Optic Chiasmatic-Hypothalamic GLIOMAS (OCHGs), Optic Pathway/Hypothalamic GLIOMAS, (OP/HGs) Optic Pathway GLIOMAS (OPGs) (Archived)
Optic pathway gliomas can arise anywhere along the length of the optic nerve, through the optic chiasm and hypothalamus, and that is the reason they may be grouped as OCHGs, OP/HGs, or OPGs.
Optic chiasm and hypothalamic gliomas are considered a single entity because no matter where they initially originated, whether in the hypothalamus or the optic chiasm, they may infiltrate the other compartment. Sometimes the tumor arises in the hypothalamus and may infiltrate the optic chiasm. Other times the tumor arises in the optic chiasm and may infiltrate the hypothalamus.
To avoid further confusion, we need to go to the basics. We must remember that GLIOMAS are derived from Glial cells, also known as Neuroglia, whose function is to support and nourish neurons.
Specifically, Glial cells or Neuroglia encompass Astrocytes, Ependymal cells, Microglia, Satellite cells, Schwann cells, and Oligodendrocyte cells.
Most OCHGs, OP/HGs, or OPGs are benign low-grade astrocytomas that arise mostly in the pediatric population. They are predominantly childhood tumors.
Furthermore, 90% of cases are diagnosed in patients <=20 years old. 75% of cases are present in the first decade of life, the peak incidence. And they account for 20% of all pediatric brain tumors in patients who are two years old or younger.
Optic pathway gliomas (OPGs) range from 3% to 6% of pediatric brain tumors. And they account for 2% of all CNS gliomas.
Optic Chiasm: Where the optic nerves cross to the opposite side.
Image credits to their source.
Even though our focus here is OCHGs, OP/HGs, or OPGs, astrocytomas are not exclusive to develop on this optic hypothalamic chiasmatic pathway in the CNS. They may develop in the brain, brainstem, or cerebellum, among other sites.
They are not exclusive to the pediatric population either. In adults, astrocytomas tend to be high-grade, more aggressive gliomas, such as glioblastoma and anaplastic astrocytomas.
For OCHGs, OP/HGs, or OPGs, the incidence of gliomas exclusively of the optic nerve is higher in females (F>M).
Nevertheless, the incidence is equally common in both genders when the primary sites are the optic nerve and the optic chiasm (M=F).
Optic pathway/hypothalamic gliomas (OP/HGs) main histological types in the pediatric population are pilocytic astrocytoma (Grade I) and pilomyxoid astrocytoma (Grade II).
Unfortunately, pilomyxoid astrocytomas may present with CSF dissemination and spinal metastasis.
They are rare astrocytomas, but for practical reasons, only the most common histologies are named here.
Patients with Optic/Chiasm/Hypothalamic pathway GLIOMAS may present with some of the following:
Seizures and lethargy are always a possibility in brain tumors. And as the intracranial pressure increases, headaches and projectile vomiting are more common. Once the tumor causes obstruction/imbalance of the CSF, hydrocephalus sets in.
Visual changes. One may see optic atrophy in a fundoscopy eye exam. Proptosis/ exophthalmos or bouncy eyes known as nystagmus, and strabismus (crossed eyes) may be present. Also, patients may have partial visual field loss which may progress to blindness.
Babies and young children may present with Diencephalic syndrome which includes failure to thrive (especially during the first 3 years of age) as they do not gain a healthy weight for their age per appropriate weight-for-height normal development tables.
Many of these cases are confused with negligence or abusive parenting. Therefore, their true diagnosis is often delayed, and it is discovered when a Brain MRI is finally done, showing a hypothalamic-optic chiasm neoplasm.
Obesity may present in other cases. But, why this fluctuation in weight? Because the hypothalamus is the center for regulating hunger and satiety. Thus, depending on how affected the hunger/satiety nuclei are in the hypothalamus, that is how the symptoms will present.
Other signs and symptoms of OCHGs, OP/HGs, or OPGs may present due to hormonal dysfunction, as in the case of polyuria/polydipsia, which are symptoms of Diabetes insipidus. Also, rare cases of precocious puberty and short stature may result from hormonal dysfunction.
DIAGNOSIS:
Brain CT scan, or Brain MRI scan
Endocrine assessment
Visual field testing
Regular Ophthalmologist evaluation in Neurofibromatosis type 1 patients
TREATMENT
Treatment may be a combination of surgery, chemotherapy, radiation, or immunotherapy.
Radiation may trigger a newer more aggressive glioma, especially in patients with Neurofibromatosis type 1.
Since radiation is associated with an increased risk of secondary CNS malignancies, chemotherapy may be favored over radiation as first-line treatment.
An example of this is anaplastic astrocytoma, which, in many cases, most likely developed malignant degeneration after radiation treatment to a more benign low-grade astrocytoma.
Molecularly targeted drug therapy is currently in clinical trials and addresses blockage to abnormal cellular growth pathways with BRAFV600E BRAF inhibitors (vemurafenib, e.g.) and MEK inhibitors (trametinib, e.g.).
