Choroid Plexus Carcinoma

Choroid plexus carcinoma is a malignant (grade 3) epithelial tumor of the choroid plexus. It makes up about 20 to 40% of choroid plexus tumors. Median age is 2 to 3 years, with 70% under 5 years, and the lateral ventricle is the usual site.

Li-Fraumeni syndrome (germline TP53 mutation) is present in up to 50% of cases, so every patient needs genetic testing. TP53-mutant tumors have a worse outlook, with 5-year survival of about 20 to 30%, compared with 40 to 70% overall. Cerebrospinal fluid dissemination occurs in about 30 to 40% at diagnosis. Complications: hydrocephalus, hemorrhage, drop metastases, second malignancy after radiotherapy in TP53 carriers, and relapse.

• Rapidly progressive raised pressure: vomiting, lethargy and headache
• Infants: macrocephaly, bulging fontanelle and irritability
• Seizures and focal deficit from brain invasion
• Red flags: acute hemorrhage, falling consciousness and spinal symptoms

1. MRI brain and whole spine with gadolinium: a large heterogeneous intraventricular mass with brain invasion, necrosis, hemorrhage, peritumoral edema and irregular enhancement.
2. Histology: loss of the papillary architecture, 5 or more mitoses in 10 high-power fields, necrosis, nuclear pleomorphism, and retained INI1 (to exclude atypical teratoid rhabdoid tumor).
3. Germline and tumor TP53 sequencing in every patient.
4. CSF cytology after surgery when safe.

Differentials: choroid plexus papilloma, atypical papilloma, atypical teratoid rhabdoid tumor, ependymoma, medulloblastoma, metastatic carcinoma in adults, glioma.

• Surgery: maximal safe resection (the strongest prognostic factor), with preoperative embolization or neoadjuvant chemotherapy to reduce vascularity. Give tranexamic acid 10 mg/kg IV (maximum 1 g) before incision, and have blood ready.
• Hydrocephalus: external ventricular drain, then third ventriculostomy or shunt.
• Adjuvant chemotherapy for all patients, in alternating cycles every 3 weeks for 6 to 8 cycles: carboplatin 500 mg/m2 IV day 1 with etoposide 100 mg/m2 IV days 1 to 3, alternating with vincristine 1.5 mg/m2 IV day 1 and cyclophosphamide 1.5 g/m2 IV on days 1 and 2 with mesna 60% of the cyclophosphamide dose IV in divided doses. Monitor blood count, creatinine, magnesium and hearing. Give filgrastim 5 micrograms/kg SC daily for neutropenia, and ondansetron 0.15 mg/kg IV (maximum 8 mg) before chemotherapy.
• Radiotherapy for children over 3 years: focal 54 Gy in 30 fractions for localized disease, or craniospinal 35.2 Gy with a boost for disseminated disease. Avoid or minimize radiotherapy in TP53 carriers because of the risk of second tumors.
• Relapse: re-resection and high-dose chemotherapy with stem cell rescue (thiotepa 300 mg/m2 IV daily for 3 days), or trial enrolment.
• Prophylaxis: trimethoprim-sulfamethoxazole (trimethoprim 150 mg/m2 a day in 2 divided doses on 3 days each week) during chemotherapy.
• Li-Fraumeni surveillance: annual whole-body and brain MRI, with avoidance of unnecessary ionizing radiation, and genetic counseling for the family.

Follow-up: MRI brain and spine every 3 months for 2 years, then every 6 months to year 5. Counsel the family candidly on prognosis.