What is an Optic Pathway/Hypothalamic Glioma?

An optic pathway glioma is a subset of low grade astrocytoma that grows in a portion of the optic pathway (optic nerve, optic chiasm, optic radiations).  Optic gliomas typically grow as an infiltrative lesion with poorly defined borders.  Because they are infiltrative they often extend and involve the entire optic pathway.  They also frequently extend into adjacent structures, such as the hypothalamus. Optic chiasmatic and hypothalamic gliomas are often considered a single entity because of their ability to infiltrate into both compartments regardless of the site of origin of the tumor.  These tumors originate from astrocytes, which are star-shaped brain cells.  Astrocytes are a type of glial cell which function to support the surrounding cells. Optic pathway/hypothalamic gliomas account for 4-6% of all brain tumors in children and 30% of all pediatric gliomas.  The peak incidence is during the first decade of life.

Astrocytomas comprise a wide range of tumors that are defined by their microscopic appearance and are graded according to the World Health Organization (WHO) classification system.  The WHO grading system divides astrocytomas into four subsets: WHO Grade I, Grade II, Grade III and Grade IV astroctyoma.  The grade of the tumor defines its growth potential and extent of invasiveness.  WHO Grade I and II Astrocytomas are slow growing tumors frequently grouped together and termed “low grade gliomas”.   WHO Grade III and IV Astrocytomas are fast growing tumors, usually termed “high grade gliomas”.   Optic pathway and hypothalamic gliomas are almost always WHO Grade I gliomas (juvenile pilocytic astrocytoma “JPA”).  Occasionally optic pathway/hypothalamic gliomas are WHO Grade II gliomas (pilomyxoid astrocytomas).  It is extremely uncommon for an optic pathway/hypothalamic glioma to be a high grade glioma (anaplastic astrocytoma or glioblastoma multiforme) unless the tumor has developed malignant degeneration following radiation.

Patients with Neurofibromatosis Type I (NF1) have an increased risk of developing optic pathway gliomas.  Approximately 15-20% of patients with NF1 will develop an optic pathway glioma identified by MRI but the majority of these tumors will never become symptomatic.

What are the symptoms of an Optic Pathway/Hypothalamic Glioma?
Most optic pathway gliomas present with some form of visual symptoms determined by the location of the tumor.  Visual loss is a common symptom, either involving one eye or both eyes.  Frequently only a portion of the visual field will be affected.  Other visual symptoms include proptosis (protrusion of the eye), nystagmus (bouncy eyes), or strabismus (wandering eye).  An eye exam by an ophthalmologist will frequently demonstrate a pale optic nerve.  Tumors that involve the hypothalamus can cause failure to thrive or obesity and precocious puberty or other hormonal dysfunction.  Tumors that extend into the third ventricle can cause hydrocephalus due to obstruction of the flow of cerebral spinal fluid resulting in symptoms of increase cranial pressure (headache, vomiting, difficulties with balance, lethargy).

Patients with NF1 have a high incidence (15-20%) of optic pathway gliomas, but the majority of these optic pathway gliomas has an indolent course and will never cause visual disturbance or require treatment.  Routine MRI screening in NF1 patients looking for optic pathway gliomas is not recommended.  Patients with NF1 should undergo yearly ophthalmology exams.  If visual impairment is identified, an MRI is recommended to assess for an optic pathway glioma.  No treatment is indicated for an optic pathway glioma in a patient with NF1 unless the tumor is causing visual impairment or other neruological symptoms.

How is an Optic Pathway/Hypothalamic Glioma diagnosed?
Patients who have an optic pathway/hypothalamic tumor require an MRI of the brain to further define the location of the tumor and the involvement of neighboring structures.  An MRI of the spine may also be recommended due to the low possibility of metastasis (spread) of the tumor, which is more common in pilomyxoid astrocytoma.  Patients require a thorough ophthalmology exam to get a good baseline evaluation.  Patients also require a blood draw to look at the pituitary hormones, which can sometimes be affected by the tumor.  The MRI appearance can often be diagnostic of an optic pathway glioma and in these cases no biopsy is needed.  If the MRI is unclear regarding the diagnosis, a biopsy of the tumor is required to make the final diagnosis.  A biopsy is always useful because it allows a definitive diagnosis, including the WHO subtype.

How is an Optic Pathway/Hypothalamic Glioma treated?
Surgery is often required to make the diagnosis of an optic pathway/hypothalamic glioma.  The typical goal of surgery is to get a piece of the tumor to make a histological diagnosis. In most cases of optic pathway/hypothalamic glioma the tumor infiltrates among normal nerve fibers making it impossible to remove the tumor without causing unacceptable injury to the optic pathway or hypothalamus.  Rare cases of optic pathway/hypothalamic glioma have a large exophytic component (i.e. the tumor is growing out of rather than infiltrating the optic pathway or hypothalmus).  In cases where there is a dominant exophytic component, the goal of surgery is to remove as much of the tumor as possible without causing significant neurological injury.  In these rare cases where all or the majority of the tumor is removed, no further treatment is required.  Even after partial resection long term control of the tumor may occur.  If the tumor recurs after surgical resection alone, further surgery or treatment with chemotherapy or radiation are all treatment options.

Chemotherapy and radiation therapy are effective treatments for optic pathway/hypothalamic gliomas.  Chemotherapy is typically considered the standard treatment for optic pathway/hypothalamic gliomas because radiation therapy has potential long term complications.   There are several different effective chemotherapy regimens, all which are well tolerated with minimal long term side effectives.  The goal of chemotherapy is to stop the tumor from growing, shrink the tumor, and delay or avoid radiation therapy.  Most optic pathway/hypothalamic gliomas will respond to chemotherapy, but unfortunately a large subset will start to grow again following cessation of chemotherapy.  Patients with optic pathway/hypothalamic gliomas often require multiple different courses of chemotherapy throughout their life to control the tumor.  There is new data suggesting that low grade astrocytomas have specific genetic alterations that promote growth of the tumor.  Researchers are trying to identify these genetic changes to better understand why these tumors form but also to identify tumor specific targets to aim future therapies.

Radiation is very effective for the treatment of optic pathway/hypothalamic gliomas, but unfortunately radiation has potential long term toxicities (cognitive impairment, secondary malignancies, and vascular injury), therefore it is typically reserved for older children or younger children who fail chemotherapy.  Radiation therapy can control the tumor for the longest period of time, and in many cases it is curative.  Patients with NF1 have an increased risk of injury to the blood vessel and an increased risk for radiation induced cancers, therefore radiation should be avoided, if possible, in patients with NF1.

About treatment for Optic Pathway/Hypothalamic Glioma at Children’s Hospitals and Clinics of Minnesota

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