Neuro-ophthalmological findings of choroid plexus papilloma

Key Points at a Glance

Highlights of This Disease

• Choroid plexus papilloma (CPP) is a rare benign intraventricular tumor arising from the choroid plexus epithelium, accounting for 0.4–0.6% of all CNS tumors.
• Excessive cerebrospinal fluid production or obstruction of CSF pathways leads to hydrocephalus and increased intracranial pressure, presenting neuro-ophthalmologic findings such as papilledema, abducens nerve palsy, transient visual obscurations, and diplopia.
• In children, it commonly occurs in the trigone of the lateral ventricle; in adults, in the fourth ventricle. Neuro-ophthalmologic findings vary depending on tumor location.
• MRI is the first-choice imaging modality, and definitive diagnosis requires histopathological examination of a tumor biopsy.
• Gross total resection (GTR) is the first-line treatment, and the 5-year survival rate after GTR is reported to be 100%.
• If intracranial pressure decreases early, papilledema improves rapidly, but if treatment is delayed, visual dysfunction becomes irreversible.

1. Neuro-ophthalmologic findings of choroid plexus papilloma

Choroid plexus papilloma (CPP) is a rare benign central nervous system (CNS) tumor arising from the choroid plexus epithelium lining the ventricles. The cuboidal epithelial cells of the choroid plexus are responsible for cerebrospinal fluid (CSF) production, and CPP causes increased intracranial pressure (ICP) due to CSF overproduction or obstruction of CSF pathways. This leads to neuro-ophthalmologic findings such as papilledema, visual impairment, transient visual obscurations (TVO), and diplopia due to abducens nerve palsy, which may prompt an ophthalmology consultation.

Epidemiology

CPP accounts for only 0.4–0.6% of all CNS tumors¹⁾. It is more common in children, constituting 2–6% of pediatric CNS tumors¹⁾. It typically occurs before age 5, with a median age at diagnosis of 3.5 years. In adults, it accounts for 0.5–1% of CNS tumors. The male-to-female ratio is 1.6:1, with a slight male predominance¹⁾.

The predilection site of the tumor varies by age. In adults, it is most common in the fourth ventricle, whereas in children, it most frequently occurs in the atrium of the lateral ventricles¹⁾. Other rare sites include the third ventricle and the cerebellopontine angle (CPA).

Choroid plexus tumors are classified by the WHO as grade I (CPP), grade II (atypical CPP), and grade III (choroid plexus carcinoma)²⁾. Benign papillomas account for about 80% of choroid plexus tumors.

Q How does choroid plexus papilloma differ between children and adults?

A

In children, it commonly occurs in the atrium of the lateral ventricle and is often discovered due to head enlargement or bulging fontanelles. In adults, it commonly occurs in the fourth ventricle and tends to present with symptoms of increased intracranial pressure (headache, vomiting, papilledema)¹⁾. It accounts for 2–6% of pediatric CNS tumors, whereas in adults, the frequency is lower at 0.5–1%.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

CPP presents with slowly progressive neurological deficits, and symptoms may become apparent only after the tumor has grown to a considerable size.

• Headache: The most common symptom associated with increased intracranial pressure.
• Nausea and vomiting: One of the classic symptoms of increased intracranial pressure.
• Blurred vision: Occurs due to edema of the optic disc.
• Transient visual obscurations (TVO): Perceived as a decrease in vision in both eyes lasting a few seconds, often triggered by changes in body position. In the early stages of increased intracranial pressure, there may be no other subjective symptoms besides TVO.
• Diplopia: Typically horizontal diplopia due to abducens nerve palsy.
• Somnolence: Appears as intracranial hypertension progresses.

In infants and young children, it presents as head enlargement, bulging fontanelles, poor feeding, somnolence, and vomiting¹⁾. It may also manifest as delayed language development or decreased level of consciousness.

Clinical Findings (Findings Confirmed by Physician Examination)

Papilledema is observed as a sign of intracranial hypertension. Ophthalmoscopic examination reveals redness and swelling of the optic disc in both eyes, blurred disc margins, hemorrhages and exudates on the disc surface, and dilation of retinal veins. If intracranial hypertension persists for several months, inferonasal or concentric visual field constriction appears, followed by visual acuity loss.

Abducens nerve palsy is a non-localizing cranial nerve palsy associated with intracranial hypertension, presenting with esotropia and limited abduction. It may be bilateral. In children, intracranial hypertension is often discovered due to esotropia caused by abducens nerve palsy.

Neuro-ophthalmologic findings vary depending on the tumor location.

Dorsal third ventricle

Vertical gaze palsy: Caused by compression of the posterior commissure. Typically presents with upward gaze impairment.

Cerebellopontine angle

Abducens nerve palsy: Presents with esotropia and unilateral abduction limitation.

Facial nerve palsy and hearing loss: Because the trigeminal, facial, and vestibulocochlear nerves are in close proximity, trigeminal neuralgia may also occur.

Ataxia: Due to compression of the cerebellum.

