Neuro-Ophthalmological Manifestations of Choroid Plexus Papilloma
Choroid plexus papillomas (CPPs) are rare, benign central nervous system (CNS) tumors arising from the choroid plexus epithelium lining the ventricles. The choroid plexus cuboidal epithelial cells are responsible for producing cerebrospinal fluid (CSF). While benign, CPPs can become symptomatic by the overproduction of CSF or blockage of CSF flow, resulting in increased intracranial pressure (ICP) and the resultant manifestations of these, which present to ophthalmologists (e.g., papilledema, visual loss, transient visual obscurations, and diplopia from cranial nerve palsies, typically abducens nerve palsy).
CPPs are rare and represent only 0.4-0.6% of all CNS tumors. They occur more commonly in children and constitute 3-4% of childhood CNS tumors. CPPs are more prevalent in children under the age of 5, with a median age of diagnosis of 3.5 years. In adults, CPPs constitute 0.5-1% of CNS tumors.
The tumors develop within the ventricular system and arise at locations where choroid plexus epithelium is present, most commonly in the atrium of the lateral ventricles in children compared to the fourth ventricle in adults. Other rare locations include the third ventricle and cerebellopontine angle (CPA). CPPs are thought to occur at the CPA due to direct extension from the foramen of Luschka or from tumor seeding along the pathway of CSF flow.
CSF is produced by the choroid plexus epithelium. Normally, CSF flows from the lateral ventricles through the interventricular foramen of Monro into the third ventricle, then through the cerebral aqueduct of Sylvius into the fourth ventricle, and into the subarachnoid space through the two lateral foramina of Luschka and the one medial foramen of Magendie. It is then drained by the arachnoid granulations into the venous sinus pathway.
Tumor cells in CPPs lead to increased secretion of CSF, eventually resulting in elevated ICP and hydrocephalus. The mass effect of the tumor itself can also result in obstruction to the normal CSF flow. Additionally, repeated microhemorrhages from the tumors can lead to arachnoid adhesions or elevated CSF protein concentration that can cause CSF flow obstruction.
Signs and Symptoms
CPPs typically present with slowly progressive neurological deficits and can grow to a significant size before the patient seeks treatment. Patients classically have symptoms of increased ICP (e.g., headache, nausea and vomiting, drowsiness, and visual disturbances including blurry vision, diplopia, and transient visual obscurations, often with change in posture). In infants, CPPs may present as an enlarging head size, bulging fontanelles, poor feeding, drowsiness, and vomiting. Papilledema may be present on exam as a manifestation of raised ICP.
Neuro-ophthalmic manifestations can vary based on tumor location. Dorsal third ventricle CPPs may manifest as a vertical gaze palsy due to compression of the posterior commissure. CPPs arising from the CPA may present with esotropia and unilateral abduction deficits due to an abducens nerve palsy. Other features of CPPs in the CPA may include ataxia, hearing loss, facial nerve palsy, or trigeminal neuralgia (due to the proximate locations of the trigeminal, facial, and vestibulocochlear nerve).
CT imaging of CPP typically demonstrates a well-defined, lobulated, isodense to hyperdense mass with enhancement. The hyperdensity is due to the presence of calcifications or microhemorrhages. Calcifications are present in 4-20% of CPP. The lobulated appearance can help differentiate CPPs from other intraventricular neoplasms.
MRI is the imaging modality of choice and classically reveals a well-defined, frond-like intraventricular lobulated mass without parenchymal invasion. MRI shows a hypointense to isointense mass on T1-weighted images, and isointense to hyperintense mass on T2-weighted images. Flow voids are commonly seen, indicating active blood flow.
Tumor biopsy is warranted to establish a definitive diagnosis of CPP. Choroid plexus tumors are classified according to the World Health Organization (WHO) 2016 classification system into CPP (grade I), atypical CPP (grade II), and carcinomas (grade III). Benign papillomas account for approximately 80% of choroid plexus tumors.
Grossly, CPPs are highly vascular, soft, pink, globular masses with irregular cauliflower-like projections. Microscopically, Grade I CPPs are well-differentiated and consist of papillae with fibrovascular cores. They are lined by cuboidal epithelium, similar to the normal choroid plexus architecture. The epithelium of CPPs is more flattened compared to normal choroid plexus. Grade I CPPs are distinguished from grade II atypical CPPs and grade III carcinomas by the lack of mitotic activity, nuclear pleomorphism, and necrosis.
Grade II (atypical) CPPs contain a mitotic index of two or more mitoses per 10 high power microscopic fields (HPF). Grade III choroid plexus carcinomas have increased mitotic activity greater than 5 mitoses per 10 HPF and other signs of malignancy such as nuclear pleomorphism, hyperchromasia, and parenchymal invasion.
Immunohistochemistry of CPPs is positive for cytokeratin, S-100, transthyretin, and vimentin. Glial Fibrillary Acidic Protein (GFAP) and Epithelial Membrane Antigen (EMA) may be focally positive in some CPPs, however is more frequent in choroid plexus carcinomas.
Prior to tumor biopsy, the location and age of the patient can facilitate the formulation of a differential diagnosis. In children, the differential for tumors located in the posterior third ventricle includes ependymomas, pineocytomas, pinealoblastomas, germ cell tumors, and astrocytomas. Common tumors in the CPA include ependymomas, schwannomas, and meningiomas. A fourth ventricle tumor differential should also include ependymomas and medulloblastomas.
Surgical resection is the treatment of choice in CPPs. Gross total resection (GTR) is generally curative and can prevent tumor recurrence and prolong survival. Many studies report 100% survival rates at 5 years after GTR. Blood loss is a major perioperative concern given the vascular nature of these tumors. In some cases, pre-operative embolization of the vascular supply (usually the choroidal artery) may be performed to minimize blood loss.
Choroid plexus carcinomas (grade III) are malignant and have a higher chance of recurrence. GTR has a favorable impact on survival, but is only achieved in less than 50% of cases. Adjuvant therapy with radiation therapy and chemotherapy may be indicated, although studies report varying success in prolonging survival and improving outcomes.
The treatment of hydrocephalus is another consideration in the treatment of CPPs. Various options include placement of an external ventricular drain (EVD) pre- or intra-operatively, placement of a ventriculoperitoneal (VP) shunt, or endoscopic third ventriculostomy. In patients presenting with acute increases in ICP, a pre-operative VP shunt followed by a definitive surgery is the preferred option. In most cases, a temporary EVD placed during surgery is sufficient to control the ICP. While GTR typically eliminates the need for ventricular shunting, some patients may require placement of permanent shunts to divert CSF.
Overall, CPP after resection has a generally good prognosis, with limited risk of recurrence, and can typically be monitored post resection. Tumor size, significance of preoperative symptoms, as well as extent of resection are all adverse prognostic factors. Neuro ophthalmic and visual outcomes postoperatively are dependent on the duration and severity of symptoms, as well as location of tumor and surgical approach.
Clinicians should be aware of the ophthalmic presentations of CPP including visual loss, TVO, diplopia (non-localizing sixth nerve palsy from elevated ICP), or papilledema. Neuroimaging studies should be performed but the diagnosis of CPP typically requires histological conformation. Gross total resection is the mainstay of treatment. Concomitant treatment of elevated ICP may be necessary to avoid permanent visual loss from papilledema.
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