For this type of glioma, the MAPK/ERK pathway is activated. The new drugs target the MAPK/ERK pathway and RAS/MAPK pathway to interrupt abnormal cell growth.
Molecularly targeted drug therapy is currently in clinical trials and addresses blockage to abnormal cellular growth pathways with BRAFV600E BRAF inhibitors (vemurafenib, e.g.) and MEK inhibitors (trametinib, e.g.).
For this type of glioma, the MAPK/ERK pathway is activated. The new drugs target the MAPK/ERK pathway and RAS/MAPK pathway to interrupt abnormal cell growth.
Consider that those optic gliomas may arise sporadically as a mutation in BRAFv600E or in association with Neurofibromatosis type 1 (NF1) or Noonan Syndrome. Fortunately, the MAPK/ERK and RAS/MAPK pathways already account for NF1, Noonan Syndrome genetic alterations, and sporadic BRAFV600E mutations.
PROGNOSIS
Pediatric low-grade gliomas (PLGG) have excellent long-term survival with treatment in contrast with high-grade gliomas.
As mentioned before, Optic gliomas may arise:
sporadically as mutations in BRAFv600E or
in association with Neurofibromatosis type 1 (NF1) or Noonan Syndrome.
VON RECKLINGHAUSEN’S disease (Neurofibromatosis type 1)
These patients have a higher risk of developing benign and malignant tumors such as Malignant Peripheral nerve Sheath tumors and Leukemias.
Also, affected patients present other specific features in the eyes (iris Lisch nodules) and the skin (cafe au lait spots and freckles). However, the most distinctive feature for these patients is where prominent nerve neurofibroma tumors cover the body due to a mutation on a tumor suppressor protein called neurofibromin because of a genetic mutation in chromosome 17
In children with Neurofibromatosis type 1, there is an increased risk, up to 20%, of developing optic pathway/hypothalamic gliomas. On the other hand, in adults with these types of tumors, there is no association with Neurofibromatosis type 1
Furthermore, in patients with Von Recklinghausen’s disease, the most common site is the optic nerve, and the tumor is smaller (in contrast with patients without NF1, where the hypothalamus and optic chiasm are more frequently involved).
NOONAN SYNDROME
The link between Noonan syndrome and Pilocytic Astrocytoma's.
Noonan syndrome patients are not only at increased risk of developing hematologic malignancies such as ALL and CML, but they may develop brain tumors such as Dysembryoplastic Neuroepithelial Tumors (DNET) and low-grade astrocytoma's.
GLIOMAS OF THE OPTIC NERVE / PILOCYTIC ASTROCYTOMAS CODING DISCREPANCIES.
There was some discrepancy in the past about coding them as malignant versus nonmalignant among different official organizations.
This is what the Journal of Neuro-Ophthalmology said:
“Consensus opinion now views them as benign neoplasm, although capable of causing significant morbidity. Despite neuro-oncologic judgment of benignancy, the Surveillance, Epidemiology, and End Results (SEER) cancer registry had maintained a policy of reporting pilocytic/juvenile astrocytoma's as behavior code/3 “malignant” until December 2018 when coding of optic nerve astrocytoma's was changed to reflect World Health Organization (WHO) guidelines as nonmalignant (behavior code/1)”
Despite the Surveillance, Epidemiology, and End Results (SEER) and the WORLD Health Organization not agreeing in the past, they finally are on the same common front, and we can see this reflected in the most recent years in the Solid Tumor Rules updates.
Solid Tumor Rules 2024 Update
Note 5: Pilocytic astrocytoma/juvenile pilocytic astrocytoma:
For cases diagnosed prior to 1/1/2023, these neoplasms are reportable in North America as malignant 9421/3 for all CNS sites with the exception of the optic nerve:
WHO Classification Tumors of the Central Nervous System and IARC designate pilocytic astrocytoma as a synonym for optic glioma
When the primary site is the optic nerve and the diagnosis is either optic glioma or pilocytic astrocytoma, the behavior is non-malignant and coded 9421/1
Beginning with cases diagnosed 1/1/2023 forward, pilocytic astrocytoma/juvenile pilocytic astrocytoma are to be reported as 9421/1 for all CNS sites.
Solid Tumor Rules CNS 2024 Update
Note 6: Pilocytic astrocytoma/juvenile pilocytic astrocytoma is reportable in North America as a malignant neoplasm 9421/3.
See the Non-malignant CNS Rules when the primary site is the optic nerve and the diagnosis is either optic glioma or pilocytic astrocytoma. The behavior for these tumors is non-malignant and coded 9421/1.
IMPORTANT FOR 2023 FORWARD: Beginning 1/1/2023, all cases diagnosed with pilocytic astrocytoma/juvenile pilocytic astrocytoma and new related terminology are to be reported with behavior /1. They will no longer be collected with malignant behavior (/3). See the Non-malignant CNS Rules.
Non-Malignant CNS Solid Tumor Rules 2024 Update. P.26
At FCDS, we hope you found this article useful.
Article written by Betty Malanowski
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