eBulletin Newsletter

NCCN Flash Update: NCCN Guidelines Updated Central Nervous System Cancers

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®), the NCCN Drugs & Biologics Compendium (NCCN Compendium^®), and the NCCN Radiation Therapy Compendium™ for Central Nervous System Cancers. These NCCN Guidelines^® are currently available as Version 1.2025.

Link directly to the Updates section of the NCCN Guidelines: Central Nervous System Cancers

Global

• Follow-up throughout the GLIO section refers the reader to Principles of Brain and Spine Tumor Imaging BRAIN-A.
• New footnote throughout the systemic therapy section: An FDA-approved biosimilar is an appropriate substitute for any recommended systemic biologic therapy in the NCCN Guidelines.
• References have been updated throughout the guidelines.

GLIO-1

Pathology

• WHO grade 2, bullet 2 deleted glioneuronal tumors.
• Added WHO grade 3.
• If IDH-mutant astrocytoma, for grade 4, see GLIO-6.

Adjuvant Treatment

• Sub-sub-bullet 3, modified: Consider BRAF and MEK inhibitors if BRAF alterations. V600E-activating mutation

Footnotes

• b, modified: Principles of Brain and Spine Tumor Surgery (BRAIN-B).
• e, new: The Panel strongly recommends multidisciplinary discussion of patients with newly diagnosed or recurrent or progressive gliomas (any grade) or referring such patients to a brain tumor center for a consultation. Similarly, if treatment with an IDH inhibitor is being considered for a patient with newly diagnosed oligodendroglioma or astrocytoma, the Panel strongly recommends multidisciplinary discussion or referral to a brain tumor center for consultation. (Also for GLIO-2A, GLIO-3, GLIO-4A, GLIO 5A, GLIO-6, GLIO-8, GLIO-9).

GLIO-2

Adjuvant Treatment

Good PS (KPS ≥60)

• No residual/measurable disease or,
  • IDH inhibitor or,
  • Consider clinical trial
• Residual/measurable disease or recurrent tumor after resection or biopsy and when upfront treatment with RT and chemotherapy is not preferred.
  • Consider clinical trial.

Poor PS (KPS <60)

• IDH inhibitor (moved up from the 2nd bullet).
• Consider clinical trial.

GLIO-2A

Footnotes

• Deleted: Principles of Brain and Spine Tumor Imaging (BRAIN-A). (Also for GLIO-4A, GLIO-5A).
• l, new: Patients with newly diagnosed grade 2 oligodendroglioma who have undergone gross total resection of tumor might remain progression free for many years; therefore, initially observing these patients is reasonable. Byeon Y, et al. Discov Oncol 2024;15:268.
• m, modified to include the following sentence: Overall survival data from this study are not yet available. Ivosidenib is an IDH1 inhibitor and is a reasonable alternative if a patient cannot tolerate vorasidenib. Byeon Y, et al. Discov Oncol 2024;15:268. (Also for GLIO-4A).
• n, new: Newly diagnosed patients with oligodendroglioma/astrocytoma (WHO grade 2 or 3) who did not have residual disease were excluded from participation in the phase 3 INDIGO study of vorasidenib versus placebo. Therefore, it remains unknown if this subset of patients would benefit from immediate treatment with an IDH inhibitor. The safety of long-term treatment with IDH inhibitors is unknown. The Panel recommends discussing the possible risks and benefits of starting treatment right away with an IDH inhibitor with these patients. (Also for GLIO-4A).

• Deleted: Ivosidenib is an IDH1 inhibitor and is a reasonable alternative if a patient with IDH1-mutated grade 2 oligodendroglioma cannot tolerate vorasidenib. (Byeon et al., Oligodendroglioma in adult patients: a single-institution experience. Discover Oncology 2024; 15:268). (Also for GLIO-4A).
• p, new: If a patient has a KPS <60 due to neurologic deficits from the brain tumor, then RT + TMZ would be the preferred treatment. However, if a patient has a KPS <60 for other reasons, such as medical comorbidities, then treatment with an IDH inhibitor would be reasonable since it may be tolerated better than radiation and/or cytotoxic chemotherapy.(Also for GLIO-3, GLIO-4A, GLIO-5A).

GLIO-3

Adjuvant Treatment

Good PS (KPS ≥60)

• Added: IDH inhibitor (category 2B).

Poor PS (KPS <60)

• Added: Consider clinical trial.
• Added: IDH inhibitor (category 2B).

