CNS and Neuroectodermal Tumor

The term CNS tumor refers to all neoplasms that arise in the central nervous system – meaning in the brain or spinal cord. A distinction is made between primary CNS tumors, which originate directly from the tissue of the nervous system, and secondary CNS tumors, i.e., metastases that have spread to the brain from a tumor located elsewhere in the body. Secondary brain tumors are more common overall than primary ones.

Primary CNS tumors develop from various cell types within the nervous system – from glial cells, nerve sheaths, meninges, blood vessels, or embryonic precursor cells. They can occur at any age, with certain types preferentially affecting children and adolescents, while others primarily affect middle-aged or older adults.

CNS tumors account for around two percent of all cancer diseases worldwide. In Switzerland, several hundred new cases of primary brain tumors are diagnosed annually. Due to their location in the most sensitive organ of the human body, they require particularly meticulous diagnostics and an individually tailored treatment approach.

Neuroectodermal tumors originate from the neuroectoderm – an embryonic cell layer from which the entire nervous system develops. The most well-known representative of this group is the primitive neuroectodermal tumor, abbreviated as PNET. It belongs to the family of small, round, blue cell tumors and is closely related to Ewing sarcoma – both share characteristic genetic alterations.

PNETs primarily occur in children and adolescents and can arise in the brain, spinal cord, or outside the central nervous system. In the brain, they were long referred to as central PNETs – in the modern WHO classification, this term is increasingly replaced today by more specific molecular genetic diagnoses, but it remains very common in clinical usage. In the cerebellum, the most well-known form is called a medulloblastoma, one of the most common malignant brain tumor forms in childhood. Neuroectodermal tumors typically grow rapidly and require intensive therapy.

The differentiation from other CNS tumors is increasingly achieved today via molecular genetic analyses, as the external appearance under the microscope alone is often insufficient to determine the exact subtype.

CNS tumors are classified according to two primary criteria: the tissue of origin and the grade of malignancy. The World Health Organization classifies brain tumors into four grades – from Grade I (benign, slow-growing) to Grade IV (high-grade malignant, rapid-growing). This staging is decisive for treatment planning and prognosis.

The largest group of primary brain tumors are gliomas – tumors that arise from glial cells, which surround and support nerve cells. They are the most common primary brain tumors in adults and encompass a wide spectrum ranging from slow-growing to highly aggressive forms.

• Astrocytoma: originates from astrocytes and can manifest in various grades of malignancy, from benign to high-grade malignant. Low-grade astrocytomas grow slowly, whereas high-grade ones grow rapidly.
• Glioblastoma: the most aggressive primary brain tumor, corresponding to WHO grade IV. It grows rapidly, infiltrates the surrounding brain tissue, and carries an unfavorable prognosis despite modern therapy.
• Oligodendroglioma: originates from oligodendrocytes, typically grows slower than a glioblastoma, and responds relatively well to chemotherapy. Frequently affects younger adults.

Tumors of the meninges and cranial nerves are frequently benign and grow slowly. Nonetheless, due to their location in the narrow skull cavity or along critical nerves, they can cause significant symptoms and require treatment.

• Meningioma: originates from the meninges and is the most common benign brain tumor. Most meningiomas grow slowly and can often be completely removed surgically. Malignant variants occur more rarely.
• Acoustic neuroma (medically correct: vestibular schwannoma): a benign tumor that usually originates from the vestibular nerve, but compresses the adjacent auditory nerve early on, thereby manifesting through hearing loss, tinnitus, or balance disorders. It grows slowly and is generally highly treatable.
• Schwannoma: originates from Schwann cells, which envelop nerve fibers. Mostly benign, but can occur along various nerves and cause different symptoms depending on its location.

Neuroectodermal tumors develop from immature embryonic nerve cells and primarily affect children and adolescents. They typically grow rapidly and require intensive combination therapy. In recent years, molecular genetic analyses have demonstrated that this tumor group is biologically significantly more diverse than was long assumed.

Primitive neuroectodermal tumor (PNET): an aggressive tumor that develops from immature nerve cells and grows rapidly. In the brain, it was long referred to as a central PNET – in the modern WHO classification, this term is increasingly replaced by more specific molecular genetic diagnoses, but it remains very common in clinical usage. Treatment typically includes surgery, radiation therapy, and chemotherapy.

Medulloblastoma: the most common malignant brain tumor in childhood, originates in the cerebellum and is today divided into various subgroups based on molecular genetics, which differ significantly in prognosis and treatment response.

In addition to classic brain tumors, there are a number of other tumors that affect the central nervous system or are closely related to it. They develop from very different cell types and accordingly have distinct courses and treatment approaches.

• Ependymoma: originates from ependymal cells, which line the brain ventricles and the spinal cord canal. Occurs in both children and adults, preferentially in the spinal cord in adults.
• Craniopharyngioma: a benign tumor near the pituitary gland that, despite its benign nature, can cause significant hormonal and neurological complaints due to its location.
• Uveal melanoma: a melanoma that originates in the uveal tract of the eye and is counted within the CNS-associated domain. It is the most common primary intraocular tumor in adults.
• Nodular melanoma and Amelanotic melanoma: aggressive melanoma variants of the skin that very frequently form metastases in the CNS in advanced stages – melanoma belongs, alongside lung and breast cancer, to the cancer types with the highest rate of brain metastases.

The location of a CNS tumor largely determines which symptoms it causes and how accessible it is surgically. Tumors in the cerebrum affect speech, motor skills, memory, or personality depending on their exact position. Tumors in the cerebellum frequently lead to balance disorders and coordination problems. Tumors in the brainstem are particularly delicate, as it controls vital functions such as breathing and heartbeat.

