🏷

Classifications

Harrison's Chapter

🔗

Mappings

MONDO

MONDO:0016717 choroid plexus neoplasm

Primary MONDO identifier for the choroid plexus neoplasm umbrella.

MONDO:0009837 choroid plexus papilloma Not Yet Curated

WHO grade 1 member of the family, modelled as the CPP subtype.

MONDO:0002684 atypical choroid plexus papilloma Not Yet Curated

WHO grade 2 member of the family, modelled as the aCPP subtype.

MONDO:0016718 choroid plexus carcinoma DisMech

WHO grade 3 member of the family, modelled as the CPC subtype and additionally curated as a standalone entry.

👪

Inheritance

1

Autosomal dominant (Li-Fraumeni-associated cases) HP:0000006

Sporadic choroid plexus tumors are not inherited. The predisposition that matters clinically is autosomal dominant heritable TP53-related cancer (Li-Fraumeni) syndrome, with variable, age-dependent penetrance. De novo germline TP53 variants occur, so absence of a family history does not exclude the syndrome.

Autosomal dominant inheritance

Show evidence (2 references)

PMID:32457520 SUPPORT Human Clinical

"germline TP53 alterations are often identified among children with cancers, in particular soft-tissue sarcomas, adrenocortical carcinomas, central nervous system tumours, or among adult females with early breast cancers, without familial history"

Supports that germline TP53 predisposition is frequently found in children with central nervous system tumors even absent a family history.

PMID:32457520 SUPPORT Human Clinical

"the penetrance of germline disease-causing TP53 variants is variable, depending both on the type of variant (dominant-negative variants being associated with a higher cancer risk) and on modifying factors"

Supports the variable penetrance qualifier.

◆

Subtypes

3

Choroid Plexus Papilloma (WHO grade 1) MONDO:0009837

WHO grade 1 papillary neoplasm of choroid plexus epithelium with orderly fronds lined by relatively uniform cuboidal-to-columnar epithelium and minimal mitotic activity. The commonest member of the family. Gross total resection is frequently curative and adjuvant therapy is usually unnecessary; 5-year overall survival is approximately 90%.

Show evidence (3 references)

PMID:30969571 SUPPORT Other

"Choroid plexus papillomas are neuroepithelial tumors that are World Health Organization grade I or II. In contrast, the rarely encountered choroid plexus carcinoma is classified as World Health Organization grade III."

Establishes the WHO grade assignment separating papilloma from carcinoma.

PMID:30969571 SUPPORT Other

"The prognosis of these benign neoplasms is favorable, and gross total resection is frequently curative."

Supports the favourable prognosis and curative role of complete resection in grade 1 disease.

PMID:34997889 SUPPORT Human Clinical

"Within the registry, histological grading was the most influential prognostic factor: for CPP (n = 55) the 5/10 year overall survival (OS) and the event free survival (EFS) probabilities were 100%/97% and 92%/92%, respectively; for APP (n = 49) 96%/96% and 76%/76%, respectively; and for CPC (n =..."

Prospective registry survival figures separating the three graded entities.

Atypical Choroid Plexus Papilloma (WHO grade 2) MONDO:0002684

WHO grade 2 intermediate entity defined operationally by increased mitotic activity - at least 2 mitoses per 10 high-power fields - which was the only atypical histologic feature independently associated with recurrence in the series that established the definition. Ancillary features (hypercellularity, nuclear pleomorphism, blurring of the papillary architecture, necrosis) may be present but are not required. Recurrence risk is intermediate between papilloma and carcinoma. Notably, DNA-methylation and copy-number profiling has not separated aCPP from CPP, so the entity is currently histologic rather than molecular.

Show evidence (4 references)

PMID:17086103 SUPPORT Human Clinical

"we propose to define atypical choroid plexus papilloma by mitotic activity (> or =2 mitoses per 10 high-power fields) corresponding to World Health Organization grade II"

The defining mitotic-count criterion for WHO grade 2 atypical choroid plexus papilloma.

PMID:17086103 SUPPORT Human Clinical

"Because mitotic activity is the sole atypical histologic feature independently associated with recurrence"

Explains why mitotic count, and not the other atypical features, was selected as the grading criterion.

PMID:17918524 SUPPORT Human Clinical

"The proportion of recurring tumors was higher in cases of atypical choroid plexus papilloma than in cases of choroid plexus papilloma"

Quantifies the elevated recurrence risk that justifies the intermediate grade.

+ 1 more reference

Choroid Plexus Carcinoma (WHO grade 3) MONDO:0016718

WHO grade 3 malignant choroid plexus tumor showing frank anaplasia - high cellularity, loss of papillary architecture, brisk mitoses, pleomorphism, necrosis and brain invasion - with a strong propensity for cerebrospinal fluid dissemination. Concentrated in infancy and early childhood. TP53 alteration is the dominant prognostic axis and germline TP53 (Li-Fraumeni syndrome) accounts for a substantial minority of cases. A dedicated dismech entry exists at kb/disorders/Choroid_Plexus_Carcinoma.yaml; this umbrella entry models the family-level mechanism only.

Show evidence (2 references)

PMID:35322202 SUPPORT Other

"Though CPP and atypical CPP are generally benign and can be resolved by surgery, CPC is a particularly aggressive and little understood cancer with a poor survival rate and a tendency for recurrence and metastasis."

Contrasts the malignant behaviour of carcinoma with the two papilloma grades.

PMID:34997889 SUPPORT Human Clinical

"Within the registry, histological grading was the most influential prognostic factor: for CPP (n = 55) the 5/10 year overall survival (OS) and the event free survival (EFS) probabilities were 100%/97% and 92%/92%, respectively; for APP (n = 49) 96%/96% and 76%/76%, respectively; and for CPC (n =..."

Prospective registry survival figures for carcinoma relative to the lower grades.

?

Discussions and Knowledge Gaps

2

Does simian virus 40 contribute to human choroid plexus tumorigenesis, or is the historical SV40 association entirely an artefact of PCR contamination and transgenic-mouse extrapolation?

KNOWLEDGE GAP OPEN sv40_aetiology

Attached to

environmental#Simian virus 40 (SV40) exposure

SV40 large T antigen reliably produces choroid plexus tumors in transgenic mice, and SV40 DNA sequences were reported in human choroid plexus tumors, which generated a long-lived aetiological hypothesis. The two strongest human tests point the other way: a nationwide Danish cohort found no excess of choroid plexus tumor after SV40-contaminated poliovirus vaccine exposure, and SV40 large T antigen was undetectable by immunohistochemistry in 82 central nervous system tumors. The residual gap is that these are negative studies of population exposure and protein detection respectively; neither formally excludes a hit-and-run or low-prevalence mechanism, and the discordance with earlier PCR-positive series has never been fully resolved. This entry therefore records the question as contested and currently unsupported rather than settled.

Proposed experiments

Contamination-controlled deep sequencing for SV40 in a contemporary cohort

sv40_contamination_controlled_sequencing

Deep sequencing of a contemporary, well-powered choroid plexus tumor cohort with rigorous contamination controls, reporting SV40 read counts against matched normal tissue from the same patients.

Would support

Reproducible SV40 reads above matched-normal background in a meaningful fraction of tumors.

Would refute

Absence of SV40 reads above background across an adequately powered cohort.

Harmonised reanalysis of discordant PCR series

sv40_harmonised_pcr_reanalysis

Pooled reanalysis of the discordant PCR-positive and PCR-negative series using harmonised assay controls, to determine whether laboratory contamination explains the geographic pattern of positivity.

Would support

Persistence of geographic positivity after assay harmonisation.

Would refute

Disappearance of positivity under common contamination controls.

Show evidence (1 reference)

PMID:12671021 REFUTE Human Clinical

"Exposure to SV40-contaminated poliovirus vaccine in Denmark was not associated with increased cancer incidence."

The strongest population-level negative test of the SV40 hypothesis.

Is atypical choroid plexus papilloma a distinct biological entity, or a histologic risk stratum within choroid plexus papilloma?

KNOWLEDGE GAP OPEN acpp_molecular_identity

Attached to

pathophysiology#Malignant Progression to High-Grade Carcinoma

WHO grade 2 atypical choroid plexus papilloma is defined purely by a mitotic-count threshold, and that threshold is genuinely prognostic for recurrence. But genome-wide copy-number, expression and methylation profiling has repeatedly failed to separate atypical papilloma from ordinary papilloma, and the authors of the largest such study concluded the two histologic subgroups are a single molecular entity. Whether the mitotic threshold captures a distinct biology or simply samples the upper tail of a continuous proliferative distribution within one entity is unresolved, and it matters for whether adjuvant decisions should be driven by grade or by molecular class.

Proposed experiments

Mitotically stratified molecular profiling of papilloma

acpp_mitotically_stratified_profiling

Prospective single-cell and methylation profiling of a papilloma cohort stratified by mitotic count, testing whether a molecular discontinuity exists at the 2-mitoses-per-10-HPF threshold.

Would support

A step change in molecular profile at the 2-mitoses-per-10-HPF threshold.

Would refute

A continuous molecular gradient across mitotic counts with no discontinuity.

Head-to-head prognostic comparison of grade versus methylation class

acpp_grade_versus_methylation_prognosis

Correlate methylation subgroup (pediatric A / pediatric B / adult) against mitotic count and recurrence in a pooled registry to determine which better predicts outcome.

Would support

Mitotic count outperforming methylation class as a predictor of recurrence.

Would refute

Methylation class outperforming mitotic count as a predictor of recurrence.

Show evidence (1 reference)

PMID:25336695 SUPPORT Human Clinical

"molecular similarities among the papillomas suggest that these two histologic subgroups are indeed a single molecular entity"

The authors' explicit statement that atypical papilloma and papilloma are molecularly one entity.

⚙

Pathophysiology

11

TP53 Pathway Inactivation

Loss of p53 tumor-suppressor function - by germline pathogenic TP53 variant (Li-Fraumeni syndrome) with somatic loss of the remaining allele, by somatic TP53 mutation, or by the combination of TP53 codon 72 and MDM2 SNP309 variants that confer p53 dysfunction in the absence of a mutation - is the only recurrent driver lesion in pediatric choroid plexus tumors. It is concentrated in carcinoma, where roughly half of tumors carry a TP53 mutation, and is absent or rare in papilloma.

choroid plexus epithelial cell CL:0000706

TP53 hgnc:11998

signal transduction by p53 class mediator GO:0072331 ↓ DECREASED

Downstream

Disruption of the GMNC-MCIDAS Multiciliogenesis Program Loss of the p53/RB tumour-suppressor axis is itself sufficient to derange the multiciliogenesis program: mouse carcinoma driven by combined Trp53 and Rb1 deletion shows multiciliation defects attributable to GMNC-MCIDAS deficiency. This places the differentiation block downstream of the tumour-suppressor lesion rather than as an independent trigger.

Chromosomal Instability and Aneuploidy Loss of p53-dependent DNA-damage checkpoint control permits accumulation of whole-chromosome copy-number changes; TP53-mutated carcinomas show markedly higher total structural variation than TP53 wild-type tumors and papillomas.

Choroid Plexus Epithelial Neoplastic Proliferation Combined p53 inactivation and oncogenic drive in choroid plexus epithelium is sufficient to initiate tumor formation in mouse models.

Show evidence (3 references)

PMID:33249490 SUPPORT Human Clinical

"Pediatric CPTs lack recurrent driver alterations except for TP53, whereas CPTs in adults show TERT promoter mutations or a novel CCDC47-PRKCA gene fusion, being associated with a more unfavorable clinical course."

Establishes TP53 as the only recurrent driver lesion in pediatric choroid plexus tumors.

PMID:20308654 SUPPORT Human Clinical

"TP53 mutations were found in 50% of choroid plexus carcinomas (CPCs)."

Quantifies the frequency of somatic TP53 mutation in carcinoma.

PMID:20308654 SUPPORT Human Clinical

"Additionally, two sequence variants known to confer TP53 dysfunction, TP53 codon72 and MDM2 SNP309, coexisted in the majority of TP53 wild-type CPCs (92%) and not in TP53 mutated CPC (P = .04), which suggests a complementary mechanism of TP53 dysfunction in the absence of a TP53 mutation."

Supports p53 dysfunction arising without a TP53 mutation via modifier variants.

Chromosomal Instability and Aneuploidy

Choroid plexus tumors are characterised by whole-chromosome copy-number alterations rather than focal driver events. Recurrent gains and losses partition the family into methylation/copy-number subgroups and vary with patient age; carcinomas show complex, hyperdiploid or hypodiploid genomes, and a greater burden of mutant TP53 copies tracks with a more aggressive course.

choroid plexus epithelial cell CL:0000706

chromosome segregation GO:0007059 ⚠ ABNORMAL DNA damage response GO:0006974 ↓ DECREASED

Downstream

Choroid Plexus Epithelial Neoplastic Proliferation Accumulated chromosomal imbalance dysregulates cell-cycle control and sustains the proliferative program of the tumor epithelium.

Malignant Progression to High-Grade Carcinoma Specific copy-number patterns are prognostic within carcinoma, with loss of 12q associated with markedly shorter survival.

Show evidence (6 references)

PMID:33249490 SUPPORT Human Clinical

"Copy-number alterations mainly represented whole-chromosomal alterations with subgroup-specific enrichments"

Establishes whole-chromosome copy-number change as the dominant genomic alteration class and its subgroup specificity.

PMID:24478045 SUPPORT Human Clinical

"Recurrent copy number losses of chromosomes 5, 6, 16, 18, 19, and 22 as well as gains of chromosomes 1, 2, 4, 12, and 20 were identified."

Enumerates the recurrent whole-chromosome imbalances in carcinoma.

PMID:25336695 SUPPORT Human Clinical

"Allele-specific CN analysis of CPCs revealed two novel subgroups according to DNA content: hypodiploid and hyperdiploid CPCs."

Supports genome-wide ploidy disturbance as a defining feature of carcinoma.

+ 3 more references

Adult-Specific TERT Promoter Activation

A separate, adult-restricted route into the same tumor. TERT promoter mutations occur in a quarter of adult choroid plexus tumor patients, reactivating telomerase and conferring replicative capacity; they are essentially absent from the pediatric-dominant subgroups, where TP53 is the recurrent lesion instead. TERT promoter mutation is prognostic in adults, associating with shorter progression-free survival, and a rare CCDC47-PRKCA fusion is a further adult-specific alteration reported in an aggressive papilloma. The pediatric counterpart of this telomere-maintenance requirement is telomerase-independent: alternative lengthening of telomeres is enriched in choroid plexus carcinoma (23% of cases) and is tied to somatic, not germline, TP53 mutation.

choroid plexus epithelial cell CL:0000706

TERT hgnc:11730

telomere maintenance GO:0000723 ↑ INCREASED

Downstream

Choroid Plexus Epithelial Neoplastic Proliferation Telomerase reactivation removes the replicative limit on the transformed choroid plexus epithelium, permitting sustained clonal expansion.

Show evidence (4 references)

PMID:33249490 SUPPORT Human Clinical

"On the contrary, TERT promoter mutations were encountered in 7/28 adult patients (25%) and associated with shorter progression-free survival (log-rank test, p=0.015)."

Establishes the frequency, adult restriction and prognostic effect of TERT promoter mutation.

PMID:33249490 SUPPORT Human Clinical

"Pediatric CPTs lack recurrent driver alterations except for TP53, whereas CPTs in adults show TERT promoter mutations or a novel CCDC47-PRKCA gene fusion, being associated with a more unfavorable clinical course."

Contrasts the adult TERT/fusion route with the pediatric TP53 route.

PMID:25315281 SUPPORT Human Clinical

"ALT was highly enriched in primitive neuroectodermal tumors (12 %), choroid plexus carcinomas (23 %) and high-grade gliomas (22 %)."

Documents the telomerase-independent alternative-lengthening-of-telomeres route to telomere maintenance in choroid plexus carcinoma, the pediatric counterpart of the adult TERT-promoter route this node models.

+ 1 more reference

Disruption of the GMNC-MCIDAS Multiciliogenesis Program

Normal choroid plexus epithelium is multiciliated. Human choroid plexus carcinomas instead carry solitary cilia, reflecting failure of the GMNC-MCIDAS transcriptional program that specifies multiciliated cell fate. In mice, NOTCH activation suppresses GMNC/MCIDAS and generates monociliated choroid plexus tumors, while disrupting the NOTCH complex restores multiciliation and reduces tumor growth - identifying loss of terminal multiciliated differentiation as a permissive step rather than a bystander finding. In mice the defect is itself downstream of tumour-suppressor loss - carcinoma driven by combined Trp53 and Rb1 deletion shows GMNC-MCIDAS-attributable multiciliation defects - so this node is modelled as a consequence of the TP53 arm rather than an independent trigger. This arm rests principally on model-system evidence.

choroid plexus epithelial cell CL:0000706

cilium assembly GO:0060271 ↓ DECREASED

Downstream

Choroid Plexus Epithelial Neoplastic Proliferation Failure of terminal multiciliated differentiation keeps tumor epithelium in a proliferative state; re-expression of GMNC/MCIDAS suppresses proliferation in model systems.

Show evidence (2 references)

PMID:35322202 SUPPORT Human Clinical

"In contrast to MCCs in the CP epithelia, CPCs in humans are characterized by solitary cilia, frequent TP53 mutations, and disturbances to multiciliogenesis program directed by the GMNC-MCIDAS transcriptional network."

Human tumor observation of the loss of multiciliation and the associated transcriptional program.

PMID:35322202 SUPPORT Model Organism

"NOTCH-driven CP tumors are monociliated, and disruption of the NOTCH complex restores multiciliation and decreases tumor growth."

Mouse experiment establishing that restoring multiciliation reduces tumor growth, supporting causality rather than correlation.

Choroid Plexus Epithelial Neoplastic Proliferation

Clonal expansion of transformed choroid plexus epithelial cells is the shared cellular event across all three graded entities. The proliferating cells retain choroid plexus epithelial identity - reliably demonstrable by Kir7.1 and stanniocalcin-1 immunoreactivity - and, critically for the disease mechanism, retain their secretory phenotype.

choroid plexus epithelial cell CL:0000706 tumor-associated macrophage CL:0000235 tumor stromal mesenchymal cell CL:0008019

positive regulation of cell population proliferation GO:0008284 ↑ INCREASED

choroid plexus epithelium UBERON:0003911

Downstream

Intraventricular Papillary Mass Formation Expanding tumor epithelium organised on a vascular stroma forms a lobulated, highly vascular papillary mass within the ventricular cavity.

Show evidence (4 references)

PMID:38867333 SUPPORT Human Clinical

"Choroid plexus tumors (CPTs) are intraventricular tumors derived from the choroid plexus epithelium and occur frequently in children."

Establishes the choroid plexus epithelium as the cell of origin for the whole family.

PMID:16330944 SUPPORT Human Clinical

"Expression of inward rectifier potassium channel Kir7.1 was confirmed in normal choroid plexus (34 of 35), choroid plexus papilloma (12 of 18), and choroid plexus carcinoma (5 of 5) but was not found in 100 other primary brain tumors and cerebral metastases."

Demonstrates retained choroid plexus epithelial identity in the neoplastic cells.

PMID:39482394 SUPPORT Human Clinical

"Here, we examine the heterogeneity of human choroid plexus tumors by single-nucleus transcriptome analysis of 23,906 cells from four disease-free choroid plexus and eleven choroid plexus tumors."

The single-nucleus atlas that resolves the tumor into its epithelial and stromal compartments.

+ 1 more reference

Intraventricular Papillary Mass Formation

The tumor grows as an intraventricular papillary mass - lateral ventricle in children, fourth ventricle in adults - occupying the cerebrospinal fluid space. This single anatomical fact generates the two mechanistically distinct routes to hydrocephalus modelled downstream: the mass is itself secretory (overproduction) and it physically occupies and obstructs the cerebrospinal fluid pathway (obstruction).

brain ventricle UBERON:0004086 lateral ventricle UBERON:0002285 fourth ventricle UBERON:0002422

Downstream

Abnormal cranial nerve physiology Direct compression of adjacent lower cranial nerves by a fourth-ventricular or cerebellopontine-angle mass.

Cerebrospinal Fluid Overproduction by Secretory Tumour Epithelium The tumor epithelium retains and amplifies the cerebrospinal-fluid-secreting function of normal choroid plexus, so tumor bulk translates directly into excess cerebrospinal fluid production.

Obstruction of Cerebrospinal Fluid Pathways by Mass Effect The intraventricular mass, and secondary changes in the subarachnoid pathways, impede cerebrospinal fluid egress independently of any change in production rate.

Show evidence (2 references)

PMID:30969571 SUPPORT Other

"Choroid plexus papillomas are more common in the infratentorial compartment in adults and the supratentorial compartment in children."

Establishes the age-dependent anatomical distribution (fourth ventricle in adults, lateral ventricle in children).

PMID:23172371 SUPPORT Human Clinical

"Although generally found within the ventricular system, they can arise ectopically in the brain parenchyma or disseminate throughout the neuraxis."

Confirms the predominantly intraventricular location while noting ectopic and disseminated presentations.

Cerebrospinal Fluid Overproduction by Secretory Tumour Epithelium

The first of the two hydrocephalus mechanisms. Neoplastic choroid plexus epithelium continues to secrete cerebrospinal fluid, and a large tumor can raise the formation rate several-fold above normal. Ventricular perfusion measurement in a child with a 74 g lateral-ventricular papilloma showed a preoperative formation rate of 1.05 ml/min falling fivefold to 0.20 ml/min after resection. Because production outstrips absorptive capacity while the pathways themselves remain patent, this route classically produces a communicating hydrocephalus.

choroid plexus epithelial cell CL:0000706

cerebrospinal fluid secretion GO:0033326 ↑ INCREASED

Downstream

Ventricular Enlargement and Raised Intracranial Pressure Cerebrospinal fluid production exceeding absorptive capacity expands the ventricular system and raises intracranial pressure.

Show evidence (3 references)

PMID:1022421 SUPPORT Human Clinical

"Utilizing a ventricular perfusion technique, the rate of CSF formation was determined in a 2-year-old child before and after removal of a 74 g choroid plexus papilloma from the left lateral ventricle."

Describes the direct measurement establishing tumor-driven cerebrospinal fluid overproduction.

PMID:30969571 SUPPORT Other

"Patients with choroid plexus papillomas often present with communicating hydrocephalus secondary to cerebrospinal fluid overproduction."

Supports overproduction as a routine clinical presentation mechanism and its communicating character.

PMID:35322202 SUPPORT Other

"The CP secretes cerebrospinal fluid that circulates within the ventricular system, driven by ependymal cilia movement."

Establishes the normal secretory function of the tissue of origin that the tumor retains.

Obstruction of Cerebrospinal Fluid Pathways by Mass Effect

The second of the two hydrocephalus mechanisms, and independent of the first. The intraventricular mass can occlude the ventricular outflow route directly - for example a fourth-ventricular tumor blocking the outlets - producing hydrocephalus with a normal cerebrospinal fluid formation rate. In addition, obstruction of the subarachnoid pathways and increased cerebrospinal fluid outflow resistance, attributed to repeated subarachnoid bleeding from these highly vascular tumors and to raised cerebrospinal fluid protein, can persist after complete tumor removal, which is why some patients remain shunt-dependent despite radical resection and no residual tumor.

cerebrospinal fluid circulation GO:0090660 ↓ DECREASED

fourth ventricle UBERON:0002422 subarachnoid space UBERON:0000315

Downstream

Ventricular Enlargement and Raised Intracranial Pressure Impeded cerebrospinal fluid egress traps fluid proximal to the block, dilating the ventricles and raising intracranial pressure.

Show evidence (3 references)

PMID:7414480 SUPPORT Human Clinical

"Dynamics of the cerebrospinal fluid were measured pre- and postoperatively in a patient with a choroid plexus papilloma associated with hydrocephalus. The production rate was 0.35 ml/min, absorption 0.0057 ml/min H2O, and the critical opening pressure 196 mm H2O."

Documents the measurement showing a normal production rate, isolating obstruction as the operative mechanism in that patient.