Footnotes

• s, new: Some Panel members felt that given the relatively slow growth rate of oligodendrogliomas, in certain circumstances it would be reasonable to first try treatment with an IDH inhibitor. However, other Panel members expressed concern about possible undertreatment of these patients by postponing the start of radiation and cytotoxic chemotherapy, which have been shown to improve survival in newly diagnosed grade 3 oligodendroglioma patients (van den Bent MJ, et al. J clin Oncol 2013;31:344-350; Cairncross G, et al. J Clin Oncol 2013;31:337-343).Newly diagnosed grade 3 oligodendroglioma patients who start treatment with an IDH inhibitor should be followed closely with brain MRIs. See Principles of Brain and Spine Tumor Management (BRAIN-D).

GLIO-4

Adjuvant treatment

Good PS (KPS ≥60)

• No residual/measurable disease or,
  • IDH inhibitor or,
  • Consider clinical trial.
• Residual/measurable disease or recurrent tumor after resection or biopsy when upfront treatment with RT and chemotherapy is not preferred.
  • IDH inhibitor or,
  • Consider clinical trial.

Poor PS (KPS<60)

• Consider clinical trial.

GLIO-4A

Footnotes

• t, new: Grade 2 astrocytomas are relatively slow growing and may not require further treatment for several years. Therefore, initial observation after gross total resection is reasonable.
• u, new: The Panel acknowledges that compared to grade 2 oligodendrogliomas, grade 2 astrocytomas typically progress faster. Therefore, delaying the need for radiation and cytotoxic chemotherapy by starting treatment with an IDH inhibitor in a grade 2 astrocytoma patient who has undergone gross total resection of tumor may also be a reasonable approach.

GLIO-5

• Deleted, WHO grade 4.
• Grade 3, modified:
  • Good PS, KPS ≥60, added: IDH inhibitor (category 2B).
  • Poor PS, KPS ˂60, added: IDH inhibitor (category 2B).

GLIO-5A

Footnotes

• Deleted: Treatment of grade 4 disease is extrapolated from interim analyses of data from the CATNON study. Final results of CATNON are not yet available.
• v, new: Strict histopathologic criteria do not currently exist for definitively diagnosing a WHO grade 2 versus a WHO grade 3 IDH-mutated astrocytoma. Therefore, some Panel members felt that it may be reasonable to try treating patients with newly diagnosed IDH-mutated grade 3 astrocytoma up front with an IDH inhibitor in certain circumstances. This includes, but is not limited to, if the enhancing portion of the tumor has been resected, and all the remaining tumor is non-enhancing, probable grade 2 tumor. Other Panel members disagreed with this approach due to possibly undertreating a patient by postponing the start of radiation and cytotoxic chemotherapy, which have been shown to improve survival (van den Bent MJ, et al. Lancet Oncol 2021;22:813-823).

GLIO-6

• Added, WHO grade 4.

GLIO-7

Footnotes

• z: modified, See Principles of Brain and Spine Tumor Imaging (BRAIN-A) for imaging recommendations to assess disease recurrence/progression. (Also for GLIO-8).

GLIO-A (1 of 9)

Circumscribed Glioma

Recurrent or Progressive Disease

Useful in Certain Circumstances

• Modified, BRAF alterations V600E activation mutation
  • BRAF fusion or rearrangement, or BRAF V600 mutation
    MEK inhibitors
    • New: Tovorafenib category 2A recommendation.
• MEK inhibitor
  • New: Trametinib (for BRAF only) category 2A recommendation.

GLIO-A (2 of 9)

Oligodendroglioma (IDH-Mutant, 1p19q- Codeleted)

• Modified: No residual/measurable disease or adjuvant treatment after surgery/biopsy and when treatment with RT and chemotherapy is not preferred, WHO grade 2, KPS ≥60.

Preferred

• Modified: Vorasidenib (if residual disease is present) (category 1 for residual/measurable disease after surgery/biopsy) for IDH1 or IDH2 mutations.

Useful in Certain Circumstances

• Modified: Ivosidenib for IDH1 mutation (if unable to tolerate vorasidenib).

Adjuvant Treatment WHO grade 3, KPS ≥60.

Useful in Certain Circumstances

• New:
  • Ivosidenib for IDH1 mutation (if unable to tolerate vorasidenib) (category 2B) recommendation (Also for GLIO-A 4).
  • Vorasidenib for IDH1 or IDH2 mutations (category 2B) recommendation (Also for GLIO-A 4).
• Modified: Adjuvant Treatment, KPS <60 WHO grade 3.

