Medical Therapy
Adjuvant chemotherapy and radiotherapy in the treatment of choroid plexus carcinoma have been demonstrated to improve survival and may be indicated for aggressive disease. The ifosfamide, carboplatin, and etoposide (ICE) regimen has been successfully used for choroid plexus carcinoma in young children, including neoadjuvant use before a second resection in patients whose initial surgery resulted in subtotal resection. [31] However, radiation therapy is not appropriate for younger children and may be helpful only for older individuals. The use of chemotherapy or radiation therapy is considered on an individual basis. [32, 9]
Hydrocephalus is frequently associated with CPP. Treatment for this secondary problem is surgical.
Surgical Therapy
The usual preoperative studies of complete blood cell count, electrolytes, and 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.
Gross total surgical resection remains the criterion standard treatment for CPP, and all efforts should be aimed toward this goal.
Upon removal of the choroid plexus or other intraventricular neoplasms, assessment of intracranial pressure is necessary. Resolution of hydrocephalus must be accomplished; treatment is required if it is not resolved.
The 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 presenting symptoms in nearly all patients. Even in choroid plexus carcinoma, total resection (if feasible) leads to the best possible outcome. [11, 14] The use of neuroendoscopic surgery and radiosurgery has been tested with some success, but these remain alternative methods. Successful endoscopic coagulation of choroid plexus hyperplasia resulting in correction of hydrocephalus without recourse to a shunt has been reported. [9, 33, 32, 34]
Obtaining a biopsy of the lesion at the time of surgery, or even before a definitive surgical procedure is performed, can be of great help in evaluation of a tumor, particularly when the diagnosis remains uncertain after other diagnostic procedures are complete.
A significant secondary problem of CPP is hydrocephalus. Treatment of hydrocephalus, when present, must be considered both before and after any surgical procedures are performed. An acute increase in intracranial pressure is best managed with a shunt. However, shunting alone without resection of the mass is not sufficient therapy. [35] Hydrocephalus may occur or may persist postoperatively; intracranial pressure should be assessed both preoperatively and postoperatively. Hydrocephalus often is resolved upon removal of the mass.
Although patients may be cured by total resection, CPP poses significant surgical risks and challenges related to intraoperative hemostasis. Transcollation devices appear to be an effective and safe addition to the armamentarium of neurosurgical hemostasis options for intracranial tumor resection in which there is high risk of intraoperative hemorrhage. [4]
In a study conducted to determine the benefit of gross total resection (GTR), the authors concluded that CPPs are not necessarily as indolent as was thought and noted that, although GTR is preferred, this is not always curative. In the study, 193 patients were identified, with a mean age of 39.9 ± 1.1 years. GTR was achieved in 72% of patients, with subtotal resection (STR) in 28%. GTR was associated with a significant increase in both progression-free survival (PFS) (P = 0.015) and overall survival (OS) (P = 0.004), as compared to STR. The authors found that only GTR was associated with recurrence (hazard ratio [HR] = 0.47, 95% confidence interval [CI] 0.25-0.90), and both age (HR = 1.03, 95% CI 1.00-1.05) and GTR (HR = 0.36, 95% CI 0.17-0.78) were associated with OS. [36]
Histologically benign CPP has a high incidence of surgical cure if totally resected and if preoperative symptoms are resolved. Such results require less frequent follow-up care. Papilloma with atypical features and choroid plexus carcinoma have a greater rate of recurrence. Appropriate follow-up care is necessary.
Examples of rare complications have been described and generally involve neurologic deficits from the surgical procedure. For cerebellopontine angle papilloma, facial nerve palsy is the most common complication. Hydrocephalus may continue and is managed by CSF shunting. Cavernous vascular malformation has been reported following surgery or radiation therapy. Diffuse metastasis and subarachnoid spread of occasional benign CPP have been reported.
Outcome and Prognosis
The prognosis for both CPP and carcinoma is determined by the completeness of lesion removal at surgery. Gross total resection of intraventricular CPP nearly always effects a cure. Multivariate analysis of 124 patients showed increased mitotic activity (2 or more per 10 high-power fields) to be the sole histologic feature associated with recurrence, increasing the likelihood of recurrence at 5 years to almost 5-fold. [30]
Analysis of 75 pediatric cases of choroid plexus carcinoma by Fitzpatrick and colleagues (2002) also revealed the benefits of gross total tumor resection: 84% of patients with gross total resection were alive compared with 18% of patients with subtotal resection at approximately 2 years. [37] Subtotally resected papilloma or carcinoma requires adjuvant therapy such as chemotherapy or craniospinal irradiation. Meta-analysis data suggest that patients with incompletely resected choroid plexus carcinoma have a better prognosis with a second resection than without. [38] Patients with a subtotal resection alone or with extensive parenchymal invasion have the worst prognosis.
Tabori and colleagues found that alterations of tumor suppressor gene TP53 define clinical subgroups of patients with choroid plexus carcinoma. [39] In a study of 64 patients, tumors that were immunopositive for TP53 conferred 5-year survival of 0% compared to 82% for those that were immunonegative. These researchers believed that patients who lack TP53 dysfunction could be treated successfully without radiotherapy.
As noted above, numerous chromosomal imbalances in choroid plexus tumors have been discovered. Although most of these genetic aberrations did not affect survival, significantly longer survival times were noted in patients with choroid plexus carcinoma associated with +9p and -10q. [40]
Gamma knife radiosurgery (GKR) can be considered for patients for whom surgical excision and re-excision have failed, or for those with surgically inaccessible tumor or with recurrence. [41]
Complications resulting in neurological or psychological problems may also influence outcomes. In some series, this number may be as high as 50%. [42]
Future and Controversies
Increasingly widespread use of endoscopic surgery may alter future therapy for 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. [43] Hallaert et al reported successful treatment of hydrocephalus due to choroid plexus hyperplasia in a young child using endoscopic coagulation. [34]
Evaluation of choroid plexus tumors, including choroid plexus papilloma, atypical papilloma, and choroid plexus carcinoma, may be aided by such markers as the proliferation index (MIB-1 labeling index) and tumor-suppressor protein p53. The CPT-SIOP-2000 chemotherapy study reported by Wrede and colleagues validated the separation of choroid plexus tumors into papillomas, atypical papillomas, and carcinomas based on MIB-1 labeling and p53 status, as confirmed by clinical outcomes in 92 patients at 5 years. [44]
Two groups found that many choroid plexus tumors express platelet-derived growth factor receptor B (PDGFRB) and, to a lesser extent, platelet-derived growth factor A (PDGFRA). [45, 46] This may represent a rationale for using treatments targeting PDGFR signaling, such as imatinib.
The recent emergence of ifosfamide, carboplatin, and etoposide (ICE) chemotherapy has increased treatment options for patients with residual disease following initial surgery. [31] Future studies will clarify whether this regimen will be useful for recurrence or for metastatic disease.
A difficult decision centers on the recommended degree of therapy, especially for 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 CPP. [42] Because of the poor prognosis associated with malignant transformation and the ability of the infant brain to compensate, most clinicians agree that complete surgical resection of CPP should be the goal, regardless of tumor size or location, or the clinical condition of the infant. [34]
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Imaging appearance of a fourth ventricular choroid plexus papilloma (CPP).
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Histologic appearance of a choroid plexus papilloma (CPP) stained with hematoxylin and eosin.
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Histologic appearance of a choroid plexus carcinoma stained with hematoxylin and eosin.