PMID:6738779 SUPPORT Human Clinical

"The persisting hydrocephalus is probably caused by an increase of the CSF outflow resistance because of a distal CSF-pathway obstruction."

Supports an outflow-resistance obstruction component that persists after the secretory tumor has been removed.

PMID:6738779 SUPPORT Human Clinical

"In spite of radical tumour removal, three years after the operation the axial computer tomography revealed a persistent hydrocephalus, but no recurrence of tumour."

Clinical demonstration that hydrocephalus can outlast removal of the overproducing tumour, requiring an obstruction/absorption mechanism.

Ventricular Enlargement and Raised Intracranial Pressure

The convergent consequence of both hydrocephalus mechanisms. Ventricular dilatation and raised intracranial pressure produce the characteristic clinical syndrome, which differs by age: in infants with open sutures, macrocephaly and a bulging fontanelle; in older children and adults, headache, vomiting and papilledema. Posterior-fossa (fourth-ventricular) tumors additionally produce cerebellar signs.

Downstream

Hydrocephalus Ventricular dilatation is by definition the hydrocephalus phenotype.

Increased intracranial pressure Expansion of the cerebrospinal fluid compartment within a closed cranium raises intracranial pressure.

Macrocephaly In infants with unfused sutures, raised intracranial pressure expands the calvarium.

Bulging fontanelle Raised intracranial pressure bows the unfused anterior fontanelle outward.

Papilledema Raised intracranial pressure is transmitted along the optic nerve sheath, producing optic disc swelling.

Headache Raised intracranial pressure is a classical cause of headache.

Vomiting Raised intracranial pressure causes non-gastrointestinal vomiting.

Ataxia Fourth-ventricular masses and posterior-fossa pressure impair cerebellar function.

Gait disturbance Ventricular enlargement produces gait impairment, both cerebellar and as part of the normal-pressure-hydrocephalus complex in adults.

Seizure Supratentorial mass effect and cortical irritation can provoke seizures.

Neurodevelopmental abnormality Chronic infantile hydrocephalus, tumor injury and the neurotoxicity of surgery, chemotherapy and radiotherapy together impair neurodevelopment.

Show evidence (1 reference)

PMID:30969571 SUPPORT Other

"Patients with choroid plexus papillomas often present with communicating hydrocephalus secondary to cerebrospinal fluid overproduction."

Establishes hydrocephalus as the dominant clinical presentation of choroid plexus tumors.

Malignant Progression to High-Grade Carcinoma

In a minority of tumors the epithelium acquires frank malignant features - hypercellularity, loss of the papillary architecture, brisk mitotic activity, pleomorphism and necrosis - defining WHO grade 3 carcinoma. This may be present de novo or, uncommonly, arise by documented progression from a previously resected grade 1 or grade 2 lesion. Carcinoma is transcriptionally distinguished from papilloma by upregulated cell-cycle and epithelial-mesenchymal transition programs.

epithelial to mesenchymal transition GO:0001837 ↑ INCREASED

Downstream

Brain Invasion and Leptomeningeal Dissemination High-grade tumors invade adjacent brain and seed the cerebrospinal fluid pathways; transcriptional metastasis programs are enriched in disseminated carcinoma.

Show evidence (2 references)

PMID:38867333 SUPPORT Human Clinical

"Differential gene expression analysis uncovered a significant overexpression of genes related to cell cycle regulation and epithelial-mesenchymal transition pathways in CPC compared to CPP."

Molecular characterisation of the papilloma-to-carcinoma difference.

PMID:17918524 SUPPORT Human Clinical

"However, two patients experienced a transition from a choroid plexus papilloma (WHO Grade I) and an atypical choroid plexus papilloma (WHO Grade II) to choroid plexus carcinomas (WHO Grade III)."

Documents that grade progression to carcinoma occurs, albeit rarely.

Brain Invasion and Leptomeningeal Dissemination

Invasion of adjacent brain parenchyma and seeding of the cerebrospinal fluid pathways is the principal route to treatment failure. Metastatic disease is present at diagnosis in about a fifth of carcinomas and a sixth of atypical papillomas, and even papilloma can occasionally disseminate through the neuraxis.

subarachnoid space UBERON:0000315

Downstream

Neoplasm of the central nervous system Invasive and disseminated disease establishes additional central nervous system tumor deposits.

Show evidence (2 references)

PMID:19543851 SUPPORT Human Clinical

"Metastases were present at diagnosis in 17% of APP patients, 5% of CPP patients, and 21% of CPC patients."

Grade-stratified frequency of dissemination at diagnosis across the family.

PMID:23172371 SUPPORT Human Clinical

"Although generally found within the ventricular system, they can arise ectopically in the brain parenchyma or disseminate throughout the neuraxis."

Confirms that even grade 1 papilloma can disseminate through the cerebrospinal fluid pathways.

✶

Histopathology

4

Papillary Architecture VERY_FREQUENT

Orderly papillary fronds of fibrovascular cores lined by a single layer of relatively uniform cuboidal-to-columnar epithelium define choroid plexus papilloma. Blurring or loss of this architecture is one of the atypical features that shifts a tumor toward higher grade.

Show evidence (1 reference)

PMID:17086103 SUPPORT Human Clinical

"a series of 164 choroid plexus tumors was evaluated for the presence of atypical histologic features, including mitotic activity, increased cellularity, nuclear pleomorphism, blurring of papillary growth pattern, and necrosis"

Lists the papillary growth pattern and its blurring among the graded histologic features of the family.

Increased Mitotic Activity OCCASIONAL

Mitotic activity of at least 2 mitoses per 10 high-power fields is the sole grading criterion for atypical choroid plexus papilloma (WHO grade 2). It was present in 15% of otherwise untreated papillomas in the defining series (a figure reported in the abstract's bracketed per-feature breakdown, which cannot be quoted inside a snippet because the reference validator strips bracketed spans) and was the only atypical feature independently associated with recurrence on multivariate analysis. The bound NCIT term used here (Two to 10 Mitoses per 10HPF) is the closest available closed-enum value; the actual WHO criterion is at least 2 mitoses per 10 high-power fields with no upper bound.

Show evidence (2 references)

PMID:17086103 SUPPORT Human Clinical

"we propose to define atypical choroid plexus papilloma by mitotic activity (> or =2 mitoses per 10 high-power fields) corresponding to World Health Organization grade II"

The defining histologic criterion and its threshold.

PMID:17086103 SUPPORT Human Clinical

"Using a multivariate model, an independent effect of mitotic activity on the probability of recurrence could be confirmed (p = 0.001)."

Establishes the prognostic independence of mitotic count.

Hypercellularity and Nuclear Pleomorphism OCCASIONAL

Increased cellularity and nuclear pleomorphism are recognised atypical features of choroid plexus tumors, present in 20% and 13% respectively of papillomas in the defining series, but neither was independently associated with recurrence and neither is used for grading in isolation. Together with necrosis and loss of papillary architecture they contribute to the diagnosis of frank carcinoma.

Show evidence (1 reference)

PMID:17086103 SUPPORT Human Clinical

"Of 124 choroid plexus papillomas that had not received adjuvant treatment, 46 tumors (37%) displayed at least one atypical feature, including increased cellularity"

Establishes that a substantial minority of choroid plexus papillomas display at least one atypical histologic feature, increased cellularity among them. The per-feature percentages quoted in the description come from the continuation of this same sentence; that continuation is not quoted verbatim because the reference validator strips square-bracketed spans from snippets before matching, so the abstract's bracketed percentages cannot be used inside a snippet.

Kir7.1 and Stanniocalcin-1 Immunoreactivity FREQUENT

Immunohistochemical expression of the inward rectifier potassium channel Kir7.1 and of stanniocalcin-1 is highly sensitive and specific for choroid plexus lineage, distinguishing choroid plexus tumors from other primary brain tumors and from metastatic carcinoma. Transthyretin is also expressed but is significantly less specific.

Show evidence (2 references)

PMID:16330944 SUPPORT Human Clinical

"Our data suggest that antibodies directed against Kir7.1 and stanniocalcin-1 might serve as sensitive and specific diagnostic markers for choroid plexus tumors."

Establishes Kir7.1 and stanniocalcin-1 as the discriminating lineage markers.

PMID:16330944 SUPPORT Human Clinical

"Transthyretin stained choroid plexus (33 of 35), choroid plexus papilloma (14 of 18), and plexus carcinoma (2 of 5), but its specificity was significantly lower."

Supports the lower diagnostic specificity of transthyretin relative to Kir7.1 and stanniocalcin-1.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

●

Phenotypes

13

Digestive 1

Vomiting OCCASIONAL Vomiting HP:0002013

Show evidence (1 reference)

PMID:21121734 SUPPORT Human Clinical

"This child presented with macrocephaly, irritability, inability to roll over, and vomiting."

Vomiting as a documented presenting symptom alongside the other raised-pressure signs.

Eye 1

Papilledema OCCASIONAL Papilledema HP:0001085

Show evidence (1 reference)

PMID:34754533 SUPPORT Human Clinical

"Case 2: a 16-year-old boy presented decreased visual acuity, papilledema, and morning headaches."

Papilledema as a documented presenting sign in an older child with a lateral-ventricular choroid plexus tumor and communicating hydrocephalus.

Head and Neck 1

Macrocephaly FREQUENT Macrocephaly HP:0000256

Show evidence (2 references)

PMID:21121734 SUPPORT Human Clinical

"This child presented with macrocephaly, irritability, inability to roll over, and vomiting."

Macrocephaly as a documented presenting sign of a third-ventricular choroid plexus papilloma in a 3-month-old.

PMID:36659972 PARTIAL Human Clinical

"Incidence was highest among children less than one year old among all subtypes (CPP AAIR: 0.278; aCPP AAIR: 0.140; CPC AAIR: 0.195), reducing as patients aged."

Supports the infantile age distribution that makes macrocephaly a characteristic sign; the abstract does not itself enumerate presenting signs.

Nervous System 6

Hydrocephalus FREQUENT Hydrocephalus HP:0000238

Show evidence (3 references)

PMID:30969571 SUPPORT Other

"Patients with choroid plexus papillomas often present with communicating hydrocephalus secondary to cerebrospinal fluid overproduction."

Supports hydrocephalus as the characteristic presentation and names the overproduction route.

PMID:7414480 SUPPORT Human Clinical

"The hydrocephalus was due solely to obstruction of the fourth ventricle."

Supports the obstructive route as an independent cause of the same phenotype.

PMID:34754533 SUPPORT Human Clinical

"Hydrocephalus is the most common presentation of choroid plexus tumors; it is thought to be caused either by mass effect obstructing the cerebrospinal fluid pathways or secretory properties of the tumor."

States the dual mechanism explicitly - obstruction by mass effect OR secretory overproduction - which is why this entry models them as two nodes.

Increased intracranial pressure FREQUENT Increased intracranial pressure HP:0002516

Show evidence (2 references)

PMID:1022421 PARTIAL Human Clinical

"Whereas these data are regarded as conclusive evidence of CSF overproduction by a choroid plexus papilloma, the pathogenesis of generalized ventricular enlargement in this case was due to part to obstruction of the subarachnoid pathways."

Documents the generalized ventricular enlargement from which raised intracranial pressure follows; the abstract does not report a pressure measurement, so support is partial.

PMID:21121734 SUPPORT Human Clinical

"He was found to have an enlarged head circumference, a full and tense fontanel, splayed sutures, and forced downward gaze."

The classical infant sign cluster of raised intracranial pressure - head expansion, tense fontanelle, sutural diastasis and the setting-sun sign - in a child with a choroid plexus papilloma.

Headache OCCASIONAL Headache HP:0002315

Show evidence (2 references)

PMID:34754533 SUPPORT Human Clinical

"Case 2: a 16-year-old boy presented decreased visual acuity, papilledema, and morning headaches."

Morning headache, the classical raised-intracranial-pressure pattern, as a presenting symptom of a choroid plexus tumor.

PMID:27913261 SUPPORT Human Clinical

"A 45-year-old woman presented with a 6-year history of headache and typical symptoms of normal-pressure hydrocephalus, including gait disturbance, urinary incontinence, and cognitive dysfunction, in addition to the more common symptoms of CPP, such as lower cranial nerve dysfunctions and ataxia."

Headache as the leading symptom in the adult, fourth-ventricular presentation.

Ataxia OCCASIONAL Ataxia HP:0001251

Show evidence (1 reference)

PMID:27913261 SUPPORT Human Clinical

"in addition to the more common symptoms of CPP, such as lower cranial nerve dysfunctions and ataxia"

The authors identify ataxia and lower cranial nerve dysfunction as the more common symptoms of choroid plexus papilloma at this site.

Seizure OCCASIONAL Seizure HP:0001250

Show evidence (1 reference)

PMID:37928807 SUPPORT Human Clinical

"We herein report a rare presentation of CPP in a 6-year-old Sudanese female child with seizures."

Documented seizure presentation of a lateral-ventricular choroid plexus papilloma; the authors themselves describe it as a rare presentation, consistent with the OCCASIONAL frequency band.

Gait disturbance OCCASIONAL Gait disturbance HP:0001288

Show evidence (2 references)

PMID:27913261 SUPPORT Human Clinical

"A 45-year-old woman presented with a 6-year history of headache and typical symptoms of normal-pressure hydrocephalus, including gait disturbance, urinary incontinence, and cognitive dysfunction"

Gait disturbance as a documented presenting feature of an adult choroid plexus papilloma with communicating hydrocephalus.

PMID:27913261 SUPPORT Human Clinical

"The symptoms of normal-pressure hydrocephalus disappeared."

Resolution after tumour excision confirms the gait disturbance was tumour-driven rather than incidental.

Other 4

Bulging fontanelle OCCASIONAL Bulging fontanelle HP:6000647

Show evidence (2 references)

PMID:34754533 SUPPORT Human Clinical

"Case 1: a 2-month-old baby girl presented with bulging fontanelle, sunsetting eyes."

Bulging fontanelle as the documented presenting sign of a third-ventricular choroid plexus tumor in a 2-month-old.

PMID:21121734 SUPPORT Human Clinical

"He was found to have an enlarged head circumference, a full and tense fontanel, splayed sutures, and forced downward gaze."

A second case documenting the tense/full fontanelle in an infant with a choroid plexus papilloma.

Abnormal cranial nerve physiology OCCASIONAL Abnormal cranial nerve physiology HP:0031910

Show evidence (1 reference)

PMID:27913261 SUPPORT Human Clinical

"in addition to the more common symptoms of CPP, such as lower cranial nerve dysfunctions and ataxia"

The authors identify lower cranial nerve dysfunction as one of the more common symptoms of choroid plexus papilloma at this site.

Neurodevelopmental abnormality FREQUENT Neurodevelopmental abnormality HP:0012759

Show evidence (1 reference)

PMID:20515336 SUPPORT Human Clinical

"None of the survivors received radiation therapy. However, 6 of 8 display significant neurocognitive and/or sensorial deficit."

Quantifies neurodevelopmental morbidity among survivors even without radiotherapy.

Neoplasm of the central nervous system VERY_FREQUENT Neoplasm of the central nervous system HP:0100006

Show evidence (1 reference)

PMID:33249490 SUPPORT Human Clinical

"Choroid plexus tumors (CPTs) are intraventricular brain tumors predominantly arising in children but also affecting adults."

Establishes the central nervous system neoplasm phenotype.

🧬

Genetic Associations

3

TP53 (Germline pathogenic TP53 variants cause Li-Fraumeni syndrome / heritable TP53-related cancer syndrome, of which choroid plexus carcinoma is a sentinel tumor. In the landmark multi-institutional series, every patient with a germline TP53 mutation fulfilled Li-Fraumeni criteria and every patient not meeting those criteria had wild-type TP53. Roughly a third of choroid plexus carcinomas occur in the setting of Li-Fraumeni syndrome. Cross-reference kb/disorders/Li-Fraumeni_Syndrome.yaml.)

Gene: TP53 hgnc:11998 relationship_type: CAUSATIVE variant_origin: GERMLINE

Show evidence (5 references)

PMID:20308654 SUPPORT Human Clinical

"All individuals with germline TP53 mutations fulfilled LFS criteria, whereas all patients not meeting these criteria harbored wild-type TP53 (P < .001)."

Establishes the tight correspondence between germline TP53 mutation and Li-Fraumeni syndrome in this tumor.

PMID:20308654 SUPPORT Human Clinical

"Choroid plexus carcinomas are pediatric tumors with poor survival rates and a strong, but poorly understood, association with Li-Fraumeni syndrome (LFS)."

States the sentinel-cancer relationship between choroid plexus carcinoma and Li-Fraumeni syndrome.

PMID:38316675 SUPPORT Human Clinical

"The review highlighted the strong association (36%) between CPCs and LFS, primarily due to TP53 germline mutations."

Quantifies the proportion of choroid plexus carcinomas arising in Li-Fraumeni syndrome.

+ 2 more references

TP53 (somatic) (Somatic TP53 mutation is the only recurrent somatic driver in pediatric choroid plexus tumors and is the dominant prognostic axis in carcinoma - TP53-wild-type carcinomas have markedly better survival than TP53-mutant carcinomas, and a greater number of mutant TP53 copies confers worse outcome still.)

Gene: TP53 hgnc:11998 relationship_type: SOMATIC_DRIVER variant_origin: SOMATIC

Show evidence (5 references)

PMID:33506206 SUPPORT Human Clinical

"Patients with TP53-wild-type tumors had a 5-year PFS of 100% as compared to 28.6 ± 17.1% for TP53-mutant tumors (P = .012)."

The strongest prospective statement of the TP53 prognostic axis, and of the markedly better survival of TP53-wild-type carcinoma.

PMID:33506206 SUPPORT Human Clinical

"TP53-mutational status was the only significant prognostic variable and should form the basis of risk-stratification in future trials."

Establishes TP53 status as the dominant prognostic variable.

PMID:20308654 SUPPORT Human Clinical

"Five-year survival rates for patients with TP53-immunopositive and -immunonegative CPCs were 0% and 82 (+/- 9%), respectively (P < .001)."

Independent, earlier demonstration of the same survival split by TP53 status.

+ 2 more references

TERT (TERT promoter mutation is an adult-specific somatic alteration in choroid plexus tumors, found in a quarter of adult patients and associated with shorter progression-free survival. It is not a germline predisposition and is not seen in the pediatric-dominant subgroups.)

Gene: TERT hgnc:11730 relationship_type: SOMATIC_DRIVER variant_origin: SOMATIC

Show evidence (1 reference)

PMID:33249490 SUPPORT Human Clinical

"On the contrary, TERT promoter mutations were encountered in 7/28 adult patients (25%) and associated with shorter progression-free survival (log-rank test, p=0.015)."

Establishes the frequency and prognostic significance of TERT promoter mutation in adult choroid plexus tumors.

💊

Medical Actions

8

Maximal Safe Surgical Resection

Category: Therapeutic Action: Gross Total Resection NCIT:C131672

Gross total resection is the cornerstone of treatment for every grade and, in carcinoma, the strongest modifiable prognostic factor; in papilloma and atypical papilloma the same population data show no overall survival difference between gross total and subtotal resection. In grade 1 papilloma it is frequently curative and needs no adjuvant therapy; in carcinoma it is independently associated with improved overall survival. Planning must account for the extreme vascularity of these tumors and the small circulating blood volume of infants, and staged or second-look surgery is often used.

Mechanism Target:

INHIBITS Cerebrospinal Fluid Overproduction by Secretory Tumour Epithelium — Removing the secretory tumor epithelium directly abolishes the excess cerebrospinal fluid production, as demonstrated by the fivefold fall in formation rate after resection.

Show evidence (1 reference)

PMID:1022421 SUPPORT Human Clinical

"Postoperatively, the CSF formation rate was reduced fivefold to 0.20 +/- SD 0.01 ml/min (288 ml/day)."

Measured fall in cerebrospinal fluid formation rate after tumor resection, directly evidencing the treatment-mechanism link.

Show evidence (4 references)

PMID:28939225 SUPPORT Human Clinical

"All patients should undergo maximal safe resection, because GTR is associated with improved survival."

Pooled individual-patient-data recommendation establishing gross total resection as the key modifiable prognostic factor.

PMID:38339361 SUPPORT Human Clinical

"Meanwhile, in patients with CPC, gross total resection (GTR) was associated with significantly better OS than subtotal resection (STR) only."

Population-level confirmation for carcinoma.

PMID:30969571 SUPPORT Other

"The prognosis of these benign neoplasms is favorable, and gross total resection is frequently curative."

Establishes the curative role of resection alone in grade 1 disease.

+ 1 more reference

Observation After Complete Resection

Category: Monitoring Action: Follow-up Examination After Treatment for Malignant Neoplasm NCIT:C171209

Following complete resection of a grade 1 papilloma - and, in most protocols, of a completely resected atypical papilloma - patients are observed with serial MRI rather than treated with adjuvant therapy. Population data show no overall survival difference between gross total and subtotal resection in papilloma or atypical papilloma, supporting a conservative posture in these grades.

Show evidence (2 references)

PMID:19543851 SUPPORT Human Clinical

"After surgery, patients who had undergone complete resection were observed, whereas patients with incompletely resected or metastasized APP were treated with six chemotherapy courses"

Protocol evidence for observation after complete resection in atypical papilloma.

PMID:38339361 SUPPORT Human Clinical

"Overall, there is no difference in OS with GTR vs. STR in CPP or aCPP."

Supports a less aggressive posture in the two lower grades.

Carboplatin-Etoposide-Vincristine (CarbEV) Chemotherapy

Category: Therapeutic Action: chemotherapy Ontology label: Chemotherapy NCIT:C15632

Agent: carboplatin CHEBI:31355 etoposide CHEBI:4911 vincristine CHEBI:28445

Multi-agent chemotherapy for high-risk disease - carcinoma, incompletely resected atypical papilloma, and any metastatic choroid plexus tumor. In the randomised high-risk arm of CPT-SIOP-2000, carboplatin/etoposide/vincristine was superior to cyclophosphamide/etoposide/vincristine for progression-free survival.

Mechanism Target:

INHIBITS Choroid Plexus Epithelial Neoplastic Proliferation — Cytotoxic chemotherapy targets the proliferating tumor epithelium.

Show evidence (1 reference)

PMID:19543851 SUPPORT Human Clinical

"All nine APP patients who received postoperative chemotherapy showed an early response after two cycles: two had complete remission, four had partial response, and three had stable disease."

Radiographic tumor response to the chemotherapy backbone evidences that it acts on the proliferating tumor mass.

Show evidence (2 references)

PMID:34997889 SUPPORT Human Clinical

"For randomized CPC, the 5/10 year progression free survival (PFS) of patients on CarbEV (n = 20) were 62%/47%, respectively, compared to 27%/18%, on CycEV (n = 15), (intention-to-treat, HR 2.6, p = 0.032)."

Randomised evidence that the carboplatin-containing backbone is superior in high-risk disease.

PMID:19543851 SUPPORT Human Clinical

"All nine APP patients who received postoperative chemotherapy showed an early response after two cycles: two had complete remission, four had partial response, and three had stable disease."

Demonstrates chemosensitivity of atypical papilloma treated on the same protocol.

Neoadjuvant ICE Chemotherapy Before Second-Look Surgery

Category: Therapeutic Action: chemotherapy Ontology label: Chemotherapy NCIT:C15632

Agent: ifosfamide CHEBI:5864 carboplatin CHEBI:31355 etoposide CHEBI:4911

Ifosfamide/carboplatin/etoposide given before a planned second operation devascularises the tumor and reduces intraoperative blood loss, raising the rate of complete or near-complete resection in carcinoma - a strategy that directly addresses the vascularity that limits primary resection in infants.

Show evidence (2 references)

PMID:20515336 SUPPORT Human Clinical

"In this experience, second surgery following neoadjuvant ICE chemotherapy led to a high rate of complete or near-complete resection."

Supports the neoadjuvant-then-resect strategy and its surgical benefit.