Other Recommended

• New:
  • Ivosidenib for IDH1 mutation (if unable to tolerate vorasidenib) (category 2B for WHO grade 3).
  • Vorasidenib for IDH1 or IDH2 mutations (category 2B for WHO grade 3).

Useful in Certain Circumstances

• Deleted:
  • Ivosidenib for IDH1 mutant grade 2.
  • Vorasidenib for IDH1 or IDH2 mutations and grade 2.

Recurrent or Progressive Disease after RT + chemotherapy WHO grade 2, KPS ≥60.

Preferred

• Bullet 4, modified: Ivosidenib for IDH1 mutation (if unable to tolerate vorasidenib) (Also for recurrent or progressive disease, WHO grade 3, KPS ≥60, GLIO-4).

Recurrent or Progressive Disease, WHO grade 3, KPS ≥60.

Preferred

• Deleted: Category 2B for Vorasidenib for IDH1 or IDH2 mutations.
• New: Ivosidenib for IDH1 mutation (if unable to tolerate vorasidenib).

Useful in Certain Circumstances

• Deleted: Ivosidenib for IDH1 mutation.

GLIO-A (3 of 9)

Footnotes

• g, modified: Vorasidenib is a dual inhibitor of IDH1 and IDH2 mutations. In a phase 3 study of vorasidenib versus placebo (Mellinghoff IK, et al. N Engl J Med 2023;389:589-601) in patients with residual or recurrent grade 2 IDH-mutant glioma (after surgery and no prior treatment), vorasidenib improved median PFS (27.7 months vs. 11.1 months), compared to placebo. Vorasidenib has the most safety data in patients with newly diagnosed grade 2 IDH-mutant gliomas. (Also for GLIO-A 5).
• h, new: Newly diagnosed patients with oligodendroglioma/astrocytoma (WHO grade 2 or 3) who did not have residual disease were excluded from participation in the phase 3 INDIGO study of vorasidenib versus placebo. Therefore, it remains unknown if this subset of patients would benefit from immediate treatment with an IDH inhibitor. The safety of long-term treatment with IDH inhibitors is unknown. The Panel recommends discussing the possible risks and benefits of starting treatment right away with an IDH inhibitor with these patients. (Also for GLIO-A 5).

GLIO-A (4 of 9)

IDH-Mutant Astrocytoma

• Modified: No residual/measurable disease or adjuvant treatment after surgery/biopsy and when treatment with RT and chemotherapy is not preferred, WHO grade 2, KPS ≥60.

Preferred

• Modified: Vorasidenib (category 1 for residual/measurable disease after surgery/biopsy) for IDH1 or IDH2 mutations.

Useful in Certain Circumstances

• Ivosidenib for IDH1 mutation (if unable to tolerate vorasidenib).

Adjuvant Treatment KPS <60

Useful in Certain Circumstances

• Modified, bullet 1: Ivosidenib for IDH1 mutation (if unable to tolerate vorasidenib) (category 2B for grade 3).
• Modified, bullet 2: Vorasidenib for IDH1 or IDH2 mutations (category 2B for grade 3).

Recurrent or Progressive Disease, WHO grade 3 or 4, KPS ≥60.

Preferred

• New, bullet 5: Ivosidenib for IDH1 mutation (if unable to tolerate vorasidenib) (category 2B).

Useful in Certain Circumstances

• Moved: Ivosidenib for IDH1 mutation (category 2B) to preferred above vorasidenib.

GLIO-A (6 of 9)

Glioblastoma

Recurrent or Progressive Disease

Preferred

• Deleted: Regorafenib.

Useful in Certain Circumstance

• New: FGFR alterations
  •  Erdafitinib (category 2B) recommendation.
• Modified: BRAF alterations

EPEN-2

Footnotes

• h, modified: Lumbar puncture is indicated when there is clinical concern for meningeal dissemination. Lumbar puncture should be done after MRI of spine is performed to avoid a false-positive imaging result. Lumbar puncture for prompt CSF analysis should be delayed at least 2 weeks after surgery to avoid possible false-positive cytology. Lumbar puncture may be contraindicated (eg, posterior fossa mass). When available, CSF-tumor-derived DNA (tDNA) testing can be considered with CSF cytology to increase sensitivity of tumor cell detection and assessment of residual disease after surgery. (Also for EPEN-3, EPEN-4, AMED-2, AMED-3).

