Introduction

Paediatric choroid plexus carcinoma (CPC) is an aggressive malignant brain tumour that affects young children.^1,2 It arises from a structure in the brain called the choroid plexus, and it is a rare type of tumour.^1,2 Paediatric CPC accounts for 10 to 20% of brain tumours diagnosed in the first year of life.³ Despite its rarity, paediatric CPC presents significant challenges in diagnosis and treatment, hence, it is crucial to understand this condition.⁴ This article will provide a comprehensive understanding of paediatric CPC, including its causes, symptoms, treatment options, prognosis, and ongoing research effort.

Understanding paediatric choroid plexus carcinoma

Paediatric choroid plexus carcinomas (CPCs) are rare types of neoplasms that develop in the central nervous system, which consists of the brain and spinal cord. They are considered malignant because they can spread to other parts of the body.² Unlike lower-grade choroid plexus tumours, like atypical choroid plexus papilloma (aCPP) and choroid plexus papilloma (CPP), CPC is different both clinically and molecularly.² As a very aggressive malignant tumour, CPC is categorised by the World Health Organisation (WHO) as a Grade III, i.e., more likely to spread across the brain and spine and more challenging to cure.⁵

What is the choroid plexus?

Paediatric CPC begins with the growth of tumorous cells within the choroid plexus. Specifically, it is believed that the choroid plexus epithelium is where choroid plexus carcinomas originate from.⁶ The choroid plexus is a complex network of blood vessels and cells found within the brain ventricles (cavities between the brain) responsible for producing cerebrospinal fluid.^1,7 CPC has been linked to the blockage of the cerebrospinal fluid pathways and, possibly, to an excess in the production of cerebrospinal fluid, which can result in hydrocephalus and higher intracranial pressure.⁶ Even though the tumour cells mostly develop inside the ventricles, they can also develop in other parts of the central nervous system.¹ Typically, they manifest as follows: 50% involvement of the lateral ventricles, 40% of the fourth ventricle, 5% of the third ventricle, and 5% of multiple ventricles.⁶

Incidence of paediatric choroid plexus carcinoma 

Paediatric CPC has an incidence rate of 0.3 per million cases per year.² About 17–30% of all choroid plexus tumours are CPCs, and they tend to occur in younger children rather than adult patients.⁵ Around 80% of choroid plexus carcinoma cases develop in children, with the average age of patients being 3 years old (around 26 to 32 months) and youngsters under the age of 18 accounting for 20% to 40% of CPC cases.^6,8,9

Potential risk factors associated with CPC development

Most tumours of the choroid plexus have an unknown cause. However, in almost half of instances, genetic alterations, most notably Li-Fraumeni syndrome, a rare hereditary disorder caused by mutations of the TP53 gene, have been connected to the development of choroid plexus carcinomas.^3,10

Symptoms of paediatric CPC

Depending on their size and location, CPC in children can produce a wide range of symptoms.

The common symptoms include:

• Increased head circumference or growth in head size^3,6
• Separated sutures⁶
• Hydrocephalus or the disruption of the regular flow of cerebrospinal fluid which might result in a brain pressure rise and skull growth³
• Enlarged fontanelles ( "soft spots" between the skull's bones in infants)³ 
• Vomiting and nausea, which are usually worse in the morning- these symptoms become better over the day³ 
• Drowsiness³ 
• Delayed development⁶
• Neurologic deficits⁶
• Strabismus or abnormal alignment of the eyes⁶
• Headache, usually as soon as woke up³ 
• Easily irritated, especially younger children who are unable to communicate their pain³ 
• Blurred vision⁵
• Seizures⁵

How CPC is diagnosed

Diagnosis of pediatric CPC involves: 

• A thorough medical history and physical examination to gain information about the symptoms, overall health, previous sickness, risk factors and developmental milestones¹¹
• Lumbar puncture or spinal tap to examine the cerebrospinal fluid for cancerous cells¹¹
• Neurological examination to assess the brain function, reflexes, mouth and eye movement, attentiveness, spinal cord health, nerve condition, and tests to measure memory, vision, hearing, muscle strength, balance, coordination, and reflexes^11,3 
• Magnetic resonance imaging (MRI) or computer tomography to produce detailed images of the brain, spinal cord, and ventricles and to view the tumour's location and size¹¹
• Biopsy by taking a small sample of the tumour using a needle during surgery to determine the exact type of tumour¹¹

Treatment options

A multidisciplinary strategy is usually used to treat pediatric choroid plexus carcinoma, which usually includes surgery, radiation treatment, and chemotherapy.

