What is choroid

The choroid is the middle layer of the eye that contains blood vessels and connective tissue between the sclera (the white of the eye) and the retina (at the back of the eye). Choroid is part of the uvea and supplies nutrients to the inner parts of the eye. Inflammation of the choroid is called choroiditis.

Choroid anatomy

The choroid is responsible for the 1/3 external vascular support of the retina, its functional and structural integrity is essential for retinal function, a compromised volume or flow in its circulation could result in photoreceptor and retinal pigment epitelium (RPE) dysfunction and death. The choroid blood supply derives from branches of the anterior and posterior ciliary arteries.

The choroid has a 5 layer histological composition from inner (retinal side) to outer (scleral side):

• Bruch Membrane
• Ruysch Layer (Choriocapillar)
• Sattler Layer (Layer of medium diameter blood vessels)
• Haller´s Layer (Layer of large diameter blood vessels)
• Suprachoroidea (Transitional zone between choroid and sclera)

The choriocapillaris has large diameter capillaries (20-25 Mm), also it has fenestrations of 700-800 nm diameter, wich allows more rapid transport and of bigger molecules.

Figure 1. Eye anatomy

Choroid of the eye function

The choroid of the eye has several functions: Its vasculature is the major supply for the outer retina; impairment of the flow of oxygen from choroid to retina may cause Age-Related Macular Degeneration. The choroidal blood flow, which is as great as in any other organ, may also cool and warm the retina. In addition to its vascular functions, the choroid contains secretory cells, probably involved in modulation of vascularization and in growth of the sclera. Finally, the dramatic changes in choroidal thickness move the retina forward and back, bringing the photoreceptors into the plane of focus, a function demonstrated by the thinning of the choroid that occurs when the focal plane is moved back by the wearing of negative lenses, and, conversely, by the thickening that occurs when positive lenses are worn.

What is choroid plexus

Choroid plexus is a network of blood capillaries in the walls of the ventricles of your brain. In human brains, the choroid plexus produces 400–600 ml of cerebrospinal fluid (CSF) each day, which is enough to turn over the cerebrospinal fluid (CSF) 3–4 times ¹. The CSF then flows from the lateral ventricles to the third and fourth ventricles, and then into the subarachnoid space of the brain and spinal cord via openings (foramena) below the cerebellum (Figures 4 and 5). The CSF returns to the peripheral circulation via resorption by arachnoid granulations in venous sinuses of the brain ². The choroid plexus-cerebrospinal fluid (CSF) therefore represents an independent circulatory system for the brain and spinal cord.

Cerebrospinal fluid (CSF) is a rich source of proteins, lipids, hormones, cholesterol, glucose, microRNAs, and many other molecules and metabolites that influence a multitude of CNS functions, including neurogenesis in embryos and adults ³. Spurred by the clinical utility of CSF biomarkers for Alzheimer’s disease, there is tremendous interest in CSF biomarker discovery for the diagnosis and management of CNS disorders, and the ability to derive secretory choroid plexus cells from embryonic stem cells sets the stage for unique choroid plexus-based strategies for treating a host of CNS diseases.

Figure 3. Choroid plexus 

Figure 4. Ventricles of the brain

Figure 5. Cerebrospinal fluid formation, absorption and circulation around and within the brain

Choroid plexus function

The choroid plexus has the highly specialized function of producing cerebrospinal fluid (CSF). It is anatomically localized to the parenchymal/ventricular junction in all four ventricles. The choroid plexus itself is derived from the ventricular epithelium along certain segments of the neural tube, and there is a common ontogeny between choroid epithelium and cells of glial origin which can lead to diagnostic confusion. Tumors arising from the choroid plexus can display a benign or malignant phenotype, but conversion to a malignant phenotype is a rare event. Surgical resection of benign choroid plexus papillomas is often curative while choroid plexus carcinomas require adjuvant therapy and recurrence is common.

Choroid plexus tumors

Choroid plexus tumors are primary central nervous system (CNS) tumors. This means they begin in the brain or spinal cord. Choroid plexus epithelial cells are the presumed cells of origin for most choroid plexus tumors, although rare intraventricular meningiomas are thought to arise from neoplastic meningeal cells in choroid plexus stroma ¹.

