You are in: eMedicine Specialties > Neurosurgery > MEDICAL TOPICS Choroid Plexus PapillomaArticle Last Updated: Jun 20, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 12
  Author: Cheryl Ann Palmer, MD, Professor, Departments of Pathology and Neurology, University of Alabama at Birmingham School of Medicine; Consulting Staff, Departments of Pathology and Neurology, University of Alabama at Birmingham Hospital; Consulting Staff, Departments of Pathology and Neurology, Veteran Affairs Medical Center; Consulting Staff, Department of Pathology, Children's Hospital of Alabama Cheryl Ann Palmer is a member of the following medical societies: American Academy of Neurology, American Association of Neuropathologists, Medical Association of the State of Alabama, Society for Neuro-Oncology, and Southern Medical Association Coauthor(s): Daniel Keith Harrison, MD, Consulting Staff, Department of Pathology, University of Alabama at Birmingham Editors: Scott C Dulebohn, MD, Assistant Professor, Department of Surgery, Division of Neurosurgery, University of Minnesota College of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Allen R Wyler, MD, Former Medical Director, Northstar Neuroscience, Inc; Herbert H Engelhard III, MD, PhD, Director, UIC Neuro-Oncology Program, Chief, Division of Neuro-Oncology, Associate Professor, Department of Neurosurgery, University of Illinois at Chicago; Allen R Wyler, MD, Former Medical Director, Northstar Neuroscience, Inc Author and Editor Disclosure Synonyms and related keywords: choroid plexus tumors, choroid plexus neoplasm, CPP, choroid plexus carcinoma, intracranial neoplasms, von Hippel-Lindau syndrome, Li-Fraumeni cancer syndrome, Aicardi syndrome, simian vacuolating virus No. 40, SV40, hydrocephalus, hydrocephaly, macrocephalus, macrocephaly, increased intracranial pressure INTRODUCTIONSection 2 of 12
  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. History of the ProcedureGuerard described the first CPP (in a 3-year-old girl) in 1832, and Perthes described the first successful surgical removal in 1919. ProblemThe 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. FrequencyCPPs 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.
EtiologyCPPs 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 (Dang, 2006). 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 (Kamly-Asl, 2006). 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 (Zhen, 1999). Research is ongoing to further elucidate the relationship between polyoma viruses and human CNS tumors. PathophysiologySymptoms 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. ClinicalPatients 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. INDICATIONSSection 3 of 12
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. RELEVANT ANATOMYSection 4 of 12
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 of adults. Rarely, they can also be found in the third ventricle. 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. CONTRAINDICATIONSSection 5 of 12
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. WORKUPSection 6 of 12
Imaging Studies
Diagnostic Procedures
Histologic FindingsHistologically, well-differentiated CPPs are difficult to distinguish from normal choroid plexus. Both have papillae with fibrovascular cores and are lined by a single layer of cuboidal-to-columnar epithelium. Normal choroid plexus epithelium tends to have a hobnail shape on the ventricular side, whereas the epithelium of CPPs is more flattened (see Image 2). Occasional examples of brain invasion in otherwise benign CPPs have been described, but parenchymal invasion more often heralds anaplasia. Atypical choroid papillomas are recognized, with intermediate histology between CPP and carcinoma. They generally have a higher proliferation of epithelial cells and increased mitotic activity, although clear diagnostic criteria are lacking. Choroid plexus carcinomas (see Image 3) are characterized by anaplastic features such as nuclear pleomorphism and hyperchromasia, increased mitotic activity, the occurrence of tumor giant cells, tumor necrosis, and frank invasion of the underlying brain parenchyma. StagingAs with most CNS neoplasms, confinement to the intracranial cavity is usual. If myelopathic symptoms are present, consideration of dissemination into the spinal canal should warrant spinal cord neuroimaging studies. TREATMENTSection 7 of 12