PMID:20515336 SUPPORT Human Clinical

"Chemotherapy appears to facilitate second-look surgery, in particular through a reduction of intraoperative blood loss."

Names the mechanism by which neoadjuvant chemotherapy improves resectability.

Risk-Adapted Radiotherapy

Category: Therapeutic Action: Radiation Therapy NCIT:C15313

Radiotherapy is used selectively and is generally withheld in children under three years. Focal fields are used for non-metastatic carcinoma and incompletely resected atypical papilloma; craniospinal fields are reserved for metastatic or non-responsive disease. Radiotherapy must be avoided or minimised where feasible in germline TP53 carriers because it contributes to subsequent primary tumours - which is why germline testing precedes treatment planning.

Show evidence (3 references)

PMID:34997889 SUPPORT Human Clinical

"Patients older than three years were recommended to receive irradiation: focal fields for non-metastatic CPC, incompletely resected atypical choroid plexus papilloma (APP) or metastatic choroid plexus papilloma (CPP); craniospinal fields for metastatic CPC/APP and non-responsive CPC."

The protocolised risk-adapted radiotherapy policy for the whole family.

PMID:32457520 SUPPORT Human Clinical

"in cancer patients with germline disease-causing TP53 variants, radiotherapy, and conventional genotoxic chemotherapy contribute to the development of subsequent primary tumours"

The basis for radiation avoidance in germline TP53 carriers.

PMID:38316675 SUPPORT Human Clinical

"Irradiation-sparing therapies are recommended for LFS-associated CPCs to mitigate the risk of secondary malignancies."

Disease-specific recommendation to spare irradiation in Li-Fraumeni-associated carcinoma.

Germline TP53 Testing and Genetic Counselling

Category: Diagnostic Action: Genetic Testing NCIT:C15709

Paired germline TP53 testing with genetic counselling is indicated in essentially every child with choroid plexus carcinoma, irrespective of family history, and must be performed before treatment starts. It is the highest-value single action in the entry because it changes three things at once: the treatment plan (avoiding radiotherapy and genotoxic chemotherapy in carriers), lifelong surveillance for the patient, and cascade testing for relatives.

Show evidence (2 references)

PMID:32457520 SUPPORT Human Clinical

"It is critical to perform TP53 testing before the initiation of treatment in order to avoid in carriers, if possible, radiotherapy and genotoxic chemotherapies."

The guideline statement that testing must precede treatment.

PMID:38316675 SUPPORT Human Clinical

"Studies emphasized the need for genetic testing in patients with CPCs, especially in pediatric cases, to identify LFS implications."

Disease-specific recommendation for germline testing in choroid plexus carcinoma.

Li-Fraumeni Surveillance in Confirmed Carriers

Category: Screening Action: Disease Screening NCIT:C15419

Confirmed germline TP53 carriers enter lifelong surveillance: in children, clinical examination and abdominal ultrasound every six months plus annual whole-body and brain MRI from the first year of life. This targets the whole Li-Fraumeni tumour spectrum, not merely recurrent choroid plexus disease.

Show evidence (1 reference)

PMID:32457520 SUPPORT Human Clinical

"In children, the recommendations are to perform clinical examination and abdominal ultrasound every 6 months, annual WBMRI and brain MRI from the first year of life, if the TP53 variant is known to be associated with childhood cancers."

The paediatric surveillance protocol for germline TP53 carriers.

Cerebrospinal Fluid Diversion

Category: Therapeutic Action: Ventriculoperitoneal Shunt Placement NCIT:C168483

Shunt placement or other cerebrospinal fluid diversion is used when hydrocephalus does not resolve after tumor removal. Because the obstruction and outflow-resistance arm of the mechanism can persist once the secretory tumor is gone, a subset of patients remain shunt-dependent despite radical resection and no residual tumour.

Mechanism Target:

INHIBITS Ventricular Enlargement and Raised Intracranial Pressure — Diversion bypasses the obstructed pathway and normalises intracranial pressure irrespective of which mechanism produced the hydrocephalus.

Show evidence (1 reference)

PMID:6738779 SUPPORT Human Clinical

"To control the hydrocephalus, a bilateral shunt with low pressure valve was necessary."

Documents shunt diversion being used, and required, to control the hydrocephalus.

Show evidence (1 reference)

PMID:6738779 SUPPORT Human Clinical

"To control the hydrocephalus, a bilateral shunt with low pressure valve was necessary."

Documents the need for cerebrospinal fluid diversion when hydrocephalus persists after resection.

🌍

Environmental Factors

1

Simian virus 40 (SV40) exposure

`presence: ABSENT` is the closest available schema value for "exposure examined and found not to be associated"; the enum has no NOT_ASSOCIATED value, and `effect:` is deliberately left unset because neither a causal nor a protective label is correct. Read the description and the REFUTE-tagged evidence, not the enum, for the intended claim. The residual uncertainty is that the negative studies address vaccine-era population exposure and large T antigen protein detection, not every proposed SV40 mechanism.

An aetiological role for SV40 in choroid plexus tumors was proposed historically on the basis of SV40 DNA sequences detected in tumor tissue and of SV40 large T antigen driving choroid plexus tumors in transgenic mice, and was linked to the accidental SV40 contamination of early poliovirus vaccine. This entry treats the claim as contested and, on current evidence, largely discounted rather than established: a nationwide Danish cohort of 69.5 million person-years found no excess of choroid plexus tumor in the vaccine-exposed birth cohorts, and immunohistochemistry for SV40 large T antigen was negative in all of 82 central nervous system tumors including choroid plexus lesions. The entry therefore asserts neither causation nor definitive exclusion; it records that the epidemiological and protein-level evidence does not support SV40 as a cause.

Show evidence (4 references)

PMID:12671021 REFUTE Human Clinical

"Specifically, SV40 exposure was not associated with increased incidence of mesothelioma, ependymoma, choroid plexus tumor, or non-Hodgkin's lymphoma."

Population-level refutation of an SV40 contribution to choroid plexus tumor incidence.

PMID:12671021 SUPPORT Human Clinical

"SV40 DNA sequences have been detected in several human malignancies, including mesothelioma, ependymoma, choroid plexus tumors, and non-Hodgkin's lymphoma."

Records the historical basis of the SV40 hypothesis that the same study set out to test.

PMID:15790713 REFUTE Human Clinical

"None of the tumours (20 ependymomas, 20 glioblastomas, 12 oligodendrogliomas, three plexus choroid adenomas, two plexus choroid carcinomas, 15 meningiomas, and 10 medulloblastomas) contained SV40 Tag positive cells."

Protein-level failure to detect the SV40 oncoprotein in choroid plexus tumors.

+ 1 more reference

🔬

Biochemical Markers

2

Kir7.1 (KCNJ13) Immunoexpression (PRESENT)

Show evidence (2 references)

PMID:16330944 SUPPORT Human Clinical

"Expression of inward rectifier potassium channel Kir7.1 was confirmed in normal choroid plexus (34 of 35), choroid plexus papilloma (12 of 18), and choroid plexus carcinoma (5 of 5) but was not found in 100 other primary brain tumors and cerebral metastases."

Establishes both the sensitivity and the specificity of Kir7.1 for choroid plexus tumors.

PMID:21276081 PARTIAL Human Clinical

"Two AT/RT cases exhibited membranous staining of Kir7.1, indicating a plexus epithelial differentiation of these tumors."

Qualifies the specificity claim by documenting Kir7.1 staining in atypical teratoid/rhabdoid tumor.

Stanniocalcin-1 Immunoexpression (PRESENT)

Show evidence (1 reference)

PMID:16330944 SUPPORT Human Clinical

"Similarly, stanniocalcin-1 stained normal choroid plexus (32 of 35), choroid plexus papilloma (16 of 18), and choroid plexus carcinoma (3 of 5), whereas staining was seen in only 2 of 100 other primary brain tumors and cerebral metastases."

Quantifies the sensitivity and specificity of stanniocalcin-1.

🔀

Differential Diagnoses

6

Conditions with similar clinical presentations that must be differentiated from Choroid Plexus Neoplasm:

Ependymoma Not Yet Curated MONDO:0016698

Overlapping Features Papillary intraventricular ependymoma is the closest radiological and histological mimic. It shares the intraventricular location and papillary appearance but lacks choroid plexus lineage markers.

Distinguishing Features

Ependymoma is negative for the choroid plexus lineage markers Kir7.1 and stanniocalcin-1.
Ependymoma typically shows GFAP positivity with perivascular pseudorosettes and ependymal rosettes rather than true fibrovascular papillae.

Show evidence (1 reference)

PMID:16330944 SUPPORT Human Clinical

"gene expression profiles of choroid plexus epithelial cells (n = 8) and ependymal cells (n = 6) microdissected from human autopsy brains as well as choroid plexus papilloma tissue were investigated using DNA microarrays"

The marker study was explicitly designed against ependymal cells, confirming ependymoma as the principal lineage differential.

Papillary meningioma MONDO:0016642

Overlapping Features Intraventricular and papillary meningiomas can present as an enhancing intraventricular mass and mimic choroid plexus papilloma both radiologically and histologically.

Distinguishing Features

Meningioma is EMA-positive and negative for the choroid plexus lineage markers Kir7.1 and stanniocalcin-1.
Stanniocalcin-1 stained only 2 of 100 non-choroid-plexus primary brain tumors and cerebral metastases in the defining marker series.

Show evidence (1 reference)

PMID:16330944 SUPPORT Human Clinical

"Similarly, stanniocalcin-1 stained normal choroid plexus (32 of 35), choroid plexus papilloma (16 of 18), and choroid plexus carcinoma (3 of 5), whereas staining was seen in only 2 of 100 other primary brain tumors and cerebral metastases."

Supports the marker-based exclusion of other primary brain tumors, the category that includes meningioma.

Metastatic papillary carcinoma Not Yet Curated MONDO:0024879

Overlapping Features Metastatic papillary adenocarcinoma to the brain (thyroid, lung, renal, ovarian) can be histologically indistinguishable from choroid plexus carcinoma on morphology alone, particularly in adults.

Distinguishing Features

Kir7.1 was absent from all 100 non-choroid-plexus primary brain tumors and cerebral metastases tested, making it the discriminating marker.
A known extracranial primary and a non-intraventricular or multifocal distribution favour metastasis.

Show evidence (1 reference)

PMID:16330944 SUPPORT Human Clinical

"Expression of inward rectifier potassium channel Kir7.1 was confirmed in normal choroid plexus (34 of 35), choroid plexus papilloma (12 of 18), and choroid plexus carcinoma (5 of 5) but was not found in 100 other primary brain tumors and cerebral metastases."

Establishes the marker that separates choroid plexus tumors from cerebral metastases.

Atypical teratoid/rhabdoid tumor MONDO:0020560

Overlapping Features AT/RT of infancy can occupy the same intraventricular compartment and the same age group as choroid plexus carcinoma, and is the most dangerous confusion because treatment differs substantially.

Distinguishing Features

Loss of nuclear INI1/SMARCB1 staining defines AT/RT and must be tested for.
A minority of AT/RTs express Kir7.1, so choroid plexus lineage markers alone cannot exclude AT/RT.

Show evidence (2 references)

PMID:21276081 SUPPORT Human Clinical

"Two AT/RT cases exhibited membranous staining of Kir7.1, indicating a plexus epithelial differentiation of these tumors."

Documents the overlap that makes AT/RT a critical differential and limits reliance on Kir7.1 alone.

PMID:21276081 SUPPORT Human Clinical

"Differential diagnosis includes choroid plexus carcinoma which has occasionally been attributed as showing an inactivation of INI1/SMARCB1 nuclear staining in immunohistochemistry."

Names choroid plexus carcinoma explicitly as the AT/RT differential and identifies the INI1/SMARCB1 discriminator.

Choroid plexus cyst

Overlapping Features A benign, usually incidental fluid-filled cyst of the choroid plexus stroma, most often detected on second-trimester fetal ultrasound and associated with trisomy 18 when other markers are present. Despite the shared anatomical name it is not a neoplasm, has no relationship to the choroid plexus tumor family, and is included here explicitly because the name similarity is a recognised source of literature and curation confusion.

Distinguishing Features

A choroid plexus cyst is a non-enhancing, non-solid cystic structure that typically resolves spontaneously, produces no mass effect and no hydrocephalus, and requires no oncological management.
Choroid plexus neoplasms are solid, intensely enhancing intraventricular masses that present with hydrocephalus.

Show evidence (2 references)

PMID:42143260 SUPPORT Human Clinical

"Choroid plexus cysts (CPCs) are fluid-filled structures within the choroid plexus of the lateral ventricles, most frequently identified during routine second-trimester ultrasound examinations."

Establishes the choroid plexus cyst as a distinct, non-neoplastic fluid-filled lesion of the same anatomical structure, detected prenatally.

PMID:42143260 SUPPORT Human Clinical

"They are reported in approximately 1-2% of second-trimester fetuses and are generally regarded as benign and transient findings, particularly when not accompanied by other abnormalities"

Supports the benign, transient, non-oncological character that separates the cyst from every member of the choroid plexus tumor family.

Choroid plexus hyperplasia (villous hypertrophy)

Overlapping Features Diffuse enlargement of the choroid plexus without a discrete neoplastic mass. It causes hydrocephalus by the same cerebrospinal fluid overproduction mechanism as a papilloma, so the mechanistic overlap is genuine even though the lesion is not a tumor - which makes it the one differential that shares this entry's core pathophysiology.

Distinguishing Features

Imaging shows bilateral diffuse plexus enlargement rather than a solitary lobulated mass.
Hydrocephalus is communicating and purely overproduction-driven, with no obstructive component from mass effect.

Show evidence (1 reference)

PMID:1022421 PARTIAL Human Clinical

"Whereas these data are regarded as conclusive evidence of CSF overproduction by a choroid plexus papilloma"

Establishes the overproduction mechanism that choroid plexus hyperplasia shares with papilloma; the hyperplasia entity itself is not described in this abstract, hence partial support.

🔬

Clinical Trials

1

NCT04994977 PHASE_I TERMINATED

Intra-arterial chemotherapy delivered before a planned second-look operation in newly diagnosed, residual or recurrent atypical choroid plexus papilloma and choroid plexus carcinoma - a locoregional extension of the neoadjuvant-then-resect strategy already used systemically. The study terminated for low accrual after enrolling a single patient, so no efficacy inference is possible; it is recorded here because it is the only interventional trial specific to this disease family rather than a broad CNS basket.

Target Phenotypes: Neoplasm of the central nervous system HP:0100006

Show evidence (2 references)

clinicaltrials:NCT04994977 SUPPORT Human Clinical

"This study will test the safety and efficacy of intra-arterial chemotherapy in subjects with newly diagnosed, residual, or recurrent atypical choroid plexus papilloma and choroid plexus carcinoma prior to a second surgery."

Defines the trial population and intervention, both specific to this disease family.

clinicaltrials:NCT04994977 PARTIAL Human Clinical

"It is believed that intra-arterial chemotherapy will be safe and feasible for this population and will result in decreased tumor size, which may further improve the goals of a second-look surgery."

States the trial hypothesis; marked PARTIAL because the trial terminated for low accrual and did not test it.

