Ventricular meningioma

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Summarize

Ventricular meningioma is a type of glial cell tumor that originates from the ventricular cells, a type of radial glial cell in the brain and spinal cord. Ventricular meningiomas usually occur within or near the cavities of the ventricular system, most commonly in the fourth ventricle near the cerebellum or in the spinal cord. They occasionally occur in brain tissue outside the posterior cranial fossa and rarely outside the central nervous system.

Epidemiological

incidence of a disease

Ventricular meningiomas account for less than 10% of all central nervous system tumors. In children and young adults, ventricular meningiomas account for 10% of intracranial tumors and 40% to 60% of spinal cord tumors, with an incidence of 0.3 cases per 100,000 people. In the United States, approximately 200 cases of pediatric ventricular meningiomas are diagnosed each year.

In terms of age distribution, intracranial ventricular meningiomas can occur at any age, but are most prevalent in young children. The incidence is slightly higher in males than in females. The median age at diagnosis is 5 years, with 25-40% of patients diagnosed at less than 2 years of age and 67% of patients diagnosed at no more than 3 years of age. In children, approximately 90% of ventricular meningiomas are intracranial (60% in the posterior cranial fossa), with the remaining tumors appearing in the spinal cord. In children under 3 years of age, ventricular meningiomas usually present as tumors in the posterior cranial fossa within or near the fourth ventricle.

Intracranial ventricular meningiomas in adults are relatively rare and are concentrated before the age of 40 years.

Spinal cord ventricular meningiomas are more common in adults and very rare in children, with a median age of diagnosis between 30-40 years.

Among the ventricular meningiomas, there is a group of tumors called subventricular ventricular meningiomas that occur predominantly in middle-aged and older adults, are more common in men, and many are encountered incidentally at autopsy. Definitive incidence information is lacking for this group of tumors, which represent approximately less than 5% of all ventricular meningiomas.

Etiolog & Risk factors

risk factor

Ventricular meningioma cells originate from the ventricular cells. Normal ventricular cells form the edge of the ventricular system in the brain and spinal cord and secrete cerebrospinal fluid. Ventricular meningioma occurs when a genetic mutation occurs in the ventricular meningeal cells, which undergo uncontrolled malignant proliferation and become cancerous. However, the exact cause is unknown.

Patients with the genetic disorder neurofibromatosis type 2 (NF2) are at increased risk of developing central nervous system tumors. Ventricular meningiomas are a type of CNS tumor, so people with neurofibromatosis type 2 are also at a higher risk of developing ventricular meningiomas than the general population.

Classification & Stage

Currently, there is no standard tumor staging for ventricular meningiomas, only WHO grading according to histologic features and staging according to histologic features or location of tumorigenesis with molecular genetic features.

The World Health Organization (WHO) grades CNS tumors based on the degree of abnormality of the tumor cells under the microscope and the rate at which the tumor grows and spreads. Low-grade (grade I) tumor cells resemble normal cells more than high-grade tumor cells (grades II and III), and grow and spread more slowly and at a relatively lower risk. Different types in ventricular meningiomas may be differently graded tumors. However, the prognostic significance of the grading of ventricular meningiomas, especially grade II versus grade III is ventricular meningiomas, is currently unclear. Tumor-specific mutation-based and molecular typing may provide better prognostic analysis in the future and eventually replace the current histologic grading.

1. WHO typing

According to the World Health Organization's classification of central nervous system tumors, ventricular meningiomas are divided into five major subtypes: typical ventricular meningioma (WHO grade II), mesenchymal ventricular meningioma (WHO grade III), RELA fusion gene-positive ventricular meningioma (WHO grade II or III), subventricular meningioma (WHO grade I), and mucosal papillary ventricular meningioma (WHO grade I).

● Typical ventricular meningioma

Typical ventricular meningioma is a WHO grade II central nervous system tumor that originates from ventricular cells in the walls of the ventricles or the central canal wall of the spinal cord. These tumors can occur anywhere in the ventricular system or spinal canal, but are most commonly found in the fourth ventricle and spinal cord. The cells of a typical ventricular meningioma usually form a daisy-shaped mass, which can assist in the diagnosis by its cellular morphology, but such a histologic pattern is not present in all patients.

In 2016, the World Health Organization further classified typical ventricular meningiomas into 3 subtypes based on tumor histologic patterns:

¡ Papillary: Typical ventricular meningiomas of this subtype form long, epithelioid surfaces on the surface of the ventricular system.

¡ Clear cell type: These tumor cells are morphologically similar to oligodendrocytes, with a halo around the nucleus. This subtype usually occurs in the supratentorial region of the brain (i.e., the area of the brain above the cerebellar vermis).

¡ Elongated cell type: This is the rarest type of typical ventricular meningioma, which mostly occurs in the spinal cord. Tumor cells are arranged in clusters of varying widths and cell densities, with little interspersing of different cells.

These histologic subtype classifications are not very useful in guiding clinical management.

● mesenchymal variant ventricular meningioma

Mesenchymal ventricular meningiomas are WHO grade III, highly malignant, and histologically similar in morphology to typical ventricular meningiomas. Compared with typical ventricular meningiomas, mesenchymal ventricular meningiomas have more cellular components, are more actively dividing, and often have capillary generation and necrosis.

This type of ventricular meningioma occurs in the supratentorial region and is WHO grade II or III. Most of the ventricular meningiomas in the supratentorial region in children are of this type. These tumors are present with a positive C11orf95-RELA fusion gene and tend to stain positively for L1CAM immunohistochemistry. It has been suggested that the RELA fusion gene leads to tumors with a less favorable prognosis, but further studies are needed.

