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Choroid Plexus Papilloma

Editor: Joe M. Das Updated: 2/28/2024 3:26:54 PM

Introduction

Choroid plexus papillomas are rare central nervous system tumors, comprising less than 1% of all brain tumors. Although choroid plexus papillomas may occur at any age, 70% of patients with this neoplasm are less than 2 years of age.[1] Choroid plexus papillomas are neuroepithelial tumors that are World Health Organization grade I or II. In contrast, the rarely encountered choroid plexus carcinoma is classified as World Health Organization grade III.[2] Choroid plexus papillomas are more common in the infratentorial compartment in adults and the supratentorial compartment in children. Patients with choroid plexus papillomas often present with communicating hydrocephalus secondary to cerebrospinal fluid overproduction. The prognosis of these benign neoplasms is favorable, and gross total resection is frequently curative.

Etiology

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Etiology

The etiology of choroid plexus papillomas is undetermined. Neonatal choroid plexus papillomas are thought to be congenital.[3] Some studies have demonstrated an association between simian virus 40 (SV40) and the occurrence of choroid plexus tumors.[4] BK virus and John Cunningham (JC) viruses have also been implicated.[5] Complexes of SV40 large T antigen and TP53 and Rb proteins have been identified in humans with choroid plexus tumors.[5] The R248W mutation of TP53 is one of the most common mutations in choroid plexus tumors, but current data do not support a causative role.[6]

Epidemiology

Choroid plexus tumors are rare tumors of neuroectodermal origin. In the pediatric population, they are the third-most common congenital brain tumor, after teratomas and gliomas, comprising 0.4% to 0.6% of all intracranial neoplasms.[7] Adults may develop choroid plexus tumors, but the neoplasm is generally a disease of childhood; the median age at diagnosis is 3.5 years, and 70% of patients are less than 2 years of age at the time of diagnosis.[1] In infants, these neoplasms are typically supratentorial within the left lateral ventricles, most commonly the atrium.[8] In contrast, adult choroid plexus papillomas are usually infratentorial in the fourth ventricle and rarely at the cerebellopontine angle.[9]

Some choroid plexus tumors occur in association with specific syndromes, including Aicardi syndrome, hypomelanosis of Ito, chromosome 9p duplication, and von Hippel-Lindau syndrome.[10]

Histopathology

The World Health Organization classifies choroid plexus tumors as papillomas (grade I), atypical tumors (grade II), or carcinomas (grade III).[11] Grossly, the tumors are soft, globular, friable pink masses with irregular projections and high vascularity.

Choroid Plexus Papilloma

Histologically, choroid plexus papillomas have a benign architecture with papillary fronds lined by bland columnar epithelium, resembling the normal choroid plexus. Mitotic activity, nuclear pleomorphism, and necrosis are typically absent.[12] Immunohistochemistry staining is typically positive for cytokeratin, vimentin, podoplanin, and S-100 protein.[13][12] Glial fibrillary acidic protein may be positive in up to 20% of choroid plexus papillomas.[14] Studies have shown that patients 20 years and older express more GFAP and transthyretin than younger patients, and fourth ventricle tumors express more S-100 protein than lateral ventricle tumors.[15]

Genetic analyses have reported germline mutations in TP53 in some patients with choroid plexus papilloma.[16] These tumors rarely show positive nuclear staining for TP53.

Atypical Choroid Plexus Papilloma

The presence of more than 2 mitoses per high-power field is indicative of atypical CPP.

Choroid Plexus Carcinoma

The presence of 4 or more of the following malignant histopathological characteristics is indicative of choroid plexus carcinoma:

  • Brisk mitotic activity (> 5 mitoses per 10 high-power fields)
  • Nuclear pleomorphism
  • High cellularity
  • Blurring of the papillary growth pattern
  • Necrosis.

DNA Methylation Profiling

DNA methylation profiling of choroid plexus tumors has revealed 3 distinct molecular subgroups or clusters that may provide prognostic information beyond that traditionally provided by routine histopathological identification.[17] Cluster 1 comprises supratentorial pediatric low-risk choroid plexus tumors, including benign papillomas and atypical tumors. Cluster 2 comprises infratentorial adult low-risk choroid plexus papillomas and atypical tumors. Cluster 3 comprises supratentorial pediatric high-risk choroid plexus tumors, including papilloma, atypical tumors, and carcinomas.[17]

History and Physical

Most patients with choroid plexus papillomas present with signs and symptoms of increased intracranial pressure secondary to hydrocephalus.[18] These symptoms may include headache, nausea with or without vomiting, fussiness, lethargy, and craniomegaly. Depending on the location of the lesion, patients may present with meningismus secondary to subarachnoid hemorrhage, seizures, and focal neurologic deficits characterized by sensory deficits, hemiparesis, cranial nerve palsies, or cerebellar signs. 

Hydrocephalus may occur as a result of direct mechanical obstruction to the flow of cerebrospinal fluid (CSF) due to an arachnoid granulation blockage from hemorrhage or from CSF overproduction.[19] Choroid plexus papillomas may exhibit rapid growth despite their benign nature.[20] In some patients, CSF rhinorrhea or hemifacial spasms may be the only clinical abnormalities.[21][22]

Evaluation

Diagnostic imaging is indicated in patients with the signs and symptoms of hydrocephalus or those suggestive of an intracranial mass. If the fontanelles are not fused, ultrasonography via the anterior fontanelle may demonstrate an echogenic lesion within the ventricles. This lesion will demonstrate bidirectional flow throughout diastole, indicating blood flow through chaotically arranged vessels. Some lesions have been diagnosed antenatally via ultrasonography.[23]

Computed tomography (CT) may reveal an isodense or slightly hyperdense lesion within the ventricles and consequent ventriculomegaly.[24] Hydrocephalus is typical. Approximately 25% of patients with a choroid plexus papilloma demonstrate speckled intralesional calcifications. The lesions are typically lobulated with slightly irregular margins and intense, somewhat heterogeneous contrast enhancement. Angiographic and cross-sectional imaging frequently demonstrate enlargement of the choroidal artery.