{ }

Source YAML

click to show

name: Choroid Plexus Neoplasm
creation_date: '2026-08-01T07:30:00Z'
description: >-
  Choroid plexus neoplasms (choroid plexus tumors, CPT) are rare intraventricular
  papillary neoplasms arising from the cerebrospinal-fluid-secreting choroid plexus
  epithelium. The WHO CNS classification recognises three graded entities that this
  umbrella entry spans: choroid plexus papilloma (CPP, grade 1), atypical choroid
  plexus papilloma (aCPP, grade 2, defined by mitotic activity of at least 2 mitoses
  per 10 high-power fields), and choroid plexus carcinoma (CPC, grade 3). Incidence
  peaks in the first year of life; tumors are typically lateral-ventricular
  (supratentorial) in children and fourth-ventricular (infratentorial) in adults.
  The dominant clinical presentation is hydrocephalus, produced by two mechanistically
  distinct and frequently co-occurring routes - cerebrospinal fluid overproduction by
  the secretory tumour epithelium, and obstruction of cerebrospinal fluid pathways by
  intraventricular mass effect - which is why hydrocephalus may persist after
  otherwise complete tumour removal. Pediatric choroid plexus tumors lack a recurrent
  driver mutation apart from TP53; TP53 status is the dominant prognostic axis in
  carcinoma, and choroid plexus carcinoma is a sentinel cancer for Li-Fraumeni
  syndrome, so germline TP53 testing with genetic counselling is indicated in
  essentially every case. Gross total resection is the strongest modifiable
  prognostic factor in carcinoma; in papilloma and atypical papilloma, population data
  show no overall survival difference between gross total and subtotal resection.
categories:
- Central Nervous System Neoplasm
- Pediatric Brain Tumor
- Intraventricular Neoplasm
parents:
- brain neoplasm
synonyms:
- choroid plexus tumor
- choroid plexus tumour
- CPT
- neoplasm of the choroid plexus
- tumor of the choroid plexus
disease_term:
  preferred_term: choroid plexus neoplasm
  term:
    id: MONDO:0016717
    label: choroid plexus neoplasm
references:
- reference: PMID:33249490
  title: The genetic landscape of choroid plexus tumors in children and adults.
- reference: PMID:34997889
  title: Final results of the Choroid Plexus Tumor study CPT-SIOP-2000.
- reference: PMID:36659972
  title: Incidence and survival of choroid plexus tumors in the United States.
- reference: PMID:20308654
  title: TP53 alterations determine clinical subgroups and survival of patients with
    choroid plexus tumors.
epidemiology:
- name: Rarity among brain tumors
  description: >-
    Choroid plexus tumors are rare, comprising roughly 1% of all brain tumors, but are
    heavily concentrated in early childhood and are over-represented among tumors
    presenting in the first year of life.
  evidence:
  - reference: PMID:38339361
    reference_title: "Prognostic Factors and Nomogram for Choroid Plexus Tumors: A Population-Based Retrospective Surveillance, Epidemiology, and End Results Database Analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Choroid plexus tumors (CPTs) are rare neoplasms found in the central nervous system, comprising 1% of all brain tumors."
    explanation: SEER-based population analysis quantifying the rarity of the choroid
      plexus tumor family among brain tumors.
  - reference: PMID:41198335
    reference_title: "An overview of the diagnosis and management of Choroid Plexus tumors."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Choroid Plexus Tumors (CPT) are rare (2-4% of all pediatric CNS tumors), predominantly early childhood brain neoplasms."
    explanation: Review establishing the share of pediatric CNS tumors accounted for by
      choroid plexus tumors and their early-childhood concentration.
- name: Infantile incidence peak
  description: >-
    Age-adjusted incidence of every choroid plexus tumor subtype is highest in children
    under one year of age and declines steadily thereafter.
  evidence:
  - reference: PMID:36659972
    reference_title: Incidence and survival of choroid plexus tumors in the United States.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Incidence was highest among children less than one year old among all subtypes (CPP AAIR: 0.278; aCPP AAIR: 0.140; CPC AAIR: 0.195), reducing as patients aged."
    explanation: CBTRUS registry data showing the infantile incidence peak across all
      three histologic subtypes.
- name: Subtype survival gradient
  description: >-
    Histologic grade is the dominant determinant of survival across the family, with a
    stepwise decline from papilloma through atypical papilloma to carcinoma.
  evidence:
  - reference: PMID:38339361
    reference_title: "Prognostic Factors and Nomogram for Choroid Plexus Tumors: A Population-Based Retrospective Surveillance, Epidemiology, and End Results Database Analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Histology was a significant predictor of OS, with 5-year OS rates of 90, 79, and 61% for CPP, aCPP, and CPC, respectively."
    explanation: Directly quantifies the grade-stratified 5-year overall survival
      gradient across the three subtypes.
  - reference: PMID:36659972
    reference_title: Incidence and survival of choroid plexus tumors in the United States.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Overall survival was worse among patients with CPC, being five times more likely to die compared to patients with CPP (HR: 5.23, 95% CI: 4.05-7.54, P < .001)."
    explanation: Independent registry confirmation of the carcinoma-versus-papilloma
      survival gap.
prevalence:
- population: United States (CBTRUS/NPCR, 2004-2017), choroid plexus papilloma
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BELOW_1_IN_1000000
  rate_per_100000: 0.034
  rate_low: 0.033
  rate_high: 0.036
  notes: >-
    Age-adjusted annual incidence rate per 100,000 for choroid plexus papilloma, the
    commonest member of the family.
  evidence:
  - reference: PMID:36659972
    reference_title: Incidence and survival of choroid plexus tumors in the United States.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "CPP had the highest overall incidence (AAIR: 0.034, 95% CI: 0.033-0.036), followed by CPC (AAIR: 0.008, 95% CI: 0.008-0.009) and aCPP (AAIR: 0.005, 95% CI: 0.005-0.006)."
    explanation: Source of the age-adjusted incidence rate for choroid plexus papilloma.
- population: United States (CBTRUS/NPCR, 2004-2017), choroid plexus carcinoma
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BELOW_1_IN_1000000
  rate_per_100000: 0.008
  rate_low: 0.008
  rate_high: 0.009
  notes: Age-adjusted annual incidence rate per 100,000 for choroid plexus carcinoma.
  evidence:
  - reference: PMID:36659972
    reference_title: Incidence and survival of choroid plexus tumors in the United States.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "CPP had the highest overall incidence (AAIR: 0.034, 95% CI: 0.033-0.036), followed by CPC (AAIR: 0.008, 95% CI: 0.008-0.009) and aCPP (AAIR: 0.005, 95% CI: 0.005-0.006)."
    explanation: Source of the age-adjusted incidence rate for choroid plexus carcinoma.
- population: United States (CBTRUS/NPCR, 2004-2017), atypical choroid plexus papilloma
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BELOW_1_IN_1000000
  rate_per_100000: 0.005
  rate_low: 0.005
  rate_high: 0.006
  notes: >-
    Age-adjusted annual incidence rate per 100,000 for atypical choroid plexus
    papilloma, the rarest of the three graded entities.
  evidence:
  - reference: PMID:36659972
    reference_title: Incidence and survival of choroid plexus tumors in the United States.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "CPP had the highest overall incidence (AAIR: 0.034, 95% CI: 0.033-0.036), followed by CPC (AAIR: 0.008, 95% CI: 0.008-0.009) and aCPP (AAIR: 0.005, 95% CI: 0.005-0.006)."
    explanation: Source of the age-adjusted incidence rate for atypical choroid plexus
      papilloma.
- population: Infants under one year of age (United States), choroid plexus papilloma
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BAND_1_9_PER_1000000
  rate_per_100000: 0.278
  notes: >-
    Age-specific annual incidence rate in the first year of life, roughly eight times
    the all-age rate.
  evidence:
  - reference: PMID:36659972
    reference_title: Incidence and survival of choroid plexus tumors in the United States.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Incidence was highest among children less than one year old among all subtypes (CPP AAIR: 0.278; aCPP AAIR: 0.140; CPC AAIR: 0.195), reducing as patients aged."
    explanation: Source of the infantile age-specific incidence rate for choroid plexus
      papilloma.
has_subtypes:
- name: CPP
  display_name: Choroid Plexus Papilloma (WHO grade 1)
  subtype_term:
    preferred_term: choroid plexus papilloma
    term:
      id: MONDO:0009837
      label: choroid plexus papilloma
  description: >-
    WHO grade 1 papillary neoplasm of choroid plexus epithelium with orderly fronds
    lined by relatively uniform cuboidal-to-columnar epithelium and minimal mitotic
    activity. The commonest member of the family. Gross total resection is frequently
    curative and adjuvant therapy is usually unnecessary; 5-year overall survival is
    approximately 90%.
  evidence:
  - reference: PMID:30969571
    reference_title: Choroid Plexus Papilloma.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Choroid plexus papillomas are neuroepithelial tumors that are World Health Organization grade I or II. In contrast, the rarely encountered choroid plexus carcinoma is classified as World Health Organization grade III."
    explanation: Establishes the WHO grade assignment separating papilloma from carcinoma.
  - reference: PMID:30969571
    reference_title: Choroid Plexus Papilloma.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The prognosis of these benign neoplasms is favorable, and gross total resection is frequently curative."
    explanation: Supports the favourable prognosis and curative role of complete
      resection in grade 1 disease.
  - reference: PMID:34997889
    reference_title: Final results of the Choroid Plexus Tumor study CPT-SIOP-2000.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Within the registry, histological grading was the most influential prognostic factor: for CPP (n = 55) the 5/10 year overall survival (OS) and the event free survival (EFS) probabilities were 100%/97% and 92%/92%, respectively; for APP (n = 49) 96%/96% and 76%/76%, respectively; and for CPC (n = 54) 65%/51% and 41%/39%, respectively."
    explanation: Prospective registry survival figures separating the three graded
      entities.
- name: aCPP
  display_name: Atypical Choroid Plexus Papilloma (WHO grade 2)
  subtype_term:
    preferred_term: atypical choroid plexus papilloma
    term:
      id: MONDO:0002684
      label: atypical choroid plexus papilloma
  description: >-
    WHO grade 2 intermediate entity defined operationally by increased mitotic activity
    - at least 2 mitoses per 10 high-power fields - which was the only atypical
    histologic feature independently associated with recurrence in the series that
    established the definition. Ancillary features (hypercellularity, nuclear
    pleomorphism, blurring of the papillary architecture, necrosis) may be present but
    are not required. Recurrence risk is intermediate between papilloma and carcinoma.
    Notably, DNA-methylation and copy-number profiling has not separated aCPP from CPP,
    so the entity is currently histologic rather than molecular.
  evidence:
  - reference: PMID:17086103
    reference_title: Prognostic implications of atypical histologic features in choroid
      plexus papilloma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "we propose to define atypical choroid plexus papilloma by mitotic activity (> or =2 mitoses per 10 high-power fields) corresponding to World Health Organization grade II"
    explanation: The defining mitotic-count criterion for WHO grade 2 atypical choroid
      plexus papilloma.
  - reference: PMID:17086103
    reference_title: Prognostic implications of atypical histologic features in choroid
      plexus papilloma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Because mitotic activity is the sole atypical histologic feature independently associated with recurrence"
    explanation: Explains why mitotic count, and not the other atypical features, was
      selected as the grading criterion.
  - reference: PMID:17918524
    reference_title: Malignant progression in choroid plexus papillomas.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The proportion of recurring tumors was higher in cases of atypical choroid plexus papilloma than in cases of choroid plexus papilloma"
    explanation: Quantifies the elevated recurrence risk that justifies the intermediate
      grade.
  - reference: PMID:25336695
    reference_title: Molecular characterization of choroid plexus tumors reveals novel
      clinically relevant subgroups.
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Unique molecular signatures distinguished choroid plexus carcinomas (CPC) from choroid plexus papillomas (CPP) and atypical choroid plexus papillomas (aCPP); however, no significantly distinct molecular alterations between CPPs and aCPPs were observed."
    explanation: Supports the caveat that aCPP is a histologic rather than a molecularly
      separable entity.
- name: CPC
  display_name: Choroid Plexus Carcinoma (WHO grade 3)
  subtype_term:
    preferred_term: choroid plexus carcinoma
    term:
      id: MONDO:0016718
      label: choroid plexus carcinoma
  description: >-
    WHO grade 3 malignant choroid plexus tumor showing frank anaplasia - high
    cellularity, loss of papillary architecture, brisk mitoses, pleomorphism, necrosis
    and brain invasion - with a strong propensity for cerebrospinal fluid dissemination.
    Concentrated in infancy and early childhood. TP53 alteration is the dominant
    prognostic axis and germline TP53 (Li-Fraumeni syndrome) accounts for a substantial
    minority of cases. A dedicated dismech entry exists at
    kb/disorders/Choroid_Plexus_Carcinoma.yaml; this umbrella entry models the
    family-level mechanism only.
  evidence:
  - reference: PMID:35322202
    reference_title: Disruption of GMNC-MCIDAS multiciliogenesis program is critical in
      choroid plexus carcinoma development.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Though CPP and atypical CPP are generally benign and can be resolved by surgery, CPC is a particularly aggressive and little understood cancer with a poor survival rate and a tendency for recurrence and metastasis."
    explanation: Contrasts the malignant behaviour of carcinoma with the two papilloma
      grades.
  - reference: PMID:34997889
    reference_title: Final results of the Choroid Plexus Tumor study CPT-SIOP-2000.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Within the registry, histological grading was the most influential prognostic factor: for CPP (n = 55) the 5/10 year overall survival (OS) and the event free survival (EFS) probabilities were 100%/97% and 92%/92%, respectively; for APP (n = 49) 96%/96% and 76%/76%, respectively; and for CPC (n = 54) 65%/51% and 41%/39%, respectively."
    explanation: Prospective registry survival figures for carcinoma relative to the
      lower grades.
progression:
- phase: Presentation
  subtype: CPP
  age_range: Peak in the first two years of life
  notes: >-
    Choroid plexus papilloma presents at any age but with a strong infantile
    predominance; site differs with age, being supratentorial in children and
    infratentorial in adults.
  evidence:
  - reference: PMID:30969571
    reference_title: Choroid Plexus Papilloma.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Although choroid plexus papillomas may occur at any age, 70% of patients with this neoplasm are less than 2 years of age."
    explanation: Establishes the age distribution at presentation for papilloma.
- phase: Presentation
  subtype: CPC
  age_range: Infancy and early childhood (median about 2 years)
  notes: >-
    Choroid plexus carcinoma is concentrated in infancy; roughly a quarter of patients
    are diagnosed in the first year of life.
  evidence:
  - reference: PMID:28939225
    reference_title: "Effect of Surgery, Adjuvant Therapy, and Other Prognostic Factors on Choroid Plexus Carcinoma: A Systematic Review and Individual Patient Data Analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The median patient age was 2 years, with 26% patients diagnosed in the first year of their life."
    explanation: Individual-patient-data pooled analysis quantifying age at diagnosis
      for carcinoma.
- phase: Recurrence and malignant progression
  notes: >-
    Recurrence after gross total resection is uncommon in grade 1 papilloma and
    substantially more frequent in atypical papilloma. Transition from a lower-grade
    papilloma to frank carcinoma is documented but rare.
  evidence:
  - reference: PMID:17918524
    reference_title: Malignant progression in choroid plexus papillomas.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Recurrent tumor growth after gross-total resection is rare in choroid plexus papillomas, but malignant progression to choroid plexus carcinoma does occur in a small percentage of tumors."
    explanation: Establishes the rate and existence of malignant progression within the
      family.
  - reference: PMID:17918524
    reference_title: Malignant progression in choroid plexus papillomas.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "However, two patients experienced a transition from a choroid plexus papilloma (WHO Grade I) and an atypical choroid plexus papilloma (WHO Grade II) to choroid plexus carcinomas (WHO Grade III)."
    explanation: Documents individual grade-to-grade progression events.
- phase: Dissemination
  notes: >-
    Cerebrospinal fluid seeding occurs across the family but is concentrated in higher
    grades; metastases are present at diagnosis in a substantial minority of atypical
    papilloma and carcinoma cases.
  evidence:
  - reference: PMID:19543851
    reference_title: "Atypical choroid plexus papilloma: clinical experience in the CPT-SIOP-2000 study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Metastases were present at diagnosis in 17% of APP patients, 5% of CPP patients, and 21% of CPC patients."
    explanation: Grade-stratified frequency of metastatic disease at presentation.
pathophysiology:
- name: TP53 Pathway Inactivation
  biological_scale: MOLECULAR
  role: trigger
  conforms_to: evading_growth_suppressors#Tumor Suppressor Inactivation
  description: >-
    Loss of p53 tumor-suppressor function - by germline pathogenic TP53 variant
    (Li-Fraumeni syndrome) with somatic loss of the remaining allele, by somatic TP53
    mutation, or by the combination of TP53 codon 72 and MDM2 SNP309 variants that
    confer p53 dysfunction in the absence of a mutation - is the only recurrent driver
    lesion in pediatric choroid plexus tumors. It is concentrated in carcinoma, where
    roughly half of tumors carry a TP53 mutation, and is absent or rare in papilloma.
  genes:
  - preferred_term: TP53
    term:
      id: hgnc:11998
      label: TP53
  biological_processes:
  - preferred_term: signal transduction by p53 class mediator
    modifier: DECREASED
    term:
      id: GO:0072331
      label: signal transduction by p53 class mediator
  cell_types:
  - preferred_term: choroid plexus epithelial cell
    term:
      id: CL:0000706
      label: choroid plexus epithelial cell
  evidence:
  - reference: PMID:33249490
    reference_title: The genetic landscape of choroid plexus tumors in children and adults.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Pediatric CPTs lack recurrent driver alterations except for TP53, whereas CPTs in adults show TERT promoter mutations or a novel CCDC47-PRKCA gene fusion, being associated with a more unfavorable clinical course."
    explanation: Establishes TP53 as the only recurrent driver lesion in pediatric
      choroid plexus tumors.
  - reference: PMID:20308654
    reference_title: TP53 alterations determine clinical subgroups and survival of
      patients with choroid plexus tumors.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "TP53 mutations were found in 50% of choroid plexus carcinomas (CPCs)."
    explanation: Quantifies the frequency of somatic TP53 mutation in carcinoma.
  - reference: PMID:20308654
    reference_title: TP53 alterations determine clinical subgroups and survival of
      patients with choroid plexus tumors.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Additionally, two sequence variants known to confer TP53 dysfunction, TP53 codon72 and MDM2 SNP309, coexisted in the majority of TP53 wild-type CPCs (92%) and not in TP53 mutated CPC (P = .04), which suggests a complementary mechanism of TP53 dysfunction in the absence of a TP53 mutation."
    explanation: Supports p53 dysfunction arising without a TP53 mutation via modifier
      variants.
  downstream:
  - target: Disruption of the GMNC-MCIDAS Multiciliogenesis Program
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Loss of the p53/RB tumour-suppressor axis is itself sufficient to derange the
      multiciliogenesis program: mouse carcinoma driven by combined Trp53 and Rb1
      deletion shows multiciliation defects attributable to GMNC-MCIDAS deficiency. This
      places the differentiation block downstream of the tumour-suppressor lesion rather
      than as an independent trigger.
    evidence:
    - reference: PMID:35322202
      reference_title: Disruption of GMNC-MCIDAS multiciliogenesis program is critical in
        choroid plexus carcinoma development.
      supports: PARTIAL
      evidence_source: MODEL_ORGANISM
      snippet: "CPC driven by deletion of Trp53 and Rb1 in mice exhibits multiciliation defects consequent to deficiencies in the GMNC-MCIDAS program."
      explanation: Mouse evidence placing the multiciliogenesis defect downstream of
        combined Trp53/Rb1 loss. Marked PARTIAL because the human lesion is TP53 alone and
        the RB1 co-requirement has not been shown in human choroid plexus tumours.
  - target: Chromosomal Instability and Aneuploidy
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Loss of p53-dependent DNA-damage checkpoint control permits accumulation of
      whole-chromosome copy-number changes; TP53-mutated carcinomas show markedly higher
      total structural variation than TP53 wild-type tumors and papillomas.
    evidence:
    - reference: PMID:20308654
      reference_title: TP53 alterations determine clinical subgroups and survival of
        patients with choroid plexus tumors.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "High-resolution single nucleotide polymorphism (SNP) array analysis revealed extremely high total structural variation (TSV) in TP53-mutated CPC tumor genomes compared with TP53 wild-type tumors and choroid plexus papillomas (CPPs; P = .006 and .004, respectively)."
      explanation: Directly links TP53 mutation status to the magnitude of structural
        genomic variation.
  - target: Choroid Plexus Epithelial Neoplastic Proliferation
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Combined p53 inactivation and oncogenic drive in choroid plexus epithelium is
      sufficient to initiate tumor formation in mouse models.
    evidence:
    - reference: PMID:29339161
      reference_title: A new genetically engineered mouse model of choroid plexus carcinoma.
      supports: PARTIAL
      evidence_source: MODEL_ORGANISM
      snippet: "Here we have created a novel mouse CPC model by expressing a stabilised form of c-Myc (MycT58A) and inactivating Trp53 in the choroid plexus of newborn mice. This induced aberrant proliferation of choroid plexus epithelial cells, leading to aggressive tumour development and death within 150 days."
      explanation: Mouse model evidence that Trp53 inactivation plus Myc drives choroid
        plexus epithelial proliferation and carcinoma. Marked PARTIAL because the
        sufficiency claim is demonstrated only in mouse; the human data establish
        association, not sufficiency.
- name: Chromosomal Instability and Aneuploidy
  biological_scale: MOLECULAR
  role: amplifier
  conforms_to: genome_instability_mutation#Mutator Phenotype and Chromosomal Instability
  description: >-
    Choroid plexus tumors are characterised by whole-chromosome copy-number alterations
    rather than focal driver events. Recurrent gains and losses partition the family
    into methylation/copy-number subgroups and vary with patient age; carcinomas show
    complex, hyperdiploid or hypodiploid genomes, and a greater burden of mutant TP53
    copies tracks with a more aggressive course.
  biological_processes:
  - preferred_term: chromosome segregation
    modifier: ABNORMAL
    term:
      id: GO:0007059
      label: chromosome segregation
  - preferred_term: DNA damage response
    modifier: DECREASED
    term:
      id: GO:0006974
      label: DNA damage response
  cell_types:
  - preferred_term: choroid plexus epithelial cell
    term:
      id: CL:0000706
      label: choroid plexus epithelial cell
  evidence:
  - reference: PMID:33249490
    reference_title: The genetic landscape of choroid plexus tumors in children and adults.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Copy-number alterations mainly represented whole-chromosomal alterations with subgroup-specific enrichments"
    explanation: Establishes whole-chromosome copy-number change as the dominant genomic
      alteration class and its subgroup specificity.
  - reference: PMID:24478045
    reference_title: Choroid plexus carcinomas are characterized by complex chromosomal
      alterations related to patient age and prognosis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Recurrent copy number losses of chromosomes 5, 6, 16, 18, 19, and 22 as well as gains of chromosomes 1, 2, 4, 12, and 20 were identified."
    explanation: Enumerates the recurrent whole-chromosome imbalances in carcinoma.
  - reference: PMID:25336695
    reference_title: Molecular characterization of choroid plexus tumors reveals novel
      clinically relevant subgroups.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Allele-specific CN analysis of CPCs revealed two novel subgroups according to DNA content: hypodiploid and hyperdiploid CPCs."
    explanation: Supports genome-wide ploidy disturbance as a defining feature of
      carcinoma.
  - reference: PMID:38867333
    reference_title: Comprehensive multiomics analysis reveals distinct differences
      between pediatric choroid plexus papilloma and carcinoma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Mutually exclusive TP53 and EPHA7 point mutations, coupled with the amplification of chromosome 1, were exclusively identified in CPC. In contrast, amplification of chromosome 9 was specific to CPP."
    explanation: Identifies the copy-number and point-mutation events that discriminate
      carcinoma from papilloma, including the mutually exclusive TP53/EPHA7 pattern.
  - reference: PMID:33249490
    reference_title: The genetic landscape of choroid plexus tumors in children and adults.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "gains of Chr1, 2 and 21q in \"pediatric B\" and gains of Chr5 and 9 and loss of Chr21q in \"adult\""
    explanation: The subgroup-specific whole-chromosome enrichments that define the
      copy-number classes.
  - reference: PMID:38867333
    reference_title: Comprehensive multiomics analysis reveals distinct differences
      between pediatric choroid plexus papilloma and carcinoma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "methylation profiling unveiled hypomethylation in major repeat regions, including long interspersed nuclear elements, short interspersed nuclear elements, long terminal repeats, and retrotransposons in CPC compared to CPP, implying that the loss of epigenetic silencing of transposable elements may play a role in tumorigenesis of CPC"
    explanation: Adds the epigenetic arm - loss of transposable-element silencing - as a
      candidate contributor to the carcinoma genomic state.
  downstream:
  - target: Choroid Plexus Epithelial Neoplastic Proliferation
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Accumulated chromosomal imbalance dysregulates cell-cycle control and sustains the
      proliferative program of the tumor epithelium.
    evidence:
    - reference: PMID:38867333
      reference_title: Comprehensive multiomics analysis reveals distinct differences
        between pediatric choroid plexus papilloma and carcinoma.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Differential gene expression analysis uncovered a significant overexpression of genes related to cell cycle regulation and epithelial-mesenchymal transition pathways in CPC compared to CPP."
      explanation: Links the carcinoma genomic state to an upregulated cell-cycle
        transcriptional program.
  - target: Malignant Progression to High-Grade Carcinoma
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Specific copy-number patterns are prognostic within carcinoma, with loss of 12q
      associated with markedly shorter survival.
    evidence:
    - reference: PMID:24478045
      reference_title: Choroid plexus carcinomas are characterized by complex chromosomal
        alterations related to patient age and prognosis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Multivariate analysis revealed that loss of 12q was associated with shorter survival"
      explanation: Demonstrates that the chromosomal alteration burden translates into
        clinical aggressiveness.
- name: Adult-Specific TERT Promoter Activation
  biological_scale: MOLECULAR
  role: driver
  description: >-
    A separate, adult-restricted route into the same tumor. TERT promoter mutations
    occur in a quarter of adult choroid plexus tumor patients, reactivating telomerase
    and conferring replicative capacity; they are essentially absent from the
    pediatric-dominant subgroups, where TP53 is the recurrent lesion instead. TERT
    promoter mutation is prognostic in adults, associating with shorter
    progression-free survival, and a rare CCDC47-PRKCA fusion is a further
    adult-specific alteration reported in an aggressive papilloma. The pediatric
    counterpart of this telomere-maintenance requirement is telomerase-independent:
    alternative lengthening of telomeres is enriched in choroid plexus carcinoma (23% of
    cases) and is tied to somatic, not germline, TP53 mutation.
  genes:
  - preferred_term: TERT
    term:
      id: hgnc:11730
      label: TERT
  biological_processes:
  - preferred_term: telomere maintenance
    modifier: INCREASED
    term:
      id: GO:0000723
      label: telomere maintenance
  cell_types:
  - preferred_term: choroid plexus epithelial cell
    term:
      id: CL:0000706
      label: choroid plexus epithelial cell
  evidence:
  - reference: PMID:33249490
    reference_title: The genetic landscape of choroid plexus tumors in children and adults.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "On the contrary, TERT promoter mutations were encountered in 7/28 adult patients (25%) and associated with shorter progression-free survival (log-rank test, p=0.015)."
    explanation: Establishes the frequency, adult restriction and prognostic effect of
      TERT promoter mutation.
  - reference: PMID:33249490
    reference_title: The genetic landscape of choroid plexus tumors in children and adults.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Pediatric CPTs lack recurrent driver alterations except for TP53, whereas CPTs in adults show TERT promoter mutations or a novel CCDC47-PRKCA gene fusion, being associated with a more unfavorable clinical course."
    explanation: Contrasts the adult TERT/fusion route with the pediatric TP53 route.
  - reference: PMID:25315281
    reference_title: Alternative lengthening of telomeres is enriched in, and impacts
      survival of TP53 mutant pediatric malignant brain tumors.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "ALT was highly enriched in primitive neuroectodermal tumors (12 %), choroid plexus carcinomas (23 %) and high-grade gliomas (22 %)."
    explanation: Documents the telomerase-independent alternative-lengthening-of-telomeres
      route to telomere maintenance in choroid plexus carcinoma, the pediatric counterpart
      of the adult TERT-promoter route this node models.
  - reference: PMID:25315281
    reference_title: Alternative lengthening of telomeres is enriched in, and impacts
      survival of TP53 mutant pediatric malignant brain tumors.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Somatic but not germline TP53 mutations were highly associated with ALT"
    explanation: Ties the alternative-lengthening route specifically to somatic TP53
      mutation, distinguishing it from the germline predisposition arm.
  downstream:
  - target: Choroid Plexus Epithelial Neoplastic Proliferation
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Telomerase reactivation removes the replicative limit on the transformed choroid
      plexus epithelium, permitting sustained clonal expansion.
    evidence:
    - reference: PMID:33249490
      reference_title: The genetic landscape of choroid plexus tumors in children and adults.
      supports: PARTIAL
      evidence_source: HUMAN_CLINICAL
      snippet: "TERT promoter mutations were encountered in 7/28 adult patients (25%) and associated with shorter progression-free survival"
      explanation: Supports the clinical consequence of the lesion; the intervening
        telomerase-reactivation steps are inferred from general TERT promoter biology
        rather than measured in this choroid plexus series, hence partial support.
- name: Disruption of the GMNC-MCIDAS Multiciliogenesis Program
  biological_scale: CELLULAR
  role: mediator
  description: >-
    Normal choroid plexus epithelium is multiciliated. Human choroid plexus carcinomas
    instead carry solitary cilia, reflecting failure of the GMNC-MCIDAS transcriptional
    program that specifies multiciliated cell fate. In mice, NOTCH activation suppresses
    GMNC/MCIDAS and generates monociliated choroid plexus tumors, while disrupting the
    NOTCH complex restores multiciliation and reduces tumor growth - identifying loss of
    terminal multiciliated differentiation as a permissive step rather than a bystander
    finding. In mice the defect is itself downstream of tumour-suppressor loss -
    carcinoma driven by combined Trp53 and Rb1 deletion shows GMNC-MCIDAS-attributable