● subventricular ventricular meningioma

Subventricular ventricular meningiomas are rare adult tumors in the fourth ventricle or lateral ventricle, usually growing on the wall of the ventricle or central canal. They have a favorable histologic appearance, are slow-growing, and are graded as WHO Grade I. These tumors have few obvious symptoms and are often discovered at autopsy.

Subventricular ventricular meningiomas are rarely seen in children. If a child is diagnosed with subventricular ventricular meningioma, further review and tumor gene sequencing and molecular typing are recommended to prevent misdiagnosis.

● Mucopapillary ventricular meningioma

Mucopapillary ventricular meningiomas occur almost exclusively in the lumbosacral and end filaments of the spinal cord. The molecular biology of mucopapillary ventricular meningiomas in adults and children is not quite the same.

Mucinous papillary ventricular meningiomas are histologically characterized by a papillary pattern of tumor cells surrounding a vascularized mucus-like stromal core. Although mucinous papillary ventricular meningiomas are graded as WHO grade I, several studies have shown that these tumors are actually more malignant, and that intracranial and spinal dissemination may exceed expectations after surgical removal.

2. Molecular typing

Tumor genomic changes are common in ventricular meningiomas and may vary with different tumor anatomic locations. Depending on the site of growth of ventricular meningiomas, they can be classified as supratentorial ventricular meningiomas, infratentorial ventricular meningiomas, and spinal cord ventricular meningiomas. Also, combined with tumor gene sequencing and analysis of epigenetic features, ventricular meningiomas can be molecularly typed as follows:

● Supratentorial ventricular meningioma: This type of tumor is located in the brain region above the cerebellar tegmentum and can be classified according to the molecular biology of the tumor as supratentorial ventricular meningioma-RELA (ST-EPN-RELA), supratentorial ventricular meningioma-YAP (ST-EPN-YAP) and supratentorial subventricular meningioma (ST-SE).

● Supratentorial ventricular neoplasm-RELA (ST-EPN-RELA)

70-80% of supratentorial ventricular meningiomas in children are positive for the C11orf95-RELA fusion gene, with an age range of 0-69 years and a median age at diagnosis of 8 years. Retrospective studies have shown that ventricular meningiomas positive for this fusion gene have a more dismal prognosis, although more studies are needed to confirm this.

● Supratentorial ependymoma-YAP1 (ST-EPN-YAP1)

¡ Supratentorial ventricular meningiomas-YAP1 account for only a small proportion of supratentorial ventricular meningiomas, occurring primarily in infants with an age range of 0-51 years and a median age at diagnosis of 1.4 years. These tumors are YAP1 fusion gene positive and may have a better prognosis than other subtypes of ventricular meningiomas. However, the typing of this subtype has not been recognized by the World Health Organization and more studies are needed to validate it.

● Supratentorial subventricular meningioma (ST-SE)

● Subventricular ventricular meningiomas growing in the supratentorial region are rare, occurring mainly in middle-aged and older adults and almost never in children.

● Subtentorial ventricular meningioma: This type of tumor is located in the brain region below the cerebellar vermis, usually in the posterior cranial fossa. They can be classified according to molecular biology into posterior cranial fossa type A ventricular meningiomas (PF-EPN-A), posterior cranial fossa type B ventricular meningiomas (PF-EPN-B), and subventricular subepithelial ventricular meningiomas (PF-SE).

● Posterior cranial fossa type A ventricular meningioma (PF-EPN-A)

Posterior cranial fossa type A ventricular meningiomas are the most common subtype of subepithelial ventricular meningiomas and have a less favorable prognosis. This subtype occurs predominantly in infants and children, with an age range of 0-51 years and a median age at diagnosis of 3 years. The molecular biology of these tumors is characterized by a CpG island methylation phenotype and transcriptional silencing of the PRC2 complex. Approximately 25% of patients with posterior cranial fossa type A ventricular meningiomas have an increase in the long arm of chromosome 1, and the prognosis for these patients is usually poor.

Also, posterior cranial fossa type A ventricular meningiomas have expression of H3K27me3 (histone 27 lysine residue trimethylation). Therefore, H3K27me3 immunohistochemical (IHC) staining can be used clinically to diagnose posterior cranial fossa type A ventricular meningioma.

● Posterior cranial fossa type B ventricular meningioma (PF-EPN-B)

These tumors occur predominantly in older children and adults and account for 15-20% of childhood subepithelial ventricular meningiomas. The age range of onset is 10-65 years, with a median age at diagnosis of 30 years and a favorable prognosis. Although an increase in the long arm of chromosome 1 is also present in some patients with posterior cranial fossa type B ventricular meningiomas, unlike posterior cranial fossa type A ventricular meningiomas, an increase in the long arm of chromosome 1 in posterior cranial fossa type B ventricular meningiomas does not appear to be prognostically associated; however, if the patient's tumor has a loss of the long arm of chromosome 13, the prognosis may be poor.

● Subventricular meningioma of the subepithelium (PF-SE)

● Subventricular ventricular meningiomas growing in the infratentorial region are rare, occurring mainly in middle-aged and older adults and almost never in children.

● Spinal cord ventricular meningioma: This type of tumor is located in the spinal cord region and occurs mainly in adults and rarely in children. They can be classified according to molecular biology into spinal cord ventricular neoplasm (SP-EPN), spinal cord mucopapillary ventricular neoplasm (SP-MPN) and spinal cord subventricular ventricular neoplasm (SP-SE).

● Spinal cord ventricular meningioma (SP-EPN)

Typical or mesenchymal ventricular meningiomas of the spinal cord occur most often in adults and less frequently in children. The age range of onset is 11-59 years and the median age at diagnosis is 41 years.

