Suprasellar pure germinoma mimicking low-grade glioma on neuroimaging

Description

A patient in early adolescence presented with a 1-year history of polyuria/polydipsia and a 1-month history of progressive visual complaints. Neurological examination was significant for bilateral pallor of the optic nerves and bitemporal hemianopsia. MRI revealed a contrast-enhancing suprasellar tumour involving the optic pathway with a radiographical appearance consistent with suprasellar low-grade glioma versus a germ cell tumour (figure 1). MRI of the spine was negative (not shown). The patient had negative cerebrospinal fluid and serum germ cell markers beta-human chorionic gonadotropin and alpha-fetoprotein, and a biopsy was recommended by the treating neurooncology team, however, family initially declined. Given the progressive visual complaints in the absence of a histological diagnosis of a tumour with neuroimaging features suggestive of a potential hypothalamic chiasmatic glioma, a short course of bevacizumab was initiated without radiographical or clinical response after two cycles and the family subsequently consented to a biopsy that demonstrated areas of germ cells with polymorphous chronic inflammatory infiltrate consistent with a histological diagnosis of pure germinoma (figure 2). The patient completed four cycles of chemotherapy with carboplatin/etoposide and focal proton radiation therapy with complete response and remains in remission 5 years post diagnosis. Unfortunately, the significant visual dysfunction and associated endocrinopathy did not improve.

Figure 1.

Neuroimaging features of suprasellar germinoma at diagnosis and post therapy with bevacizumab and chemoradiation. T1-weighted MRI (A) reveals a suprasellar tumour (arrow) with enlargement of prechiasmatic optic nerves and chiasm without areas of susceptibility artefact on SWI sequence (arrow) (B). The suprasellar tumour reveals homogeneous enhancement on post-T1 gadolinium weighted sequences (arrows) that highlights the optic nerve and chiasmatic involvement (C, D). Following two cycles of bevacizumab, the suprasellar tumour did not demonstrate a treatment response on post-T1 gadolinium weighted sequences (arrows) (E, F). MRI post-treatment with standard germ cell chemotherapy and radiation therapy reveals complete response on post-T1 gadolinium and fluid-attenuated inversion recovery sequences (arrows) (G, H).

Figure 2.

Histological features of suprasellar germinoma. (A) H&E stained suprasellar biopsy specimens reveals areas of germ cells with polymorphous chronic inflammatory infiltrate (200×). (B) On higher power magnification (400×), large germ cells with prominent nucleoli are seen with associated inflammatory infiltrate. Immunohistochemistry staining revealed positivity for germ cell markers OCT3/4 (C) and cKIT (D) consistent with a histological diagnosis of germinoma.

Germinoma is a rare type of primary brain tumour more commonly occurring in children and adolescents and is associated with a cure rate of more than 90% following therapy.¹ Intracranial germinomas manifest with hypothalamic pituitary axis dysfunction and may present with prolonged symptomatology leading to delays in diagnosis.² Germinomas can involve the optic nerve and chiasm presenting with progressive visual field disturbance.^2–5 Genetically, they are characterised by global demethylation, chromosomal instability and mutational deactivation of Kit, Ras/Raf/Erk and Akt pathways.⁶ Typical MRI features include either homogeneous or heterogeneous contrast enhancement associated with reduced diffusivity on diffusion-weighted and apparent diffusion coefficient sequences.⁷ Cases of intracranial germ cell tumours mimicking low-grade gliomas on neuroimaging and specifically when optic pathways are involved have been reported obviating the need for biopsy to establish confirmatory diagnosis.4 5 8–10 Bevacizumab, a humanised monoclonal antibody against vascular endothelial growth factor A, has demonstrated radiographical and clinical response in paediatric low-grade gliomas including those involving the suprasellar region,^11–13 even in cases without histological confirmation of low-grade glioma.¹⁴ Although we are not aware of the efficacy of bevacizumab in intracranial germinoma, the lack of response would be somewhat atypical for a low-grade glioma^11–14 and led to the consensus of biopsy and eventual diagnosis. Given that bevacizumab has been associated with improvement in visual symptoms in cases of suprasellar low-grade glioma even after a few doses,¹³ its use in the upfront setting in our patient with progressive visual loss seemed reasonable in the absence of a biopsy as has been previously reported.¹⁴ We hypothesise that the lack of radiographical response to bevacizumab may be due to the uniqueness of the germ cell tumour vascular microenvironment that may prohibit antibody penetration or reactivity and worthy of future analysis in similar patients with non-low-grade glial suprasellar tumours.

In summary, we report a case of an intracranial germinoma mimicking suprasellar low-grade glioma on neuroimaging with negative germ cell markers and non-responsive to upfront bevacizumab where biopsy led to eventual diagnosis of germinoma, thus highlighting the importance of biopsy as part of the definitive diagnosis of intracranial pure germinoma.

Learning points.

• Germinoma can mimic suprasellar low-grade glioma on neuroimaging when optic pathways are involved and may be associated with progressive visual field deficits.

• Suprasellar tumours cannot be easily differentiated by MRI features alone and often warrant biopsy for confirmatory diagnosis.

• Biopsy is the definitive way to diagnose a pure germinoma in the absence of elevated tumour markers.

Ethics statements

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Consent obtained from parent(s)/guardian(s).