    multiciliation defects - so this node is modelled as a consequence of the TP53 arm
    rather than an independent trigger. This arm rests principally on model-system
    evidence.
  biological_processes:
  - preferred_term: cilium assembly
    modifier: DECREASED
    term:
      id: GO:0060271
      label: cilium assembly
  cell_types:
  - preferred_term: choroid plexus epithelial cell
    term:
      id: CL:0000706
      label: choroid plexus epithelial cell
  evidence:
  - reference: PMID:35322202
    reference_title: Disruption of GMNC-MCIDAS multiciliogenesis program is critical in
      choroid plexus carcinoma development.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In contrast to MCCs in the CP epithelia, CPCs in humans are characterized by solitary cilia, frequent TP53 mutations, and disturbances to multiciliogenesis program directed by the GMNC-MCIDAS transcriptional network."
    explanation: Human tumor observation of the loss of multiciliation and the associated
      transcriptional program.
  - reference: PMID:35322202
    reference_title: Disruption of GMNC-MCIDAS multiciliogenesis program is critical in
      choroid plexus carcinoma development.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "NOTCH-driven CP tumors are monociliated, and disruption of the NOTCH complex restores multiciliation and decreases tumor growth."
    explanation: Mouse experiment establishing that restoring multiciliation reduces
      tumor growth, supporting causality rather than correlation.
  downstream:
  - target: Choroid Plexus Epithelial Neoplastic Proliferation
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Failure of terminal multiciliated differentiation keeps tumor epithelium in a
      proliferative state; re-expression of GMNC/MCIDAS suppresses proliferation in
      model systems.
    evidence:
    - reference: PMID:35322202
      reference_title: Disruption of GMNC-MCIDAS multiciliogenesis program is critical
        in choroid plexus carcinoma development.
      supports: PARTIAL
      evidence_source: MODEL_ORGANISM
      snippet: "NOTCH suppresses multiciliation in tumor cells by inhibiting the expression of GMNC and MCIDA"
      explanation: Mechanistic link between the NOTCH-driven differentiation block and
        the tumor-cell state. Marked PARTIAL because this is mouse evidence; the human
        observation is the solitary-cilium phenotype, not the causal chain.
- name: Choroid Plexus Epithelial Neoplastic Proliferation
  biological_scale: CELLULAR
  role: central_effector
  description: >-
    Clonal expansion of transformed choroid plexus epithelial cells is the shared
    cellular event across all three graded entities. The proliferating cells retain
    choroid plexus epithelial identity - reliably demonstrable by Kir7.1 and
    stanniocalcin-1 immunoreactivity - and, critically for the disease mechanism, retain
    their secretory phenotype.
  cell_types:
  - preferred_term: choroid plexus epithelial cell
    term:
      id: CL:0000706
      label: choroid plexus epithelial cell
  - preferred_term: tumor-associated macrophage
    term:
      id: CL:0000235
      label: macrophage
  - preferred_term: tumor stromal mesenchymal cell
    term:
      id: CL:0008019
      label: mesenchymal cell
  biological_processes:
  - preferred_term: positive regulation of cell population proliferation
    modifier: INCREASED
    term:
      id: GO:0008284
      label: positive regulation of cell population proliferation
  locations:
  - preferred_term: choroid plexus epithelium
    term:
      id: UBERON:0003911
      label: choroid plexus epithelium
  evidence:
  - reference: PMID:38867333
    reference_title: Comprehensive multiomics analysis reveals distinct differences
      between pediatric choroid plexus papilloma and carcinoma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Choroid plexus tumors (CPTs) are intraventricular tumors derived from the choroid plexus epithelium and occur frequently in children."
    explanation: Establishes the choroid plexus epithelium as the cell of origin for the
      whole family.
  - reference: PMID:16330944
    reference_title: "Identification of novel diagnostic markers for choroid plexus tumors: a microarray-based approach."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Expression of inward rectifier potassium channel Kir7.1 was confirmed in normal choroid plexus (34 of 35), choroid plexus papilloma (12 of 18), and choroid plexus carcinoma (5 of 5) but was not found in 100 other primary brain tumors and cerebral metastases."
    explanation: Demonstrates retained choroid plexus epithelial identity in the
      neoplastic cells.
  - reference: PMID:39482394
    reference_title: Single-nucleus RNA-seq dissection of choroid plexus tumor cell
      heterogeneity.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Here, we examine the heterogeneity of human choroid plexus tumors by single-nucleus transcriptome analysis of 23,906 cells from four disease-free choroid plexus and eleven choroid plexus tumors."
    explanation: The single-nucleus atlas that resolves the tumor into its epithelial and
      stromal compartments.
  - reference: PMID:39482394
    reference_title: Single-nucleus RNA-seq dissection of choroid plexus tumor cell
      heterogeneity.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We further characterize tumor type-specific stromal microenvironments that include altered macrophage and mesenchymal cell states, as well as changes in extracellular matrix components."
    explanation: Establishes that the neoplastic epithelium sits in a tumor-type-specific
      stromal microenvironment with altered macrophage and mesenchymal states - the
      non-epithelial compartment of this node.
  downstream:
  - target: Intraventricular Papillary Mass Formation
    causal_link_type: DIRECT
    description: >-
      Expanding tumor epithelium organised on a vascular stroma forms a lobulated,
      highly vascular papillary mass within the ventricular cavity.
    evidence:
    - reference: PMID:33249490
      reference_title: The genetic landscape of choroid plexus tumors in children and
        adults.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Choroid plexus tumors (CPTs) are intraventricular brain tumors predominantly arising in children but also affecting adults."
      explanation: Establishes the intraventricular location of the resulting mass.
- name: Intraventricular Papillary Mass Formation
  biological_scale: TISSUE
  role: effector
  description: >-
    The tumor grows as an intraventricular papillary mass - lateral ventricle in
    children, fourth ventricle in adults - occupying the cerebrospinal fluid space. This
    single anatomical fact generates the two mechanistically distinct routes to
    hydrocephalus modelled downstream: the mass is itself secretory (overproduction) and
    it physically occupies and obstructs the cerebrospinal fluid pathway (obstruction).
  locations:
  - preferred_term: brain ventricle
    term:
      id: UBERON:0004086
      label: brain ventricle
  - preferred_term: lateral ventricle
    term:
      id: UBERON:0002285
      label: telencephalic ventricle
  - preferred_term: fourth ventricle
    term:
      id: UBERON:0002422
      label: fourth ventricle
  evidence:
  - reference: PMID:30969571
    reference_title: Choroid Plexus Papilloma.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Choroid plexus papillomas are more common in the infratentorial compartment in adults and the supratentorial compartment in children."
    explanation: Establishes the age-dependent anatomical distribution (fourth ventricle
      in adults, lateral ventricle in children).
  - reference: PMID:23172371
    reference_title: "Choroid plexus papillomas: advances in molecular biology and understanding of tumorigenesis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Although generally found within the ventricular system, they can arise ectopically in the brain parenchyma or disseminate throughout the neuraxis."
    explanation: Confirms the predominantly intraventricular location while noting
      ectopic and disseminated presentations.
  downstream:
  - target: Abnormal cranial nerve physiology
    causal_link_type: DIRECT
    description: >-
      Direct compression of adjacent lower cranial nerves by a fourth-ventricular or
      cerebellopontine-angle mass.
  - target: Cerebrospinal Fluid Overproduction by Secretory Tumour Epithelium
    causal_link_type: DIRECT
    description: >-
      The tumor epithelium retains and amplifies the cerebrospinal-fluid-secreting
      function of normal choroid plexus, so tumor bulk translates directly into excess
      cerebrospinal fluid production.
    evidence:
    - reference: PMID:1022421
      reference_title: "Choroid plexus papilloma. I. Proof of cerebrospinal fluid overproduction."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Preoperatively, the CSF formation rate was 1.05 +/- SD 0.01 ml/min (1,656 ml/day). Postoperatively, the CSF formation rate was reduced fivefold to 0.20 +/- SD 0.01 ml/min (288 ml/day)."
      explanation: Direct ventricular-perfusion measurement in a patient before and
        after tumor removal, attributing the excess production to the tumor itself.
  - target: Obstruction of Cerebrospinal Fluid Pathways by Mass Effect
    causal_link_type: DIRECT
    description: >-
      The intraventricular mass, and secondary changes in the subarachnoid pathways,
      impede cerebrospinal fluid egress independently of any change in production rate.
    evidence:
    - reference: PMID:7414480
      reference_title: "Choroid plexus papilloma: hydrocephalus and cerebrospinal fluid dynamics."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "It was concluded that no over-production of cerebrospinal fluid was present in this case. The hydrocephalus was due solely to obstruction of the fourth ventricle."
      explanation: A case in which cerebrospinal fluid dynamics were measured and
        overproduction was excluded, establishing obstruction as an independent
        sufficient mechanism.
- name: Cerebrospinal Fluid Overproduction by Secretory Tumour Epithelium
  biological_scale: TISSUE
  role: effector
  description: >-
    The first of the two hydrocephalus mechanisms. Neoplastic choroid plexus epithelium
    continues to secrete cerebrospinal fluid, and a large tumor can raise the formation
    rate several-fold above normal. Ventricular perfusion measurement in a child with a
    74 g lateral-ventricular papilloma showed a preoperative formation rate of 1.05
    ml/min falling fivefold to 0.20 ml/min after resection. Because production outstrips
    absorptive capacity while the pathways themselves remain patent, this route
    classically produces a communicating hydrocephalus.
  biological_processes:
  - preferred_term: cerebrospinal fluid secretion
    modifier: INCREASED
    term:
      id: GO:0033326
      label: cerebrospinal fluid secretion
  cell_types:
  - preferred_term: choroid plexus epithelial cell
    term:
      id: CL:0000706
      label: choroid plexus epithelial cell
  evidence:
  - reference: PMID:1022421
    reference_title: "Choroid plexus papilloma. I. Proof of cerebrospinal fluid overproduction."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Utilizing a ventricular perfusion technique, the rate of CSF formation was determined in a 2-year-old child before and after removal of a 74 g choroid plexus papilloma from the left lateral ventricle."
    explanation: Describes the direct measurement establishing tumor-driven cerebrospinal
      fluid overproduction.
  - reference: PMID:30969571
    reference_title: Choroid Plexus Papilloma.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Patients with choroid plexus papillomas often present with communicating hydrocephalus secondary to cerebrospinal fluid overproduction."
    explanation: Supports overproduction as a routine clinical presentation mechanism and
      its communicating character.
  - reference: PMID:35322202
    reference_title: Disruption of GMNC-MCIDAS multiciliogenesis program is critical in
      choroid plexus carcinoma development.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The CP secretes cerebrospinal fluid that circulates within the ventricular system, driven by ependymal cilia movement."
    explanation: Establishes the normal secretory function of the tissue of origin that
      the tumor retains.
  downstream:
  - target: Ventricular Enlargement and Raised Intracranial Pressure
    causal_link_type: DIRECT
    description: >-
      Cerebrospinal fluid production exceeding absorptive capacity expands the
      ventricular system and raises intracranial pressure.
    evidence:
    - reference: PMID:1022421
      reference_title: "Choroid plexus papilloma. I. Proof of cerebrospinal fluid overproduction."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Whereas these data are regarded as conclusive evidence of CSF overproduction by a choroid plexus papilloma, the pathogenesis of generalized ventricular enlargement in this case was due to part to obstruction of the subarachnoid pathways."
      explanation: Links overproduction to ventricular enlargement while explicitly
        noting the co-contribution of obstruction in the same patient.
- name: Obstruction of Cerebrospinal Fluid Pathways by Mass Effect
  biological_scale: TISSUE
  role: effector
  description: >-
    The second of the two hydrocephalus mechanisms, and independent of the first. The
    intraventricular mass can occlude the ventricular outflow route directly - for
    example a fourth-ventricular tumor blocking the outlets - producing hydrocephalus
    with a normal cerebrospinal fluid formation rate. In addition, obstruction of the
    subarachnoid pathways and increased cerebrospinal fluid outflow resistance,
    attributed to repeated subarachnoid bleeding from these highly vascular tumors and
    to raised cerebrospinal fluid protein, can persist after complete tumor removal,
    which is why some patients remain shunt-dependent despite radical resection and no
    residual tumor.
  biological_processes:
  - preferred_term: cerebrospinal fluid circulation
    modifier: DECREASED
    term:
      id: GO:0090660
      label: cerebrospinal fluid circulation
  locations:
  - preferred_term: fourth ventricle
    term:
      id: UBERON:0002422
      label: fourth ventricle
  - preferred_term: subarachnoid space
    term:
      id: UBERON:0000315
      label: subarachnoid space
  evidence:
  - reference: PMID:7414480
    reference_title: "Choroid plexus papilloma: hydrocephalus and cerebrospinal fluid dynamics."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Dynamics of the cerebrospinal fluid were measured pre- and postoperatively in a patient with a choroid plexus papilloma associated with hydrocephalus. The production rate was 0.35 ml/min, absorption 0.0057 ml/min H2O, and the critical opening pressure 196 mm H2O."
    explanation: Documents the measurement showing a normal production rate, isolating
      obstruction as the operative mechanism in that patient.
  - reference: PMID:6738779
    reference_title: Persistent hydrocephalus following removal of choroid plexus
      papilloma of the lateral ventricle.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The persisting hydrocephalus is probably caused by an increase of the CSF outflow resistance because of a distal CSF-pathway obstruction."
    explanation: Supports an outflow-resistance obstruction component that persists after
      the secretory tumor has been removed.
  - reference: PMID:6738779
    reference_title: Persistent hydrocephalus following removal of choroid plexus
      papilloma of the lateral ventricle.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In spite of radical tumour removal, three years after the operation the axial computer tomography revealed a persistent hydrocephalus, but no recurrence of tumour."
    explanation: Clinical demonstration that hydrocephalus can outlast removal of the
      overproducing tumour, requiring an obstruction/absorption mechanism.
  downstream:
  - target: Ventricular Enlargement and Raised Intracranial Pressure
    causal_link_type: DIRECT
    description: >-
      Impeded cerebrospinal fluid egress traps fluid proximal to the block, dilating the
      ventricles and raising intracranial pressure.
    evidence:
    - reference: PMID:7414480
      reference_title: "Choroid plexus papilloma: hydrocephalus and cerebrospinal fluid dynamics."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The hydrocephalus was due solely to obstruction of the fourth ventricle."
      explanation: Attributes the ventricular enlargement in that patient exclusively to
        obstruction.
- name: Ventricular Enlargement and Raised Intracranial Pressure
  biological_scale: ORGANISM
  role: consequence
  description: >-
    The convergent consequence of both hydrocephalus mechanisms. Ventricular dilatation
    and raised intracranial pressure produce the characteristic clinical syndrome, which
    differs by age: in infants with open sutures, macrocephaly and a bulging fontanelle;
    in older children and adults, headache, vomiting and papilledema. Posterior-fossa
    (fourth-ventricular) tumors additionally produce cerebellar signs.
  evidence:
  - reference: PMID:30969571
    reference_title: Choroid Plexus Papilloma.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Patients with choroid plexus papillomas often present with communicating hydrocephalus secondary to cerebrospinal fluid overproduction."
    explanation: Establishes hydrocephalus as the dominant clinical presentation of
      choroid plexus tumors.
  downstream:
  - target: Hydrocephalus
    causal_link_type: DIRECT
    description: Ventricular dilatation is by definition the hydrocephalus phenotype.
  - target: Increased intracranial pressure
    causal_link_type: DIRECT
    description: Expansion of the cerebrospinal fluid compartment within a closed cranium
      raises intracranial pressure.
  - target: Macrocephaly
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: In infants with unfused sutures, raised intracranial pressure expands
      the calvarium.
  - target: Bulging fontanelle
    causal_link_type: DIRECT
    description: Raised intracranial pressure bows the unfused anterior fontanelle
      outward.
  - target: Papilledema
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Raised intracranial pressure is transmitted along the optic nerve
      sheath, producing optic disc swelling.
  - target: Headache
    causal_link_type: DIRECT
    description: Raised intracranial pressure is a classical cause of headache.
  - target: Vomiting
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Raised intracranial pressure causes non-gastrointestinal vomiting.
  - target: Ataxia
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Fourth-ventricular masses and posterior-fossa pressure impair cerebellar
      function.
  - target: Gait disturbance
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Ventricular enlargement produces gait impairment, both cerebellar and as part of the
      normal-pressure-hydrocephalus complex in adults.
  - target: Seizure
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Supratentorial mass effect and cortical irritation can provoke seizures.
  - target: Neurodevelopmental abnormality
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Chronic infantile hydrocephalus, tumor injury and the neurotoxicity of surgery,
      chemotherapy and radiotherapy together impair neurodevelopment.
- name: Malignant Progression to High-Grade Carcinoma
  biological_scale: TISSUE
  role: consequence
  description: >-
    In a minority of tumors the epithelium acquires frank malignant features -
    hypercellularity, loss of the papillary architecture, brisk mitotic activity,
    pleomorphism and necrosis - defining WHO grade 3 carcinoma. This may be present de
    novo or, uncommonly, arise by documented progression from a previously resected
    grade 1 or grade 2 lesion. Carcinoma is transcriptionally distinguished from
    papilloma by upregulated cell-cycle and epithelial-mesenchymal transition programs.
  biological_processes:
  - preferred_term: epithelial to mesenchymal transition
    modifier: INCREASED
    term:
      id: GO:0001837
      label: epithelial to mesenchymal transition
  evidence:
  - reference: PMID:38867333
    reference_title: Comprehensive multiomics analysis reveals distinct differences
      between pediatric choroid plexus papilloma and carcinoma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Differential gene expression analysis uncovered a significant overexpression of genes related to cell cycle regulation and epithelial-mesenchymal transition pathways in CPC compared to CPP."
    explanation: Molecular characterisation of the papilloma-to-carcinoma difference.
  - reference: PMID:17918524
    reference_title: Malignant progression in choroid plexus papillomas.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "However, two patients experienced a transition from a choroid plexus papilloma (WHO Grade I) and an atypical choroid plexus papilloma (WHO Grade II) to choroid plexus carcinomas (WHO Grade III)."
    explanation: Documents that grade progression to carcinoma occurs, albeit rarely.
  downstream:
  - target: Brain Invasion and Leptomeningeal Dissemination
    causal_link_type: DIRECT
    description: >-
      High-grade tumors invade adjacent brain and seed the cerebrospinal fluid pathways;
      transcriptional metastasis programs are enriched in disseminated carcinoma.
    evidence:
    - reference: PMID:38867333
      reference_title: Comprehensive multiomics analysis reveals distinct differences
        between pediatric choroid plexus papilloma and carcinoma.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Overexpression of genes associated with tumor metastasis and progression was observed in the CPC subgroup with leptomeningeal dissemination."
      explanation: Links the high-grade transcriptional state to leptomeningeal spread.
- name: Brain Invasion and Leptomeningeal Dissemination
  biological_scale: TISSUE
  role: outcome
  description: >-
    Invasion of adjacent brain parenchyma and seeding of the cerebrospinal fluid
    pathways is the principal route to treatment failure. Metastatic disease is present
    at diagnosis in about a fifth of carcinomas and a sixth of atypical papillomas, and
    even papilloma can occasionally disseminate through the neuraxis.
  locations:
  - preferred_term: subarachnoid space
    term:
      id: UBERON:0000315
      label: subarachnoid space
  evidence:
  - reference: PMID:19543851
    reference_title: "Atypical choroid plexus papilloma: clinical experience in the CPT-SIOP-2000 study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Metastases were present at diagnosis in 17% of APP patients, 5% of CPP patients, and 21% of CPC patients."
    explanation: Grade-stratified frequency of dissemination at diagnosis across the
      family.
  - reference: PMID:23172371
    reference_title: "Choroid plexus papillomas: advances in molecular biology and understanding of tumorigenesis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Although generally found within the ventricular system, they can arise ectopically in the brain parenchyma or disseminate throughout the neuraxis."
    explanation: Confirms that even grade 1 papilloma can disseminate through the
      cerebrospinal fluid pathways.
  downstream:
  - target: Neoplasm of the central nervous system
    causal_link_type: DIRECT
    description: >-
      Invasive and disseminated disease establishes additional central nervous system
      tumor deposits.
histopathology:
- name: Papillary Architecture
  finding_term:
    preferred_term: Papillary Growth Pattern
    term:
      id: NCIT:C35911
      label: Papillary Growth Pattern
  frequency: VERY_FREQUENT
  diagnostic: true
  description: >-
    Orderly papillary fronds of fibrovascular cores lined by a single layer of
    relatively uniform cuboidal-to-columnar epithelium define choroid plexus papilloma.
    Blurring or loss of this architecture is one of the atypical features that shifts a
    tumor toward higher grade.
  evidence:
  - reference: PMID:17086103
    reference_title: Prognostic implications of atypical histologic features in choroid
      plexus papilloma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "a series of 164 choroid plexus tumors was evaluated for the presence of atypical histologic features, including mitotic activity, increased cellularity, nuclear pleomorphism, blurring of papillary growth pattern, and necrosis"
    explanation: Lists the papillary growth pattern and its blurring among the graded
      histologic features of the family.
- name: Increased Mitotic Activity
  finding_term:
    preferred_term: Two to 10 Mitoses per 10HPF
    term:
      id: NCIT:C60306
      label: Two to 10 Mitoses per 10HPF
  frequency: OCCASIONAL
  diagnostic: true
  description: >-
    Mitotic activity of at least 2 mitoses per 10 high-power fields is the sole grading
    criterion for atypical choroid plexus papilloma (WHO grade 2). It was present in 15%
    of otherwise untreated papillomas in the defining series (a figure reported in the
    abstract's bracketed per-feature breakdown, which cannot be quoted inside a snippet
    because the reference validator strips bracketed spans) and was the only atypical
    feature independently associated with recurrence on multivariate analysis. The bound NCIT term used here (Two to 10 Mitoses per 10HPF) is the closest available closed-enum value; the actual WHO criterion is at least 2 mitoses per 10 high-power fields with no upper bound.
  evidence:
  - reference: PMID:17086103
    reference_title: Prognostic implications of atypical histologic features in choroid
      plexus papilloma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "we propose to define atypical choroid plexus papilloma by mitotic activity (> or =2 mitoses per 10 high-power fields) corresponding to World Health Organization grade II"
    explanation: The defining histologic criterion and its threshold.
  - reference: PMID:17086103
    reference_title: Prognostic implications of atypical histologic features in choroid
      plexus papilloma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Using a multivariate model, an independent effect of mitotic activity on the probability of recurrence could be confirmed (p = 0.001)."
    explanation: Establishes the prognostic independence of mitotic count.
- name: Hypercellularity and Nuclear Pleomorphism
  finding_term:
    preferred_term: Hypercellularity
    term:
      id: NCIT:C177116
      label: Hypercellularity
  frequency: OCCASIONAL
  description: >-
    Increased cellularity and nuclear pleomorphism are recognised atypical features of
    choroid plexus tumors, present in 20% and 13% respectively of papillomas in the
    defining series, but neither was independently associated with recurrence and
    neither is used for grading in isolation. Together with necrosis and loss of
    papillary architecture they contribute to the diagnosis of frank carcinoma.
  evidence:
  - reference: PMID:17086103
    reference_title: Prognostic implications of atypical histologic features in choroid
      plexus papilloma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Of 124 choroid plexus papillomas that had not received adjuvant treatment, 46 tumors (37%) displayed at least one atypical feature, including increased cellularity"
    explanation: Establishes that a substantial minority of choroid plexus papillomas
      display at least one atypical histologic feature, increased cellularity among them.
      The per-feature percentages quoted in the description come from the continuation of
      this same sentence; that continuation is not quoted verbatim because the reference
      validator strips square-bracketed spans from snippets before matching, so the
      abstract's bracketed percentages cannot be used inside a snippet.
- name: Kir7.1 and Stanniocalcin-1 Immunoreactivity
  frequency: FREQUENT
  diagnostic: true
  description: >-
    Immunohistochemical expression of the inward rectifier potassium channel Kir7.1 and
    of stanniocalcin-1 is highly sensitive and specific for choroid plexus lineage,
    distinguishing choroid plexus tumors from other primary brain tumors and from
    metastatic carcinoma. Transthyretin is also expressed but is significantly less
    specific.
  evidence:
  - reference: PMID:16330944
    reference_title: "Identification of novel diagnostic markers for choroid plexus tumors: a microarray-based approach."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Our data suggest that antibodies directed against Kir7.1 and stanniocalcin-1 might serve as sensitive and specific diagnostic markers for choroid plexus tumors."
    explanation: Establishes Kir7.1 and stanniocalcin-1 as the discriminating lineage
      markers.
  - reference: PMID:16330944
    reference_title: "Identification of novel diagnostic markers for choroid plexus tumors: a microarray-based approach."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Transthyretin stained choroid plexus (33 of 35), choroid plexus papilloma (14 of 18), and plexus carcinoma (2 of 5), but its specificity was significantly lower."
    explanation: Supports the lower diagnostic specificity of transthyretin relative to
      Kir7.1 and stanniocalcin-1.
imaging_findings:
- name: Enhancing Intraventricular Mass with Hydrocephalus
  modality: MRI
  imaging_finding_term:
    preferred_term: Enhancing Lesion
    term:
      id: NCIT:C113842
      label: Enhancing Lesion
  located_in:
    preferred_term: brain ventricle
    term:
      id: UBERON:0004086
      label: brain ventricle
  description: >-
    Contrast-enhanced MRI shows a lobulated, frond-like, intensely enhancing and highly
    vascular intraventricular mass with associated ventricular dilatation, and is also
    used to assess transependymal oedema, invasion and residual disease. Spine MRI is
    added when carcinoma or atypical papilloma is suspected because of the dissemination
    risk.
  diagnostic: true
  evidence:
  - reference: PMID:33249490
    reference_title: The genetic landscape of choroid plexus tumors in children and adults.
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Choroid plexus tumors (CPTs) are intraventricular brain tumors predominantly arising in children but also affecting adults."
    explanation: Supports the intraventricular location that the imaging finding
      identifies; the enhancement characteristics themselves are described in the
      clinical literature rather than in this abstract.
phenotypes:
- category: Clinical
  name: Hydrocephalus
  phenotype_term:
    preferred_term: Hydrocephalus
    term:
      id: HP:0000238
      label: Hydrocephalus
  frequency: FREQUENT
  diagnostic: true
  description: >-
    The dominant presenting feature across the family. It arises by two distinct routes
    - cerebrospinal fluid overproduction by the secretory tumor epithelium (classically
    communicating) and obstruction of the cerebrospinal fluid pathways by mass effect -
    and both may operate in the same patient.
  evidence:
  - reference: PMID:30969571
    reference_title: Choroid Plexus Papilloma.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Patients with choroid plexus papillomas often present with communicating hydrocephalus secondary to cerebrospinal fluid overproduction."
    explanation: Supports hydrocephalus as the characteristic presentation and names the
      overproduction route.
  - reference: PMID:7414480
    reference_title: "Choroid plexus papilloma: hydrocephalus and cerebrospinal fluid dynamics."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The hydrocephalus was due solely to obstruction of the fourth ventricle."
    explanation: Supports the obstructive route as an independent cause of the same
      phenotype.
  - reference: PMID:34754533
    reference_title: "Persistence of communicating hydrocephalus post choroid plexus tumor resection: Case reports and review of literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Hydrocephalus is the most common presentation of choroid plexus tumors; it is thought to be caused either by mass effect obstructing the cerebrospinal fluid pathways or secretory properties of the tumor."
    explanation: States the dual mechanism explicitly - obstruction by mass effect OR
      secretory overproduction - which is why this entry models them as two nodes.
- category: Clinical
  name: Increased intracranial pressure
  phenotype_term:
    preferred_term: Increased intracranial pressure
    term:
      id: HP:0002516
      label: Increased intracranial pressure
  frequency: FREQUENT
  description: >-
    Expansion of the cerebrospinal fluid compartment raises intracranial pressure, which
    drives the headache, vomiting, papilledema and (in infants) fontanelle and
    head-circumference signs.
  evidence:
  - reference: PMID:1022421
    reference_title: "Choroid plexus papilloma. I. Proof of cerebrospinal fluid overproduction."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Whereas these data are regarded as conclusive evidence of CSF overproduction by a choroid plexus papilloma, the pathogenesis of generalized ventricular enlargement in this case was due to part to obstruction of the subarachnoid pathways."
    explanation: Documents the generalized ventricular enlargement from which raised
      intracranial pressure follows; the abstract does not report a pressure measurement,
      so support is partial.
  - reference: PMID:21121734
    reference_title: Treatment of third ventricular choroid plexus papilloma in an
      infant with embolization alone.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "He was found to have an enlarged head circumference, a full and tense fontanel, splayed sutures, and forced downward gaze."
    explanation: The classical infant sign cluster of raised intracranial pressure -
      head expansion, tense fontanelle, sutural diastasis and the setting-sun sign - in a
      child with a choroid plexus papilloma.
- category: Clinical
  name: Macrocephaly
  phenotype_term:
    preferred_term: Macrocephaly
    term:
      id: HP:0000256
      label: Macrocephaly
  frequency: FREQUENT
  description: >-
    In infants with unfused cranial sutures, chronic hydrocephalus expands the calvarium
    and produces an abnormally large head circumference. Because the incidence peak is
