
- Absence of IDH mutations
- Variable prognosis
Embryonal tumor with multilayered rosettes, C19MC-altered
- Amplification of C19MC region on chromosome 19 (19q13.42)
- Consider embryonal tumor with multilayered rosettes, not otherwise specified (NOS), and medulloepithelioma in the absence of C19MC amplification
Atypical teratoid/rhabdoid tumor (AT/RT) (WHO grade IV)
- Defined by alterations of INI1 or very rarely BRG1
- Loss of nuclear expression correlates with genetic alteration

ARUP Lab Tests

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

1p/19q Deletion by FISH 2008604
Method: Fluorescence in situ Hybridization

Recommended Use

Diagnose oligodendroglioma brain tumors; indicated in both low-grade and high-grade (anaplastic) oligodendrogliomas

Predict response to therapy in oligodendrogliomas

Refer to Additional Technical Information document for further content

Limitations

Test should not be used alone for diagnosis of malignancy

IDH1 and IDH2 Mutation Analysis, exon 4 2006444
Method: Polymerase Chain Reaction/Sequencing

Recommended Use

Detect IDH1 R132 and IDH2 R140/R172 mutations in whole blood or bone marrow

Aid in assessment for possible treatment of relapsed/refractory AML patients with enasidenib (IDHIFA)

For FFPE tissues, please use IDH1 and IDH2 mutation analysis, exon 4 FFPE tissue test

Refer to Additional Technical Information document for further content

Limitations

Negative test result does not exclude mutations below limit of detection and presence of mutations other than those detected by the test

This marker should be interpreted within the group of CN-AML prognostic markers

IDH1 and IDH2 Mutation Analysis, Exon 4, Formalin-Fixed, Paraffin-Embedded (FFPE) Tissue 2014188
Method: Polymerase Chain Reaction/Sequencing

Recommended Use

IDH1/IDH2 mutational status is a prognostic marker in individuals with low- and high-grade gliomas

Aid in distinguishing a primary from a secondary glioblastoma

Refer to Additional Technical Information document for further content

Limitations

Negative test result does not exclude mutations below limit of detection and presence of mutations other than those detected by the test

This marker should be interpreted within the group of CN-AML prognostic markers

ATRX by Immunohistochemistry 2014499
Method: Immunohistochemistry

Recommended Use

Aid in astrocytic differentiation

Stained and returned to client pathologist for interpretation; consultation available if needed

IDH1 R132H by Immunohistochemistry 2005857
Method: Immunohistochemistry

Recommended Use

Use when morphology indicates tumor may be a glioma

Use to differentiate tumors from reactive gliosis

Stained and returned to client pathologist for interpretation; consultation available if needed

Limitations

Test should not be used alone for diagnosis of malignancy

MGMT Methylation Detection by PCR 2009310
Method: Real-Time Polymerase Chain Reaction/Fluorescence Resonance Energy Transfer

Recommended Use

Aid in therapeutic decisions in individuals with gliomas

Recommended for WHO grade II-IV astrocytic, oligodendroglial, and gliosarcoma brain tumors

Refer to Additional Technical Information document for further content

Limitations

Methylation at locations other than those covered by the primers and probes not detected

Results of this test must always be interpreted within the clinical context and other relevant data

Results should not be used as a sole determinant of alkylating chemotherapy in standard clinical practice

Ki-67 with Interpretation by Immunohistochemistry 2007182
Method: Immunohistochemistry

Recommended Use

Aid in diagnosis of central nervous system (CNS) tumor

Stained and resulted by ARUP

Glial Fibrillary Acidic Protein (GFAP) by Immunohistochemistry 2003899
Method: Immunohistochemistry

Recommended Use

Aid in diagnosis of CNS tumor

Stained and returned to client pathologist for interpretation; consultation available if needed

S-100 Protein by Immunohistochemistry 2004127
Method: Immunohistochemistry

Recommended Use

Aid in diagnosis of CNS tumor

Stained and returned to client pathologist for interpretation; consultation available if needed

CD56 (NCAM) by Immunohistochemistry 2003589
Method: Immunohistochemistry

Recommended Use

Aid in diagnosis of CNS tumor

Stained and returned to client pathologist for interpretation; consultation available if needed

p53 with Interpretation by Immunohistochemistry 0049250
Method: Immunohistochemistry

Recommended Use

Aid in diagnosis and prognosis of CNS tumor

Stained and resulted by ARUP

CD117 (c-Kit) by Immunohistochemistry 2003806
Method: Immunohistochemistry

Recommended Use

Aid in histologic diagnosis of CNS tumors

Stained and returned to client pathologist for interpretation; consultation available if needed

Placental Alkaline Phosphatase (PLAP) by Immunohistochemistry 2004097
Method: Immunohistochemistry