Surgery as the primary treatment

Surgery is typically the primary treatment for pediatric CPC. Obtaining tissue to identify the type of tumour and excising as much of it as possible without resulting in new symptoms are the two main objectives of surgery.¹

Total tumour removal/resection through surgery has a major impact on overall prognosis and survival.¹² However, because of factors like tumour vascularity and vast dispersion, especially in children, attaining total resection or complete removal of cancer cells through surgery might be difficult.¹² Hence, following surgery, therapies such as radiation and chemotherapy, are performed.¹²

Adjuvant therapies

Adjuvant chemotherapy and radiation therapy are essential for enhancing the prognosis of pediatric CPC patients, especially those who have had their tumours partially removed by surgery.¹² Adjuvant therapies are dependent on factors like the child's age, as medical experts generally avoid administering radiation to children younger than three years old.¹³ Chemotherapy is frequently employed as the main adjuvant treatment method in this group of patients, considering the possibility of long-term neurological damage in young children from radiation.¹²

Chemotherapy as neo-adjuvant therapy

A growing body of research indicates that chemotherapy may be beneficial as a neoadjuvant treatment (given before the primary treatment, such as surgery), to shrink the tumour size and vascularity, increasing the likelihood of a full surgical resection.¹²

Conformal radiation techniques

Proton Stereotactic Radiotherapy (PSRT), Proton Stereotactic Radiosurgery (PSRS) and Gamma knife based radiosurgery are examples of advanced radiation treatments that show promise in the treatment of CPC as they can precisely target cancer cells while causing the least amount of harm to surrounding healthy tissue.¹²

Immunopositivity for TP53 as a prognostic marker

Recent studies have highlighted the significance of TP53 immunopositivity in prognostic prediction, suggesting that patients may benefit from better outcomes of treatment and survival rates when TP53 functions normally, thereby potentially reducing the need for intense radiation therapy.¹²

Marrow-ablative chemotherapy with autologous hematopoietic cell rescue 

It involves using high-dose chemotherapy to destroy bone marrow cells, followed by infusion of the patient's own stem cells to restore blood cell production, aiming to delay or avoid radiation therapy and improve survival outcomes.⁹

Novel therapeutic approaches

Significant advancements are also being made in the search for novel choroid plexus cancer treatments. For example, scientists are studying drugs that can block the PDGF signalling pathways (which regulate cell growth and division), particularly a molecule called PDGFR-β. By targeting this pathway, drugs like imatinib or dasatinib could potentially slow down or stop the growth of choroid plexus carcinoma.⁹ These researches present encouraging possibilities for enhancing the prognosis and quality of life for choroid plexus cancer patients.⁹

Targeted therapies based on molecular landscape

Based on knowledge of the molecular landscape of pediatric choroid plexus carcinoma, targeted therapies that can selectively target certain molecules linked to cancer growth have been created. Researchers have discovered several potential targets inside the tumour cells, such as ATR inhibitors, PI3K-mTOR, Notch, SHH, and PDGFR, promising more efficient treatments.⁹ 

Prognosis and long-term outlook

Pediatric CPC has a 5-year survival rate of 40–60%.¹⁰ However, if the TP53 mutation is present, the rate drops to 30%.¹⁰ Compared to patients with other choroid plexus tumours like CPP, those with CPC had much worse survival rates and were nearly five times more likely to experience life-threatening or critical situations at any given moment.^2,14The prognosis for pediatric CPC patients varies depending on several factors, including the extent of tumour resection, age at diagnosis, and response to treatment.^11,15 

Studies have demonstrated that there are clear racial differences in incidence and survival, particularly white patients having higher rates than patients of other racial groups.¹⁴ If surgery is not completed, the prognosis for choroid plexus carcinoma can be quite bad. To survive, the tumour must be surgically removed aggressively.¹⁶ Considering the challenges persisting in achieving favourable outcomes for CPC patients, there is a need for continued research and targeted interventions to address this aggressive form of brain tumour.¹⁴

Summary

Pediatric choroid plexus carcinoma is a rare and aggressive malignant brain tumour. It primarily affects young children with an average age of 3 years. It originates from the brain's choroid plexus and is responsible for 10–20% of pediatric brain tumours. 

Common symptoms of choroid plexus carcinoma include enlarged head size, greater intracranial pressure, developmental delays, bulging fontanelles, vomiting, headaches, neurological issues, and alterations in vision or behaviour. Diagnosis involves a medical history and physical examination, and imaging tests like an MRI, CT scan, and biopsy. Treatment of pediatric choroid plexus carcinoma typically involves surgery, adjuvant chemotherapy, and radiation therapy. The total tumour resection significantly impacts the prognosis of this carcinoma. The prognosis also varies depending on factors like age, extent of tumour resection, and response to treatment. 

Promising new therapy options are provided by recent developments in targeted medicines, such as inhibiting PDGF signalling pathways and targeting molecules linked to the progression of cancer. However, continuous research is essential to further improve outcomes for choroid plexus carcinoma in pediatric populations.