diffuse low-grade glioma, MAPK pathway–altered

Diffuse Low-Grade Glioma, MAPK Pathway-Altered: An Overview

Diffuse low-grade glioma, MAPK pathway-altered is a type of brain tumor that has been included in the 5th Edition (2021) of the WHO brain tumor classification [1]. This novel tumor type is characterized by its infiltrative growth pattern and glial tumor cells without a neuronal component [2].

Common Molecular Alterations

Research has identified several common molecular alterations associated with diffuse low-grade glioma, MAPK pathway-altered. These include:

• TKD duplication
• FGFR1 mutation
• FGFR1 fusion
• BRAF V600E mutation
• BRAF V600 [3]

These genetic alterations or upregulation of the RAS-RAF-mitogen activated protein kinase (MAPK) pathway are the molecular drivers in the vast majority of pilocytic low-grade gliomas (pLGG), which is a subtype of diffuse low-grade glioma, MAPK pathway-altered [6].

Histological Features

Diffuse low-grade glioma, MAPK pathway-altered has been described as having a diffuse growth pattern with astrocytic and oligodendroglioma components. Alterations in the MAPK pathway are also characteristic of this tumor type [8].

References:

[1] Dec 7, 2021 — Diffuse low-grade glioma, MAPK pathway-altered is a novel tumor type included in the 5th Edition (2021) of the WHO brain tumor classification.

[2] May 5, 2022 — Diffuse low grade glioma, MAPK pathway altered · General features: infiltrative, glial tumor cells without a neuronal component

[3] by J Chen · 2023 · Cited by 5 — Common molecular alterations of diffuse low-grade glioma, MAPK pathway-altered include TKD duplication, FGFR1 mutation, FGFR1 fusion, BRAF V600E mutation, BRAF ...

[6] by HB Lindsay · 2023 · Cited by 3 — Genetic alterations or upregulation of the RAS-RAF-mitogen activated protein kinase (MAPK) pathway are the molecular drivers in the vast majority of pLGG (80–95 ...

[8] May 16, 2024 — Diffuse low-grade glioma, MAPK pathway altered: Diffuse growth pattern with astrocytic and oligodendroglioma components. Alterations in MAPK ...

Common symptoms of diffuse low-grade glioma, MAPK pathway-altered include:

• Increased intracranial pressure-related symptoms such as headache, nausea, and vomiting [1]
• Site-dependent neurological deficits [1]
• Long-standing epilepsy is also common in this tumor type [6]

Additionally, the growth pattern of this tumor can cause:

• Diffuse growth with astrocytic and oligodendroglioma components [7]
• Expansion of the pons can lead to obstructive hydrocephalus, causing symptoms such as ataxia [9]

It's worth noting that nonspecific symptoms may also be present, making diagnosis challenging. The prognosis for this tumor type requires further data.

References: [1] - Symptoms related to increased intracranial pressure [6] - Long standing epilepsy is also common in diffuse low-grade glioma, MAPK pathway-altered [7] - Diffuse growth pattern with astrocytic and oligodendroglioma components [9] - Obstructive hydrocephalus caused by expansion of the pons

Diagnostic Tests for Diffuse Low-Grade Glioma, MAPK Pathway-Altered

Diffuse low-grade gliomas that are MAPK pathway-altered can be challenging to diagnose. However, several diagnostic tests can help identify this type of tumor.

• Imaging tests: Imaging tests like magnetic resonance imaging (MRI) and computed tomography (CT) scans can aid in the diagnosis of low-grade gliomas. MRI with and without contrast is considered the study of choice [10].
• Histological evaluation: A combination of histological evaluation, including immunohistochemistry and molecular testing, is required to diagnose diffuse low-grade glioma, MAPK pathway-altered [7].
• Molecular diagnostic tests: Molecular diagnostic tests such as IDH1/IDH2 mutation analysis can help identify the presence of a MAPK pathway alteration in diffuse low-grade gliomas [6].