● Spinal mucinous papillary ventricular neoplasm (SP-MPN)

Mucinous papillary ventricular meningiomas occur most often in adults and less frequently in children. The age range of onset is 9-66 years and the median age at diagnosis is 32 years.

● Spinal subventricular ventricular meningioma (SP-SE)

Subventricular ventricular meningiomas, which grow in the spinal cord, are rare, occurring primarily in middle-aged and older adults and almost never in children. The age range of onset is 22-65 years, with a median age at diagnosis of 49 years.

Clinical manifestations

The clinical presentation of ventricular meningioma depends on the location of the tumor and the age of the patient. In children, the most common symptoms include frequent headaches, seizures, nausea and vomiting, neck and back pain, loss of balance or difficulty walking, muscle weakness in the legs, blurred vision, changes in gastrointestinal function, urinary difficulties, cognitive impairment, or irritability.

1. Typical symptoms

When the tumor occurs episodically, symptoms are usually nonspecific, with headaches being the most common. Seizures or localized neurological deficits can also be more common.

For most patients whose tumors are located in the posterior cranial fossa, there is an increase in intracranial pressure due to obstructive hydrocephalus. Common results are headaches, nausea and vomiting, ataxia (loss of balance), vertigo, and optic papillae edema (which causes blurred vision). Cranial nerve palsies are also common, especially involving the VI to X cranial nerves.

If the tumor invades the brainstem, common symptoms are gait and coordination abnormalities, and cerebral nerve palsy.

Tumors that invade the spinal cord can involve specific upward and downward nerve bundles or peripheral nerves, and therefore can exhibit particular symptoms. Specific symptoms are related to the specific anatomical location of the tumor, with back pain and/or weakness and gait abnormalities being the most common.

In infants, the cranial sutures are not fused, so the child is able to adapt to the elevated intracranial pressure without acute neurologic damage. Thus, in patients with intracranial ventricular meningiomas in infancy, macrosomia is a common presenting symptom, and nausea and vomiting may also be manifested. In addition, infants may not be able to express certain symptoms (e.g., headaches) and therefore may simply present as irritable.

2. Accompanying symptoms

Ventricular meningiomas occurring in the posterior cranial fossa may lead to obstructive hydrocephalus (also known as non-traffic hydrocephalus). This is due to the gradual growth of a tumor in the posterior cranial fossa that compresses the fourth ventricle in front of it, which may cause a blockage in the normal flow of cerebrospinal fluid, resulting in an excessive buildup of cerebrospinal fluid. Obstructive hydrocephalus is almost always accompanied by increased intracranial pressure and may cause signs such as headaches, behavioral changes, developmental delays, nausea and vomiting, lethargy, and an increase in the infant's head circumference.

Clinical Department

It is difficult to make an early diagnosis of ventricular meningioma. Doctors can infer the possible presence of a ventricular meningioma before surgery based on imaging features, tumor location, and the patient's age. However, the diagnosis of this disease requires histologic confirmation.

Because total tumor resection is important for the diagnosis of intracranial ventricular meningiomas and differential diagnosis from other brain tumors, the definitive diagnosis of ventricular meningiomas is usually accomplished by histopathology after surgery.

Patients may also be assisted in confirming the diagnosis with a tissue biopsy in cases where there is uncertainty in the diagnosis or high surgical risk.

Clinical Department

Pediatric neurosurgery or neurosurgery

Examination & Diagnosis

1. Relevant inspections

1) Physical Examination

The general signs of the body are examined, including checking for signs of disease, such as lumps or any other unusual manifestations. The patient's health habits, previous illnesses and treatment history are also recorded.

2) Neurological examination

This is a series of questions and tests to check the functioning of the brain, spinal cord and nerves. It checks a person's mental state, coordination and ability to walk normally, as well as muscles, senses and reflexes.

3) Imaging

Imaging tests such as CT and magnetic resonance imaging (MRI) are helpful in the diagnosis of all brain tumors including ventricular meningiomas, the extent of tumor spread, and the assessment of the effectiveness of tumor treatment. For ventricular meningioma, the commonly used imaging tests are:

i) CT

CT is usually the first imaging study performed because it is more widely available, requires a shorter examination time, and usually does not require sedation. CT is the preferred choice for initial studies in emergency situations, such as a child suspected of having elevated intracranial pressure but in an unstable state. It must be noted, however, that a normal CT does not completely rule out the possibility of a brain lesion.

However, CT has an advantage in the demonstration of calcification, and this is especially true for subventricular ventricular meningiomas.

ii) Magnetic Resonance (MRI) and Enhanced Magnetic Resonance (Enhanced MRI)

MRI is the best neuroimaging method for brain tumors. It provides more detailed images of substantial lesions than CT and is more sensitive in detecting posterior cranial fossa, subarachnoid space and soft meningeal lesions.

An imaging technique based on magnetic resonance, enhanced magnetic resonance, has also been derived and is also used in brain tumor imaging. In this type of imaging, a substance called gadolinium is injected into a vein into the circulatory system, and the gadolinium collects around the cancer cells, making them appear brighter in the image. Enhanced MRI can provide information suggestive of specific tumor types. In children with suspected spinal cord tumors, it is the imaging modality of choice because it is less invasive than CT myelography and provides superior imaging of soft tissue structures. It is important to note that if a spinal cord tumor is suspected, spinal cord compression may lead to permanent nerve damage and therefore needs to be detected by rapid imaging prior to this.