EPEN-3

• Column 3, 3rd row, deleted cytology positive.

Footnotes

• m, modified: RT has been associated with improved disease control (Weber D, et al. Neuro Oncol 2015;17:588-595). Given the different therapies available at recurrence, potential for salvage therapy Close observation may be clinically appropriate in some cases (Kotecha R, et al. J Neurosurg Spine 2020;1:392-397).

PCNS-1

• Column 2, Bullet 1: Hold initiation of steroids, if possible, prior to diagnostic procedure. (Moved to first bullet from fourth).
• Column 3, new: Primary vitreoretinal lymphoma/primary CNS Lymphoma ocular variant.

Footnote

• f, modified: Brain biopsy is recommended as the primary procedure to obtain diagnosis. CSF analysis should include flow cytometry, CSF cytology, cell count, and possibly gene rearrangements, specifically the IGH heavy chain rearrangement, and CSF-tDNA. Polymerase chain reaction (PCR) of MYD88 in the CSF is helpful. (Also for PCNS-2A).

PCNS-2

• This page has been significantly updated.

Footnote

• i, modified: CRu refers to no enhancement, any steroids, normal eye examination and negative CSF, or minimal contrast abnormality, any steroids, minor retinal pigment epithelium, and negative CSF (Abrey LE, et al. J Clin Oncol 2005;23:5034-5043). (Also for PCNS-3).
• k, modified: CSF analysis should include flow cytometry, CSF cytology, and cell count, and may consider gene rearrangements and CSF-tDNA.

PCNS-3

Footnote

• Deleted: A low KPS should not be a reason to withhold systemic therapy. KPS may improve dramatically after treatment.

PCNS-A

Primary CNS Lymphoma

Induction therapy

Useful in Certain Circumstances

• Bullet 2, first sub-bullet deleted: high-dose.

Relapsed or Refractory Disease

Useful in Certain Circumstances

• New: Zanubrutinib ± high-dose cytarabine (only at first recurrence; consider age and PS) Category 2A recommendation.

MENI-1

Footnote

• a, modified: Multidisciplinary input for treatment planning if feasible. See NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic and Prostate.

MENI-2

Follow-Up

• New: Principles of Brain and Spine Tumor Imaging (BRAIN-A).
• Deleted: WHO grades 1, 2, and 3.

Footnote

• Deleted: Within the first 3 months after completion of RT and concomitant TMZ, diagnosis of recurrence can be indistinguishable from pseudoprogression on neuroimaging.

LTD-1

Footnote

• Deleted: For secondary CNS lymphoma, treatment may include systemic treatment, WBRT or focal RT, or a combination.

LTD-2

Clinical Presentation

• Top and bottom pathways, flipped.

Treatment

• Top pathway, new: Surgical resection for management of mass effect or symptoms followed by SRS (BRAIN-C) to the surgical bed and other brain metastases or Systemic therapy in select patients.
  •  Deleted: WBRT without HA ± memantine.
• Bottom pathway, modified: SRS in select patients.

Footnote

• j, modified: SRS is preferred when safe, especially for low tumor volume to both the resection cavity and any other non-­resected brain metastases and when safe and feasible. For disease volume or distribution not feasible for SRS, consider HA-WBRT. Ideally, cognitive sparing radiotherapy should be employed in these settings. WBRT is generally not recommended but may be appropriate in some rare clinical circumstances.

LTD-3

Recurrence

• Modified, column 2, top pathway: Recurrent disease after radiation; local site.
• Deleted: Previous surgery only.
  •  Previous WBRT or Prior SRS.
• Modified, column 2, bottom pathway: Recurrent disease after radiation; distant brain ± local recurrence.

Treatment

• Deleted, top pathway: Single-dose or fractionated stereotactic RT (SRT).
• Added, top and bottom pathway: SRS.
• Deleted, Row 2: Surgery followed by SRS or RT to the surgical bed or Single-dose (category 2B) or fractionated SRT or Consider systemic therapy.

LTD-3A

Footnotes

• i, 2nd sentence, new: See LTD-3 for reirradiation doses for brain metastases.

• n, 2nd sentence, modified: Consider advanced MRI imaging, including perfusion or spectroscopy, multidisciplinary input, or observation
  with early repeat imaging.
• r, new: In certain cases, retreatment with radiation, (eg, WBRT or SRS) is possible. If patient cannot be treated with repeat radiation, other possible options include laser thermal ablation or palliative/best supportive care.

