Choroid Plexus Carcinoma: Symptoms, Types, Causes and Treatment

Choroid plexus carcinoma (CPC) is a rare but aggressive brain tumor, mostly affecting young children and infrequently seen in adults. Understanding its symptoms, types, causes, and treatment options is crucial for timely diagnosis and management. This article provides a detailed, evidence-based overview, synthesizing current research to support patients, families, and healthcare professionals navigating this challenging diagnosis.

Symptoms of Choroid Plexus Carcinoma

Choroid plexus carcinoma often presents with symptoms related to increased intracranial pressure due to obstruction of cerebrospinal fluid (CSF) flow. These symptoms can be subtle at first but may rapidly worsen as the tumor grows. Early recognition is key for effective management and improved outcomes.

Main Symptom	Description	Common in Ages	Sources
Headache	Persistent, severe, morning-worse	Children, Adults	1 2 3 5
Vomiting	Often occurs in the morning	Children	2 3 5
Gait Disturbance	Ataxia, unsteady walking	All ages	1 2
Vision Changes	Blurred, double vision (diplopia)	All ages	1 2 3
Lethargy	Drowsiness, altered consciousness	Children	2 5
Enlarged Head	Increased head circumference	Infants	2 5
Papilledema	Swelling of optic disc	All ages	2
Cranial Nerve Signs	Sixth nerve palsy, others	All ages	2 3 5

Table 1: Key Symptoms of Choroid Plexus Carcinoma

Overview of Core Symptoms

Choroid plexus carcinoma symptoms are primarily the result of the tumor’s location within the brain’s ventricular system and its impact on CSF flow.

Intracranial Pressure and Hydrocephalus

• Headache and vomiting are hallmark features, often worse in the morning due to increased intracranial pressure overnight. Hydrocephalus (fluid buildup in the brain) frequently develops, especially in children, due to blockage of CSF pathways by the tumor mass 1 2 3 5.
• Lethargy and changes in the level of consciousness may indicate significant pressure or acute hydrocephalus.

Neurological Signs

• Ataxia (unsteady gait) is common when the tumor is located in the fourth ventricle, impacting cerebellar function 1 2.
• Vision problems such as blurred or double vision (diplopia) can result from increased pressure or direct tumor effect on cranial nerves 1 2 3.
• Papilledema, observed by an eye doctor as swelling of the optic disc, is a direct sign of raised intracranial pressure 2.

Age-Specific Features

• Enlarged head circumference is particularly notable in infants due to the flexibility of the skull bones 2 5.
• In adults, symptoms may be subtler and progress more slowly, but the underlying mechanisms are similar 1 7.

Less Common Symptoms

• Cranial nerve palsies, especially sixth nerve palsy, can occur if the tumor affects specific neural pathways 2.
• Seizures are rare but may occur depending on the tumor’s location.

Early detection of these symptoms, especially in young children, can lead to timely diagnosis and intervention.

Types of Choroid Plexus Carcinoma

Choroid plexus tumors are classified based on their histological features and biological behavior. Understanding the distinctions between types is critical for prognosis and tailoring treatment.

Tumor Type	WHO Grade	Age Group Most Affected	Sources
Choroid Plexus Papilloma	I	Infants, Young Children	2 3 5
Atypical Papilloma	II	Children, Rare in Adults	5 11
Choroid Plexus Carcinoma	III	Children, Rare in Adults	1 3 5 7

Table 2: Types of Choroid Plexus Tumors

Classification Overview

Choroid plexus tumors are divided into three main categories, each with distinct clinical and pathological features.

Choroid Plexus Papilloma (CPP)

• WHO Grade I, benign
• Represents the majority of choroid plexus tumors, especially in children 5.
• Typically slow-growing, with an excellent prognosis after surgical removal.
• Often found in the lateral ventricles of children and in the fourth ventricle in adults 3 5 7.

Atypical Choroid Plexus Papilloma (aCPP)

• WHO Grade II, intermediate malignancy
• Displays some features of increased cellularity or mitotic activity compared to CPP.
• Less common than both CPP and CPC, but represents a spectrum between benign and malignant forms 5 11.

Choroid Plexus Carcinoma (CPC)

• WHO Grade III, malignant
• Highly aggressive, accounting for 15–20% of choroid plexus tumors 5.
• Predominantly affects children under the age of 5; very rare in adults 1 3 5 7.
• Tends to grow rapidly, invade surrounding brain tissue, and spread via CSF pathways.

Tumor Location and Age Correlation

• Children: Most CPCs arise in the lateral ventricles, especially in very young children 3 5 7.
• Adults: When present, CPCs more commonly occur in the fourth ventricle 1 7.
• Papillomas: Can be found in any ventricle but are most often in the lateral (children) or fourth (adults) ventricles 3 5.

Clinical and Prognostic Implications

• CPCs are associated with a much poorer prognosis than papillomas due to their aggressive nature and high recurrence risk 3 5 12.
• The extent of surgical removal and tumor grade are the most important prognostic factors.

Causes of Choroid Plexus Carcinoma

The precise causes of CPC remain under investigation, but research points to a combination of genetic, molecular, and possibly environmental factors. Understanding these underpinnings is vital for developing new treatments and preventive strategies.

Cause/Mechanism	Description	Age Impact	Sources
Genetic Alterations	Chromosomal gains/losses, gene mutations	Children > Adults	4 6 8 9 10
Oncogene Activation	MYC, TAF12, NFYC, RAD54L	Pediatric CPC	8 9 10
Tumor Suppressor Loss	p53 pathway disruption	Pediatric CPC	9 10
Unknown/Other	Potential environmental/idiopathic factors	All ages	5 14

Table 3: Key Causes and Mechanisms in Choroid Plexus Carcinoma

Genetic and Chromosomal Alterations

CPC is characterized by complex genetic changes, distinguishing it from less aggressive choroid plexus tumors.