Tumors arising in the spinal cord can lead to paralysis, sensory disturbances, or bladder and bowel dysfunction, depending on the level at which they are located. Tumors of the cranial nerves, such as an acoustic neuroma, manifest through specific deficits of the affected nerve. In children, CNS tumors develop more frequently in the posterior cranial region, i.e., in the cerebellum and brainstem, whereas in adults, the cerebrum is more commonly affected.

The symptoms of a CNS tumor depend heavily on its location and size. A common feature of many forms is that the symptoms begin insidiously and initially seem non-specific, which complicates diagnosis in the early stages.

If a tumor grows inside the skull, the pressure within the closed cranial cavity increases. Typical consequences include headaches, which are often particularly severe in the morning, nausea and vomiting, as well as increasing fatigue and listlessness. In advanced cases, clouding of consciousness or epileptic seizures can occur. These symptoms are not specific to brain tumors, but they should be investigated promptly if they persist or increase in intensity.

Depending on the location of the tumor, specific neurological deficits are added. Tumors in the speech center lead to word-finding difficulties or language comprehension problems. Tumors in motor areas cause paralysis or loss of strength in the arms or legs. Visual disturbances, visual field defects, or double vision arise with tumors near the optic pathway or brainstem. Personality changes, mood swings, or concentration problems can point to tumors in the frontal lobe. In children, CNS tumors often become noticeable through balance disorders, an altered gait, or drops in academic performance.

The diagnosis of a CNS tumor begins with a thorough neurological examination and medical history. The most important imaging technique is MRI (magnetic resonance imaging), which depicts tumors in the brain and spinal cord in great detail and provides indications regarding size, location, and characteristics. If metastases are suspected or for surgical planning, a CT scan is used supplementarily.

For a more precise characterization of the tumor, PET scans are utilized to visualize the metabolism of the tumor tissue. The final diagnosis is established through the histological and molecular genetic examination of tumor tissue obtained during surgery or a targeted biopsy. Beside the microscopic appearance, the current 2021 WHO classification also incorporates molecular markers, making the diagnosis more precise and treatment planning more targeted.

If a brain tumor is suspected, the investigation should take place in a specialized neuro-oncological center, as the misdiagnosis rate for rare subtypes is increased without appropriate experience.

The treatment of a CNS tumors is guided by tumor type, location, WHO grade, general condition, and the age of the patient. It is planned within an interdisciplinary team comprising neurosurgeons, radiation therapists, oncologists, and neurologists.

The neurosurgical removal of the tumor is the primary and most important treatment step for many CNS tumors. The goal is a resection that is as complete as possible while sparing the surrounding functional brain tissue. Modern surgical techniques, such as awake craniotomy, where the patient is conscious during the procedure, enable the removal of tumors in speech-critical or motorically important areas.

Radiation therapy is frequently used additionally, especially for high-grade tumors or when complete surgical removal is not possible. For certain tumors such as glioblastoma, it is combined with concurrent chemotherapy. Low-grade tumors like Grade I meningiomas can be observed initially in some cases without treating immediately.

Targeted therapies and immunotherapies are also increasingly gaining importance in neuro-oncology but are so far only approved for certain subtypes.

Radiation to the brain and neurosurgical interventions leave specific traces: cognitive impairments, pronounced exhaustion, and accompanying neurological symptoms such as chronic pain, sensory disturbances, or sleep problems. Complementary medical support directly targets these burdens and can complement conventional therapy valuably.

The acupuncture has established itself in neuro-oncology as an effective supportive measure for treating therapy-induced headaches, neuropathic pain, and the often debilitating fatigue. The neural therapy can be used supplementarily for chronic accompanying neurological symptoms such as pain or functional disorders. Since nerve cells depend to a high degree on a functioning energy metabolism, mitochondrial therapy can be used to promote the cellular energy supply after the completion of intensive treatment phases.

An individually dosed mistletoe therapy as well as targeted measures of phytotherapy can contribute to supporting general resilience – always in coordination with the neuro-oncological treatment team.

Since radiation therapy unfolds its effect partly via oxidative stress, antioxidant infusions are strictly separated in time from the radiation cycles and are preferably used during the recovery phase. An accompanying intestinal cleanse can improve the tolerability of therapy in cases of chemotherapy-induced intestinal strain – here too, the temporal coordination is carefully arranged with the treating team.

The prognosis for CNS tumors varies extraordinarily widely and depends primarily on the tumor type, WHO grade, and location. A generalized statement regarding life expectancy is not possible for this heterogeneous tumor group.

Benign tumors such as Grade I meningiomas or acoustic neuromas are permanently cured in many cases following complete surgical removal. Low-grade gliomas have a significantly better prognosis than high-grade ones but can transition into more aggressive forms after years. Glioblastoma carries a median survival time of about 15 months despite modern therapy, though individual patients survive significantly longer – particularly when certain molecular markers such as MGMT promoter methylation are present.

Neuroectodermal tumors like medulloblastoma have achieved five-year survival rates of over 80 percent in certain risk groups of children with modern combination therapy. Early diagnosis, treatment in a specialized center, and consistent follow-up care are the most critical factors for a favorable outcome in CNS tumors as well.

CNS tumors are a complex and diverse group of conditions. We have summarized the most common questions asked by affected individuals and their relatives in an objective and easy-to-understand manner here.

The information listed contains relevant topics and serves to improve understanding.