Neuro-Ophthalmic Manifestations of Suprasellar Pilomyxoid Astrocytoma

ABSTRACT

This case report highlights a case of suprasellar pilomyxoid astrocytoma (PMA) presenting with the diencephalic syndrome (DS) that was initially diagnosed as pilocytic astrocytoma (PA) but had subsequent histopathological re-classification as PMA. A 14-year-old male treated with four subtotal resections for PMA and post-operative radiation therapy presented with bilateral visual loss. The patient was initially diagnosed with PA until the fourth craniotomy was performed and the histopathology was revised from PA to PMA. The patient’s ocular examination was remarkable for right cranial nerve III and VI nerve palsy and bilateral optic atrophy. This unique case demonstrated the behavior of a rare and aggressive variant of PA. Awareness of this glioma may help ophthalmologists distinguish PMA from PA. Due to the many histopathological similarities, previously diagnosed cases of PA may be the more aggressive variant, PMA. As PMA progresses, it affects the patient’s vision; therefore, an ophthalmological evaluation should be included to monitor disease progression and vision loss.

Introduction

PMA is a rare aggressive variant of PA and is associated with shorter progression-free-survival and reduced overall survival compared with typical PA.¹ PMA tends to affect infants and younger children and has a higher probability of local recurrence and cerebrospinal fluid infiltration than PA.^2,3 Although there are many histopathological similarities between the two disorders, up to 10% of previously labeled PA have been retroactively reclassified as PMA after careful histopathology reexamination.³ PMA can involve the hypothalamic-chiasmatic region and thus can present to neuro-ophthalmology clinic.

Case report

A 12 month-old male patient developed unexplained abdominal pain and gastrointestinal (GI) symptoms including failure to thrive, recurrent nausea, and vomiting. During the patient’s stay in the hospital, he gained weight, but no structural GI diagnosis was made. Cranial computed tomography (CT) and magnetic resonance imaging (MRI) showed a hypothalamic mass.

Subtotal neurosurgical resection was performed and the final histopathology after this initial surgery was PA. The patient was stable until the age of 5 years old (2014) when a radiographic recurrence was noted on serial cranial MRI. A second and then a third subtotal resection with debulking and adjuvant radiation therapy was performed over the next two years.

In 2018, he experienced blurred vision, nausea, and vomiting. Cranial MRI demonstrated a large heterogeneous mass with compression of the optic chiasm. His exam at that time showed bilateral optic atrophy and a right third nerve palsy. A fourth craniotomy was performed, and the histopathology was revised from PA to PMA.

The patient presented to the neuro ophthalmology clinic at 14-years-old with bilateral vision loss to establish pretreatment baseline prior to gamma knife radiation therapy. At the time of his visit, he had undergone a total of four surgical subtotal resections of tumor and post-operative radiation therapy. Past surgical, family, and social histories were otherwise noncontributory. His medications included Cephalexin, Trametinib, Levetiracetam, Metformin, and levothyroxine sodium capsules. Cranial MRI, Figure 1, displayed a stable, 10 mm x 8 mm, residual tumor in the hypothalamic region and postoperative changes. The optic chiasm and hypothalamic/infundibular recess appear distorted from prior treatment.

Figure 1.

Post temporal lobectomy axial T1-weighted MRI (a), axial T2-weighted MRI (b), sagittal FLAIR MRI (c), coronal T1-weighted MRI (d).

On neuro-ophthalmic examination, his visual acuity was hand motions in the right eye (OD) and 20/80 in the left eye (OS). The pupil was dilated and nonreactive OD at 7 mm and 4 mm and reactive OS. There was a right relative afferent pupillary defect (reverse testing). Automated perimetry (Humphrey 24–2), Figure 2, showed an inferior arcuate defect OS and was diffuse depression OD. He had a right cranial nerve III nerve palsy on motility examination but the left eye moved normally. The right third nerve palsy was attributed to the right cavernous sinus and right midbrain compression from the previous treatment effect. The fundus exam showed bilateral optic atrophy OD > OS. OCT of retinal nerve fiber layer, Figure 3, demonstrated bilateral thinning of the optic nerves.

Figure 2.

Humphrey 24–2 automated perimetry results.

Figure 3.

OCT RNFL analysis.

Discussion

PMA and PA, while sharing several characteristics, possess unique clinical, histological, and radiological features that differentiate these gliomas. PA is the most common brain tumor among pediatric patients and considered a relatively benign low-grade glioma that rarely exhibits an aggressive course.² PA is frequently located in the cerebellum but is also found in the supratentorial compartment, optic pathway, and hypothalamus.⁴ In contrast, PMA commonly inhabits the hypothalamic/chiasmatic region and displays a more aggressive behavior with a lower overall survival than PA.^1,2 One study reported a 1-year progression-free survival (PFS) rate of 38.7% for PMA, compared to 69.2% PA.⁵ PMA also occurs in younger patients compared to PA with a mean age of diagnosis of 18 and 58 months, respectively.² Histologically, PA displays Rosenthal fibers with a eosinophilic granular bodies, while PMA lacks Rosenthal fibers and has a rich myxoid background.^1,2 Radiologically, PMA tenda to have solid components rather than the mixed solid and cystic components typically found in PA.³ A definitive diagnosis of PMA usually requires a biopsy and histopathological examination, but the distinct radiologic features of these two tumors can be used to aid diagnosis.

Proper ophthalmological evaluation can identify early visual defects as the patient ages. One study found that 15.2% of children previously diagnosed with a primary brain tumor had an unrecognized visual field defect that were later discovered upon neuro-ophthalmological examination.⁶ Early recognition of rapid changes in the visual fields can aid in diagnosis of more aggressive tumors such as PMA, modify treatment plans, and prevent irreversible visual loss. Secondary amblyopia induced from tumor progression or treatment needs to be addressed to preserve and restore proper vision. Treatment such as patching or vision exercises can improve visual outcomes and should be implemented early for optimal treatment.

The specific ophthalmic findings for PMA will present similar to other optic pathway gliomas. Suprasellar PMA can produce decreased vision, optic atrophy, nystagmus, proptosis, and strabismus.¹ The most common ophthalmic presentation of PMA is visual loss and optic atrophy.¹ PMA has been associated with NF1, although to a lesser extent than PA, therefore additional skin and eye findings may be present including iris lisch nodules and café au lait spots.³ Due to the aggressive nature of PMA, patients may not initially present with ophthalmological symptoms but will manifest with tumor progression.

Of six case reports of PMA presenting as DS in the literature, four had ophthalmic signs upon presentation and two lacked any information regarding ophthalmic findings. These findings show similar results to retrospective studies that investigate the ophthalmic presentation of PMA. One retrospective report found that while 47% of PMA cases present with ophthalmic complaints, all examined patients had ophthalmic signs.¹ None of the cases reported in the literature described a case of PA that was revised to PMA.

Conclusion

Although both PA and PMA are classified as World Health Organization (WHO) grade I tumors, they represent distinct tumors with varying clinical characteristics and outcomes. PMA exhibits a more aggressive behavior in comparison to PA, making it important for neuro-ophthalmologists to familiarize themselves with the distinguishing features of PMA. PMA will typically reside in the hypothalamic/chiasmatic axis, have more solid components radiographically than PA, affect patients predominantly between 10 and 18 months of age, and display a more aggressive behavior than PA.^2,7 Case studies and retrospective reports have demonstrated that visual impairment is common in PMA patients and may worsen despite treatment. Including ophthalmological evaluation as part of the initial and longitudinal treatment plan is essential to monitor disease progression and reduce future vision loss.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Patient consent

The patient consented in writing to the publication of the case