• Chromosomal Imbalances: Common alterations include gains of chromosomes 1, 2, 4, 12, 20 and losses of 5, 6, 16, 18, 19, and 22 4 6.
• Age-Related Patterns: Younger children (<3 years) are more likely to show losses of chromosomes 9, 19p, and 22q, whereas older patients have more gains on chromosomes 7, 19, 8q, 14q, and 21q 6.
• Prognostic Markers: Some genetic changes, such as loss of 12q, are linked to shorter survival, while others (gain of 9p, loss of 10q) may predict better outcomes 4 6.

Oncogenes and Tumor Suppressors

• MYC Activation: Overexpression of the MYC oncogene, especially in neural precursor cells, is a potent driver of CPC formation. MYC expression also correlates with tumor aggressiveness 9 10.
• Other Oncogenes: TAF12, NFYC, and RAD54L have been identified as oncogenes frequently gained in both mouse models and human CPC, implicating them in disease progression 8.
• Tumor Suppressor Loss: Inactivation of the p53 pathway, a key tumor suppressor, cooperates with MYC activation to promote CPC development 9.

Molecular Pathways

• Cell Cycle and DNA Repair: CPC tumors often show altered expression of genes regulating the cell cycle and DNA damage response, further fueling uncontrolled growth 9.
• Epigenetic Regulation: Disruption of transcription factors and the epigenetic machinery (such as TAF12, NFYC) also plays a role 8.

Environmental and Other Factors

• While most cases are sporadic, the potential influence of environmental or other unidentified factors cannot be ruled out, although no clear associations have been established 5 14.

Distinct Pathways by Age and Tumor Type

• Genetic evidence supports that pediatric and adult tumors, as well as papillomas versus carcinomas, may arise through different molecular mechanisms 4 6.

Treatment of Choroid Plexus Carcinoma

Choroid plexus carcinoma requires a highly coordinated, multidisciplinary approach. Treatment options are guided by tumor location, patient age, and molecular features, with the primary goals of maximal tumor removal and preservation of neurological function.

Treatment Modality	Main Approach	Key Considerations	Sources
Surgery	Maximal safe resection	Best survival, challenging in some sites	2 3 5 11 12 14
Chemotherapy	Multi-agent regimens	Used post-op or for unresectable tumors	3 12 13 14
Radiation Therapy	Adjuvant, limited in young children	Avoided in <3 yrs	3 12 14
Targeted/Novel	Experimental drugs	Under investigation	8 9 13

Table 4: Main Treatment Options for Choroid Plexus Carcinoma

Surgical Management

Gross Total Resection (GTR)

• The cornerstone of CPC treatment is maximal safe surgical removal 2 3 5 11 12 14.
• GTR is associated with significantly improved progression-free and overall survival, especially in children over 5 years old 12.
• Complete resection can be difficult due to the tumor’s location, size, and tendency to infiltrate surrounding brain tissue.

Surgical Challenges

• Tumors in the lateral ventricles (children) or fourth ventricle (adults) may be difficult to access 3 7.
• Risk of postoperative neurological deficits or persistent CSF disturbances, sometimes requiring shunt placement for hydrocephalus 11.

Adjuvant Therapies

Chemotherapy

• Chemotherapy is recommended for residual or inoperable tumors, and as adjuvant therapy after resection 3 12 13 14.
• Multi-agent regimens are common; etoposide, cyclophosphamide, and carboplatin have shown the highest response rates 13.
• Chemotherapy is particularly important for younger children, where radiation is less favored.

Radiation Therapy

• May be used in older children and adults as an adjunct to surgery and chemotherapy 3 12 14.
• Generally avoided in children under 3 years due to risk of developmental harm 14.
• The optimal dose and schedule remain topics of ongoing research.

Novel and Targeted Treatments

Experimental Approaches

• High-throughput drug screening and preclinical models have identified potential new drug targets, including inhibitors of specific molecular pathways involved in CPC 8 9.
• These approaches are still investigational but offer hope for future advances.

Prognosis and Follow-Up

• Despite aggressive treatment, CPC has a guarded prognosis, with median progression-free survival of 13 months and median overall survival of 29 months 12.
• Long-term survival is possible, especially with gross total resection and effective adjuvant therapy.
• Recurrence is common, and regular imaging is essential for early detection.

Multidisciplinary Care

• Optimal management requires a team including neurosurgeons, neuro-oncologists, radiologists, pathologists, and supportive care specialists.
• Treatment plans must be individualized, balancing tumor control with the quality of life, especially in young children.

Conclusion

Choroid plexus carcinoma is a formidable pediatric brain tumor with unique challenges in diagnosis, treatment, and research. Early recognition of symptoms, accurate classification, and advances in genetic understanding are essential for improving outcomes.

Key Takeaways:

• Symptoms: CPC typically presents with signs of increased intracranial pressure (headache, vomiting, ataxia), often progressing rapidly, especially in children.
• Types: There are three main choroid plexus tumor types—papilloma (benign), atypical papilloma (intermediate), and carcinoma (malignant), with CPC being the most aggressive.
• Causes: CPC arises from complex genetic alterations, including chromosomal imbalances, oncogene activation (MYC, TAF12), and tumor suppressor loss (p53), with distinct pathways for children and adults.
• Treatment: Maximal safe surgical removal is the mainstay, complemented by chemotherapy and, in select cases, radiation therapy. Experimental targeted therapies are being explored, but prognosis remains guarded.

Continued research and collaboration are vital to unraveling the mysteries of choroid plexus carcinoma and improving the lives of those affected by this rare disease.