Choroid Plexus Papilloma Treatment & Management

Adjuvant chemotherapy and radiotherapy have been demonstrated to increase survival in the treatment of choroid plexus carcinoma 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 prior to a second resection in patients whose initial surgery resulted in subtotal resection.^[17] However, 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.

Hydrocephalus is frequently associated with CPP. The treatment for this secondary problem is surgical.

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 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. However, successful endoscopic coagulation of choroid plexus hyperplasia has been recently reported and resulted in correction of hydrocephalus without recourse to a shunt.^[18]

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.

A significant secondary problem of CPP is hydrocephalus. The treatment of hydrocephalus when present, 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.^[19] Hydrocephalus may occur or persist postoperatively as well; intracranial pressure should be assessed both preoperatively and postoperatively. However, hydrocephalus often resolves following removal of the mass.

The 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.

Gross total surgical resection remains the criterion standard treatment for CPP, and all efforts should be aimed towards this goal.

Upon 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.

Histologically 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.

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.

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. 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.^[15]

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.^[20] 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.^[21] Patients with either a subtotal resection alone or with extensive parenchymal invasion have the worst prognosis.

Recent work by Tabori and colleagues indicates that alterations of tumor suppressor gene TP53 define clinical subgroups of patients with choroid plexus carcinoma.^[22] In a study of 64 patients, tumors that were immunopositive for TP53 conferred a 5-year survival of 0% compared to 82% for those that were immunonegative. These researchers felt that patients who lack TP53 dysfunction could be treated successfully without radiotherapy.

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.^[23]

Gamma knife radiosurgery (GKR) can be considered for those patients for whom surgical excision and re-excision have failed or for surgically inaccessible tumors and recurrences.^[24]

Complications resulting in neurological or psychological problems may also influence outcome. In some series, this number may be as high as 50%.^[25]

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.^[26] Hallaert et al have recently reported the successful treatment of hydrocephalus due to choroid plexus hyperplasia in a young child using endoscopic coagulation.^[18]

The evaluation of choroid plexus tumors, including choroid plexus papillomas, atypical papillomas, and choroid plexus carcinomas 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 has validated the separation of choroid plexus tumors into papilloma, atypical papilloma, and carcinoma based on MIB-1 labeling and p53 status, as confirmed by clinical outcomes in 92 patients at 5 years.^[27]

Two groups have recently 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).^{[28, 29]} This may, therefore, represent a rationale for using treatments targeting PDGFR signaling, such as imatinib.

The recent emergence of ifosfamide, carboplatin, and etoposide (ICE) chemotherapy increases treatment options for those patients with residual disease following initial surgery.^[17] Future studies will clarify whether this regimen will be useful for recurrences or metastatic disease.

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).^[25] 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 CPPs should be the goal, regardless of tumor size, location, or clinical condition of the infant.^[18]