Lateral Ventricle and Fourth Ventricle

Papilledema: Reflects increased intracranial pressure due to obstruction or overproduction of cerebrospinal fluid.

Abducens nerve palsy: Appears as a non-localizing sign associated with increased intracranial pressure.

Q What happens if papilledema is left untreated?

A

If increased intracranial pressure persists for several months, hemorrhages and exudates associated with papilledema are absorbed, and nasal or concentric visual field defects appear. Further progression leads to visual acuity loss, and once optic atrophy occurs, visual dysfunction becomes irreversible. Early reduction of intracranial pressure is essential for preserving visual function.

3. Causes and Risk Factors

CPP is a tumor that arises from the cuboidal epithelial cells of the choroid plexus and occurs at sites where the choroid plexus is present within the ventricular system. No established risk factors are known.

There are multiple mechanisms by which CPP causes increased intracranial pressure.

• CSF overproduction: Tumor cells increase CSF secretion, leading to communicating hydrocephalus ¹⁾.
• Obstruction of CSF pathways: The mass effect of the tumor itself obstructs normal CSF flow, resulting in obstructive hydrocephalus ¹⁾.
• Arachnoid adhesions: Repeated microbleeding from the tumor causes arachnoid adhesions.
• CSF absorption impairment: Elevated CSF protein concentration hinders absorption at the arachnoid granulations.

Prevention and Daily Care

There is no established prevention method for CPP. If symptoms of increased intracranial pressure such as headache, vomiting, or vision loss persist, or if rapid head enlargement is observed in infants, seek medical attention promptly.

4. Diagnosis and Examination Methods

Imaging Diagnosis

MRI is the first-choice imaging modality.

• MRI findings: Well-defined, frond-like intraventricular lobulated mass. Hypo- to isointense on T1-weighted images, iso- to hyperintense on T2-weighted images. Flow voids indicating active blood flow are characteristic¹⁾. Contrast enhancement shows homogeneous to heterogeneous enhancement¹⁾.
• CT findings: Depicted as a well-defined, lobulated, iso- to hyperdense mass with contrast enhancement. Hyperdensity is due to calcification (seen in 4–20% of CPPs) or microhemorrhage. The lobulated cauliflower-like appearance helps differentiate from other intraventricular tumors ¹⁾.

Ophthalmic examination

• Ophthalmoscopy: Check for bilateral papilledema. Evaluate redness, swelling, blurred margins, and presence of hemorrhages or exudates.
• Fluorescein angiography (FAG): Dye leakage from the optic disc aids diagnosis.
• Optical coherence tomography (OCT): Useful as an adjunctive diagnostic tool, allowing quantitative assessment of papilledema.
• Diplopia test: Detects concurrent abducens nerve palsy.
• Visual field test: Evaluate Mariotte blind spot enlargement (early stage) and inferonasal or concentric visual field constriction (advanced stage).

Pathological Diagnosis

Tumor biopsy is necessary for a definitive diagnosis of CPP. Grading based on the WHO classification is shown below.

Grade	Name	Main histological features
I	Choroid plexus papilloma	Well-differentiated, no mitosis or necrosis
II	Atypical choroid plexus papilloma	Mitosis ≥2/10 HPF
III	Choroid plexus carcinoma	Mitosis >5/10 HPF, invasion

Grossly, it is a vascular, soft, pink cauliflower-like mass. Histologically, it consists of papillary structures with fibrovascular cores lined by cuboidal epithelium resembling normal choroid plexus.

Immunohistochemistry shows positivity for cytokeratin, S-100, transthyretin, and vimentin ²⁾. The Ki-67 proliferation index is very low in CPP (almost 0% in normal choroid plexus) ²⁾.

Differential diagnosis

Differential diagnosis is narrowed based on tumor location and patient age.

• Children, posterior third ventricle: Ependymoma, pineocytoma, pineoblastoma, germ cell tumor, astrocytoma
• Cerebellopontine angle: Ependymoma, schwannoma, meningioma
• Fourth ventricle: Ependymoma, medulloblastoma

5. Standard Treatment

Surgical Treatment

Gross total resection (GTR) is the first-line treatment for CPP. GTR is curative, and many studies report a 5-year survival rate of 100% after GTR.

Intracranial pressure-lowering treatment is primarily based on neurosurgical procedures such as resection of space-occupying lesions or ventriculoperitoneal shunt placement.

• Preoperative embolization: CPP is highly vascular, and intraoperative bleeding is a major challenge. To minimize bleeding, embolization of the feeding vessels (usually the choroidal arteries) may be performed before surgery.
• Management of hydrocephalus:
  • External ventricular drain (EVD): Placed temporarily during surgery to control intracranial pressure. This is sufficient in most cases.
  • Ventriculoperitoneal (VP) shunt: May be placed preoperatively in patients with acute intracranial hypertension. GTR usually eliminates the need for a shunt, but some patients require a permanent shunt.
  • Endoscopic third ventriculostomy: Creates an alternative pathway for cerebrospinal fluid circulation.