    in the first year of life, this is a common mode of presentation.
  evidence:
  - reference: PMID:21121734
    reference_title: Treatment of third ventricular choroid plexus papilloma in an
      infant with embolization alone.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This child presented with macrocephaly, irritability, inability to roll over, and vomiting."
    explanation: Macrocephaly as a documented presenting sign of a third-ventricular
      choroid plexus papilloma in a 3-month-old.
  - reference: PMID:36659972
    reference_title: Incidence and survival of choroid plexus tumors in the United States.
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Incidence was highest among children less than one year old among all subtypes (CPP AAIR: 0.278; aCPP AAIR: 0.140; CPC AAIR: 0.195), reducing as patients aged."
    explanation: Supports the infantile age distribution that makes macrocephaly a
      characteristic sign; the abstract does not itself enumerate presenting signs.
- category: Clinical
  name: Bulging fontanelle
  phenotype_term:
    preferred_term: Bulging fontanelle
    term:
      id: HP:6000647
      label: Bulging fontanelle
  frequency: OCCASIONAL
  description: >-
    Outward bowing of the unfused anterior fontanelle is a direct infant sign of raised
    intracranial pressure from tumor-associated hydrocephalus.
  evidence:
  - reference: PMID:34754533
    reference_title: "Persistence of communicating hydrocephalus post choroid plexus tumor resection: Case reports and review of literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Case 1: a 2-month-old baby girl presented with bulging fontanelle, sunsetting eyes."
    explanation: Bulging fontanelle as the documented presenting sign of a
      third-ventricular choroid plexus tumor in a 2-month-old.
  - reference: PMID:21121734
    reference_title: Treatment of third ventricular choroid plexus papilloma in an
      infant with embolization alone.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "He was found to have an enlarged head circumference, a full and tense fontanel, splayed sutures, and forced downward gaze."
    explanation: A second case documenting the tense/full fontanelle in an infant with a
      choroid plexus papilloma.
- category: Clinical
  name: Papilledema
  phenotype_term:
    preferred_term: Papilledema
    term:
      id: HP:0001085
      label: Papilledema
  frequency: OCCASIONAL
  description: >-
    Optic disc swelling from transmitted raised intracranial pressure; a classical sign
    in older children and adults whose sutures have fused and who therefore cannot
    decompress by head expansion.
  evidence:
  - reference: PMID:34754533
    reference_title: "Persistence of communicating hydrocephalus post choroid plexus tumor resection: Case reports and review of literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Case 2: a 16-year-old boy presented decreased visual acuity, papilledema, and morning headaches."
    explanation: Papilledema as a documented presenting sign in an older child with a
      lateral-ventricular choroid plexus tumor and communicating hydrocephalus.
- category: Clinical
  name: Headache
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
  frequency: OCCASIONAL
  description: >-
    A presenting symptom of raised intracranial pressure, more prominent in older
    children and adults - the group in whom fourth-ventricular tumors predominate.
  evidence:
  - reference: PMID:34754533
    reference_title: "Persistence of communicating hydrocephalus post choroid plexus tumor resection: Case reports and review of literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Case 2: a 16-year-old boy presented decreased visual acuity, papilledema, and morning headaches."
    explanation: Morning headache, the classical raised-intracranial-pressure pattern, as
      a presenting symptom of a choroid plexus tumor.
  - reference: PMID:27913261
    reference_title: Typical Symptoms of Normal-Pressure Hydrocephalus Caused by Choroid
      Plexus Papilloma in the Cerebellopontine Angle.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A 45-year-old woman presented with a 6-year history of headache and typical symptoms of normal-pressure hydrocephalus, including gait disturbance, urinary incontinence, and cognitive dysfunction, in addition to the more common symptoms of CPP, such as lower cranial nerve dysfunctions and ataxia."
    explanation: Headache as the leading symptom in the adult, fourth-ventricular
      presentation.
- category: Clinical
  name: Vomiting
  phenotype_term:
    preferred_term: Vomiting
    term:
      id: HP:0002013
      label: Vomiting
  frequency: OCCASIONAL
  description: >-
    Non-gastrointestinal vomiting from raised intracranial pressure, often with
    headache, and a common trigger for the imaging that reveals the tumor.
  evidence:
  - reference: PMID:21121734
    reference_title: Treatment of third ventricular choroid plexus papilloma in an
      infant with embolization alone.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This child presented with macrocephaly, irritability, inability to roll over, and vomiting."
    explanation: Vomiting as a documented presenting symptom alongside the other
      raised-pressure signs.
- category: Clinical
  name: Ataxia
  phenotype_term:
    preferred_term: Ataxia
    term:
      id: HP:0001251
      label: Ataxia
  frequency: OCCASIONAL
  description: >-
    Cerebellar dysfunction from fourth-ventricular and cerebellopontine-angle tumors,
    the sites that predominate in adults.
  evidence:
  - reference: PMID:27913261
    reference_title: Typical Symptoms of Normal-Pressure Hydrocephalus Caused by Choroid
      Plexus Papilloma in the Cerebellopontine Angle.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "in addition to the more common symptoms of CPP, such as lower cranial nerve dysfunctions and ataxia"
    explanation: The authors identify ataxia and lower cranial nerve dysfunction as the
      more common symptoms of choroid plexus papilloma at this site.
- category: Clinical
  name: Seizure
  phenotype_term:
    preferred_term: Seizure
    term:
      id: HP:0001250
      label: Seizure
  frequency: OCCASIONAL
  description: >-
    A less common presentation, associated with supratentorial (lateral-ventricular)
    tumors and secondary parenchymal effects.
  evidence:
  - reference: PMID:37928807
    reference_title: "Case Report: Detailed Clinical Course and Management Plan for Status Epilepticus Pediatric Patient with Resected Choroid Plexus Papilloma: A Case Report and a Single Center Experience."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We herein report a rare presentation of CPP in a 6-year-old Sudanese female child with seizures."
    explanation: Documented seizure presentation of a lateral-ventricular choroid plexus
      papilloma; the authors themselves describe it as a rare presentation, consistent
      with the OCCASIONAL frequency band.
- category: Clinical
  name: Gait disturbance
  phenotype_term:
    preferred_term: Gait disturbance
    term:
      id: HP:0001288
      label: Gait disturbance
  frequency: OCCASIONAL
  description: >-
    Gait impairment arises both from posterior-fossa/cerebellar involvement and, in
    adults with a communicating hydrocephalus, as part of a normal-pressure-hydrocephalus
    symptom complex that resolves after tumour removal.
  evidence:
  - reference: PMID:27913261
    reference_title: Typical Symptoms of Normal-Pressure Hydrocephalus Caused by Choroid
      Plexus Papilloma in the Cerebellopontine Angle.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A 45-year-old woman presented with a 6-year history of headache and typical symptoms of normal-pressure hydrocephalus, including gait disturbance, urinary incontinence, and cognitive dysfunction"
    explanation: Gait disturbance as a documented presenting feature of an adult choroid
      plexus papilloma with communicating hydrocephalus.
  - reference: PMID:27913261
    reference_title: Typical Symptoms of Normal-Pressure Hydrocephalus Caused by Choroid
      Plexus Papilloma in the Cerebellopontine Angle.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The symptoms of normal-pressure hydrocephalus disappeared."
    explanation: Resolution after tumour excision confirms the gait disturbance was
      tumour-driven rather than incidental.
- category: Clinical
  name: Abnormal cranial nerve physiology
  phenotype_term:
    preferred_term: Abnormal cranial nerve physiology
    term:
      id: HP:0031910
      label: Abnormal cranial nerve physiology
  frequency: OCCASIONAL
  description: >-
    Lower cranial nerve dysfunction from direct mass effect, characteristic of
    fourth-ventricular and cerebellopontine-angle tumours, which are the adult-predominant
    sites.
  evidence:
  - reference: PMID:27913261
    reference_title: Typical Symptoms of Normal-Pressure Hydrocephalus Caused by Choroid
      Plexus Papilloma in the Cerebellopontine Angle.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "in addition to the more common symptoms of CPP, such as lower cranial nerve dysfunctions and ataxia"
    explanation: The authors identify lower cranial nerve dysfunction as one of the more
      common symptoms of choroid plexus papilloma at this site.
- category: Clinical
  name: Neurodevelopmental abnormality
  phenotype_term:
    preferred_term: Neurodevelopmental abnormality
    term:
      id: HP:0012759
      label: Neurodevelopmental abnormality
  frequency: FREQUENT
  subtype: CPC
  description: >-
    Neurodevelopmental and sensorineural impairment in carcinoma survivors reflects the
    combined burden of infantile hydrocephalus, tumor and surgical injury, and treatment
    neurotoxicity. Even in radiation-sparing protocols the majority of survivors have
    significant neurocognitive or sensorial deficits. The FREQUENT band and the scope of
    this claim are deliberately restricted to choroid plexus carcinoma survivors, the
    only group in which it has been quantified; grade 1 papilloma, usually cured by
    resection alone, is not covered by this evidence.
  evidence:
  - reference: PMID:20515336
    reference_title: "Use of ifosfamide, carboplatin, and etoposide chemotherapy in choroid plexus carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "None of the survivors received radiation therapy. However, 6 of 8 display significant neurocognitive and/or sensorial deficit."
    explanation: Quantifies neurodevelopmental morbidity among survivors even without
      radiotherapy.
- category: Clinical
  name: Neoplasm of the central nervous system
  phenotype_term:
    preferred_term: Neoplasm of the central nervous system
    term:
      id: HP:0100006
      label: Neoplasm of the central nervous system
  frequency: VERY_FREQUENT
  description: >-
    The defining phenotype - an intraventricular central nervous system neoplasm, with
    additional deposits when invasion or leptomeningeal dissemination has occurred.
  evidence:
  - reference: PMID:33249490
    reference_title: The genetic landscape of choroid plexus tumors in children and adults.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Choroid plexus tumors (CPTs) are intraventricular brain tumors predominantly arising in children but also affecting adults."
    explanation: Establishes the central nervous system neoplasm phenotype.
biochemical:
- name: Kir7.1 (KCNJ13) Immunoexpression
  presence: PRESENT
  specificity: >-
    Highly specific for choroid plexus lineage - absent from 100 other primary brain
    tumors and cerebral metastases - though rare atypical teratoid/rhabdoid tumors can
    stain.
  frequency: FREQUENT
  cell_types:
  - preferred_term: choroid plexus epithelial cell
    term:
      id: CL:0000706
      label: choroid plexus epithelial cell
  notes: >-
    Kir7.1 is the single most useful lineage marker in the differential diagnosis
    against ependymoma, papillary meningioma and metastatic papillary carcinoma.
  evidence:
  - reference: PMID:16330944
    reference_title: "Identification of novel diagnostic markers for choroid plexus tumors: a microarray-based approach."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Expression of inward rectifier potassium channel Kir7.1 was confirmed in normal choroid plexus (34 of 35), choroid plexus papilloma (12 of 18), and choroid plexus carcinoma (5 of 5) but was not found in 100 other primary brain tumors and cerebral metastases."
    explanation: Establishes both the sensitivity and the specificity of Kir7.1 for
      choroid plexus tumors.
  - reference: PMID:21276081
    reference_title: Atypical teratoid/rhabdoid tumors may show morphological and
      immunohistochemical features seen in choroid plexus tumors.
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Two AT/RT cases exhibited membranous staining of Kir7.1, indicating a plexus epithelial differentiation of these tumors."
    explanation: Qualifies the specificity claim by documenting Kir7.1 staining in
      atypical teratoid/rhabdoid tumor.
- name: Stanniocalcin-1 Immunoexpression
  presence: PRESENT
  specificity: >-
    Stains only 2 of 100 other primary brain tumors and cerebral metastases,
    complementing Kir7.1.
  frequency: VERY_FREQUENT
  notes: >-
    Used alongside Kir7.1 as the second-line lineage marker for choroid plexus tumors.
  evidence:
  - reference: PMID:16330944
    reference_title: "Identification of novel diagnostic markers for choroid plexus tumors: a microarray-based approach."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Similarly, stanniocalcin-1 stained normal choroid plexus (32 of 35), choroid plexus papilloma (16 of 18), and choroid plexus carcinoma (3 of 5), whereas staining was seen in only 2 of 100 other primary brain tumors and cerebral metastases."
    explanation: Quantifies the sensitivity and specificity of stanniocalcin-1.
genetic:
- name: TP53
  gene_term:
    preferred_term: TP53
    term:
      id: hgnc:11998
      label: TP53
  relationship_type: CAUSATIVE
  variant_origin: GERMLINE
  presence: PRESENT
  association: >-
    Germline pathogenic TP53 variants cause Li-Fraumeni syndrome / heritable
    TP53-related cancer syndrome, of which choroid plexus carcinoma is a sentinel tumor.
    In the landmark multi-institutional series, every patient with a germline TP53
    mutation fulfilled Li-Fraumeni criteria and every patient not meeting those criteria
    had wild-type TP53. Roughly a third of choroid plexus carcinomas occur in the
    setting of Li-Fraumeni syndrome. Cross-reference
    kb/disorders/Li-Fraumeni_Syndrome.yaml.
  frequency: >-
    Reported estimates range widely with cohort and ascertainment: approximately 36% in
    a 10-study narrative review, and 4 of 13 patients in the prospective SJYC07 cohort
    were germline carriers. Li-Fraumeni guideline sources quote higher fractions in
    children. Treat any single point estimate as cohort-dependent.
  notes: >-
    Because a tumor-only TP53 result cannot distinguish germline from somatic origin,
    paired germline testing with genetic counselling is indicated in essentially every
    choroid plexus carcinoma, irrespective of family history, and must precede treatment
    planning because it changes radiotherapy and genotoxic-chemotherapy decisions.
  evidence:
  - reference: PMID:20308654
    reference_title: TP53 alterations determine clinical subgroups and survival of
      patients with choroid plexus tumors.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "All individuals with germline TP53 mutations fulfilled LFS criteria, whereas all patients not meeting these criteria harbored wild-type TP53 (P < .001)."
    explanation: Establishes the tight correspondence between germline TP53 mutation and
      Li-Fraumeni syndrome in this tumor.
  - reference: PMID:20308654
    reference_title: TP53 alterations determine clinical subgroups and survival of
      patients with choroid plexus tumors.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Choroid plexus carcinomas are pediatric tumors with poor survival rates and a strong, but poorly understood, association with Li-Fraumeni syndrome (LFS)."
    explanation: States the sentinel-cancer relationship between choroid plexus carcinoma
      and Li-Fraumeni syndrome.
  - reference: PMID:38316675
    reference_title: "Correlation between choroid plexus carcinoma and Li-Fraumeni syndrome: implications of TP53 mutations and management strategies-a case-based narrative review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The review highlighted the strong association (36%) between CPCs and LFS, primarily due to TP53 germline mutations."
    explanation: Quantifies the proportion of choroid plexus carcinomas arising in
      Li-Fraumeni syndrome.
  - reference: PMID:33506206
    reference_title: "Outcome and molecular analysis of young children with choroid plexus carcinoma treated with non-myeloablative therapy: results from the SJYC07 trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Seven patients had TP53-mutant tumors, including 4 who were germline carriers."
    explanation: Prospective-trial evidence for the germline carrier fraction.
  - reference: PMID:36963804
    reference_title: Genomic profile of two Brazilian choroid plexus tumors by whole-exome
      sequencing.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The CPC tumor had only a pathogenic germline TP53 variant, based on American College of Medical Genetics (ACMG) criteria, with a clinical and familiar history of Li-Fraumeni syndrome."
    explanation: Worked case demonstrating germline TP53 as the sole pathogenic finding
      in a Li-Fraumeni-associated carcinoma.
- name: TP53 (somatic)
  gene_term:
    preferred_term: TP53
    term:
      id: hgnc:11998
      label: TP53
  relationship_type: SOMATIC_DRIVER
  variant_origin: SOMATIC
  presence: PRESENT
  association: >-
    Somatic TP53 mutation is the only recurrent somatic driver in pediatric choroid
    plexus tumors and is the dominant prognostic axis in carcinoma - TP53-wild-type
    carcinomas have markedly better survival than TP53-mutant carcinomas, and a greater
    number of mutant TP53 copies confers worse outcome still.
  frequency: >-
    About 50% of choroid plexus carcinomas by immunohistochemistry/sequencing; 15% of
    the whole choroid plexus tumor family (7/47) in an unselected molecular series.
  subtype: CPC
  evidence:
  - reference: PMID:33506206
    reference_title: "Outcome and molecular analysis of young children with choroid plexus carcinoma treated with non-myeloablative therapy: results from the SJYC07 trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Patients with TP53-wild-type tumors had a 5-year PFS of 100% as compared to 28.6 ± 17.1% for TP53-mutant tumors (P = .012)."
    explanation: The strongest prospective statement of the TP53 prognostic axis, and of
      the markedly better survival of TP53-wild-type carcinoma.
  - reference: PMID:33506206
    reference_title: "Outcome and molecular analysis of young children with choroid plexus carcinoma treated with non-myeloablative therapy: results from the SJYC07 trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "TP53-mutational status was the only significant prognostic variable and should form the basis of risk-stratification in future trials."
    explanation: Establishes TP53 status as the dominant prognostic variable.
  - reference: PMID:20308654
    reference_title: TP53 alterations determine clinical subgroups and survival of
      patients with choroid plexus tumors.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Five-year survival rates for patients with TP53-immunopositive and -immunonegative CPCs were 0% and 82 (+/- 9%), respectively (P < .001)."
    explanation: Independent, earlier demonstration of the same survival split by TP53
      status.
  - reference: PMID:25336695
    reference_title: Molecular characterization of choroid plexus tumors reveals novel
      clinically relevant subgroups.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Investigating the number of mutated copies of p53 per sample revealed a high-risk group of patients with CPC carrying two copies of mutant p53, who exhibited poor 5-year event-free (EFS) and overall survival (OS) compared with patients with CPC carrying one copy of mutant p53"
    explanation: Refines the prognostic axis to mutant-allele dosage.
  - reference: PMID:33249490
    reference_title: The genetic landscape of choroid plexus tumors in children and adults.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "WES and targeted sequencing showed TP53 mutations in 7/47 CPTs (15%), five of which were children."
    explanation: Frequency of TP53 mutation across the unselected choroid plexus tumor
      family.
- name: TERT
  gene_term:
    preferred_term: TERT
    term:
      id: hgnc:11730
      label: TERT
  relationship_type: SOMATIC_DRIVER
  variant_origin: SOMATIC
  presence: PRESENT
  association: >-
    TERT promoter mutation is an adult-specific somatic alteration in choroid plexus
    tumors, found in a quarter of adult patients and associated with shorter
    progression-free survival. It is not a germline predisposition and is not seen in
    the pediatric-dominant subgroups.
  frequency: 7 of 28 adult patients (25%)
  evidence:
  - reference: PMID:33249490
    reference_title: The genetic landscape of choroid plexus tumors in children and adults.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "On the contrary, TERT promoter mutations were encountered in 7/28 adult patients (25%) and associated with shorter progression-free survival (log-rank test, p=0.015)."
    explanation: Establishes the frequency and prognostic significance of TERT promoter
      mutation in adult choroid plexus tumors.
inheritance:
- name: Autosomal dominant (Li-Fraumeni-associated cases)
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  description: >-
    Sporadic choroid plexus tumors are not inherited. The predisposition that matters
    clinically is autosomal dominant heritable TP53-related cancer (Li-Fraumeni)
    syndrome, with variable, age-dependent penetrance. De novo germline TP53 variants
    occur, so absence of a family history does not exclude the syndrome.
  evidence:
  - reference: PMID:32457520
    reference_title: Guidelines for the Li-Fraumeni and heritable TP53-related cancer
      syndromes.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "germline TP53 alterations are often identified among children with cancers, in particular soft-tissue sarcomas, adrenocortical carcinomas, central nervous system tumours, or among adult females with early breast cancers, without familial history"
    explanation: Supports that germline TP53 predisposition is frequently found in
      children with central nervous system tumors even absent a family history.
  - reference: PMID:32457520
    reference_title: Guidelines for the Li-Fraumeni and heritable TP53-related cancer
      syndromes.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the penetrance of germline disease-causing TP53 variants is variable, depending both on the type of variant (dominant-negative variants being associated with a higher cancer risk) and on modifying factors"
    explanation: Supports the variable penetrance qualifier.
environmental:
- name: Simian virus 40 (SV40) exposure
  presence: ABSENT
  description: >-
    An aetiological role for SV40 in choroid plexus tumors was proposed historically on
    the basis of SV40 DNA sequences detected in tumor tissue and of SV40 large T antigen
    driving choroid plexus tumors in transgenic mice, and was linked to the accidental
    SV40 contamination of early poliovirus vaccine. This entry treats the claim as
    contested and, on current evidence, largely discounted rather than established: a
    nationwide Danish cohort of 69.5 million person-years found no excess of choroid
    plexus tumor in the vaccine-exposed birth cohorts, and immunohistochemistry for SV40
    large T antigen was negative in all of 82 central nervous system tumors including
    choroid plexus lesions. The entry therefore asserts neither causation nor definitive
    exclusion; it records that the epidemiological and protein-level evidence does not
    support SV40 as a cause.
  notes: >-
    `presence: ABSENT` is the closest available schema value for "exposure examined and
    found not to be associated"; the enum has no NOT_ASSOCIATED value, and `effect:` is
    deliberately left unset because neither a causal nor a protective label is correct.
    Read the description and the REFUTE-tagged evidence, not the enum, for the intended
    claim. The residual uncertainty is that the negative studies address vaccine-era
    population exposure and large T antigen protein detection, not every proposed SV40
    mechanism.
  evidence:
  - reference: PMID:12671021
    reference_title: Cancer incidence in Denmark following exposure to poliovirus vaccine
      contaminated with simian virus 40.
    supports: REFUTE
    evidence_source: HUMAN_CLINICAL
    snippet: "Specifically, SV40 exposure was not associated with increased incidence of mesothelioma, ependymoma, choroid plexus tumor, or non-Hodgkin's lymphoma."
    explanation: Population-level refutation of an SV40 contribution to choroid plexus
      tumor incidence.
  - reference: PMID:12671021
    reference_title: Cancer incidence in Denmark following exposure to poliovirus vaccine
      contaminated with simian virus 40.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "SV40 DNA sequences have been detected in several human malignancies, including mesothelioma, ependymoma, choroid plexus tumors, and non-Hodgkin's lymphoma."
    explanation: Records the historical basis of the SV40 hypothesis that the same study
      set out to test.
  - reference: PMID:15790713
    reference_title: Immunodetection of SV40 large T antigen in human central nervous
      system tumours.
    supports: REFUTE
    evidence_source: HUMAN_CLINICAL
    snippet: "None of the tumours (20 ependymomas, 20 glioblastomas, 12 oligodendrogliomas, three plexus choroid adenomas, two plexus choroid carcinomas, 15 meningiomas, and 10 medulloblastomas) contained SV40 Tag positive cells."
    explanation: Protein-level failure to detect the SV40 oncoprotein in choroid plexus
      tumors.
  - reference: PMID:15790713
    reference_title: Immunodetection of SV40 large T antigen in human central nervous
      system tumours.
    supports: REFUTE
    evidence_source: HUMAN_CLINICAL
    snippet: "The lack of SV40 Tag in 82 CNS tumours of various types is at variance with previous studies from different countries, and suggests that the virus may not be an important factor in CNS tumorigenesis, at least in French cases."
    explanation: The authors' own framing of the result as contradicting the earlier
      positive reports, which is why this entry treats the question as contested rather
      than settled in either direction.
treatments:
- name: Maximal Safe Surgical Resection
  action_category: THERAPEUTIC
  description: >-
    Gross total resection is the cornerstone of treatment for every grade and, in
    carcinoma, the strongest modifiable prognostic factor; in papilloma and atypical
    papilloma the same population data show no overall survival difference between
    gross total and subtotal resection. In grade 1 papilloma it is frequently
    curative and needs no adjuvant therapy; in carcinoma it is independently associated
    with improved overall survival. Planning must account for the extreme vascularity of
    these tumors and the small circulating blood volume of infants, and staged or
    second-look surgery is often used.
  treatment_term:
    preferred_term: Gross Total Resection
    term:
      id: NCIT:C131672
      label: Gross Total Resection
  therapeutic_modality: SURGERY
  target_mechanisms:
  - target: Cerebrospinal Fluid Overproduction by Secretory Tumour Epithelium
    treatment_effect: INHIBITS
    description: >-
      Removing the secretory tumor epithelium directly abolishes the excess
      cerebrospinal fluid production, as demonstrated by the fivefold fall in formation
      rate after resection.
    evidence:
    - reference: PMID:1022421
      reference_title: "Choroid plexus papilloma. I. Proof of cerebrospinal fluid overproduction."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Postoperatively, the CSF formation rate was reduced fivefold to 0.20 +/- SD 0.01 ml/min (288 ml/day)."
      explanation: Measured fall in cerebrospinal fluid formation rate after tumor
        resection, directly evidencing the treatment-mechanism link.
  evidence:
  - reference: PMID:28939225
    reference_title: "Effect of Surgery, Adjuvant Therapy, and Other Prognostic Factors on Choroid Plexus Carcinoma: A Systematic Review and Individual Patient Data Analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "All patients should undergo maximal safe resection, because GTR is associated with improved survival."
    explanation: Pooled individual-patient-data recommendation establishing gross total
      resection as the key modifiable prognostic factor.
  - reference: PMID:38339361
    reference_title: "Prognostic Factors and Nomogram for Choroid Plexus Tumors: A Population-Based Retrospective Surveillance, Epidemiology, and End Results Database Analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Meanwhile, in patients with CPC, gross total resection (GTR) was associated with significantly better OS than subtotal resection (STR) only."
    explanation: Population-level confirmation for carcinoma.
  - reference: PMID:30969571
    reference_title: Choroid Plexus Papilloma.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The prognosis of these benign neoplasms is favorable, and gross total resection is frequently curative."
    explanation: Establishes the curative role of resection alone in grade 1 disease.
  - reference: PMID:1022421
    reference_title: "Choroid plexus papilloma. I. Proof of cerebrospinal fluid overproduction."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Postoperatively, the CSF formation rate was reduced fivefold to 0.20 +/- SD 0.01 ml/min (288 ml/day)."
    explanation: Direct measurement showing that resection reverses the overproduction
      mechanism.
- name: Observation After Complete Resection
  action_category: MONITORING
  description: >-
    Following complete resection of a grade 1 papilloma - and, in most protocols, of a
    completely resected atypical papilloma - patients are observed with serial MRI
    rather than treated with adjuvant therapy. Population data show no overall survival
    difference between gross total and subtotal resection in papilloma or atypical
    papilloma, supporting a conservative posture in these grades.
  treatment_term:
    preferred_term: Follow-up Examination After Treatment for Malignant Neoplasm
    term:
      id: NCIT:C171209
      label: Follow-up Examination After Treatment for Malignant Neoplasm
  therapeutic_modality: BEHAVIORAL
  evidence:
  - reference: PMID:19543851
    reference_title: "Atypical choroid plexus papilloma: clinical experience in the CPT-SIOP-2000 study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "After surgery, patients who had undergone complete resection were observed, whereas patients with incompletely resected or metastasized APP were treated with six chemotherapy courses"
    explanation: Protocol evidence for observation after complete resection in atypical
      papilloma.
  - reference: PMID:38339361
    reference_title: "Prognostic Factors and Nomogram for Choroid Plexus Tumors: A Population-Based Retrospective Surveillance, Epidemiology, and End Results Database Analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Overall, there is no difference in OS with GTR vs. STR in CPP or aCPP."
    explanation: Supports a less aggressive posture in the two lower grades.
- name: Carboplatin-Etoposide-Vincristine (CarbEV) Chemotherapy
  action_category: THERAPEUTIC
  description: >-
    Multi-agent chemotherapy for high-risk disease - carcinoma, incompletely resected
    atypical papilloma, and any metastatic choroid plexus tumor. In the randomised
    high-risk arm of CPT-SIOP-2000, carboplatin/etoposide/vincristine was superior to
    cyclophosphamide/etoposide/vincristine for progression-free survival.
  treatment_term:
    preferred_term: chemotherapy
    term:
      id: NCIT:C15632
      label: Chemotherapy
    therapeutic_agent:
    - preferred_term: carboplatin
      term:
        id: CHEBI:31355
        label: carboplatin
    - preferred_term: etoposide
      term:
        id: CHEBI:4911
        label: etoposide
    - preferred_term: vincristine
      term:
        id: CHEBI:28445
        label: vincristine
  therapeutic_modality: SMALL_MOLECULE
  target_mechanisms:
  - target: Choroid Plexus Epithelial Neoplastic Proliferation
    treatment_effect: INHIBITS
    description: Cytotoxic chemotherapy targets the proliferating tumor epithelium.
    evidence:
    - reference: PMID:19543851
      reference_title: "Atypical choroid plexus papilloma: clinical experience in the CPT-SIOP-2000 study."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "All nine APP patients who received postoperative chemotherapy showed an early response after two cycles: two had complete remission, four had partial response, and three had stable disease."
      explanation: Radiographic tumor response to the chemotherapy backbone evidences
        that it acts on the proliferating tumor mass.
  evidence:
  - reference: PMID:34997889
    reference_title: Final results of the Choroid Plexus Tumor study CPT-SIOP-2000.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "For randomized CPC, the 5/10 year progression free survival (PFS) of patients on CarbEV (n = 20) were 62%/47%, respectively, compared to 27%/18%, on CycEV (n = 15), (intention-to-treat, HR 2.6, p = 0.032)."
    explanation: Randomised evidence that the carboplatin-containing backbone is superior
      in high-risk disease.
  - reference: PMID:19543851
    reference_title: "Atypical choroid plexus papilloma: clinical experience in the CPT-SIOP-2000 study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "All nine APP patients who received postoperative chemotherapy showed an early response after two cycles: two had complete remission, four had partial response, and three had stable disease."
    explanation: Demonstrates chemosensitivity of atypical papilloma treated on the same
      protocol.
- name: Neoadjuvant ICE Chemotherapy Before Second-Look Surgery
  action_category: THERAPEUTIC
  description: >-