LTD-4

• Deleted: Revisions to LTD-4 have been incorporated into LTD-3 and this page has been deleted.

BRAIN-METS-A,1

Breast Cancer/HER2 positive

Preferred

• Modified: Tucatinib + trastuzumab + capecitabine (category 1) if previously treated with ≥1 or more anti-HER2–based regimens.
• Moved: Fam-trastuzumab deruxtecan-nxki from "Other Recommended" to Preferred.
  •  Modified to include: if previously treated with ≥1 regimen.

Other Recommended Regimen

• New: Neratinib and T-DM1, (category 2A) recommendation.

Breast Cancer/HER2 low

Useful in Certain Circumstances

• Modified: Fam-trastuzumab deruxtecan-nxki (may also be used in patients with breast cancer that is HER2 immunohistochemistry [IHC] 1+ or 2+/in situ hybridization [ISH] negative). (Category 2A) recommendation.

Non-Small Cell Lung Cancer (NSCLC)

EGFR-sensitizing mutation positive/Preferred

• New:
  • Amivantamab-vmjw + lazertinib (for exon 19 deletion or L858R), preferred, (category 2A) recommendation.
  • Amivantamab-vmjw + carboplatin + pemetrexed (for exon 19 deletion or L858R), preferred, (category 2A) recommendation.

EGFR-sensitizing mutation positive/Other Recommended

• Modified: Osimertinib plus platinum-pemetrexed (cisplatin or carboplatin) (category 1), Other Recommended Recommendation.

ROS1 positive

• New: Repotrectinib (category 2A) recommendation.

Small Cell Lung Cancer (SCLC)

• New: Tarlatamab-dlle (category 2A recommendation).

LEPT-1

Footnotes

• c, new: Lumbar puncture should be done after MRI of spine is performed to avoid a false-positive imaging result.
• e, modified: CSF analysis should include: a cell count, differential, glucose, and protein. For solid malignancies, order cytopathology. When available, assessment of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs) increases sensitivity of tumor cell detection and assessment of response to treatment. For hematologic malignancies, use flow cytometry. When available, assessment of CSF-tDNA increases sensitivity of tumor cell detection and assessment of response to treatment.
• f, new: Opening pressure should be recorded and consideration should be made of palliative CSF diversion for symptomatic benefit
  or hydrocephalus.

LEPT-3

• Middle pathway, new bullet: Principles of Brain and Spine Imaging (BRAIN-A).

Footnote

• Deleted: Within the first 3 months after completion of RT and concomitant TMZ, diagnosis of recurrence can be indistinguishable from pseudoprogression on neuroimaging.

LEPT-A

Treatment

Breast cancer/Preferred

• New:
  •  Fam-trastuzumab deruxtecan-nxki, (category 2A) recommendation.

Non-Small Cell Lung Cancer/Other Recommended

• New:
• Osimertinib EGFR mutation positive (double dose), (category 2A) recommendation.

Melanoma/Useful in Certain Circumstances

• Modified:
  •  IT and intravenous (IV) nivolumab (category 2B).

SPINE-2

Footnotes

• e, modified: Principles of Radiation Therapy for Brain and Spinal Cord (BRAIN-C). Ablative doses of RT yield significantly higher rates of pain improvement and disease control (Sahgal A, et al. Lancet Oncol 2021;22:1023-1033 and Palma DA, et al. J Clin Oncol 2020;38:2830-2838). (Also for SPINE-3).
• j, modified: Consider alternative diagnosis of leptomeningeal disease (LEPT-1). Questions of spine stability should be determined in consultation with a spinal surgeon.

BRAIN-A

Principles of Brain and Spine Tumor Imaging

• This section has been significantly updated.

BRAIN-B

Principles Surgery

• Title modified: Principles of Brain and Spine Tumor Surgery.
• This section is divided into 2 sections: Brain Surgery and Spine Surgery.
• Modified: Brain surgery:
  •  Tissue: Bullet 4, sentence 2: Postoperative spine MRI should be delayed by at least 2–3 weeks to avoid post-surgical artifacts. Staging spine MRI, when appropriate, should be obtained either pre-op, or delayed by at least 2–3 weeks to avoid post-surgical artifacts.
• New: Spine surgery: This is a new section in the guidelines.