Treatment of Choroid Plexus Carcinoma (Grade III)

Choroid plexus carcinoma is malignant and has a high risk of recurrence. GTR positively impacts survival but is achieved in less than 50% of cases. Adjuvant therapy with radiation or chemotherapy may be indicated.

Precautions and Side Effects in Treatment

If intracranial pressure decreases early, papilledema improves rapidly and visual function may be preserved. However, if treatment is delayed and visual impairment occurs, it becomes irreversible. The role of the ophthalmologist is to detect papilledema early and, upon recognizing the risk of visual impairment, immediately refer to a neurosurgeon.

Q Is a shunt necessary after total resection?

A

Usually, GTR eliminates the need for a ventricular shunt. Intracranial pressure can often be controlled with a temporary external ventricular drain placed during surgery. However, if CSF circulation does not recover after surgery, permanent shunt placement may be necessary.

6. Pathophysiology and Detailed Mechanisms

CSF Production and Circulation

CSF is produced by the choroid plexus epithelium. The normal circulation pathway is as follows:

• CSF produced in the lateral ventricles flows through the foramen of Monro (interventricular foramen) into the third ventricle.
• It then passes through the cerebral aqueduct (aqueduct of Sylvius) into the fourth ventricle.
• Drains into the subarachnoid space through two lateral foramina (foramina of Luschka) and one median foramen (foramen of Magendie).
• Is drained into the venous sinuses via the arachnoid granulations.

Mechanisms of increased intracranial pressure and hydrocephalus

Hydrocephalus due to CPP occurs through multiple mechanisms¹⁾.

• Overproduction type (communicating hydrocephalus): Tumor cells increase CSF secretion, leading to accumulation of CSF exceeding absorption capacity.
• Obstructive type (obstructive hydrocephalus): The mass effect of the tumor obstructs narrow passages such as the foramen of Monro or the cerebral aqueduct.
• Adhesive type: Repeated microbleeds from the tumor cause adhesion of the arachnoid membrane, obstructing CSF flow. Elevated CSF protein levels also contribute to impaired absorption at the arachnoid granulations.

Mechanism of papilledema

Elevated intracranial pressure spreads to the perioptic space via the subarachnoid space. Increased pressure in the perioptic subarachnoid space compresses the optic nerve, causing stagnation of axoplasmic flow at the optic disc. This stagnation is the essence of papilledema (choked disc). Initially, only enlargement of the Mariotte blind spot occurs, but chronic progression leads to optic atrophy, resulting in visual field constriction and decreased visual acuity.

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7. Latest research and future perspectives (research-stage reports)

For patients: Please be sure to read

The following content is currently at the research stage or under clinical trial and is not standard treatment available at general hospitals. It is reference information for professionals regarding future medical developments.

Spinal Metastasis of Benign CPP

Even benign CPP (WHO grade I) has been reported to cause spinal drop metastasis via the CSF pathway.

Nozzoli et al. (2025) aggregated 24 cases from the literature and examined spinal drop metastasis of CPP. The median age at diagnosis was 38 years (range: 7–74 years), and the median time from primary tumor to spinal metastasis was 3 years (range: 0–19 years). Among the 24 cases, 9 already had spinal metastasis at initial diagnosis. Although spinal metastasis has been considered a rare event, the accumulation of reported cases suggests that its frequency may be underestimated ²⁾.

Biomarkers and Molecular Classification

Research is underway to identify biomarkers that predict the malignancy and clinical behavior of CPP.

The Ki-67 proliferation index is useful for grading choroid plexus tumors.

Tumor type	Ki-67 (mean)
CPP (grade I)	1.3–4.5%
Atypical CPP (grade II)	5.8–9.1%
Choroid plexus carcinoma (grade III)	13.4–20.3%

In the WHO 5th edition classification, increased mitotic activity is considered an independent predictor of recurrence and is positioned as a major criterion for grading ²⁾.

Cytogenetic studies have shown duplications of chromosomes 7, 12, 15, 17, and 18 in CPP. However, the total number of specific chromosomal gains or losses does not significantly affect overall survival. While CPP and atypical CPP are cytogenetically similar, choroid plexus carcinomas exhibit numerous chromosomal deletions and have a distinctly different profile from the two groups ²⁾.

Methylation profiling has been reported to provide prognostic information in addition to histology and may help identify patients at high risk of recurrence ²⁾.

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8. References

1. Kabashi A, Ahmetgjekaj I. Choroid Plexus Papilloma - Case Presentation. Curr Health Sci J. 2021;47(2):310-313.
2. Nozzoli F, Pedone A, Nucci E, et al. Spinal drop metastases of choroid plexus papilloma: a brief report and updated literature review. Pathologica. 2025;117:430-435.
3. Pereira S, Vieira B, Maio T, Moreira J, Sampaio F. Susac’s Syndrome: An Updated Review. Neuroophthalmology. 2020;44(6):355-360. PMID: 33408428.