Key Diagnostic Features

The key molecular diagnostic tests for diffuse low-grade glioma, MAPK pathway-altered include:

• IDH1/IDH2 mutations
• RAS-RAF-mitogen activated protein kinase (MAPK) pathway alterations

These diagnostic features can help differentiate diffuse low-grade gliomas with MAPK pathway alterations from other types of brain tumors.

References

[6] DN Louis. Cited by 3 — KEY MOLECULAR DIAGNOSTIC TESTS · IDH1/IDH2 ...

[7] by J Chen · 2023 · Cited by 5 — Diffuse low-grade glioma, MAPK pathway-altered is also a newly defined tumor type in the 2021 WHO CNS5...

[10] May 16, 2024 — Both CT scan and MRI can aid in the diagnosis of low-grade gliomas. Generally, MRI with and without contrast is considered the study of choice.

Treatment Options for Diffuse Low-Grade Glioma (dLGG) with MAPK Pathway Alteration

Diffuse low-grade gliomas (dLGGs) are a type of brain tumor that can be challenging to treat. The MAPK pathway is a key signaling pathway involved in the development and progression of dLGGs. Recent studies have explored various treatment options for patients with dLGGs and MAPK pathway alterations.

MEK Inhibitors

Research has shown that MEK inhibitors, such as selumetinib and trametinib, can be effective in treating dLGGs with MAPK pathway alterations [2][5]. These medications work by inhibiting the MEK enzyme, which is a key component of the MAPK signaling pathway. Studies have demonstrated that MEK inhibitors can delay disease progression and improve patient outcomes.

BRAF Inhibitors

Additionally, BRAF inhibitors like vemurafenib and dabrafenib have been investigated as potential treatments for dLGGs with MAPK pathway alterations [1]. These medications target the BRAF enzyme, which is often mutated in dLGGs. While results are promising, further research is needed to fully understand their efficacy.

Other Treatment Options

Other treatment options for dLGGs include surgery, chemotherapy, and radiation therapy. However, these treatments may not be effective for all patients, particularly those with MAPK pathway alterations [3][4].

Emerging Therapies

Recent studies have explored the use of emerging therapies, such as IDH inhibitors and mirdametinib, in treating dLGGs with MAPK pathway alterations [6][8]. These medications target specific genetic mutations associated with dLGGs. While results are promising, further research is needed to confirm their efficacy.

Conclusion

In conclusion, treatment options for diffuse low-grade glioma (dLGG) with MAPK pathway alteration include MEK inhibitors, BRAF inhibitors, and emerging therapies like IDH inhibitors and mirdametinib. Further research is necessary to fully understand the efficacy of these treatments and to identify the most effective therapeutic strategies for patients with dLGGs.

References:

[1] by N Manoharan · 2023 · Cited by 52 [2] by HB Lindsay · 2023 · Cited by 3 [3] by SF Sait · 2023 · Cited by 18 [4] Jun 17, 2024 [5] by N Manoharan · 2023 · Cited by 52 [6] Study goal: The main goal of this study is to test the experimental drug mirdametinib in hopes of finding a treatment that may be effective against low-grade ... [7] by K Yang · 2022 · Cited by 471 [8] by LR Schaff · 2024 · Cited by 4

The differential diagnosis for diffuse low-grade glioma, MAPK pathway-altered involves ruling out other types of brain tumors that may present with similar characteristics.

According to the search results, one of the key considerations in the differential diagnosis is diffuse astrocytoma, MYB or MYBL1 altered, CNS WHO grade 1 [2]. This type of tumor also presents with a diffuse growth pattern and alterations in the MAPK pathway, making it a potential mimic for diffuse low-grade glioma, MAPK pathway-altered.

Another consideration is angiocentric glioma, which is a rare type of brain tumor that can present with a similar histological appearance to diffuse low-grade glioma, MAPK pathway-altered [2].

Additionally, the differential diagnosis may also include other types of low-grade gliomas, such as diffuse astrocytoma or oligodendroglioma, which can also present with alterations in the MAPK pathway [5].

It's worth noting that the diagnosis of diffuse low-grade glioma, MAPK pathway-altered requires a combination of histological evaluation and molecular analysis to confirm the presence of MAPK pathway alterations [6].