Choroid plexus tumors occur in both children and adults, but are more common in children in the first year of life. Choroid plexus tumors are rare in children and adults, accounting for <2% of all pediatric brain tumors ⁴, they are most commonly observed in infants (accounting for 10–20% of brain tumors in infants in their first year; median age of diagnosis, 3.5 years) ⁵. Choroid plexus tumors occur slightly more often in males than females.

Footnote: Child age 3 months. MRI of choroid plexus carcinoma demonstrating the mass with intraventricular and leptomeningeal spread. The 4th ventricle is now trapped and ballooned. The child passed away shortly after this scan.

[Source ⁸ ]

Choroid plexus carcinoma

Choroid plexus carcinomas are malignant neoplasms arising from the choroid plexus. They are classified as a WHO grade III tumor and while there is considerable overlap in imaging characteristics it carries significantly poorer prognosis than both WHO grade II atypical choroid plexus papilloma, and WHO grade I choroid plexus papilloma.

Pathology

Choroid plexus carcinomas originate from choroid plexus epithelium and typically arise de novo; rarely they may represent malignant transformation of a pre-existing choroid plexus papilloma ⁹.

Epidemiology

Choroid plexus carcinomas occur predominantly in children, typically in the first 5 years of life. They are rare, far less common than choroid plexus papillomas (which account for 80% of primary choroid plexus tumors), representing only 1-4% of pediatric brain tumors ¹⁰.

Clinical presentation

As is the case with choroid plexus papillomas, presentation usually is as a result of hydrocephalus. Symptoms include increasing head circumference and headaches. Papilloedema may be visible on fundoscopy. In addition, choroid plexus carcinomas have a tendency to invade the adjacent brain and thus may present with focal neurological dysfunction ¹¹.

Choroid plexus carcinoma associations

• Li-Fraumeni syndrome ¹⁰
• Aicardi syndrome ¹²
• Simian virus 40 (SV40) on the basis of this virus’ DNA having been identified in up to 50% of cases ¹⁰

Treatment and prognosis

Choroid plexus carcinomas are rapidly growing tumors with a 40% 5-year survival. TP53 mutation, brain invasion and CSF seeding are considered poor prognostic factors ¹⁰.

Surgical en-bloc resection is the mainstay of treatment and can result in a cure, achieved in as many as 50% of cases, but this result has only been reported in some selected series ¹⁰. In general, survival seems to be much worse than this, and hinges upon the ability to achieve gross complete macroscopic resection. In such cases, a 5-year survival of up to 86% can be achieved. In cases where resection is incomplete, 5-year survival is much lower 26% ¹³. Both radiotherapy and chemotherapy are used ¹⁰.

Choroid plexus papilloma

Choroid plexus papillomas are an uncommon, benign (WHO grade I) neuroepithelial intraventricular tumor which can occur in both the pediatric (more common) and adult population.

On imaging, choroid plexus papillomas are usually identified in the fourth ventricle in adults and in the lateral ventricles in the pediatric population. They commonly present as a solid vascular tumor with vivid frond-like enhancement pattern. In a quarter of cases, speckled calcifications are present.

Figure 6. Choroid plexus papilloma

Footnote: A vividly but heterogeneously enhancing mass in the right side of the 4th ventricle is associated with significant surrounding edema and mass effect. There is ventricular enlargement consistent with non-communicating hydrocephalus.

[Source ¹⁴ ]

Pathology

Choroid plexus papillomas are WHO grade I lesions, with a low mitotic rate (<2 mitoses are present per 10 high-power field), and to a lesser degree histological features, distinguishing them from atypical choroid plexus papillomas (WHO grade II) and choroid plexus carcinomas (WHO Grade III) ¹⁵.

Epidemiology

Overall these choroid plexus papillomas account for approximately 1% of all brain tumors, 2-6% of all pediatric brain tumors and 0.5% of the adult brain tumors. Choroid plexus papillomas are, however, disproportionately represented in brain tumors in children under the age of 1 10. Approximately 85% of all choroid plexus papillomas occur in children under the age of 5 years ¹⁶.

Interestingly, the age distribution is very different for infratentorial (fourth ventricle) versus supratentorial (usually lateral ventricle). The vast majority of supratentorial tumours are seen in children, whereas posterior fossa tumours are evenly distributed at all age groups, including the elderly ¹⁷.