MRI can also help to stage ventricular meningiomas. For optimal tumor staging results, spine MRI needs to be done prior to lumbar puncture or surgical intervention to avoid interference. If preoperative imaging is not possible, spine MRI should be done at least 14 days after surgery to minimize the impact of the procedure.

iii) PET scan (electron emission tomography)

PET scanning is not currently used by all healthcare providers as part of the standard screening for brain tumors, but it can still provide useful information to supplement the results of an MRI scan.PET scanning can differentiate between areas of malignant lesions with a high metabolic rate and areas of benign lesions with a low metabolic rate or surrounding normal tissue.

For tissue biopsies, PET scanning can be used to identify areas within a tumor with the highest metabolic rate, guiding the neurosurgeon to sample the most malignant areas within the tumor. It can also be used to differentiate recurrent tumors from tumor changes produced during radiation therapy.

4) Lumbar puncture examination (cerebrospinal fluid cytology)

A lumbar puncture, also known as a lumbar puncture, is a method of collecting cerebrospinal fluid from the spinal cord. A lumbar puncture places a needle in the cerebrospinal fluid between two bones in the spine and around the spinal cord and removes a sample of the fluid. A pathologist will examine the cerebrospinal fluid sample under a microscope for signs of tumor cells. The amount of protein and glucose in the sample may also be examined; higher-than-normal protein or lower-than-normal glucose may both be signs of an underlying tumor.

In the diagnosis of ventricular meningiomas, cerebrospinal fluid cytology is important in the staging of patients with typical or interstitial ventricular meningiomas. Cerebrospinal fluid examination will also be important in evaluating the staging of patients with mucinous papillary ventricular meningiomas if, based on imaging, there are concerns about spread. Metastatic spread of the tumor is observed in cerebrospinal fluid in less than 5% of patients with ventricular meningioma at the time of initial diagnosis. To confirm the extent of disease spread, all patients with suspected or confirmed ventricular meningiomas should undergo a whole-brain, whole-spine MRI with lumbar puncture.

Although dissemination of ventricular meningiomas is uncommon, if present, it can significantly affect the treatment and prognosis of ventricular meningiomas. Moreover, in 1/3 of patients with disseminated ventricular meningiomas, dissemination can only be detected by cerebrospinal fluid cytology. Because ventricular meningiomas rarely appear to be disseminated at the time of diagnosis and because the cytologic appearance of ventricular meningioma cells is sometimes similar to that of nontumorigenic or reactive cells, a second lumbar puncture is generally recommended for confirmation if the patient's cerebrospinal fluid cytology is positive.

Because surgery creates cellular debris in the cerebrospinal fluid, making it more difficult to draw conclusions from a cerebrospinal fluid test, ideally, a cerebrospinal fluid sample should be obtained by lumbar puncture before the patient's surgery. If the patient has obstructive hydrocephalus, a lumbar puncture is often contraindicated at the time of the patient's visit, so cerebrospinal fluid sampling is often delayed until after surgery. In this case, postoperative cerebrospinal fluid sampling should be delayed for 10-14 days to allow removal of surgical debris.

5) Biopsy and pathology

For ventricular meningiomas, obtaining tumor tissue for histopathological examination is very important and is the gold standard for confirming the diagnosis. This examination is usually done after surgical resection. Postoperative treatment options, including radiation and/or chemotherapy, also depend on the histologic diagnosis.

2. Differential diagnosis

1) Differential diagnosis with common childhood diseases

Because ventricular meningiomas in children, like other CNS tumors, have many signs and symptoms that are nonspecific, they may be misdiagnosed as common childhood illnesses (e.g., viral gastroenteritis, tension headaches, and migraines). Other rare neurologic conditions that present similarly to brain tumors include brain abscesses, intracranial hemorrhages, nonneoplastic hydrocephalus, arteriovenous malformations, aneurysms, or inert viral infections.

It is important to note that children with CNS tumors, such as ventricular meningiomas, often have more than one tumor-related sign or symptom, which can help physicians differentiate them clinically from other disorders. For example, headaches in children with CNS tumors are often accompanied by other manifestations such as vomiting, visual impairment, unsteady gait, changes in behavior or academic performance, sleep disturbances, and growth disturbances. To clearly distinguish CNS tumors from other diagnoses, any child suspected of having a CNS lesion needs imaging.

3. Differential diagnosis with other tumors of the posterior cranial fossa

The imaging differential diagnosis of common pediatric posterior cranial fossa tumors involves distinguishing ventricular meningiomas from medulloblastomas, hairy cell astrocytomas, embryonal tumors, and choroid plexus tumors. Although histopathology is ultimately needed to differentiate these tumors, there are imaging features that can be used to surmise which tumor is more likely prior to surgery.

For example, ventricular meningiomas most often originate in the fourth ventricle and often show a restricted degree of diffusion on diffusion-weighted MRI. This feature helps to differentiate ventricular meningiomas from hairy cell astrocytomas of the posterior cranial fossa.

In addition, in some patients, ventricular meningiomas extend from the posterior cranial fossa down to the craniocervical junction, which is rare in other posterior cranial fossa tumors. Posterior cranial fossa ventricular meningiomas also often extend significantly through the lateral foramen of the fourth ventricle (foramen of Luschka), a feature that is less common in medulloblastomas.

On the other hand, if the tumor appears in the supratentorial area, the possibility of glioma, embryonal tumor, choroid plexus carcinoma, or papilloma should be considered in addition to ventricular meningioma.

Clinical Management

The mainstay of treatment for ventricular meningiomas is removal of all tumors as far as safely possible and adjuvant radiation therapy after surgery. Chemotherapy is only appropriate for the treatment of young children, patients with large volume tumors with residual lesions and recurrent/refractory tumors.

