28/07/2025
Optic Pathway Glioma (OPG)
OPG is the most common CNS tumor in the NF1, it typically occurs in the 1st 2decades, with a peak incidence around 4–5 years. The incidence ranges from 5%–30% to 70% of cases, the incidence of symptomatic patients is lower.
OPG usually unilateral (40%–50%) or bilateral (20%), with possible extension to the posterior optic pathways.
OPG occurring in NF1 patients is considered a separate entity from isolated OPG, with different clinical findings, prognosis, and imaging features.
The clinical course is extremely variable. OPGs frequently are asymptomatic and nonprogressive (especially if limited to the optic nerves), but may enlarge rapidly, leading to visual impairment and .
Spontaneous regression can occurs.
Around 30% of NF1-related OPGs are symptomatic at presentation, whereas non-NF patients with OPG usually elicit medical attention because of either visual or nonvisual symptoms. Smaller tumor size and relative sparing of the hypothalamus might account for the milder clinical picture. Furthermore, visual disturbances may be hindered by young patient age.
Involvement of optic tracts and radiations is usually associated with more aggressive courses and increased risk of hypothalamic dysfunction, precocious puberty related to compression and .
OPGs occurring in NF1 patients remain stable in around 50% of cases, compared with only 5% of non-NF cases.
🧠💯Neuropathological findings of OPG
Most OPGs are benign, slow growing, low-grade pilocytic astrocytomas. Although these tumors are benign, vascularity may occasionally be prominent, with a slow tendency to infiltrate the adjacent nervous tissue along perivascular spaces.
OPGs are usually fusiform, intradural masses that
stretch, rather than disrupt, the overlying meninges. One or both nerves may be involved.
Macroscopically, it may be difficult to separate tumor from normal nerve at the margins of the lesion. Histologically, neoplastic glial cells may not be distinguishable from reactive gliosis in some areas.
2 architectural forms of OPG have been described, depending on whether subarachnoid spread is present.
1️⃣The 1st type is characterized by a diffuse expansion of the optic nerve without subarachnoid tumor.
2️⃣The 2nd type, characterized by predominant infiltration of the subarachnoid space, is associated with extensive thickening of the perioptic meninges, called “arachnoidal hyperplasia” or “arachnoidal gliomatosis”.
On CT, enlargement of the optic nerve is recognizable. Bone algorithm reveals enlargement of the optic canals. MRI is the best imaging modality for assessing both the intra- and extracranial portion of these lesions.
Signal intensity is variable on both T1- and T2, as well as the degree of enhancement.
T1 show distortion of the normal morphology and enlargement of the affected optic nerves. In the presence of arachnoidal hyperplasia, the relative hypointensity of the orbital portion of OPGs may correlate with the pathological finding of peritumoral arachnoidal hyperplasia and fibrocollagenous reactive changes in association with neoplastic tissue. Contrast-enhanced MRI detects arachnoidal hyperplasia as a thick rim of meningeal surrounding an abnormally enlarged optic .
Chiasmatic and retrochiasmatic involvement is usually associated with abrupt signal change to moderate or strong T2 hyperintensity, variably considered the result of edema, demyelination, , Wallerian degeneration, atypical glial proliferation, and true neoplastic extension. In these cases, MRS can be useful to discriminate the true extent of tumor from nontumoral signal changes. Contrast enhancement is highly variable in this location. It has been reported in around 60% of cases, and may be striking when the lesion involves the posterior optic pathways. In cases of diffuse involvement of the optic pathways, both signal intensity and enhancement pattern may differ in individual cases, and even within different portions of the same tumor.
NF-related OPGs are small neoplasms that only rarely show cystic-necrotic components; they involve preferentially the optic nerve, with preservation of the original shape of the optic pathway. Conversely, isolated OPGs often involve primarily the and optic chiasm with possible extension to adjacent structures; they usually are larger masses showing necrotic-cystic components.
Spontaneous regression of OPGs has been reported in children with NF1, but also in non-NF1 cases. However, since spontaneous involution occurs more frequently in NF1 cases, this behavior has been related to the NF1-gene activity as tumor suppressor. Alternatively, it has been hypothesized that so-called OPGs in NF1 are dysplastic, rather than neoplastic, lesions. Alternate periods of involution and progression have also been described.
Classification
The classification divides these tumors into just three groups based on anatomical localization:
1. type A: optic nerves only
2. type B: chiasm involved (with or without optic nerve involvement)
3. type C: hypothalamic involvement and/or other adjacent structures
A modification of the Dodge classification has been proposed which further subdivides each stage.
1. site 1 (equivalent to type A)
1a: single optic nerve
1b: bilateral optic nerves
1c: cisternal segment (prechiasmatic)
2. site 2 (equivalent to type B)
2a: central chiasmatic
2b: asymmetric chiasmatic
3. site 3 or 4 (equivalent to type C)
3: optic tract involvement
3b: asymmetric optic tract involvement
4: diffuse posterior tracts
4b: asymmetric posterior tracts
Additionally, modifiers can be added:
H + or - : hypothalamic involvement
LM + or - : leptomeningeal dissemination
NF1 + or - : in the context of neurofibromatosis type 1
Management
OPGs can be managed with surgery, chemotherapy, Targeted therapy radiotherapy alone, or with combinations of these treatment modalities.