Medical therapyHydrocephalus is frequently associated with CPP. Treatment of hydrocephalus must be considered both before and after any surgical procedures. An acute increase in intracranial pressure is best managed with a shunt. However, shunting alone without resection of the mass is not sufficient therapy (Buxton, 1997). Hydrocephalus may occur or persist postoperatively as well; intracranial pressure should be assessed both preoperatively and postoperatively. Hydrocephalus often resolves following removal of the mass. In addition to surgery, adjuvant chemotherapy and radiotherapy have been demonstrated to increase survival in the treatment of choroid plexus carcinoma, although gross total resection remains the primary treatment. Adjuvant radiation therapy is not appropriate in younger children and may be helpful only in older individuals. The use of chemotherapy or radiation therapy is considered on an individual basis. Surgical therapyThe primary treatment of CPP is surgical, and total surgical resection is the goal. Complete removal of the tumor is generally curative and leads to resolution of the presenting symptoms in nearly all patients. Even in choroid plexus carcinoma, total resection (if feasible) leads to the best possible outcome. The use of neuroendoscopic surgery and radiosurgery has been tested with some success, but these remain alternate methodologies to date. Obtaining a biopsy of the lesion at the time of surgery, or even prior to a definitive surgical procedure, can be of great help in evaluation of a tumor, particularly when the diagnosis remains uncertain after other diagnostic procedures are complete. Preoperative detailsThe usual preoperative studies of complete blood cell count, electrolytes, blood type and match, as well as measurement of intracranial pressure and imaging studies of the tumor are required. During imaging of the lesion, determination of the location of the tumor stalk is crucial because stalk location dictates the surgical approach. Postoperative detailsUpon removal of choroid plexus or other intraventricular neoplasms, assessment of intracranial pressure is necessary. Resolution of hydrocephalus must be accomplished and requires treatment if not resolved. Follow-upHistologically benign CPPs have a high incidence of surgical cure if totally resected and the preoperative symptoms resolve. Such results require less frequent follow-up care. Papillomas with atypical features and choroid plexus carcinomas have a greater rate of recurrence. Appropriate follow-up care is necessary. COMPLICATIONSSection 8 of 12
Examples of rare complications have been described and generally involve neurologic deficits from the surgical procedure. For cerebellopontine angle papillomas, facial nerve palsy is the most common complication. Hydrocephalus may continue and is managed by CSF shunting. Cavernous vascular malformations have been reported following surgery or radiation therapy. Diffuse metastasis and subarachnoid spread of occasional benign CPPs have been reported. OUTCOME AND PROGNOSISSection 9 of 12
The prognosis for both CPPs and carcinomas is determined by the completeness of lesion removal at surgery. Gross total resection of intraventricular CPPs nearly always effects a cure. Analysis of 75 pediatric cases of choroid plexus carcinomas by Fitzpatrick and colleagues (2002) also reveals the benefit of gross total tumor resection: 84% of patients with gross total resections were alive compared with 18% of patients with subtotal resections at approximately 2 years. Subtotally resected papillomas or carcinomas require adjuvant therapy such as chemotherapy or craniospinal irradiation. Meta-analysis data suggests that patients with incompletely resected choroid plexus carcinomas have a better prognosis with a second resection than without (Wrede, 2005). Patients with either a subtotal resection alone or with extensive parenchymal invasion have the worst prognosis. Complications resulting in neurological or psychological problems may also influence outcome. In some series, this number may be as high as 50% (Chow, 1999). As noted above, numerous chromosomal imbalances have been discovered in choroid plexus tumors. Although most of these genetic aberrations did not affect survival, significantly longer survival times were noted in patients with choroid plexus carcinomas associated with +9p and -10q (Rickert, 2002). FUTURE AND CONTROVERSIESSection 10 of 12
Increasingly widespread use of endoscopic surgery may alter the future therapy of choroid plexus neoplasms. In Gaab and Schroeder's 1998 series, many types of intraventricular lesions could be totally resected through the endoscope, with fewer and less severe complications. The evaluation of atypical papillomas, or of more widespread, benign-appearing papillomas, may be aided by evaluation of the proliferation index or by presence or absence of various tumor markers. Patients with CPPs with a higher proliferation index or the presence of certain markers have been shown to have worse outcomes, generally observed as tumor recurrence. A difficult decision centers on the degree of therapy, especially in very young children. Tumor surgery adjacent to functionally important areas in the brain requires caution. Nevertheless, the infant brain is able to accommodate insults to functional areas, often without permanent deficits. Malignant transformation has been reported in pediatric patients with subtotal resection of choroid plexus papilloma (CPP) (Chow, 1999). Because of the poor prognosis associated with malignant transformation and the ability of the infant brain to compensate, many widely agree that complete surgical resection of CPPs should be the goal, regardless of tumor size, location or clinical condition of the infant. MULTIMEDIASection 11 of 12
REFERENCESSection 12 of 12
Choroid Plexus Papilloma excerpt Article Last Updated: Jun 20, 2006 | ||||||||||||||||||||||||||
