Choroid Plexus Tumors: Papilloma and Carcinoma — Etiology, Classification, and Treatment

The choroid plexus produces cerebrospinal fluid (CSF) and is located within the ventricles of the brain. Tumor localization is age-related: the lateral ventricles are more commonly affected in children, while in adults, the tumors are generally found in the fourth ventricle.

Choroid plexus papilloma (CPP) is a benign epithelial tumor of the choroid plexus. According to the WHO classification, it is designated Grade 1. Note that it is the most common type of choroid plexus tumors.

Choroid plexus carcinoma (CPC) is a rare, highly malignant tumor (WHO Grade 3) arising from the epithelium of the choroid plexus within the brain ventricles. It is most frequently diagnosed in children under 5 years of age. CPC is characterized by aggressive growth, invasion, CNS metastasis, and an extremely poor prognosis.

Etiology and Epidemiology of Choroid Plexus Tumors

Etiology and Genetic Factors

The exact causes of CPP remain unknown. CPP is not typically associated with specific driver mutations, but some cases are linked to rare genetic syndromes, such as Aicardi syndrome.

• Atypical CPP (aCPP) and malignant CPC: These forms may arise in association with TP53 mutations, especially in children with Li — Fraumeni syndrome (LFS).
• Up to 60 % of CPC patients harbor somatic TP53 mutations, while 40 % of cases are associated with germline TP53 mutations in LFS.
• Other genetic alterations may involve PTEN and CDKN2A, which regulate cell cycle progression.

Epidemiology

Low incidence and strong age-related features are the main predictors of epidemiology of choroid plexus tumors.

• Incidence: Choroid plexus tumors are rare, accounting for < 1 % of all intracranial tumors. In infants under 1 year, they represent 10–15 % of all intracranial neoplasms.
• Age: Peak incidence occurs within the first three years of life.
• Localization: In children, tumors are more often found in the lateral ventricles; in adults, in the fourth ventricle. Gender ratio: Approximately equal between males and females.

Clinical Manifestations and Symptoms of CPT

Primary symptom: Intracranial hypertension due to hydrocephalus (excess CSF production). It typically presents as headache; infants show progressive head enlargement.

• Other symptoms: Nausea, vomiting, seizures, hemiparesis, lethargy, visual disturbances (depending on tumor location).
• Rarely, intracranial hemorrhage may occur.

Classification of Choroid Plexus Tumors

The current WHO Classification (5th Edition, 2021) is based on morphological, immunohistochemical, and molecular features of the tumors.

WHO Grade

Molecular Subtypes

Recent studies identify three molecular subtypes based on methylation and gene expression:

1. Pediatric supratentorial low-risk (CPP/aCPP)
2. Pediatric supratentorial high-risk (CPC)
3. Adult infratentorial low-risk (CPP/aCPP)

Thus, clinical practice now integrates morphology, proliferative activity, molecular markers, and TP53 statusto determine prognosis and treatment strategy.

Diagnosis and Differential Diagnosis

Diagnostic Methods

MRI: Primary diagnostic tool. CT/Ultrasound: Used when MRI is unavailable (e.g., ultrasound in infants via the fontanelle).

• MRI and CT: Hyperintense on T2 in MRI, calcifications on CT, intense contrast enhancement.

CPC: Heterogeneous structure, necrotic areas, invasion, intense contrast enhancement, signs of vasogenic edema around the tumor.

• Molecular diagnostics: TP53 germline (LFS) screening is mandatory in CPC.
• Lumbar puncture: Performed to exclude tumor cells in CSF (especially in CPC).

Differential Diagnosis

Thus, in children, differential diagnosis focuses primarily on ependymomas and embryonal tumors, while in adults, it is aimed at meningiomas and metastatic carcinomas.

Treatment Methods and Prognostic Strategies for CPT

Management of these tumors is multimodal and begins with surgical intervention, which determines subsequent therapeutic strategy and overall prognosis.

1. Surgical therapy

• Gold standard:Gross total resection (GTR).. Endoscopic techniques are commonly used.
• CPP prognosis: Even subtotal resection of a typical CPP may yield favorable outcomes.
• CPC challenges: Complete removal is often difficult due to invasion and intraoperative bleeding.
• Postoperative care: CSF shunting may be required.

2. Radiation Therapy

• CPP: Generally not required after radical resection.
• Indications: Recurrent or atypical CPP, incomplete resection.
• CPC: Patients > 3 years may receive craniospinal irradiation following chemotherapy.
• Limitations: Avoided in children due to high cognitive impairment risk. In younger <(< 3 years) and LFS patients, this method is used with caution due to secondary tumor risk.

3. Chemotherapy

• Indications: High-risk patients (CPC, residual aCPP, metastases).
• Regimens: Carboplatin/Etoposide/Vincristine (CarbEV); CycEV. CarbEV shows superior survival rates in CPC.
• In some LFS cases, high-dose consolidation chemotherapy along with autologous bone marrow transplantation may be used.

Prognosis and Survival Factors

• Favorable: Following complete resection of CPP/aCPP, 10-year survival exceeds 90 %. Recurrence rates in aCPP are higher; adjuvant (postoperative) therapy is more common.
• Unfavorable: CPC has poorer outcomes, with 5-year survival around 40 %, especially in patients with TP53 mutations. Prognosis worsens with genetic syndromes, metastases, incomplete resection, and LFS.