Clinical presentation

Hydrocephalus is very common, seen in over 80% of cases ¹⁶. Although the exact mechanism remains uncertain, it is believed to be due to a combination of CSF overproduction and decreased arachnoid granulation resorption.

Choroid plexus papilloma associations

An association with Aicardi syndrome and von Hippel-Lindau disease (as well as the more frequently associated hemangioblastoma) is recognized.

Treatment and prognosis

Total excision should be the aim of therapy and is curative in a vast majority of cases. Overall there is 90% 1-year-survival, and 77% 5-year-survival ¹².

CSF seeding is uncommon in choroid plexus papillomas, but far more frequently seen in higher grade tumors atypical choroid plexus papillomas and choroid plexus carcinomas ¹².

Choroid plexus cyst

Antenatal choroid plexus cysts are benign and are often transient typically resulting in utero from an infolding of the neuroepithelium.

They should not be confused with adult choroid plexus cysts (which are very commonly found at autopsy and likely degenerative), large intraventricular simple cysts (some of which arise from the choroid plexus) or choroid plexus xanthogranulomas ¹⁸.

Pathology

The cysts have no epithelial lining, and as such these are not true cysts, but rather spaces within the choroid plexus filled with clear fluid (CSF) and cellular debris. They can range in size from a few millimeters to 1-2 cm.

Location

Typically seen at the level of atria involving the lateral ventricles.

Choroid plexus cyst complications

• Obstructive hydrocephalus: rare but can happen if the choroid plexus cyst is large

Epidemiology

Choroid plexus cyst estimated occurrence is ~2% (range 0.2-3.5%) of pregnancies ¹⁹.

Choroid plexus cyst associations

There is a soft association with aneuploidy (therefore sometimes considered as a soft marker), however, the vast majority of cases have no associated abnormality.

Recognized associations however include:

• Trisomy 18
  • ~1% if no other abnormality
  • ~4% if there are other anomalous features
  • the increased risk is essentially the same whether there is a single choroid plexus cyst or multiple cysts
  • choroid plexus cyst, however, may be seen in up to 50% of those with trisomy 18
• Trisomy 21
• Klinefelter syndrome
• Aicardi syndrome ²⁰

Treatment and prognosis

They generally disappear by 26-28 weeks in utero and are of no significance in most cases 1-2. However, if one is seen in antenatal imaging it would warrant careful surveillance of the rest of the fetus due to weak associations with karyotypic abnormalities. Choroid plexus cysts are of concern if the cysts are large (>1 cm) (controversial evidence), bilateral, multiple and associated with structural abnormalities when the maternal age is equal to or greater than 32 years, or if the maternal serum screening results are abnormal.

Amniocentesis is suggested when there are other abnormalities or when there is a high risk for trisomy 18.

The cysts themselves resolve in the 3rd trimester and are generally not associated with abnormal CNS development. It is usually the associated conditions that are of concern.

Adult choroid plexus cyst

Adult choroid cysts and xanthogranulomas should not be confused with antenatal choroid cysts (described above), which usually regress by birth. Adult choroid cysts are found in adults, and are relatively common (~7%) ²¹, identified most commonly in older patients ²². Choroid plexus xanthogranulomas are common, incidental and almost invariably asymptomatic lesions. It is unclear in much of the literature whether they represent a distinct entity from adult choroid plexus cysts, but they share imaging characteristics and are only likely to be distinguishable on autopsy. As the clinical history is the same, the distinction, at least from a radiologist’s and clinician’s point of view, is largely irrelevant.

Pathology

These lesions represent desquamated epithelium into the lumen of choroid cysts within the choroid plexus. As a result cholesterol/lipid rich content of epithelial cells accumulates, sometimes combined with blood products, and results in a xanthomatous response, as this material is ingested by mononuclear cells ²².

Clinical presentation

In almost all cases these lesions are asymptomatic. Rarely they are large enough to cause local mass effect or may be complicated by hemorrhage ²³.

Treatment and prognosis

Adult choroid cysts and xanthogranulomas require no treatment. They do not require histological confirmation and no follow up is needed.

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