Light at the End of the Tunnel - Slides

The patient underwent mini-craniotomy and brain biopsy. Intraoperative findings included diffuse leptomeningeal thickening, atrophic optic nerves and a thickened hyperemic pituitary stalk which was biopsied. Histology showed germinoma (CD117+, OCT3/4+). Pre-operative hormonal profile revealed hypopituitarism and he was also diagnosed with central diabetes insipidus. MRI whole spine did not show germinoma involvement. Ultrasound of scrotum was normal. CT scan of thorax, abdomen and pelvis showed no evidence of malignant lesion. He referred to oncology and planned for radiotherapy (CSI 24Gy/16fr + boost 21Gy/14fr), which is due to start shortly. CNS germ cell tumors (GCT) are classified as germinomas or non-germinoma germ cell tumors. Most patients are diagnosed between the age of 10-21, with a male predominance. The most common presentation of CNS GCT are diabetes insipidus, hypopituitarism and visual field defect. These tumors sometimes secrete AFP and b-HCG and finding elevated levels of these tumor marks may aide diagnosis. On MRI, germinomas are isointense or slightly hypointense on T1-weighted images, and isointense or hyperintense on T2-weighted images, and they enhance with gadolinium. They usually appear as midline mass lesions, most commonly near the pineal gland, and less frequently in the suprasellar region, basal ganglia and thalamus. Diffuse involvement is unusual, and to the best of our knowledge, there has only been one other reported case of germinoma mimicking multiple sclerosis and that case did not present with visual symptoms. Radiotherapy is the first line treatment for germinomas and the 2-year survival is better than 90% with radiotherapy alone More recently, systemic chemotherapy with reduced doses of radiation has been advocated as alternative treatment, however longer-term follow-up is required to determine if it will replace standard radiotherapy.

"Light at the end of the tunnel?" Noel CHAN, Carmen CHAN Tak Lap POON, Joyce CHOW Wai Lun POON, Sherman LO Wing Hung LAU, Ka Hong AU Financial disclosures None History of Present Illness • 24-year-old Chinese man presented with progressive blurring of vision for 1 year - Right eye (Feb 2017) → Left eye (May 2017) - No acute loss - Seen and managed in private and other eye units • Subjective ↓sweating over body (neck downwards) • Right sided headache since young, not worse in morning/ when supine Medical History • Past medical history • Past ocular history • Medications • Family history • Allergies • Social history - Migraine - Nil - Nil - Moderate myopia - Non contributory - Graduate student - Denied alcohol/ tobacco/ illicit drug use Examination at presentation OD OS BCVA 20/100 20/30 Ishihara Failed test plate 3/14 Pupils APD+ IOP (mmHg) 15 15 Motility Normal Normal Anterior segment NAD NAD Discs Pallor, CDR 0.9 Pallor, CDR 0.7 Vitreous, maculae, retina Normal Normal Other ocular examinations • Visual fields (Humphrey 30-2) OS tunnel vision & OD general depression MRI brain & orbits Radiology comments: • Absence of optic nerve abnormalities MRI brain & orbits - Abnormal T2 hyperintensities at the genu of corpus callosum and the adjacent white matter, which were highly suggestive of demyelinating disease Workup • • • • • • CRP (normal) ANA (-) RF (-) Vitamin B12(normal) Folate (normal) Anti-Aquaporin 4 Ab (-) • Lumbar puncture: - WCC 13 (99% lymphocytes) - Oligoclonal bands (+) Live Content Slide When playing as a slideshow, this slide will display live content Poll: How would you manage the patient at this point? Progress • Multiple sclerosis was suspected • Intravenous steroid therapy was considered but withheld in view of uncertain diagnosis and absence of acute deterioration • Patient was reviewed 2 months later in our clinic: - BCVA dropped to 20/400 (OD) & 20/100 (OS) • MRI was repeated and films were reviewed MRI brain & orbits MRI A diagnostic procedure was performed • Craniotomy and brain biopsy were performed • Intraoperative findings: - diffuse leptomeningeal thickening - atrophic optic nerves - a thickened hyperemic pituitary stalk which was biopsied 1 mm biopsy specimen showing an aggregate of tiny pieces of crushed lymphoid cell-rich stromal fragments (arrows) being admixed with blood clots. CD117 OCT3/4 Diagnosis • CNS Germinoma (non-secreting) CNS Germ Cell Tumors • Classification: Germinomas or non-germinoma germ cell tumor • Prevalence: Age 10-21, M>F • Most frequent: pineal gland Less frequent: suprasellar region, basal ganglia, thalamus • Common presentations: - Diabetes insipidus - Hypopituitarism - Visual field defect CNS Germ Cell Tumors • Potential positive findings: - Lab: Elevated levels of AFP & b-HCG - Imaging: T1W iso/hypointense , T2W iso/hyperintense midline lesions, enhance with gadolinium • Treatment: - First line: Radiotherapy (2-year survival: >90%) - Alternative: systemic chemotherapy with reduced doses of radiation Progress of the patient • Pre-operative hormonal profile: - hypopituitarism - central diabetes insipidus • MRI whole spine: no germinoma involvement • CT scan of thorax, abdomen and pelvis: no evidence of malignant lesion • Ultrasound of scrotum: normal • Referred to Oncology for radiotherapy Progress - 2 months post RT OD VA: 1/60 OS VA: 0.1 Summary • This patient's MRI was reported as highly suggestive of demyelinating disease and the CSF oligoclonal bands were positive, pointing to the diagnosis of multiple sclerosis • However careful review of the MRI revealed atypical involvement of the hypothalamus and pituitary stalk, which led to the diagnostic brain biopsy and diagnosis of CNS germinoma. Thank you!