medulloblastoma non-WNT/non-SHH

Medulloblastoma Non-WNT/Non-SHH: A Rare and Aggressive Brain Tumor

Medulloblastoma non-WNT/non-SHH is a rare and aggressive type of brain tumor that originates in the cerebellum, an area at the back of the brain. It is one of the most common cancerous brain tumors in childhood, accounting for about 20% of all pediatric brain cancers.

Characteristics

• Molecular Subtype: Medulloblastoma non-WNT/non-SHH is a molecular subtype that does not involve activation of the WNT pathway or sonic hedgehog (SHH) pathway.
• Genetic Alterations: This subtype is characterized by genetic alterations such as MYC amplifications and TP53 mutations are absent.
• Age Distribution: Most cases occur in children, although up to 25% of adult medulloblastomas fall into this category.

Classification

Medulloblastoma non-WNT/non-SHH is classified into two subgroups: Group 3 and Group 4. Group 3 is exceedingly rare in adults, while the majority of adult cases belong to subgroup 4.

Immunohistochemical Markers

This subtype can be differentiated from other medulloblastomas using a set of immunohistochemical markers, including β-Catenin, Yap1, and p75NGFR (or CD271).

Prognosis

The prognosis for patients with medulloblastoma non-WNT/non-SHH is generally poor compared to other subtypes. However, recent advances in genetic and epigenetic analysis have led to the development of novel therapeutic options.

References

• [1] Medulloblastoma not associated with activation of the WNT pathway or sonic hedgehog (SHH) pathway.
• [10] Group 3 and group 4 medulloblastomas are classified as non-WNT/non-SHH.
• [11] The most frequent genetic alterations in groups 3 and 4 involve KDM6A, OTX2, ZMYM3, KMT2D, TBR1 ...
• [14] Medulloblastoma (MB) is the most common malignant pediatric posterior fossa tumor.

Common Signs and Symptoms of Medulloblastoma (non-WNT/non-SHH)

Medulloblastoma, a type of malignant brain tumor, can exhibit various signs and symptoms. Here are some common ones associated with the non-WNT/non-SHH subtype:

• Morning Headaches: A frequent symptom, often worse in the morning [3][6]
• Nausea and Vomiting: These can be severe and may worsen in the morning [3][6]
• Seizures: Can occur due to the tumor's mass effect or obstructive hydrocephalus [6]
• Changes in Ability to Think: May manifest as changes in mood, behavior, appetite, or cognitive function [5]
• Increased Pressure on the Brain: Symptoms can include headache, nausea, vomiting, and diplopia (double vision) due to a mass effect from the tumor or obstructive hydrocephalus [6][7]

Additionally, other signs and symptoms may include:

• Lethargy
• Ataxia (truncal unsteadiness)
• Nystagmus (abnormal eye movement)
• Papilledema (swelling of the optic disc)
• Macrocephaly (enlarged head size)

It's essential to note that these symptoms can vary in severity and may not be present in all cases. If you or someone you know is experiencing any of these symptoms, it's crucial to seek medical attention promptly.

References: [1] Not applicable [2] Not applicable [3] Symptoms often include headache, nausea, and vomiting. These tend to be worse in the morning. [4] Symptoms of medulloblastoma · Headache, especially in the morning · Nausea and vomiting, which may be worst in the morning · Seizures · Changes in ability to think ... [5] Jan 3, 2023 — changes in their mood and behaviour, which doesn't fit the situation or is out of character for them. The symptoms can be very mild or severe. [6] Symptoms, due to a mass effect from the tumor or to obstructive hydrocephalus, include morning headaches, nausea, vomiting, diplopia (manifestation of sixth ... [7] The most common symptoms of medulloblastoma include changes in appetite and symptoms of increased pressure on the brain (e.g., headache, nausea, vomiting, and ... [8] Not applicable [9] by C Brain — Nausea and/or vomiting. Lethargy. Ataxia, including truncal unsteadiness. Some degree of nystagmus. Papilledema. Twenty percent of patients with ... [10] Such signs and symptoms include headache, irritability, nausea/vomiting, papilledema, and macrocephaly.1 Symptoms caused by local effects of the tumor in the ...

Medulloblastoma, particularly the non-WNT/non-SHH subtype, requires accurate diagnosis for effective treatment and prognosis. Here are some diagnostic tests used to identify this type of tumor:

• Magnetic Resonance Imaging (MRI): A neurological exam by a doctor is often accompanied by an MRI scan to visualize the brain and detect any abnormalities [3].
• Molecular Testing: Molecular testing is crucial in determining the tumor's group, which affects treatment and prognosis. This test helps identify the non-WNT/non-SHH subtype [6].
• Current molecular classification methods: While current methods are limited to detecting a single WNT molecular group, they can still provide valuable information for diagnosis [7].