BRAIN-C,1

Principles of Radiation Therapy for Brain and Spinal Cord

• RT Dosing: Bullet 4, modified: In patients with poor PS or older patients, a hypofractionated...

BRAIN-C, 2

Reirradiation for Brain Metastases: New section.

BRAIN-C, 4

Principles of Radiation Therapy for Brain and Spinal Cord

Primary CNS Lymphoma

• Modified: WBRT is typically used as consolidation following high-dose methotrexate (HDMTX)-based induction therapy in withheld in the primary setting in for patients who are ineligible for autologous hematopoietic cell transplant (HCT) or is used in the palliative setting treated with systemic therapy.
  • Adjuvant RT: Can be tailored or given for patients who are ineligible for consolidation autologous HCT
  • Definitive: Primary RT should be first-line therapy after progression on HDMTX based on upfront treatment. Following progression for primary salvage, Cranial radiation to 20–24 Gy followed by boost to radiographically visible T1/T2 disease to 40–50 Gy is recommended. Primary RT should also be considered in patients who are ineligible for MTX-based primary therapy.

Secondary CNS Lymphoma

• RT Dosing:
  • Sub, sub-bullet, new: For patients with KPS ≥70 and no extracranial disease, then cranial radiation can be given to 20–24 Gy followed by boost to radiographically visible T1/T2 disease to 40 Gy. If poor KPS (<70) or extracranial disease, then RT can be limited to either cranial RT alone to 20–24 Gy or focal involved-site RT (ISRT) to gross disease to 24–30 Gy.
  • 3rd sub-bullet, modified: Palliative: Primary RT should be first-line after progression on HDMTX-based upfront treatment.

BRAIN-C,5

Meningiomas

General Treatment Information

• New: Sensitive and specific imaging modalities for radiation treatment planning in meningioma can be helpful, including MR perfusion and PET imaging (eg, Ga-68 DOTATATE PET-MRI and/or CT).

WHO Grade 3 Meningiomas

General Treatment Information

• Modified, 1st sub-sub-bullet: Treat as malignant tumors with treatment directed to gross tumor (if present), surgical bed, and a margin (1–2–3 cm, depending on distribution of disease and histopathology).

BRAIN-C,7

Metastatic Spine Tumors

RT Dosing

• Modified, 4th sub-sub-bullet: When lower biologically effective dose (BED) with alpha/beta ratio of 2 for spinal cord regimens....
• Modified, 5th sub-sub-bullet, last sentence: For radiation-associated edema and treatment-related necrosis, please see BRAIN-D, 2 of 7.

BRAIN-D,2

Principles of Brain and Spine Tumor Management

• Modified, sub title: Mass Effect, Brain Edema and Treatment-Associated Necrosis/Radionecrosis
• 1st sub-bullet, modified: Corticosteroids or and confirmatory diagnostic study.
• 2nd sub-sub-bullet, modified: Consider bevacizumab for 2-3 doses if symptoms do not resolve with corticosteroids or patient is unable to tolerate corticosteroids.
• 4th sub-sub-bullet, new: Consider hyperbaric oxygen treatment in select cases that are unresponsive to corticosteroids.

If asymptomatic:

• 1st sub-bullet, modified: Follow with serial MR and neurologic exam every 2–3 months.

BRAIN-D,4

Principles of Brain and Spine Tumor Management

• Venous Thromboembolism (VTE), new: Treatment with direct oral anticoagulants is recommended for VTE prophylaxis in patients with adult-type diffuse gliomas who are deemed to be at high risk of VTE.

BRAIN-E, 4

Principles of Brain Tumor Pathology: Molecular Markers

ATRX Mutation

• Diagnostic value, modified: A lack of ATRX immunostaining in glioblastoma should trigger IDH1/2 sequencing if IDH1 R132H immunostaining is negative, due to the frequent co-occurrence of ATRX and IDH mutations. Since the ATRX immunostain can be false-negative due to thermal artifact, always interpret ATRX immunostaining using admixed nonneoplastic cells as positive controls (eg, endothelial cells, neurons, inflammatory cells).

BRAIN-E, 6

Medulloblastoma Molecular Subtyping

Bullet 3, Detection, modified: Nuclear immunoreactivity for beta-catenin is a very useful way to identify WNT medulloblastomas, in conjunction with CTNNB1 sequencing and chromosome 6 FISH. However, nuclear staining for beta-catenin in WNT-medulloblastomas can be very focal and might be misinterpreted as negative or equivocal.

 

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