1. Surgical treatment

Initial treatment of patients with suspected ventricular meningiomas consists of maximal tumor resection, provided it is safe. Ventricular meningiomas are usually located in the posterior cranial fossa, in close proximity to the cranial nerves and brainstem, making surgery risky. The degree of surgical resection is closely related to tumor prognosis and survival, and patients benefit greatly from an initial surgery with complete resection. If the tumor invades the brainstem, surgery can be more difficult.

Because patients who achieve total resection have a better prognosis, many hospitals will consider chemotherapy before radiation therapy or a second surgery if the lesion is visible to the naked eye and can be safely removed.

After surgery, histopathologic diagnosis is required and the extent of resection is assessed by magnetic resonance. If the MRI reveals the presence of residual tumor and assesses the possibility of total resection, a second surgery may be considered.

Since all primary ventricular meningiomas are at risk for cerebrospinal fluid dissemination, an MRI of the brain and spinal cord with cerebrospinal fluid cytology is required after 2-3 weeks postoperatively.

2. Radiotherapy

Most patients with ventricular meningiomas require radiation therapy and/or chemotherapy as adjuvant treatment after surgery in order to kill residual tumor cells to reduce the risk of recurrence.

Radiation therapy, referred to as radiotherapy, is a cancer treatment that uses high-energy X-rays or other types of radiation to kill cancer cells or to stop their growth. In the local treatment of ventricular meningiomas, conformal radiotherapy is often recommended. This is a type of radiotherapy that uses a computer to image the tumor in three dimensions and shape the radiation beam to fit the tumor, which can help reduce the damage caused by radiotherapy radiation to nearby healthy tissue.

Chemotherapy, short for chemotherapy, treats cancer by using chemicals to stop the growth of cancer cells, kill them, or stop them from dividing. When chemotherapy is given by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach the entire body, acting on cancer cells throughout the body. Some of the more commonly used chemotherapy drugs in the treatment of ventricular meningiomas are cisplatin, carboplatin, cyclophosphamide, and etoposide.

1) Treatment Programs

i) Primary treated intracranial WHO grade II-III ventricular meningioma

The extent of resection is assessed by total resection as far as possible, diagnosed postoperatively by pathohistology, and by magnetic resonance. If MRI reveals the presence of residual tumor and assesses the possibility of total resection, a second surgery may be considered.

Since all primary ventricular meningiomas carry a risk of cerebrospinal fluid dissemination, an MRI of the brain and spinal cord with cerebrospinal fluid cytology is required after 2-3 weeks postoperatively.

● Children under 1 year of age

Post-operative chemotherapy with Baby UK regimen, radiotherapy is not recommended. Children with residual tumor after chemotherapy may be considered for a second surgery.

● Children between the ages of 1 year and 1.5 years

The 2017 edition of the European Association of Neuro-Oncology (EANO) published Guidelines for the Diagnosis and Treatment of Ventricular Tuberous Tumors, in which it was recommended that the age for receiving radiotherapy be adjusted downward to 1 year. A more cautious attitude is still common in domestic clinical practice for various reasons.

The European Society for Neuro-Oncology guidelines recommend a total postoperative conformal radiotherapy dose of 59.4 Gy and a single dose of 1.6-1.8 Gy for children between 1 and 1.5 years of age; if the patient's neurological status is poor, the total dose can be adjusted to 54 Gy. According to a recent study, an upward adjustment in the total radiotherapy dose to 67.4 Gy and a single dose of 4 Gy may be considered if tumor remnants are visible in the postoperative period. If the dose is adjusted upward, it is recommended to choose 3D conformal radiotherapy, conformal intensity-modulated radiotherapy, or proton radiotherapy to minimize the damage to normal tissues.

● For supratentorial ventricular meningiomas-RELA and posterior cranial fossa type A ventricular meningiomas, postoperative localized radiotherapy is strongly recommended due to the frequency of occurrence in infants and young children and the less favorable prognosis. If the tumor is a supratentorial WHO grade II ventricular meningioma and is completely resected, recovery is usually possible without adjuvant radiotherapy. The role of adjuvant radiotherapy in such cases is controversial. Therefore, delayed radiotherapy and watchful waiting may be considered.

● If there is visible tumor residue after surgery, a VEC regimen (vincristine + etoposide + cyclophosphamide) is recommended for chemotherapy after surgery and before radiotherapy, which may be combined with cisplatin and/or high-dose methotrexate. If there are no visible tumor remnants after surgery, maintenance chemotherapy with Baby UK regimen is recommended.

● Pediatric patients over 1 1/2 years of age

The European Society for Neuro-Oncology guidelines recommend a total postoperative conformal radiotherapy dose of 59.4 Gy, with a single dose of 1.8 Gy; if the patient's neurological status is poor, the total dose can be adjusted to 54 Gy. Three-dimensional conformal radiotherapy, conformal intensity-modulated radiotherapy, or proton radiotherapy are recommended to minimize damage to normal tissue.

For supratentorial ventricular meningiomas-RELA and posterior cranial fossa type A ventricular meningiomas, postoperative localized radiotherapy is strongly recommended due to the frequency of occurrence in infants and young children and the less favorable prognosis. If the tumor is a supratentorial WHO grade II ventricular meningioma and is completely resected, recovery is usually possible without adjuvant radiotherapy. The role of adjuvant radiotherapy in this situation is controversial, so delayed radiotherapy with watchful waiting may be considered.

If there is cerebrospinal fluid or spinal cord dissemination of the tumor, whole-brain whole-spinal cord radiotherapy is required, with a total radiotherapy dose of 24-36 Gy, which can be increased up to a maximum of 59 Gy for focal lesion sites, and the specific radiotherapy dose needs to be determined according to age. In children under 3 years of age, whole brain whole spinal cord radiotherapy has more neurological side effects and should therefore be avoided as much as possible.

