Unilateral malignant optic glioma following glioblastoma multiforme in the young: a case report and literature review

Glioblastoma multiforme (GBM) is the most frequent and lethal type of malignant primary brain tumor in humans, and it has the poorest prognosis with a median survival of generally < 1 year from the time of diagnosis [1‐3]. GBM is rarely observed in children, which comprising only 5–10% of childhood intracranial neoplasms [4].

Malignant optic glioma is rare and was first defined by Hoyt et al. in 1973 [5]. It is a high grade astrocytoma, presenting as an anaplastic astrocytoma (AA) (WHO grade III) or glioblastoma (WHO grade IV) [6]. Patients frequently have bilateral visual loss within a few weeks and die within 1–2 years [7, 8]. Here, we report a young man presenting with unilateral malignant optic glioma after having GBM for >5 years.

The 21-year old man was diagnosed with brain GBM at 13 years of age (Fig. 2a, b). After tumor extirpation, he regularly underwent temozolomide chemotherapy and radiotherapy (66.6 Gy) from February 2007 to April 2007 and no brain GBM recurrence was shown at brain MRI during this round of treatment. However, progressing in cystic size was noted during regular clinics visit after previous treatment, radical resection of tumor was done in August 2007. Then he maintained with Temozolomide treatment for 8 more years (111 cycles). In August 2015, he visited our clinic complaining of an intermittent shadow in his vision when changing positions (duration 1–2 min/attack, >5 times/day) for several years. The best-corrected visual acuity (BCVA) was 20/20 in both eyes. Ocular examinations revealed a right relative afferent pupillary defect (RAPD) and optic disc swelling (OD; Fig. 1a). Visual field (VF) testing with a Humphrey automated perimeter (Swedish Interactive Threshold Algorithm, SITA) revealed an enlarged blind spot (OD; Fig. 1c). Optical coherence tomography showed severe optic disc head swelling and normal central macular thickness. The patient received intravenous methylprednisolone for 3 days for suspected optic neuritis (OD). Orbital MRI revealed a pre-chiasmatic enhanced fusiform optic nerve tumor on a T1- weighted contrast image, typical of optic nerve glioma (Modified Dodge classification : 1aR) [9] (Fig. 2e, f). No tumor recurrence was found in brain MRI (Fig. 2d). Cerebrospinal fluid (CSF) examination revealed no definite malignant cells. Based on the diagnosis of an optic nerve tumor, likely secondary to GBM, aggressive chemotherapy (temozolomide 380 mg) was administered. Three months later, BCVA (OD) deteriorated to 20/30 and the VF was severely constricted with only central area preservation (Fig. 1d). A follow-up orbital MRI showed progressive changes in the right optic nerve lesion involving the chiasm on a T1- weighted image (Modified Dodge classification : 2cR) [9] (Fig. 2h, i). One month later, BCVA (OD) worsened to 2/200. Histopathology from a right optic nerve biopsy revealed glioblastoma. One month after the biopsy, the patient received combined concurrent chemoradiotherapy (CCRT) with temozolomide (140 mg/day) and irradiation of the involved field (60 Gy, 30 times). Afterwards, a new regimen of chemotherapy was administered (Bevacizumab) and he reported no light perception (OD). The complete clinical course is presented as time table (Table 1).

However, at 11 months after symptom onset, brain MRI showed a right optic nerve tumor extending to the optic chiasm with progression in size (Modified Dodge classification : 2b R/L) [9] (Fig. 2k, l). He underwent a right optic nerve tumor resection.

One year after symptom onset, BCVA and VF were within the normal range in the left eye (oculus sinister, OS) and no recurrence or metastasis was noted in the latest follow-up brain MRI.

GBM is a highly malignant brain tumor with a poor prognosis. GBM constitutes approximately 17 and 6.5% of intracranial neoplasms in adult and pediatric populations, respectively [10, 11].

Currently, standard care to improve GBM patient survival begins with surgical removal followed by radiation and chemotherapy [2]. Despite optimal treatment, most patients die of the disease, and the median overall survival time is 12–15 months [1, 12]. The main parameters associated with long-term survival are younger age (<40 years), good performance status, and the ability to undergo gross total resection, followed by radiotherapy and chemotherapy [2, 10, 13]. GBM can easily metastasize within the neuroaxis (i.e., the meninges or spinal cord) via the CSF occurring in approximately 20% of GBM patients [14]. GBM metastases outside the central nervous system are rare [15], but may be found in the extraocular muscles, limbus, or orbit [16, 17]. Systemic chemotherapy is the only treatment that considerably prolongs overall survival times [12], which seem not to differ regardless of GBM developing extracranial metastasis.

The most common tumor of the optic nerve is optic nerve glioma, which represents approximately 66% of all primary optic nerve tumors. Approximately 90% of optic gliomas occur in children and most cases are relatively benign [18]. Malignant optic gliomas are rare, and mostly present in middle aged men [19]. From 1900 to 2015, only 22 cases of pathology proven optic nerve glioblastomas were recorded among 66 cases of primary malignant optic gliomas [7, 8]. At onset, 70% patients with malignant optic nerve gliomas present with symptoms of acute unilateral visual loss, spreading rapidly over the chiasm and leading to total blindness typically within 3 months [8].

Neuroradiologic findings are unspecific and typically described as contrast enhancement and thickening of the optic nerve, chiasm, or tract, with lesions having hypo- to iso-intensity on T1-weighted images [20]. Biopsies continue to be necessary to confirm a diagnosis [7].

The current standard therapy consists of surgical resection or biopsy as feasible, followed by radiotherapy and/or temozolomide chemotherapy for high grade astrocytomas [7, 21]. The prognosis of a malignant optic glioma is fatal and most patients die within 1 year [7, 8].

Our case was challenging; diagnosis was difficult before biopsy because the optic nerve tumor appeared 7 years after brain GBM and visual function was initially normal. In addition, the complications of radiotherapy were a concern. The relationship between delayed radiotherapy and the progression and extension of the optic nerve tumor was unclear. Fortunately, BCVA and VF in the fellow eye remained unchanged despite the chiasm becoming involved 1 year after the symptom onset. Compared with previous reports, the progression of the optic malignant tumor was slower and the prognosis was better.

In summary, malignant optic tumors may appear >5 years after brain GBM. Regular ophthalmic examinations and brain MRIs are recommended for early diagnosis. Additional studies should evaluate the role and optimal timing of early adjuvant radiotherapy before visual function decreases. Young age, good health, and the ability to undergo CCRT can palliate the clinical course and preserve visual function in the fellow eye.