Choroid Plexus Papilloma 

Choroid plexus papillomas (CPPs) are benign neoplasms of the choroid plexus, a structure made from tufts of villi within the ventricular system that produces cerebrospinal fluid (CSF). CPPs are commonly observed in the lateral ventricles of children, but they can be encountered in adults. While the vast majority of these neoplasms are benign, a small percentage can be malignant.

An image depicting a choroid plexus papilloma can be seen below.

Guerard described the first CPP (in a 3-year-old girl) in 1832, and Perthes described the first successful surgical removal in 1919.

The choroid plexus is a neuroepithelial-lined papillary projection of the ventricular ependyma. The papillae consist of cores of fibrovascular tissue lined by low-cuboidal neuroepithelial cells. While benign cystic lesions of the choroid plexus are not uncommon, neoplasms are rare. Although most choroid plexus neoplasms are benign, they can become symptomatic by obstructing CSF flow, eventually leading to generalized increased intracranial pressure or mass effect.

Frequency

CPPs are rare, comprising less than 1% of brain tumors in patients of all ages. However, CPPs most often occur in children and constitute up to 3% of childhood intracranial neoplasms with a predilection for younger ages. CPPs comprise 4-6% of the intracranial neoplasms in children younger than 2 years and 12-13% of intracranial neoplasms in children younger than 1 year.

• CPPs have been associated with von Hippel-Lindau syndrome.
• The frequency of CPPs in children is similar in China (1.5%)^[1] and France (2.3%)^[2] .
• The male-to-female incidence ratio of CPP is 2.8:1.
• No distribution by race has been described.

CPPs arise from the single layer of cuboidal epithelial cells lining the papillae of the choroid plexus. The choroid plexus is associated with the ventricular lining of the body, trigone, and inferior horn of the lateral ventricles; the foramen of Monro; the roof of the third ventricle; and the posterior portion of the roof of the fourth ventricle. The typical locations of normal choroid plexus correspond to the most common locations for a CPP to occur.

A recent study points to the role of a transmembrane receptor protein (Notch3) in the pathogenesis of human choroid plexus tumors. The Notch pathway helps regulate development of the mammalian nervous system, and activation of the Notch pathway has been increasingly recognized in human cancers. Notch3 is expressed in ventricular zone progenitor cells in the fetal brain and, when activated, can function as an oncogene.^[3]

CPPs are associated with the Li-Fraumeni cancer syndrome (an autosomal dominant syndrome characterized by a mutation in the TP53 gene) and the Aicardi syndrome (a rare X-linked dominant condition observed in females, characterized by visual impairment, developmental delay, and seizures).

Both somatic and germline abnormalities that involve multiple genetic loci have been associated with the development of choroid plexus tumors. Recent genomic hybridization data shows that choroid plexus papillomas and choroid plexus carcinomas have characteristic chromosomal additions and deletions, which suggests that the genetic basis for these tumors is distinct.^[4]

The polyoma viruses SV40, JC, and BK have also been implicated in the development of choroid plexus tumors. Choroid plexus tumors have been induced experimentally in transgenic mice using the polyomavirus common gene product, T antigen. The mechanism is thought to involve the binding of T antigen with both pRb and p53 tumor suppressor proteins, as these complexes have been identified in humans with choroid plexus tumors.^[5] Research is ongoing to further elucidate the relationship between polyoma viruses and human CNS tumors.

Recent research has also demonstrated differential expression of several genes in choroid papilloma tumor cells using DNA microarray techniques on cells from 7 choroid plexus papillomas. Among the abnormalities identified was up-regulation of the TWIST-1 transcription factor, which was shown to promote proliferation and in vitro invasion. TWIST-1 is involved in the p53 tumor suppressor pathway as an inhibitor.^[6]

Symptoms from choroid plexus tumors generally result from secretion of CSF by tumor cells, leading to an increased amount of fluid and, eventually, to hydrocephalus. Not infrequently, the tumor itself can cause mass effect, with symptoms depending on tumor location. In either case, eventual progression and increased intracranial pressure can occur. Cases of hydrocephalus occasionally do not resolve with surgery, possibly because of derangement of reabsorption mechanisms or blockage at other sites in the ventricular system.

Patients usually present with the following signs of increased intracranial pressure: headache, nausea and vomiting, drowsiness, ocular or gaze palsies (cranial nerves [CN] III and VI), papilledema, visual disturbances, and, eventually, blindness.

Infants, especially those with a tumor located in the third ventricle, can present with hydrocephalus or macrocephalus, as well as with associated increased intracranial pressure.

Unusual presentations include trochlear palsies (CN IV), psychosis, or occasionally, seizures.

As CPPs grow, they eventually obstruct the flow of CSF. Once the intracranial space can no longer compensate for the increase in pressure, a tension-obstruction type of hydrocephalus develops. Persistently increased intracranial pressure is not compatible with life. The pressure is alleviated by resection of the tumor or a ventricular shunting procedure.

Because the choroid plexus is located within the ventricles, the CPP can expand into a space-occupying lesion that may not cause symptoms until either the flow of CSF is blocked or the papilloma becomes large enough to press against the ventricular walls and, subsequently, the brain parenchyma.

These tumors most often occur in the lateral ventricles in children and in the fourth ventricle or cerebellopontine angle (CPA) of adults. Bilateral CPA choroid plexus papillomas have also been reported in the setting of neurofibromatosis Type 2.^[7] Rarely, CPPs can also be found in the third ventricle. Other unusual sites include the sella.^[8] Occasionally, CPPs show extensive calcification or even ossification or may lack their usual radiographic contrast enhancement.^{[9, 10]}

In some instances, choroid plexus can be found in the cerebellopontine angle, where it has escaped the ventricle via the lateral foramen of Luschka. From this unusual placement of the choroid, or from exophytic growth of the papilloma through the foramen of Luschka, CPPs sometimes manifest in the cerebellopontine angle.

The appearance of CPPs in unusual sites most frequently occurs in the setting of von Hippel-Lindau syndrome.

Grossly, these tumors are tan and lobulated. They fill the ventricles and compress the walls; when they are benign, they do not generally invade brain parenchyma.

Contraindications to surgical correction of CPP are based on the patient's comorbidities and his or her ability to tolerate surgery. However, watchful waiting is inappropriate in most cases. As choroid plexus tumors grow, the resulting hydrocephalus and other complications usually result in greater morbidity than occurs if tumors are removed when they are first discovered and smaller.