    Ifosfamide/carboplatin/etoposide given before a planned second operation
    devascularises the tumor and reduces intraoperative blood loss, raising the rate of
    complete or near-complete resection in carcinoma - a strategy that directly
    addresses the vascularity that limits primary resection in infants.
  treatment_term:
    preferred_term: chemotherapy
    term:
      id: NCIT:C15632
      label: Chemotherapy
    therapeutic_agent:
    - preferred_term: ifosfamide
      term:
        id: CHEBI:5864
        label: ifosfamide
    - preferred_term: carboplatin
      term:
        id: CHEBI:31355
        label: carboplatin
    - preferred_term: etoposide
      term:
        id: CHEBI:4911
        label: etoposide
  therapeutic_modality: SMALL_MOLECULE
  evidence:
  - reference: PMID:20515336
    reference_title: "Use of ifosfamide, carboplatin, and etoposide chemotherapy in choroid plexus carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In this experience, second surgery following neoadjuvant ICE chemotherapy led to a high rate of complete or near-complete resection."
    explanation: Supports the neoadjuvant-then-resect strategy and its surgical benefit.
  - reference: PMID:20515336
    reference_title: "Use of ifosfamide, carboplatin, and etoposide chemotherapy in choroid plexus carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Chemotherapy appears to facilitate second-look surgery, in particular through a reduction of intraoperative blood loss."
    explanation: Names the mechanism by which neoadjuvant chemotherapy improves
      resectability.
- name: Risk-Adapted Radiotherapy
  action_category: THERAPEUTIC
  description: >-
    Radiotherapy is used selectively and is generally withheld in children under three
    years. Focal fields are used for non-metastatic carcinoma and incompletely resected
    atypical papilloma; craniospinal fields are reserved for metastatic or
    non-responsive disease. Radiotherapy must be avoided or minimised where feasible in
    germline TP53 carriers because it contributes to subsequent primary tumours - which
    is why germline testing precedes treatment planning.
  treatment_term:
    preferred_term: Radiation Therapy
    term:
      id: NCIT:C15313
      label: Radiation Therapy
  therapeutic_modality: RADIOTHERAPY
  evidence:
  - reference: PMID:34997889
    reference_title: Final results of the Choroid Plexus Tumor study CPT-SIOP-2000.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Patients older than three years were recommended to receive irradiation: focal fields for non-metastatic CPC, incompletely resected atypical choroid plexus papilloma (APP) or metastatic choroid plexus papilloma (CPP); craniospinal fields for metastatic CPC/APP and non-responsive CPC."
    explanation: The protocolised risk-adapted radiotherapy policy for the whole family.
  - reference: PMID:32457520
    reference_title: Guidelines for the Li-Fraumeni and heritable TP53-related cancer
      syndromes.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "in cancer patients with germline disease-causing TP53 variants, radiotherapy, and conventional genotoxic chemotherapy contribute to the development of subsequent primary tumours"
    explanation: The basis for radiation avoidance in germline TP53 carriers.
  - reference: PMID:38316675
    reference_title: "Correlation between choroid plexus carcinoma and Li-Fraumeni syndrome: implications of TP53 mutations and management strategies-a case-based narrative review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Irradiation-sparing therapies are recommended for LFS-associated CPCs to mitigate the risk of secondary malignancies."
    explanation: Disease-specific recommendation to spare irradiation in
      Li-Fraumeni-associated carcinoma.
- name: Germline TP53 Testing and Genetic Counselling
  action_category: DIAGNOSTIC
  description: >-
    Paired germline TP53 testing with genetic counselling is indicated in essentially
    every child with choroid plexus carcinoma, irrespective of family history, and must
    be performed before treatment starts. It is the highest-value single action in the
    entry because it changes three things at once: the treatment plan (avoiding
    radiotherapy and genotoxic chemotherapy in carriers), lifelong surveillance for the
    patient, and cascade testing for relatives.
  treatment_term:
    preferred_term: Genetic Testing
    term:
      id: NCIT:C15709
      label: Genetic Testing
  therapeutic_modality: OTHER
  evidence:
  - reference: PMID:32457520
    reference_title: Guidelines for the Li-Fraumeni and heritable TP53-related cancer
      syndromes.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It is critical to perform TP53 testing before the initiation of treatment in order to avoid in carriers, if possible, radiotherapy and genotoxic chemotherapies."
    explanation: The guideline statement that testing must precede treatment.
  - reference: PMID:38316675
    reference_title: "Correlation between choroid plexus carcinoma and Li-Fraumeni syndrome: implications of TP53 mutations and management strategies-a case-based narrative review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Studies emphasized the need for genetic testing in patients with CPCs, especially in pediatric cases, to identify LFS implications."
    explanation: Disease-specific recommendation for germline testing in choroid plexus
      carcinoma.
- name: Li-Fraumeni Surveillance in Confirmed Carriers
  action_category: SCREENING
  description: >-
    Confirmed germline TP53 carriers enter lifelong surveillance: in children, clinical
    examination and abdominal ultrasound every six months plus annual whole-body and
    brain MRI from the first year of life. This targets the whole Li-Fraumeni tumour
    spectrum, not merely recurrent choroid plexus disease.
  treatment_term:
    preferred_term: Disease Screening
    term:
      id: NCIT:C15419
      label: Disease Screening
  therapeutic_modality: OTHER
  evidence:
  - reference: PMID:32457520
    reference_title: Guidelines for the Li-Fraumeni and heritable TP53-related cancer
      syndromes.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In children, the recommendations are to perform clinical examination and abdominal ultrasound every 6 months, annual WBMRI and brain MRI from the first year of life, if the TP53 variant is known to be associated with childhood cancers."
    explanation: The paediatric surveillance protocol for germline TP53 carriers.
- name: Cerebrospinal Fluid Diversion
  action_category: THERAPEUTIC
  description: >-
    Shunt placement or other cerebrospinal fluid diversion is used when hydrocephalus
    does not resolve after tumor removal. Because the obstruction and outflow-resistance
    arm of the mechanism can persist once the secretory tumor is gone, a subset of
    patients remain shunt-dependent despite radical resection and no residual tumour.
  treatment_term:
    preferred_term: Ventriculoperitoneal Shunt Placement
    term:
      id: NCIT:C168483
      label: Ventriculoperitoneal Shunt Placement
  therapeutic_modality: DEVICE
  target_mechanisms:
  - target: Ventricular Enlargement and Raised Intracranial Pressure
    treatment_effect: INHIBITS
    description: >-
      Diversion bypasses the obstructed pathway and normalises intracranial pressure
      irrespective of which mechanism produced the hydrocephalus.
    evidence:
    - reference: PMID:6738779
      reference_title: Persistent hydrocephalus following removal of choroid plexus
        papilloma of the lateral ventricle.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "To control the hydrocephalus, a bilateral shunt with low pressure valve was necessary."
      explanation: Documents shunt diversion being used, and required, to control the
        hydrocephalus.
  evidence:
  - reference: PMID:6738779
    reference_title: Persistent hydrocephalus following removal of choroid plexus
      papilloma of the lateral ventricle.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "To control the hydrocephalus, a bilateral shunt with low pressure valve was necessary."
    explanation: Documents the need for cerebrospinal fluid diversion when hydrocephalus
      persists after resection.
diagnosis:
- name: Contrast-enhanced brain MRI
  diagnosis_term:
    preferred_term: Magnetic Resonance Imaging
    term:
      id: NCIT:C16809
      label: Magnetic Resonance Imaging
  description: >-
    MRI identifies the intraventricular mass, the degree of hydrocephalus,
    transependymal oedema, haemorrhage and invasion, and defines residual disease after
    surgery. Spine MRI is added when higher-grade disease is suspected.
  results: >-
    An enhancing, lobulated intraventricular mass with ventricular dilatation in a young
    child is the characteristic finding.
  evidence:
  - reference: PMID:33249490
    reference_title: The genetic landscape of choroid plexus tumors in children and adults.
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Choroid plexus tumors (CPTs) are intraventricular brain tumors predominantly arising in children but also affecting adults."
    explanation: Supports the intraventricular target of the imaging study; the
      enhancement pattern is not described in this abstract.
- name: Histopathologic examination with lineage immunohistochemistry
  description: >-
    Definitive diagnosis and grading rest on histology - papillary architecture, mitotic
    count, cellularity, pleomorphism, necrosis and invasion - supplemented by Kir7.1 and
    stanniocalcin-1 immunohistochemistry to confirm choroid plexus lineage against
    ependymoma, meningioma and metastatic papillary carcinoma.
  results: >-
    Kir7.1- and stanniocalcin-1-positive papillary epithelial tumor; mitotic count of at
    least 2 per 10 high-power fields upgrades papilloma to atypical papilloma; frank
    anaplasia and brain invasion define carcinoma.
  evidence:
  - reference: PMID:16330944
    reference_title: "Identification of novel diagnostic markers for choroid plexus tumors: a microarray-based approach."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Our data suggest that antibodies directed against Kir7.1 and stanniocalcin-1 might serve as sensitive and specific diagnostic markers for choroid plexus tumors."
    explanation: Establishes the immunohistochemical panel used to confirm lineage.
  - reference: PMID:17086103
    reference_title: Prognostic implications of atypical histologic features in choroid
      plexus papilloma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "we propose to define atypical choroid plexus papilloma by mitotic activity (> or =2 mitoses per 10 high-power fields) corresponding to World Health Organization grade II"
    explanation: Establishes the histologic grading threshold applied at diagnosis.
- name: DNA methylation profiling
  description: >-
    Methylation classification resolves choroid plexus tumors into three clinically
    relevant subgroups - pediatric A, pediatric B and adult - that complement rather
    than replace histology, and that can reassign histologically low-grade tumors to a
    high-risk molecular class.
  results: >-
    Assignment to pediatric A, pediatric B or adult methylation subgroup, with pediatric
    B carrying the highest recurrence risk.
  evidence:
  - reference: PMID:33249490
    reference_title: The genetic landscape of choroid plexus tumors in children and adults.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Tumors comprised the molecular subgroups \"pediatric A\" (N=11), \"pediatric B\" (N=12) and \"adult\" (N=27)."
    explanation: Names the three methylation subgroups asserted in the description.
  - reference: PMID:39482394
    reference_title: Single-nucleus RNA-seq dissection of choroid plexus tumor cell
      heterogeneity.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "all CPC, but also a considerable number of pediatric CPP and aCPP, are assigned to high-risk methylation cluster 3"
    explanation: Sources the claim that the pediatric-B cluster is the high-risk class
      and can capture histologically lower-grade tumors.
  - reference: PMID:25336695
    reference_title: Molecular characterization of choroid plexus tumors reveals novel
      clinically relevant subgroups.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Our data demonstrate that differences in CN, gene expression, and DNA methylation signatures distinguish CPCs from CPPs and aCPPs"
    explanation: Supports the diagnostic discriminating power of methylation and
      copy-number profiling.
- name: Germline TP53 sequencing
  diagnosis_term:
    preferred_term: Genetic Testing
    term:
      id: NCIT:C15709
      label: Genetic Testing
  description: >-
    Paired germline TP53 testing in every choroid plexus carcinoma, performed before
    treatment planning. Tumor-only sequencing cannot distinguish germline from somatic
    origin and therefore cannot substitute.
  results: >-
    Identification of a germline pathogenic TP53 variant establishes heritable
    TP53-related cancer (Li-Fraumeni) syndrome and changes treatment and surveillance.
  evidence:
  - reference: PMID:32457520
    reference_title: Guidelines for the Li-Fraumeni and heritable TP53-related cancer
      syndromes.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It is critical to perform TP53 testing before the initiation of treatment in order to avoid in carriers, if possible, radiotherapy and genotoxic chemotherapies."
    explanation: Establishes germline TP53 testing as a pre-treatment diagnostic step.
differential_diagnoses:
- name: Ependymoma
  disease_term:
    preferred_term: ependymoma
    term:
      id: MONDO:0016698
      label: ependymoma
  description: >-
    Papillary intraventricular ependymoma is the closest radiological and histological
    mimic. It shares the intraventricular location and papillary appearance but lacks
    choroid plexus lineage markers.
  distinguishing_features:
  - Ependymoma is negative for the choroid plexus lineage markers Kir7.1 and
    stanniocalcin-1.
  - Ependymoma typically shows GFAP positivity with perivascular pseudorosettes and
    ependymal rosettes rather than true fibrovascular papillae.
  evidence:
  - reference: PMID:16330944
    reference_title: "Identification of novel diagnostic markers for choroid plexus tumors: a microarray-based approach."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "gene expression profiles of choroid plexus epithelial cells (n = 8) and ependymal cells (n = 6) microdissected from human autopsy brains as well as choroid plexus papilloma tissue were investigated using DNA microarrays"
    explanation: The marker study was explicitly designed against ependymal cells,
      confirming ependymoma as the principal lineage differential.
- name: Papillary meningioma
  disease_term:
    preferred_term: meningioma
    term:
      id: MONDO:0016642
      label: meningioma
  description: >-
    Intraventricular and papillary meningiomas can present as an enhancing
    intraventricular mass and mimic choroid plexus papilloma both radiologically and
    histologically.
  distinguishing_features:
  - Meningioma is EMA-positive and negative for the choroid plexus lineage markers
    Kir7.1 and stanniocalcin-1.
  - Stanniocalcin-1 stained only 2 of 100 non-choroid-plexus primary brain tumors and
    cerebral metastases in the defining marker series.
  evidence:
  - reference: PMID:16330944
    reference_title: "Identification of novel diagnostic markers for choroid plexus tumors: a microarray-based approach."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Similarly, stanniocalcin-1 stained normal choroid plexus (32 of 35), choroid plexus papilloma (16 of 18), and choroid plexus carcinoma (3 of 5), whereas staining was seen in only 2 of 100 other primary brain tumors and cerebral metastases."
    explanation: Supports the marker-based exclusion of other primary brain tumors, the
      category that includes meningioma.
- name: Metastatic papillary carcinoma
  disease_term:
    preferred_term: metastatic carcinoma
    term:
      id: MONDO:0024879
      label: metastatic carcinoma
  description: >-
    Metastatic papillary adenocarcinoma to the brain (thyroid, lung, renal, ovarian) can
    be histologically indistinguishable from choroid plexus carcinoma on morphology
    alone, particularly in adults.
  distinguishing_features:
  - Kir7.1 was absent from all 100 non-choroid-plexus primary brain tumors and cerebral
    metastases tested, making it the discriminating marker.
  - A known extracranial primary and a non-intraventricular or multifocal distribution
    favour metastasis.
  evidence:
  - reference: PMID:16330944
    reference_title: "Identification of novel diagnostic markers for choroid plexus tumors: a microarray-based approach."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Expression of inward rectifier potassium channel Kir7.1 was confirmed in normal choroid plexus (34 of 35), choroid plexus papilloma (12 of 18), and choroid plexus carcinoma (5 of 5) but was not found in 100 other primary brain tumors and cerebral metastases."
    explanation: Establishes the marker that separates choroid plexus tumors from
      cerebral metastases.
- name: Atypical teratoid/rhabdoid tumor
  disease_term:
    preferred_term: atypical teratoid rhabdoid tumor
    term:
      id: MONDO:0020560
      label: atypical teratoid rhabdoid tumor
  description: >-
    AT/RT of infancy can occupy the same intraventricular compartment and the same age
    group as choroid plexus carcinoma, and is the most dangerous confusion because
    treatment differs substantially.
  distinguishing_features:
  - Loss of nuclear INI1/SMARCB1 staining defines AT/RT and must be tested for.
  - A minority of AT/RTs express Kir7.1, so choroid plexus lineage markers alone cannot
    exclude AT/RT.
  evidence:
  - reference: PMID:21276081
    reference_title: Atypical teratoid/rhabdoid tumors may show morphological and
      immunohistochemical features seen in choroid plexus tumors.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Two AT/RT cases exhibited membranous staining of Kir7.1, indicating a plexus epithelial differentiation of these tumors."
    explanation: Documents the overlap that makes AT/RT a critical differential and
      limits reliance on Kir7.1 alone.
  - reference: PMID:21276081
    reference_title: Atypical teratoid/rhabdoid tumors may show morphological and
      immunohistochemical features seen in choroid plexus tumors.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Differential diagnosis includes choroid plexus carcinoma which has occasionally been attributed as showing an inactivation of INI1/SMARCB1 nuclear staining in immunohistochemistry."
    explanation: Names choroid plexus carcinoma explicitly as the AT/RT differential and
      identifies the INI1/SMARCB1 discriminator.
- name: Choroid plexus cyst
  description: >-
    A benign, usually incidental fluid-filled cyst of the choroid plexus stroma, most
    often detected on second-trimester fetal ultrasound and associated with trisomy 18
    when other markers are present. Despite the shared anatomical name it is not a
    neoplasm, has no relationship to the choroid plexus tumor family, and is included
    here explicitly because the name similarity is a recognised source of literature and
    curation confusion.
  distinguishing_features:
  - A choroid plexus cyst is a non-enhancing, non-solid cystic structure that typically
    resolves spontaneously, produces no mass effect and no hydrocephalus, and requires
    no oncological management.
  - Choroid plexus neoplasms are solid, intensely enhancing intraventricular masses that
    present with hydrocephalus.
  notes: >-
    The HPO term HP:0002190 Choroid plexus cyst records this distinct, non-neoplastic
    concept; it is not bound as `disease_term` here because the descriptor takes a
    disease rather than a phenotype term.
  evidence:
  - reference: PMID:42143260
    reference_title: "Natural history and prognostic significance of fetal choroid plexus cysts: a systematic review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Choroid plexus cysts (CPCs) are fluid-filled structures within the choroid plexus of the lateral ventricles, most frequently identified during routine second-trimester ultrasound examinations."
    explanation: Establishes the choroid plexus cyst as a distinct, non-neoplastic
      fluid-filled lesion of the same anatomical structure, detected prenatally.
  - reference: PMID:42143260
    reference_title: "Natural history and prognostic significance of fetal choroid plexus cysts: a systematic review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "They are reported in approximately 1-2% of second-trimester fetuses and are generally regarded as benign and transient findings, particularly when not accompanied by other abnormalities"
    explanation: Supports the benign, transient, non-oncological character that separates
      the cyst from every member of the choroid plexus tumor family.
- name: Choroid plexus hyperplasia (villous hypertrophy)
  description: >-
    Diffuse enlargement of the choroid plexus without a discrete neoplastic mass. It
    causes hydrocephalus by the same cerebrospinal fluid overproduction mechanism as a
    papilloma, so the mechanistic overlap is genuine even though the lesion is not a
    tumor - which makes it the one differential that shares this entry's core
    pathophysiology.
  distinguishing_features:
  - Imaging shows bilateral diffuse plexus enlargement rather than a solitary lobulated
    mass.
  - Hydrocephalus is communicating and purely overproduction-driven, with no obstructive
    component from mass effect.
  evidence:
  - reference: PMID:1022421
    reference_title: "Choroid plexus papilloma. I. Proof of cerebrospinal fluid overproduction."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Whereas these data are regarded as conclusive evidence of CSF overproduction by a choroid plexus papilloma"
    explanation: Establishes the overproduction mechanism that choroid plexus hyperplasia
      shares with papilloma; the hyperplasia entity itself is not described in this
      abstract, hence partial support.
discussions:
- discussion_id: sv40_aetiology
  kind: KNOWLEDGE_GAP
  status: OPEN
  prompt: >-
    Does simian virus 40 contribute to human choroid plexus tumorigenesis, or is the
    historical SV40 association entirely an artefact of PCR contamination and
    transgenic-mouse extrapolation?
  attaches_to:
  - environmental#Simian virus 40 (SV40) exposure
  rationale: >-
    SV40 large T antigen reliably produces choroid plexus tumors in transgenic mice,
    and SV40 DNA sequences were reported in human choroid plexus tumors, which
    generated a long-lived aetiological hypothesis. The two strongest human tests
    point the other way: a nationwide Danish cohort found no excess of choroid plexus
    tumor after SV40-contaminated poliovirus vaccine exposure, and SV40 large T
    antigen was undetectable by immunohistochemistry in 82 central nervous system
    tumors. The residual gap is that these are negative studies of population exposure
    and protein detection respectively; neither formally excludes a hit-and-run or
    low-prevalence mechanism, and the discordance with earlier PCR-positive series has
    never been fully resolved. This entry therefore records the question as contested
    and currently unsupported rather than settled.
  proposed_experiments:
  - experiment_id: sv40_contamination_controlled_sequencing
    name: Contamination-controlled deep sequencing for SV40 in a contemporary cohort
    description: >-
      Deep sequencing of a contemporary, well-powered choroid plexus tumor cohort with
      rigorous contamination controls, reporting SV40 read counts against matched
      normal tissue from the same patients.
    would_support:
    - Reproducible SV40 reads above matched-normal background in a meaningful fraction
      of tumors.
    would_refute:
    - Absence of SV40 reads above background across an adequately powered cohort.
  - experiment_id: sv40_harmonised_pcr_reanalysis
    name: Harmonised reanalysis of discordant PCR series
    description: >-
      Pooled reanalysis of the discordant PCR-positive and PCR-negative series using
      harmonised assay controls, to determine whether laboratory contamination explains
      the geographic pattern of positivity.
    would_support:
    - Persistence of geographic positivity after assay harmonisation.
    would_refute:
    - Disappearance of positivity under common contamination controls.
  evidence:
  - reference: PMID:12671021
    reference_title: Cancer incidence in Denmark following exposure to poliovirus vaccine
      contaminated with simian virus 40.
    supports: REFUTE
    evidence_source: HUMAN_CLINICAL
    snippet: "Exposure to SV40-contaminated poliovirus vaccine in Denmark was not associated with increased cancer incidence."
    explanation: The strongest population-level negative test of the SV40 hypothesis.
- discussion_id: acpp_molecular_identity
  kind: KNOWLEDGE_GAP
  status: OPEN
  prompt: >-
    Is atypical choroid plexus papilloma a distinct biological entity, or a histologic
    risk stratum within choroid plexus papilloma?
  attaches_to:
  - pathophysiology#Malignant Progression to High-Grade Carcinoma
  rationale: >-
    WHO grade 2 atypical choroid plexus papilloma is defined purely by a mitotic-count
    threshold, and that threshold is genuinely prognostic for recurrence. But
    genome-wide copy-number, expression and methylation profiling has repeatedly failed
    to separate atypical papilloma from ordinary papilloma, and the authors of the
    largest such study concluded the two histologic subgroups are a single molecular
    entity. Whether the mitotic threshold captures a distinct biology or simply samples
    the upper tail of a continuous proliferative distribution within one entity is
    unresolved, and it matters for whether adjuvant decisions should be driven by grade
    or by molecular class.
  proposed_experiments:
  - experiment_id: acpp_mitotically_stratified_profiling
    name: Mitotically stratified molecular profiling of papilloma
    description: >-
      Prospective single-cell and methylation profiling of a papilloma cohort stratified
      by mitotic count, testing whether a molecular discontinuity exists at the
      2-mitoses-per-10-HPF threshold.
    would_support:
    - A step change in molecular profile at the 2-mitoses-per-10-HPF threshold.
    would_refute:
    - A continuous molecular gradient across mitotic counts with no discontinuity.
  - experiment_id: acpp_grade_versus_methylation_prognosis
    name: Head-to-head prognostic comparison of grade versus methylation class
    description: >-
      Correlate methylation subgroup (pediatric A / pediatric B / adult) against mitotic
      count and recurrence in a pooled registry to determine which better predicts
      outcome.
    would_support:
    - Mitotic count outperforming methylation class as a predictor of recurrence.
    would_refute:
    - Methylation class outperforming mitotic count as a predictor of recurrence.
  evidence:
  - reference: PMID:25336695
    reference_title: Molecular characterization of choroid plexus tumors reveals novel
      clinically relevant subgroups.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "molecular similarities among the papillomas suggest that these two histologic subgroups are indeed a single molecular entity"
    explanation: The authors' explicit statement that atypical papilloma and papilloma
      are molecularly one entity.
clinical_trials:
- name: NCT04994977
  phase: PHASE_I
  status: TERMINATED
  description: >-
    Intra-arterial chemotherapy delivered before a planned second-look operation in newly
    diagnosed, residual or recurrent atypical choroid plexus papilloma and choroid plexus
    carcinoma - a locoregional extension of the neoadjuvant-then-resect strategy already
    used systemically. The study terminated for low accrual after enrolling a single
    patient, so no efficacy inference is possible; it is recorded here because it is the
    only interventional trial specific to this disease family rather than a broad CNS
    basket.
  target_phenotypes:
  - preferred_term: Neoplasm of the central nervous system
    term:
      id: HP:0100006
      label: Neoplasm of the central nervous system
  evidence:
  - reference: clinicaltrials:NCT04994977
    reference_title: "Intra-Arterial (IA) Chemotherapy for Newly Diagnosed, Residual, or Recurrent Atypical Choroid Plexus Papilloma (ACPP) and Choroid Plexus Carcinoma (CPC) Prior to Second-Look Surgery"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This study will test the safety and efficacy of intra-arterial chemotherapy in subjects with newly diagnosed, residual, or recurrent atypical choroid plexus papilloma and choroid plexus carcinoma prior to a second surgery."
    explanation: Defines the trial population and intervention, both specific to this
      disease family.
  - reference: clinicaltrials:NCT04994977
    reference_title: "Intra-Arterial (IA) Chemotherapy for Newly Diagnosed, Residual, or Recurrent Atypical Choroid Plexus Papilloma (ACPP) and Choroid Plexus Carcinoma (CPC) Prior to Second-Look Surgery"
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "It is believed that intra-arterial chemotherapy will be safe and feasible for this population and will result in decreased tumor size, which may further improve the goals of a second-look surgery."
    explanation: States the trial hypothesis; marked PARTIAL because the trial terminated
      for low accrual and did not test it.
animal_models:
- species: Mus musculus
  genotype: Otx2-lineage conditional MycT58A expression with Trp53 inactivation
  category: GENETICALLY_ENGINEERED
  genes:
  - preferred_term: TP53
    term:
      id: hgnc:11998
      label: TP53
  description: >-
    Conditional expression of a stabilised c-Myc together with Trp53 inactivation in the
    choroid plexus of newborn mice produces choroid plexus carcinoma with complete
    penetrance across all brain ventricles, with a lateral- and fourth-ventricular
    predominance matching the human site distribution, and death from hydrocephalus within
    150 days. The tumours recapitulate human carcinoma histology and show dysregulated
    cell-cycle and DNA-damage-response programs. Translational caveat: MYC stabilisation is
    an engineered lesion, not a recurrent human alteration, so the model demonstrates
    sufficiency of the p53-loss-plus-oncogene combination rather than fidelity to the
    human genotype.
  evidence:
  - reference: PMID:29339161
    reference_title: A new genetically engineered mouse model of choroid plexus carcinoma.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Choroid plexus tumours occurred with a complete penetrance in all brain ventricles, with prevalence in the lateral and fourth ventricles."
    explanation: Penetrance and site distribution of the model, both matching the human
      disease.
  - reference: PMID:29339161
    reference_title: A new genetically engineered mouse model of choroid plexus carcinoma.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Comparison of gene expression profiles of CPCs and non-neoplastic tissues revealed profound alterations in cell cycle regulation and DNA damage responses, suggesting that dysregulation of cell division and DNA checkpoint pathways may represent key vulnerabilities."
    explanation: Identifies the cell-cycle and DNA-damage-response programs that the model
      shares with the human chromosomal-instability node.
- species: Mus musculus
  genotype: Combined NOTCH and Sonic Hedgehog pathway perturbation in choroid plexus
  category: GENETICALLY_ENGINEERED
  description: >-
    Mice with combined NOTCH and Sonic Hedgehog signalling defects develop tumours
    resembling human choroid plexus carcinoma. The tumours are monociliated, and
    disrupting the NOTCH complex restores multiciliation and reduces tumour growth,
    which is the experimental basis for the GMNC-MCIDAS multiciliogenesis arm of the
    pathograph.
  evidence:
  - reference: PMID:35322202
    reference_title: Disruption of GMNC-MCIDAS multiciliogenesis program is critical in
      choroid plexus carcinoma development.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Here we show that combined defects in NOTCH and Sonic Hedgehog signaling in mice generates tumors that are similar to CPC in humans."
    explanation: Establishes the model and its resemblance to human carcinoma.
classifications:
  harrisons_chapter:
  - classification_value: ONCOLOGY_HEMATOLOGY
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0016717
      label: choroid plexus neoplasm
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
    mapping_justification: Primary MONDO identifier for the choroid plexus neoplasm
      umbrella.
  - term:
      id: MONDO:0009837
      label: choroid plexus papilloma
    mapping_predicate: skos:narrowMatch
    mapping_source: MONDO
    mapping_justification: WHO grade 1 member of the family, modelled as the CPP subtype.
  - term:
      id: MONDO:0002684
      label: atypical choroid plexus papilloma
    mapping_predicate: skos:narrowMatch
    mapping_source: MONDO
    mapping_justification: WHO grade 2 member of the family, modelled as the aCPP
      subtype.
  - term:
      id: MONDO:0016718
      label: choroid plexus carcinoma
    mapping_predicate: skos:narrowMatch
    mapping_source: MONDO
    mapping_justification: WHO grade 3 member of the family, modelled as the CPC subtype
      and additionally curated as a standalone entry.
notes: >-
  Scope and relationship to the standalone carcinoma entry: this is the umbrella entry
  for MONDO:0016717, covering the mechanism shared by all three graded entities. Choroid
  plexus carcinoma additionally has its own dismech entry at
  kb/disorders/Choroid_Plexus_Carcinoma.yaml (MONDO:0016718), which carries the
  carcinoma-specific molecular risk strata, chemotherapy detail and subtype structure;
  carcinoma-specific depth belongs there rather than being duplicated here. A small
  number of carcinoma findings (the SJYC07 TP53 progression-free-survival split, the
  CarbEV randomised result, the mutant-p53 dosage risk group and the SEER
  gross-total-resection finding) are deliberately restated here, because they are the
  family-level prognostic and treatment backbone and the umbrella would be misleading
  without them; everything else carcinoma-specific is left to the standalone entry.


