Pilocytic astrocytoma

Pilocytic astrocytomas are the most common benign brain tumors of children and young adults, and account for approximately 5% of all gliomas *. They arise from astrocytes, which are part of the supporting tissue (glial cells) of the central nervous system and are therefore classified as gliomas. Microscopically, pilocytic astrocytomas have a fibrous "pilocytic" character. Macroscopically, they are often cystic, meaning that pilocytic astrocytomas consist of a mixture of fluid-filled cavities and solid portions. Most pilocytic astrocytomas are slow-growing tumors that do not spread to other parts of the body and have a very good prognosis.

In children, pilocytic astrocytomas arise frequently from the astrocyte cells of the cerebellum, a region that plays a crucial role in movement and balance. However, pilocytic astrocytomas can also arise in the visual pathway, cerebrum, or brainstem *, *.

Pilocytic astrocytomas are the most common primary benign brain tumors in children aged 0–14 years. However, they may continue to occur into adulthood and are slightly more common in males than females (1.1:1 ratio). Pilocytic astrocytomas occur in children at a frequency of 0.8 per 100,000 persons per year.

Pilocytic astrocytomas can increase the pressure inside the skull due to their growth and then lead to:

• morning headaches
• nausea and vomiting
• fatigue

In addition, other symptoms may occur depending on the location of the tumor:

• gait and coordination disorders
• double images
• visual disturbances
• increasing somnolence (sleepiness, drowsiness)
• in rare cases epileptic seizures
• movement and speech disorders
• creeping change of mood and personality

Due to the usually very slow growth of pilocytic astrocytomas, symptoms may appear gradually and go unnoticed for a long time.

The causes for the development of pilocytic astrocytomas are currently the subject of intensive research. In a large proportion of these tumors, a special variant of a gene called BRAF is found, which is involved in the control of cell division *. In pilocytic astrocytomas, the BRAF gene has a mutation that initiates uncontrolled division of the tumor cells. The effect is mediated by the so-called mitogen-activated protein kinase pathway (MAP kinase pathway or MAPK pathway) *. This is also associated with cell senescence genes, which may explain the slow growth and spontaneous regression of pilocytic astrocytomas described in rare cases * *.

If a residual pilocytic astrocytoma remains after surgery and cannot be surgically removed, radiotherapy is an effective option. In recent years, radiosurgery in particular, a very targeted and intensive type of radiation, has become increasingly important. With radiosurgery, good tumor control can be achieved both in the case of a small residual tumor and in the case of a recurrence *, *, *. Alternatively, in the case of residual tumor, one can also wait with further therapy and monitor the patient closely until the residual tumor continues to grow.

Radiation in early childhood can lead to cognitive and hormonal problems, as well as vascular changes *, *. For this reason, in younger children under 5–10 years of age, attempts are made to delay radiation and to address any residual tumor after surgery with chemotherapy to spare the growing brain the potentially harmful effect of radiation *, *.

In some cases, pilocytic astrocytomas are due to a hereditary disease, neurofibromatosis type 1 (NF1). In this case, the tumors appear with a different distribution pattern and usually grow even more slowly.

In patients with neurofibromatosis type 1, pilocytic astrocytomas occur most frequently (two-thirds) in the optic nerve or tract, 20% in the brainstem, and only rarely (5%) in the cerebellum *. These tumors exhibit different growth behavior and require adapted therapy. NF1-associated tumors have a better prognosis than sporadic gliomas. There are even reports of spontaneous regression, which is attributed to the aforementioned activation of cellular aging mechanisms *.

In children with neurofibromatosis type 1, gliomas of the visual pathway are detected in 15–20% of cases, of which, however, only half of these patients ever experience symptoms *. More than half of the tumors of the visual pathway are pilocytic astrocytomas on fine tissue examination *. For gliomas of the visual pathway, no treatment is necessary in most cases *. If treatment is eventually required, it is primarily by chemotherapy.

Related to pilocytic astrocytomas are pilomyxoid astrocytomas. While they share many genetic features with pilocytic astrocytomas, they form a distinct subgroup with a more aggressive behavior *. While pilocytic astrocytomas are classified as grade I tumors according to WHO, pilomyxoid astrocytomas are no longer given a grade classification in the new WHO classification of 2016 (formerly grade II) *.