For patients older than 1.5 years of age with visible residual postoperative lesions, chemotherapy with the VEC regimen (which may be combined with cisplatin) is recommended after surgery and before radiotherapy in order to shrink the tumor and create conditions for a second surgery for total resection. Postoperative chemotherapy should also be considered in children between 1 and 3 years of age who have visible residual postoperative lesions but are not eligible for postoperative radiotherapy.

The need for chemotherapy is controversial if the patient is older than 1 ½ years and the surgery is total. Patient-specific information is usually required, and chemotherapy is recommended if there are poor prognostic factors such as high WHO grade (WHO grade III), poor prognosis of the tumor type (e.g., mesenchymal ventricular meningiomas), high Ki67 values, and RELA fusion gene positivity.

● Adult patients

In adults, patients with WHO grade II tumors and failure to make total resection should undergo postoperative conformal radiotherapy with a total dose of 54-59.4 Gy. Adult patients with mesenchymal ventricular meningiomas should be treated with a total dose of 60 Gy for postoperative conformal radiotherapy, regardless of whether or not total resection is achieved.

Chemotherapy is usually applied to patients in whom surgery fails to provide total resection and is usually followed by 1-4 cycles of multidrug chemotherapy.

If the tumor is a supratentorial WHO grade II ventricular meningioma and is completely resected, it is usually possible to recover well without adjuvant radiotherapy. The role of adjuvant radiotherapy in this situation is controversial, so delayed radiotherapy with watchful waiting may be considered.

If cerebrospinal fluid or spinal cord dissemination of the tumor is present, whole-brain whole-spinal cord radiotherapy is required at a total dose of 36 Gy, raised to 45-54 Gy at focal lesion sites.

ii) Intracranial WHO grade I ventricular meningioma (subventricular ventricular meningioma)

Subventricular ventricular meningiomas that do not cause any symptoms are observed and do not require intervention.

If the tumor is large and causes associated symptoms, the tumor may be surgically removed. The prognosis for this type of tumor is good when it is removed in its entirety. If it is not possible to remove all of it, it can be treated with radiotherapy.

iii) Recurrent intracranial ventricular meningioma

Currently, there are no standard treatment options for recurrent ventricular meningiomas. Reoperation and/or re-radiation should be performed if conditions permit. If total resection is not possible at the time of primary surgery to preserve function, the same limitations may be faced at the time of secondary surgery, and therefore the choice of surgery should be made with caution.

In addition to surgery, it is recommended that whole brain and spinal cord radiotherapy and chemotherapy be considered. Radiotherapy for children is recommended to choose three-dimensional conformal radiotherapy, conformal intensity-modulated radiotherapy, proton radiotherapy, or low-dose fractionated radiotherapy to minimize the damage to normal tissues. For children under 3 years of age, whole brain whole spinal cord radiotherapy has more neurological side effects and should be avoided as much as possible.

Chemotherapy should be given to recurrent patients, especially those with central nervous system dissemination, when surgery is not suitable. In terms of chemotherapy regimens, adult patients can consider platinum-based or temozolomide-based regimens; pediatric patients can consider etoposide, temozolomide, nitrosoureas, and platinum-based regimens as single agents or in combination, etc. There are also studies that report that bevacizumab is effective in the treatment of recurrent ventricular schwannomas when used alone or in combination with irinotecan, carboplatin, or temozolomide.

Since the prognosis of recurrent ventricular meningiomas is often poor, appropriate palliative care options may also be chosen depending on the patient's condition in order to ensure a better quality of life.

iv) WHO grade II-III ventricular meningioma of the spinal cord

Total resection is maximized and the extent of resection is assessed by MRI after surgery. If the MRI reveals the presence of residual tumor and assesses the possibility of total resection, a second surgery may be considered.

For example, since all primary ventricular meningiomas are at risk of cerebrospinal fluid dissemination, an MRI of the brain and spinal cord with cerebrospinal fluid cytology is required after 2-3 weeks postoperatively.

If it is a WHO grade II ventricular meningioma and completely resected, watchful waiting is recommended.

In case of WHO grade II ventricular meningioma but only partially resected, local radiotherapy at a total dose of 45-54 Gy is recommended.

In the case of mesenchymal ventricular meningiomas (WHO grade III), local radiotherapy at a total dose of 45-54 Gy is recommended, regardless of whether or not total excision is performed.

v) WHO grade I ventricular meningioma of the spinal cord (mucopapillary ventricular meningioma)

Total resection (laminectomy) is done as much as possible, and the extent of resection is assessed by MRI after surgery. If the MRI reveals the presence of residual tumor and assesses the possibility of total resection, a second surgery may be considered.

If resection is incomplete, postoperative radiotherapy at a total dose of at least 50 Gy is recommended.

If recurrence occurs, re-surgery, re-radiation and chemotherapy should be considered.

3. Adverse reactions

Side effects of chemotherapy depend on the type of drug given, the dose and the length of time it is taken. General side effects can include: hair loss, mouth sores, loss of appetite, nausea and vomiting, diarrhea or constipation, increased chance of infection, easy bruising or bleeding, and fatigue. The severity of side effects is related to the type of drug, the dose and the duration of chemotherapy. Usually, these side effects go away after the treatment is over. It is important to note that platinum-based chemotherapeutic drugs may be ototoxic to children and, if overdosed, may cause irreversible hearing loss.