It's essential to note that medulloblastoma treatment strategy is multimodal and includes maximal safe resection, radiotherapy, and chemotherapy. The treatment type and intensity depend on the tumor's characteristics and the patient's overall health.

References:

• [3] - A neurological exam by a doctor, as well as magnetic resonance imaging (MRI), are used to evaluate the signs and symptoms of medulloblastoma.
• [6] - Molecular testing is necessary to determine the tumor's group, which affects treatment and prognosis.
• [7] - Current methods of molecular classification available in most clinical laboratories are restricted to detection of a single WNT molecular group.

Current Treatment Options for Medulloblastoma Non-WNT/Non-SHH

Medulloblastoma, a type of brain cancer, is typically treated with surgery, chemotherapy, and radiotherapy. However, for patients with the non-WNT/non-SHH subtype, new treatment options are being explored.

• Chemotherapy: Chemotherapy remains a standard treatment option for medulloblastoma, including the non-WNT/non-SHH subtype [1][2]. The goal of chemotherapy is to kill cancer cells that may have spread beyond the primary tumor site.
• Targeted Therapy: Researchers are investigating targeted therapies, such as SMO inhibitors, which can specifically target and inhibit the growth of cancer cells with specific genetic mutations [3].
• Clinical Trials: Several clinical trials are ongoing to evaluate new chemotherapy regimens and targeted therapies for medulloblastoma non-WNT/non-SHH. These trials aim to improve treatment outcomes and reduce side effects [4][5].

Emerging Treatment Options

While surgery, chemotherapy, and radiotherapy remain the mainstay of treatment for medulloblastoma non-WNT/non-SHH, emerging evidence suggests that targeted therapies may offer new hope.

• Vismodegib (GDC-0449): Although not FDA-approved for medulloblastoma, vismodegib has shown promise in treating SHH-dependent cancers. Its potential application to medulloblastoma non-WNT/non-SHH is an area of ongoing research [6].
• New Chemotherapy Regimens: Researchers are exploring new chemotherapy regimens that may be more effective and have fewer side effects than current treatments.

Conclusion

While treatment options for medulloblastoma non-WNT/non-SHH continue to evolve, surgery, chemotherapy, and radiotherapy remain the primary treatment modalities. Emerging evidence suggests that targeted therapies and new chemotherapy regimens may offer improved outcomes for patients with this subtype of medulloblastoma.

References:

[1] Context 6 [2] Context 4 [3] Context 8 [4] Context 3 [5] Context 2 [6] Context 8

Medulloblastoma, particularly the non-WNT/non-SHH subtype, can be challenging to diagnose due to its complex genetic and clinical heterogeneity. However, several conditions can be considered in the differential diagnosis:

• Ependymoma: This type of brain tumor is characterized by the presence of GFAP (glial fibrillary acidic protein) in the tumor cells. Ependymomas are often located near the ependymal lining of the ventricles and central canal.
• Choroid plexus papilloma: A rare, benign tumor that arises from the choroid plexus, which is responsible for producing cerebrospinal fluid.
• Subependymoma: A slow-growing, usually benign tumor that originates from the subependymal region of the brain.
• Posterior fossa ependymoma: A type of ependymoma that occurs in the posterior fossa, which contains the cerebellum and brainstem.
• Cerebellar metastasis - small cell lung cancer: In rare cases, medulloblastoma can be mistaken for a metastatic tumor from another primary site, such as small cell lung cancer.

It's essential to note that accurate diagnosis of non-WNT/non-SHH medulloblastoma requires a comprehensive evaluation, including histopathological examination, molecular analysis, and clinical correlation. A team of experts in neuro-oncology, neuropathology, and radiology should work together to provide an accurate diagnosis and develop an appropriate treatment plan.

References:

• [9] The category non-WNT/non-SHH medulloblastoma summarizes medulloblastoma groups 3 and 4 and is characterized by considerable genetic and clinical heterogeneity.
• [10] Essential to the diagnosis of genetically-defined medulloblastoma are either evidence of pathway activation (i.e. WNT or SHH) or an appropriate molecular profile.
• [5] Medulloblastoma treatment strategy is multimodal, including maximal safe resection, radiotherapy, and chemotherapy. The treatment type and intensity depend on the tumor's genetic and clinical characteristics.