Pineal Germinoma

Pineal germinoma is a germ cell tumor of the pineal region and the most common germ cell tumor at that site. Pineal region tumors are about 1% of adult and 3 to 8% of childhood brain tumors, and are more frequent in East Asia. Peak age is 10 to 20 years, with a male to female ratio of about 3 to 1 for pineal tumors.

Histology: large germ cells with prominent nucleoli and a lymphocytic infiltrate, positive for OCT4, PLAP and CD117. Pure germinoma produces little or no AFP, and β-hCG is only mildly raised (under 50 IU/L) from syncytiotrophoblastic cells. A raised AFP or high β-hCG indicates a non-germinomatous germ cell tumor, which needs different treatment. Bifocal tumors (pineal and suprasellar) occur in about 10% and cerebrospinal fluid dissemination in about 10%.

The tumor is highly radiosensitive and chemosensitive, with 5-year survival over 90%. Complications: obstructive hydrocephalus, Parinaud syndrome, diabetes insipidus and hypopituitarism (bifocal disease), precocious puberty, and neurocognitive effects of radiotherapy.

• Headache, vomiting and papilledema from hydrocephalus
• Parinaud syndrome: upgaze palsy, convergence-retraction nystagmus, light-near dissociation and eyelid retraction
• Diplopia, ataxia and memory impairment
• Polyuria and polydipsia, or visual field loss in bifocal disease
• Red flags: reduced consciousness, rapid visual loss and spinal symptoms

1. MRI brain and whole spine with gadolinium: a homogeneously enhancing pineal mass engulfing the pineal calcification, with hydrocephalus. Spinal deposits indicate dissemination.
2. Serum and CSF AFP and β-hCG: AFP normal and β-hCG under 50 IU/L in pure germinoma. AFP over 10 ng/mL or β-hCG over 100 IU/L suggests a secreting non-germinomatous tumor.
3. Biopsy (endoscopic, during third ventriculostomy) when markers are not diagnostic.
4. CSF cytology after surgery when the pressure is safe.
5. Pituitary and visual assessment in bifocal disease.

Differentials: pineocytoma, pineoblastoma, non-germinomatous germ cell tumor, pineal cyst, glioma and meningioma.

• Hydrocephalus: endoscopic third ventriculostomy with simultaneous biopsy. Avoid a peritoneal shunt, which risks seeding.
• Chemotherapy then radiotherapy: carboplatin 600 mg/m2 IV day 1 and etoposide 100 mg/m2 IV days 1 to 3, every 3 weeks for 4 cycles. Give ondansetron 0.15 mg/kg IV (maximum 8 mg) and filgrastim 5 micrograms/kg SC daily for febrile neutropenia. Monitor blood count, creatinine and hearing.
• Radiotherapy for localized disease: whole ventricular irradiation 24 Gy in 15 fractions of 1.6 Gy with a boost to 40 Gy at the tumor. After complete response to chemotherapy, reduce to 18 to 24 Gy and omit the boost.
• Disseminated disease: craniospinal irradiation 24 to 30 Gy in fractions of 1.5 to 1.8 Gy with a boost to 40 to 45 Gy at bulky sites.
• Relapse: salvage chemotherapy followed by high-dose thiotepa-based therapy with autologous stem cell rescue.
• Supportive care: dexamethasone 0.1 to 0.25 mg/kg orally or IV every 6 hours (maximum 4 mg a dose) for edema, with desmopressin 100 to 200 micrograms orally at night for diabetes insipidus, and hormone replacement as needed.

Follow-up: MRI every 3 months for 2 years, then every 6 months to year 5. Endocrine, neurocognitive and hearing surveillance. Counsel on fertility, and offer sperm banking before chemotherapy.