Recommended Use

Aid in diagnosis of CNS tumor

Stained and returned to client pathologist for interpretation; consultation available if needed

Human Chorionic Gonadotropin (Beta-hCG) by Immunohistochemistry 2003920
Method: Immunohistochemistry

Recommended Use

Aid in diagnosis of CNS tumor

Stained and returned to client pathologist for interpretation; consultation available if needed

Alpha-1-Fetoprotein (AFP) by Immunohistochemistry 2003436
Method: Immunohistochemistry

Recommended Use

Aid in diagnosis of CNS tumor

Stained and returned to client pathologist for interpretation; consultation available if needed

Inhibin by Immunohistochemistry 2003969
Method: Immunohistochemistry

Recommended Use

Aid in diagnosis of CNS tumor

Stained and returned to client pathologist for interpretation; consultation available if needed

D2-40 by Immunohistochemistry 2003857
Method: Immunohistochemistry

Recommended Use

Aid in diagnosis of CNS tumor

Stained and returned to client pathologist for interpretation; consultation available if needed

Synaptophysin by Immunohistochemistry 2004139
Method: Immunohistochemistry

Recommended Use

Aid in diagnosis of CNS tumor

Stained and returned to client pathologist for interpretation; consultation available if needed

Medical Reviewers

Bayrak-Toydemir, Pinar, MD, PhD, Medical Director, Molecular Genetics and Genomics at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Kelley, Todd, MD, MS, Medical Director, Molecular Hematopathology and Hematopathology; Co-Scientific Director, NGS and Biocomputing, at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Klonoski, Joshua M., MD, PhD, Assistant Medical Director of Informatics and Content Editor at ARUP Laboratories; Resident Physician, Department of Pathology, University of Utah

Miller, Christine E., MS, LCGC, Genetic Counselor, Molecular Genetics at ARUP Laboratories; Faculty, Graduate Program in Genetic Counseling, University of Utah

Palmer, Cheryl Ann, MC, Medical Director at ARUP Laboratories; Professor of Anatomic Pathology, University of Utah

Samowitz, Wade S., MD, Medical Director, Anatomic Pathology, at ARUP Laboratories; Professor of Anatomic Pathology, University of Utah

References

Guidelines

Olson JJ, Fadul CE, Brat DJ, Mukundan S, Ryken TC. Management of newly diagnosed glioblastoma: guidelines development, value and application. J Neurooncol. 2009; 93(1): 1-23. PubMed
Protocol for the Examination of Specimens from Patients with Tumors of the Brain/Spinal Cord. No AJCC/UICC TNM Staging System. Protocol web posting date: Dec 2014. College of American Pathologists (CAP). Northfield, IL [Last Modified: Dec 2014; Accessed: Jun 2018]
Preusser M, Capper D, Hartmann C, Euro-CNS Research Committee. IDH testing in diagnostic neuropathology: review and practical guideline article invited by the Euro-CNS research committee. Clin Neuropathol. 2011; 30(5): 217-30. PubMed
NCCN Clinical Practice Guidelines in Oncology, Central Nervous System Cancers. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Aug 2017]
Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Jun 2018]
Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL, Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2015; 17(1): 70-87. PubMed
Cancer Genome Atlas Research Network, Brat DJ, Verhaak RG, et al. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. N Engl J Med. 2015; 372(26): 2481-98. PubMed
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016; 131(6): 803-20. PubMed

General References

Brain and spinal cord tumors in adults. American Cancer Society. Atlanta, GA [Accessed: Aug 2017]

Buckner JC, Brown PD, O'Neill BP, Meyer FB, Wetmore CJ, Uhm JH. Central nervous system tumors. Mayo Clin Proc. 2007; 82(10): 1271-86. PubMed

Dhall G. Medulloblastoma. J Child Neurol. 2009; 24(11): 1418-30. PubMed

Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H, Pekmezci M, Rice T, Kosel ML, Smirnov IV, Sarkar G, Caron AA, Kollmeyer TM, Praska CE, Chada AR, Halder C, Hansen HM, McCoy LS, Bracci PM, Marshall R, Zheng S, Reis GF, Pico AR, O'Neill BP, Buckner JC, Giannini C, Huse JT, Perry A, Tihan T, Berger MS, Chang SM, Prados MD, Wiemels J, Wiencke JK, Wrensch MR, Jenkins RB. Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. N Engl J Med. 2015; 372(26): 2499-508. PubMed

Frühwald MC, Rutkowski S. Tumors of the central nervous system in children and adolescents. Dtsch Arztebl Int. 2011; 108(22): 390-7. PubMed

Jansen M, Yip S, Louis DN. Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers. Lancet Neurol. 2010; 9(7): 717-26. PubMed

Magdum SA. Neonatal brain tumours - a review. Early Hum Dev. 2010; 86(10): 627-31. PubMed