Side effects of radiation therapy include fatigue, mild skin discomfort, nausea, and diarrhea. Radiotherapy to the brain may affect the growth and development of children. Radiotherapy to the whole brain and spinal cord significantly increases the incidence of neurological complications, including neurocognitive dysfunction. In developing children, it may also lead to delayed bone growth, hypothyroidism, adrenal insufficiency, and hypogonadism.

In addition, radiotherapy may increase the risk of secondary cancers in the distant future.

4. Frontline treatment

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) have received increasing attention as potential molecular therapeutic targets in the treatment of recurrent ventricular meningiomas. However, these still need to be validated in clinical trials.

For recurrent refractory ventricular meningiomas, PD-L1 inhibitors can be tried in combination with chemotherapy can be tried, but the efficacy is currently uncertain. Patients with the condition can perform whole-exon gene testing and use PD-L1 inhibitors cautiously with reference to the predicted efficacy of other tumor immune point inhibitors and treatment experience.

Prognosis

1. Survival rate

The 10-year overall survival rate for intracranial ventricular meningiomas in children is approximately 50-70%, and the 10-year overall survival rate for intracranial ventricular meningiomas in adults is approximately 67-85%. Factors that influence prognosis include:

l Extent of surgical resection: studies have shown that patients who can be fully resected have a better prognosis.

l Tumor location: supratentorial tumors have an overall better prognosis for intracranial tumors. Also, patients with spinal cord tumors have a lower survival rate compared to intracranial tumors.

l Age: In children, the older the age, the better the prognosis. Infants may fare less well than older children. This is partly because of the higher incidence of sub-surface tumors in infants, and partly because infants often do not receive radiotherapy in a timely manner due to concerns about side effects on brain development.

l Histologic grading: The prognostic significance of histologic grading (WHO grade II versus grade III) in ventricular meningiomas remains controversial. Although some studies have found that grade III tumors have a worse prognosis compared to grade II tumors, other studies have failed to corroborate this finding due to the difficulty of accurately grading the tumor at the time of diagnosis.

l Molecular genetic subgroup classification: whole genome sequencing based on a series of ventricular meningioma samples has identified a number of molecular subgroups, which may ultimately be more useful than histology in prognostic differentiation.

l Genomic alterations: In a series of retrospective studies, increased copy number of chromosome arm 1q was associated with poor prognosis in pediatric PF-EPN patients. Prospective clinical trials have supported this correlation in pediatric PF-EPN-A tumors. In contrast, the prognostic significance of increased copy number of 1q in PF-EPN-B tumors remains to be determined.

2. Sequelae

Whole-brain, whole-spinal cord radiotherapy in developing children increases the incidence of neurocognitive dysfunction, which can have an impact on a child's intellectual development and cognitive function. Some studies have shown that the effects of this neurocognitive dysfunction can be most pronounced if the child's age at diagnosis is under 7 years old.

Also, radiotherapy to the brain may affect the functioning of the endocrine system. At the end of tumor treatment, the child may require endocrine therapy depending on the condition.

In addition, radiotherapy increases the risk of secondary cancers, including distant secondary cancers years later. In one study, the cumulative 10-year incidence of secondary cancers after initial treatment for medulloblastoma was 4.2%, and nearly half were malignant gliomas of the central nervous system.

3. Rehabilitation

If functional or speech impairment occurs as a result of the treatment of ventricular meningioma, rehabilitation in the rehabilitation department may be considered. There is no standardized protocol for this type of rehabilitation and it should be done according to the actual condition as prescribed by the doctor.

4. Complications

1) Hydrocephalus

Due to the gradual growth of the tumor in the posterior cranial fossa, which fills the fourth ventricle, the normal flow of cerebrospinal fluid (CSF) may be obstructed or the absorption of CSF may be impeded, resulting in an excessive accumulation of CSF, causing obstructive hydrocephalus (also known as non-traffic hydrocephalus). However, after the tumor is removed and the obstruction is lifted, this type of hydrocephalus can usually resolve on its own. However, some patients may still have or develop hydrocephalus after surgery. The causes of hydrocephalus in this case are more complicated and diverse, including decreased arachnoid resorption ability after postoperative radiotherapy, decreased brain tissue compliance, tumor residuals, tumor recurrence, failure to completely release the compression, postoperative intracranial infections, intraoperative/postoperative hemorrhage flowing into the subarachnoid space causing arachnoid adhesion, and so on.

Postoperative hydrocephalus after tumor surgery is usually hydrocephalus caused by impaired absorption of cerebrospinal fluid, called traffic hydrocephalus. For traffic hydrocephalus, there is a lack of etiologic treatment, which relies on ventriculoperitoneal shunting, in which a catheter is placed to shunt the hydrocephalus into the peritoneal cavity. The feasibility of a triventriculostomy can also be evaluated based on the pathologic type of the tumor, the cause of the hydrocephalus, and the current severity of the hydrocephalus.

2) Cerebellar ataxia

Patients may develop new or exacerbated ataxia after posterior cranial fossa tumor removal. Lateral hemispheric cerebellar injuries may manifest as limb ranging deficits, and midline cerebellar injuries are more likely to cause gait ataxia.

3) Posterior group cranial nerve injury

Lesions of the pontine cerebellar angle often result in significant posterior group cranial nerve damage, leading to hemifacial muscle weakness, dysarthria, dysphagia, or hearing loss. At least in infants, these functions may be restored after successful removal of the tumor.