Magnetic resonance imaging (MRI) of choroid plexus papillomas usually demonstrates well-defined, frond-like intraventricular lobulated masses that are hypointense on T1-weighted sequences and hyperintense on T2-weighted sequences.[25] Flow voids indicative of active blood flow are typical, and this rich vascularity promotes avid enhancement. Arterial spin labeling may help distinguish choroid plexus papilloma from carcinoma.[26] A prominent blush with enlarged choroidal arteries can be visualized on digital subtraction angiography.[2]

Treatment / Management

There is controversy regarding the timing of surgical intervention for incidentally detected choroid plexus papillomas.[27] Prompt surgical resection is one option. However, surgery may be delayed until the patient becomes symptomatic or follow-up imaging demonstrates radiographic tumor progression or hydrocephalus. Tumor resection is facilitated by hydrocephalus; the length of the cortical corridor to the ventricles reduces, and space around the tumor increases. The disadvantage of delayed intervention is the interim development of focal deficits from mass effect, cognitive deficits, subarachnoid hemorrhage, or seizures.[28]

Gross total resection of these benign tumors is the treatment of choice in symptomatic patients. Recent advances in radiographic imaging, surgical approaches, operating microscopy, and quality of intensive care have improved surgical outcomes; long-term cure rates approach 100%.[8] Unfortunately, the pediatric perioperative mortality is 12%; choroid plexus neoplasms are highly vascular, and catastrophic hemorrhage is problematic.[29] Preoperative tumor embolization can minimize this risk and optimize complete resection of the tumor.[30] Percutaneous stereotactic intratumoral embolization with a sclerosing agent has been reported.[31] Radiosurgery may be a possible treatment option; further studies are required.[32](B2)

Postoperative subdural collections may occur following transcortical tumor excision, occasionally resulting from a persistent ventriculosubdural fistula; subdural-peritoneal shunt placement may be required.[1] Although limited in use, adjuvant chemotherapy can prevent recurrence and prolong survival.[33] Expanding residual choroid plexus papillomas may be irradiated with subsequent subtotal resection to improve longevity. Adjuvant therapy is also necessary for malignant tumors and those that exhibit leptomeningeal spread.[34] Recent studies show an increasing role of bevacizumab in disseminated choroid plexus tumors.[35](B2)

Differential Diagnosis

Differential diagnoses for choroid plexus papillomas include other intraventricular tumors, infectious processes, or vascular lesions.[36] These diagnoses include but are not limited to:

  • Ependymoma
  • Central neurocytoma
  • Subependymal giant cell tumor
  • Subependymoma
  • Atypical choroid plexus papilloma
  • Choroid plexus carcinoma 
  • Medulloblastoma
  • Meningioma
  • Chordoid glioma
  • Rosette-forming glioneuronal tumor
  • Central nervous system lymphoma
  • Metastases
  • Colloid cyst 
  • Arachnoid cyst
  • Epidermoid or dermoid cyst 
  • Craniopharyngioma
  • Infectious etiology such as cysticercosis caused by the parasite Taenia solium 
  • Arteriovenous malformation.

Prognosis

Improvements in surgical and intensive care techniques have vastly improved the prognosis of patients with WHO grade I choroid plexus papillomas.[37] Maximum tumor resection correlates with an increase in progression-free and overall survival.[38] Recurrences are rare, and complete resection can be curative. WHO grade II atypical choroid plexus papillomas are more likely to recur than their grade I counterparts. Suprasellar metastases and craniospinal seeding, though rare, have been reported, more commonly in choroid plexus carcinomas.[39]

Complications

Children with features of prolonged raised intracranial pressure, such as papilledema, optic atrophy, and visual loss, may not achieve postoperative resolution of these symptoms.[40] Some may develop persistent cognitive deficits, intracranial hemorrhage, and seizures.[41][27]

The risk of excessive intraoperative blood loss is high for patients with choroid plexus papillomas.[30] Postoperative CSF rhinorrhea has been reported.[42] 

Deterrence and Patient Education

Choroid plexus papillomas are rare, benign intracranial tumors occurring primarily in the pediatric population. The typical clinical presentation is that of hydrocephalus, which may present with headache, nausea with or without vomiting, or altered sensorium. However, these lesions may also present with a focal neurologic deficit, such as numbness, weakness, or cranial nerve palsy. Prompt evaluation via cranial imaging is warranted; MRI is preferred. A cure is achievable with complete tumor resection. Choroid plexus papillomas are benign lesions; adjuvant therapy is typically not required.

Enhancing Healthcare Team Outcomes

Effectively treating patients with choroid plexus papillomas requires an interprofessional team that includes the referring pediatrician or primary care practitioner, neurosurgeon, anesthesiologist, ophthalmologist, neurologist, and neuroscience specialty–trained nurses. Ancillary staff, including physical, occupational, and speech therapy may also be of assistance for disposition evaluation, treatment while in the hospital, and after-discharge rehabilitation in some instances. 

Educating parents and family members is imperative; even though these lesions are benign, complications can occur during surgery. A thorough discussion between the neurosurgeon and family should take place. With adequate preparation and complete removal of the lesion, outcomes are excellent.[43]

Media


(Click Image to Enlarge)
Choroid plexus papilloma
Choroid plexus papilloma
Image courtesy S Bhimji MD

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