Manoranjan B, Provias JP. Congenital brain tumors: diagnostic pitfalls and therapeutic interventions. J Child Neurol. 2011; 26(5): 599-614. PubMed

Nikiforova MN, Hamilton RL. Molecular diagnostics of gliomas. Arch Pathol Lab Med. 2011; 135(5): 558-68. PubMed

Perkins A, Liu G. Primary brain tumors in adults: diagnosis and treatment. Am Fam Physician. 2016; 93(3): 211-7. PubMed

Pfister S, Hartmann C, Korshunov A. Histology and molecular pathology of pediatric brain tumors. J Child Neurol. 2009; 24(11): 1375-86. PubMed

Pytel P, Lukas RV. Update on diagnostic practice: tumors of the nervous system. Arch Pathol Lab Med. 2009; 133(7): 1062-77. PubMed

Ricard D, Idbaih A, Ducray F, Lahutte M, Hoang-Xuan K, Delattre J. Primary brain tumours in adults. Lancet. 2012; 379(9830): 1984-96. PubMed

Takei H, Bhattacharjee MB, Rivera A, Dancer Y, Powell SZ. New immunohistochemical markers in the evaluation of central nervous system tumors: a review of 7 selected adult and pediatric brain tumors. Arch Pathol Lab Med. 2007; 131(2): 234-41. PubMed

van den Bent MJ, Kros JM. Predictive and prognostic markers in neuro-oncology. J Neuropathol Exp Neurol. 2007; 66(12): 1074-81. PubMed

Weller M, Pfister SM, Wick W, Hegi ME, Reifenberger G, Stupp R. Molecular neuro-oncology in clinical practice: a new horizon. Lancet Oncol. 2013; 14(9): e370-9. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology^®

Cohen A, Sato M, Aldape K, Mason CC, Alfaro-Munoz K, Heathcock L, South ST, Abegglen LM, Schiffman JD, Colman H. DNA copy number analysis of Grade II-III and Grade IV gliomas reveals differences in molecular ontogeny including chromothripsis associated with IDH mutation status. Acta Neuropathol Commun. 2015; 3: 34. PubMed

Layfield LJ, Willmore C, Tripp S, Jones C, Jensen RL. Epidermal growth factor receptor gene amplification and protein expression in glioblastoma multiforme: prognostic significance and relationship to other prognostic factors. Appl Immunohistochem Mol Morphol. 2006; 14(1): 91-6. PubMed

Lloyd IE, Clement PW, Salzman KL, Jensen RL, Salama ME, Palmer CA. An unusual and challenging case of HIV-associated primary CNS Lymphoma with Hodgkin-like morphology and HIV encephalitis. Diagn Pathol. 2015; 10: 152. PubMed

Modzelewska K, Boer EF, Mosbruger TL, Picard D, Anderson D, Miles RR, Kroll M, Oslund W, Pysher TJ, Schiffman JD, Jensen R, Jette CA, Huang A, Stewart RA. MEK Inhibitors Reverse Growth of Embryonal Brain Tumors Derived from Oligoneural Precursor Cells. Cell Rep. 2016; 17(5): 1255-1264. PubMed

Paxton CN, Rowe LR, South ST. Observations of the genomic landscape beyond 1p19q deletions and EGFR amplification in glioma. Mol Cytogenet. 2015; 8: 60. PubMed

Tomsic J, Senter L, Liyanarachchi S, Clendenning M, Vaughn CP, Jenkins MA, Hopper JL, Young J, Samowitz W, de la Chapelle A. Recurrent and founder mutations in the PMS2 gene. Clin Genet. 2013; 83(3): 238-43. PubMed

Tripp SR, Willmore-Payne C, Layfield LJ. Relationship between EGFR overexpression and gene amplification status in central nervous system gliomas. Anal Quant Cytol Histol. 2005; 27(2): 71-8. PubMed

Walter AW, Ennis S, Best H, Vaughn CP, Swensen JJ, Openshaw A, Gripp KW. Constitutional mismatch repair deficiency presenting in childhood as three simultaneous malignancies. Pediatr Blood Cancer. 2013; 60(11): E135-6. PubMed

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Central Nervous System Tumors - Brain Tumors

Diagnosis

Indications for Testing

Laboratory Testing

Histology

Imaging Studies

Familial Genetic Testing

Prognosis

Differential Diagnosis

Background

Epidemiology

Risk Factors

Classification

Pathophysiology

Genetics

Pediatrics

Clinical Background

Epidemiology

Risk Factors

Indications

Specific tumors​

ARUP Lab Tests

Medical Reviewers

References

Guidelines

General References

References from the ARUP Institute for Clinical and Experimental Pathology®

Specific tumors

References from the ARUP Institute for Clinical and Experimental Pathology^®