4) Posterior Cranial Fossa Syndrome

Surgical removal of tumors in the midline area of the cerebellum can cause posterior cranial fossa syndrome, also known as cerebellar vermis syndrome. Posterior cranial fossa syndrome is more likely to occur when a ventricular meningioma involves the upper or middle cerebellar peduncle. Symptoms include:

● Delayed speech production or aphasia

● Ataxia (a motor coordination disorder)

● eye movement disorder

● Decreased muscle tone

l Emotional instability or behavioral disorders

l Inability to move spontaneously (temporary)

l Neurocognitive dysfunction

5) Whole Brain Whole Spinal Cord Radiotherapy Side Effects

Whole brain and spinal cord radiotherapy significantly increases the incidence of neurological complications, including neurocognitive dysfunction. Irradiation of the nervous system may result in neurocognitive dysfunction, affecting attention, memory, and processing ability, among other things, with risk factors including young age, high-risk disease, and radiotherapy dose.

In addition, due to radiation to the thyroid, jaw, pharynx and larynx, this may increase the risk of delayed hypothyroidism or mandibular hypoplasia in developing children. It can also lead to delayed bone growth, adrenal insufficiency and hypogonadism.

These side effects may be minimized by reducing the dose of radiotherapy and/or using new radiotherapy techniques. For example, irradiation of the medial temporal lobe, inner ear, thyroid, lungs, heart, and abdominal organs can be avoided or reduced with proton beams, thus reducing side effects.

6) Hearing loss

Platinum-based chemotherapy may be ototoxic to children and, if overdosed, may cause irreversible hearing loss.

5. Recurrence and metastasis

All first-treatment ventricular meningiomas are at risk for cerebrospinal fluid dissemination, although actual cerebrospinal fluid dissemination occurs in less than 5% of all ventricular meningiomas.

Recurrence of intracranial ventricular meningiomas usually occurs within 5 years of diagnosis, although there are clinical cases of late recurrence after more than 5 years. Approximately 80% of recurrences are localized.

In general, patients with total excision have a lower recurrence rate than those with partial excision. However, even when total resection is achieved, there is some chance of recurrence. After recurrence, treatment of the tumor becomes more difficult. Therefore, treatment of recurrent intracranial ventricular meningiomas has a poor long-term prognosis, despite the fact that it is possible to achieve long-term remission for up to several years.

Follow-up & Review

After the treatment of ventricular meningioma is completed, it is important to have regular reviews and follow-ups to monitor the side effects of the treatment on the one hand, and to keep a close eye on the recurrence of the disease on the other.

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Ventricular meningiomas carry a risk of asymptomatic and/or late recurrence and have the potential for distant recurrence, thus long-term follow-up and detection of recurrence by magnetic resonance are required.

For the first 3 years after the end of treatment, an MRI of the brain is recommended every 3-4 months.

An MRI of the brain is recommended every 6 months for 3-5 years after the end of treatment.

Five years after the end of treatment, another 2-5 years of brain MRIs, once a year, are recommended.

If the brain tumor progresses, or if there are symptoms indicating that the tumor may involve the spinal cord, a spinal cord enhancement MRI follow-up is required, once a year, at the same time as the brain MRI.

If the patient has received radiotherapy to the brain, cognitive and endocrine function should be monitored continuously after completion of treatment, if available. For endocrine abnormalities that may result from treatment, a baseline assessment of endocrine status is recommended within one year of completing treatment, followed by annual screening for hypothyroidism, growth hormone deficiency, and adrenal insufficiency through blood tests.

Routine

1. Management of daily life

1) Rest and exercise

The patient needs to be guaranteed a sleep schedule. Regular and quality sleep is helpful for recovery and immunity. A suitable sleep environment (usually dimly lit, quiet, and at the right temperature) may be helpful in improving the patient's quality of sleep.

If the patient's physical condition permits, you can encourage and assist the patient to perform some simple activities. Moderate exercise is helpful in preventing muscle atrophy, enhancing physical strength and endurance, and promoting appetite.

2) Diet

Care should be taken to provide patients with a nutritious and balanced diet, guaranteeing the intake of high-quality proteins (e.g. meat, eggs, milk, poultry, fish and shrimp, soybeans and soybean products, etc.), as well as more grains and cereals, vegetables and fruits, and dairy products and nuts in moderation, in order to ensure the intake of other nutrients. Clinical dietitians in the nutrition department of the hospital can be consulted to provide appropriate nutritional programs for patients. If weight loss is severe, nutritional support through tube feeding or parenteral nutrition may be considered.

3) Living habits

If the patient has neutropenia caused by treatment, attention should be paid to preventing infections. It is important to pay attention to personal and living environment hygiene, do not approach patients with infectious diseases, and do not go to crowded places.

If the treatment causes thrombocytopenia, care needs to be taken to avoid bleeding by staying away from sharp, prickly toys and objects, as well as avoiding impact-intensive sports (e.g., bouncing, soccer, basketball, etc.).

2. Special considerations

Pediatric patients treated with radiotherapy for ventricular meningiomas are at risk for long-term side effects and secondary tumors, which may develop many years after the end of treatment, and which are related to the regimen and dosage of the treatment. Therefore, it is important to keep all of the patient's medical and treatment records for future reviews and medical appointments.

3. Daily disease monitoring

Post-operative complications, chemotherapy-induced side effects (e.g., hair loss, fatigue, vomiting, etc.), recurrence of tumor metastasis, and growth problems need to be attended to. Consult your doctor when fever, worsening of symptoms, new symptoms, and treatment-induced side effects occur.

4. Prevention

Since the exact cause of ventricular meningiomas is not known, there is no better way to prevent them from occurring. However, regular follow-up and maintenance of good healthy lifestyle habits can help prevent and detect the recurrence of the disease or the emergence of long-term effects as early as possible.

Cutting-edge Therapeutic & Clinical Research

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