  Why a Disease rather than a Grouping: MONDO:0016717 carries the `disease_grouping`
  and `ordo_group_of_disorders` subsets, and dismech's convention is that curated unions
  over already-distinct entries belong in `kb/groupings/` as the `Grouping` class. This
  is modelled as a Disease instead because two of its three members - choroid plexus
  papilloma and atypical choroid plexus papilloma - have no standalone dismech entries,
  so there is no union to point at; the shared hydrocephalus mechanism is genuinely
  family-level and needs a pathograph of its own. If CPP and aCPP are later curated
  separately, converting this to a Grouping over the three entries would be the right
  refactor.

  ICD-O morphology is deliberately omitted. The closed ICDOMorphologyEnum offers only
  Carcinoma, Adenocarcinoma, Squamous Cell Carcinoma, Sarcoma, Leukemia, Lymphoma,
  Multiple Myeloma, Melanoma, Glioma and Embryonal Neoplasm. This umbrella spans ICD-O
  9390/0 (papilloma, benign), 9390/1 (atypical, uncertain behaviour) and 9390/3
  (carcinoma, malignant); tagging the family "Carcinoma" would misclassify the two
  non-malignant members, and no papilloma or mixed-behaviour value exists. The correct
  value is absent from the enum rather than merely hard to choose.

  Module conformance is claimed only for the TP53 arm, and only where the module node
  semantics actually match - `evading_growth_suppressors#Tumor Suppressor Inactivation`
  for the p53-axis lesion, and `genome_instability_mutation#Mutator Phenotype and
  Chromosomal Instability` for the whole-chromosome copy-number instability that follows
  it. Conformance is NOT claimed for papilloma, which carries no recurrent
  tumour-suppressor lesion, nor for the downstream hallmark nodes of either module, for
  which there is no choroid-plexus-specific evidence in the curated sources.

📚

References & Deep Research

References

4

PMID:33249490

The genetic landscape of choroid plexus tumors in children and adults.

No top-level findings curated for this source.

PMID:34997889

Final results of the Choroid Plexus Tumor study CPT-SIOP-2000.

No top-level findings curated for this source.

PMID:36659972

Incidence and survival of choroid plexus tumors in the United States.

No top-level findings curated for this source.

PMID:20308654

TP53 alterations determine clinical subgroups and survival of patients with choroid plexus tumors.

No top-level findings curated for this source.

Deep Research

1

Falcon ▸

Choroid Plexus Neoplasm: Disease-Characteristics Research Report

Edison Scientific Literature 41 citations 2026-08-01T07:02:48.315073

Choroid Plexus Neoplasm: Disease-Characteristics Research Report

Scope and evidence date. This report treats choroid plexus neoplasm/tumor (CPT) as an umbrella diagnosis encompassing choroid plexus papilloma (CPP), atypical CPP (aCPP), and choroid plexus carcinoma (CPC). Recent human molecular studies from 2023–2024 are prioritized, supplemented by landmark clinical, genetic, and model-system evidence. Database identifiers and ontology mappings should be verified against the release used by the target knowledge base.

Executive summary

Choroid plexus neoplasms are rare intraventricular epithelial tumors arising from the cerebrospinal-fluid-producing choroid plexus. WHO CNS classification recognizes CPP (grade 1), aCPP (grade 2), and CPC (grade 3). They account for less than 1% of all brain tumors but approximately 10–20% of tumors arising during the first year of life; one 2024 pediatric cohort review gives 2–6% of all pediatric brain tumors. CPP is usually cured by complete resection, aCPP has increased recurrence risk, and CPC is an aggressive, highly vascular tumor prone to invasion and cerebrospinal-fluid dissemination. (garcia2023genomicprofileof pages 1-2, li2022disruptionofgmncmcidas pages 1-2, choi2024comprehensivemultiomicsanalysis pages 1-2, thomas2021thegeneticlandscape pages 1-3)

The strongest established predisposition is autosomal-dominant heritable TP53-related cancer/Li–Fraumeni syndrome (LFS). Tumor TP53 status is also prognostic: in the prospective SJYC07 cohort, 5-year progression-free survival (PFS) was 100% for TP53-wild-type CPC versus 28.6% for TP53-mutant CPC. Current translational advances include methylation classification, paired tumor-normal sequencing, 2024 single-nucleus transcriptomics, multiomics identification of cell-cycle/epithelial–mesenchymal-transition programs, and experimental locoregional chemotherapy and CAR-T approaches. (liu2021outcomeandmolecular pages 1-2, hill2024singlenucleusrnaseqdissection pages 1-2, choi2024comprehensivemultiomicsanalysis pages 1-2)

Entity	WHO grade	Typical demographics/site	Molecular features	Clinical behavior	Standard management
Choroid plexus papilloma (CPP)	1	Intraventricular choroid plexus tumor; often pediatric but also occurs in adults; molecular subgrouping supports pediatric supratentorial low-risk and adult infratentorial low-risk groups (ontology/site labels requiring validation) (garcia2023genomicprofileof pages 1-2, hill2024singlenucleusrnaseqdissection pages 1-2)	Usually lacks recurrent driver mutations; adult CPTs may harbor TERT promoter mutations (7/28 adults across CPTs, associated with shorter PFS) or rare CCDC47-PRKCA fusion in aggressive adult CPP; chromosome 9 amplification reported as CPP-specific in one 2024 multiomics cohort (hill2024singlenucleusrnaseqdissection pages 1-2)	Generally benign/low-risk; favorable prognosis relative to CPC; recurrence risk lower than aCPP/CPC but molecular subgroup can refine risk (garcia2023genomicprofileof pages 1-2, hill2024singlenucleusrnaseqdissection pages 1-2)	Maximal safe surgical resection is standard; adjuvant therapy usually not required after complete resection (general CPT management evidence), with radiotherapy considered selectively in incompletely resected/recurrent cases (garcia2023genomicprofileof pages 1-2)
Atypical choroid plexus papilloma (aCPP)	2	Pediatric intraventricular tumor; example pediatric case with hydrocephalus and ataxia; grouped with low-risk or high-risk methylation classes depending age/site, requiring molecular risk assessment (garcia2023genomicprofileof pages 2-5, hill2024singlenucleusrnaseqdissection pages 1-2)	Example tumor had BRD1 frameshift deletion with gains of chromosomes 12/18/20 and losses of 13q/22q; p53 IHC may be negative; no recurrent universal somatic driver established (garcia2023genomicprofileof pages 2-5, garcia2023genomicprofileof pages 1-2)	Intermediate behavior; higher recurrence risk than CPP; histology alone can be insufficient for risk stratification, so methylation profiling may add prognostic value (garcia2023genomicprofileof pages 1-2, hill2024singlenucleusrnaseqdissection pages 1-2)	Surgery is primary treatment; adjuvant radiotherapy/chemotherapy individualized, especially for subtotal resection or higher-risk molecular features; one reported case received 36 Gy RT and remained disease-free at 78 months (garcia2023genomicprofileof pages 2-5)
Choroid plexus carcinoma (CPC)	3	Rare aggressive malignant CPT of infancy/early childhood; median diagnosis age about 3 years, annual incidence about 0.3 per million; often supratentorial/pediatric high-risk methylation class; highly vascular, invasive, CSF-disseminating (liu2021outcomeandmolecular pages 1-2, hill2024singlenucleusrnaseqdissection pages 1-2)	TP53 is the dominant recurrent alteration: TP53 mutations in 7/47 CPTs overall and frequent in CPC; germline TP53/Li-Fraumeni common, with estimates of 50-80% in children with CPC from LFS guidelines; LOH at TP53, hyperdiploidy/genomic instability, whole-chromosome CNAs, chromosome 1 amplification, mutually exclusive TP53 and EPHA7 point mutations in one 2024 cohort; hypomethylation of repeat elements; multiciliogenesis program disruption (GMNC-MCIDAS), NOTCH/SHH involvement, MYC/TP53 cooperation in models (liu2021outcomeandmolecular pages 1-2, garcia2023genomicprofileof pages 5-8, fortuno2024cancerrisksassociated pages 1-2, hill2024singlenucleusrnaseqdissection pages 1-2)	Most aggressive subtype; recurrent/metastatic propensity and worse survival, especially with TP53 mutation. In SJYC07, 5-year PFS 61.5% and OS 68.4%; TP53-wild-type 5-year PFS 100% vs 28.6% for TP53-mutant tumors (liu2021outcomeandmolecular pages 9-10, liu2021outcomeandmolecular pages 1-2)	Maximal safe resection plus intensive chemotherapy is standard backbone; SJYC07 used high-dose methotrexate-containing non-myeloablative therapy with durable survival in >50% of patients. Radiotherapy is individualized and may be avoided or minimized in germline TP53 carriers because of secondary malignancy risk (liu2021outcomeandmolecular pages 9-10, liu2021outcomeandmolecular pages 1-2, frebourg2020guidelinesforthe pages 7-8)
Choroid plexus tumor molecular subgroup: pediatric A (pedA)	Not a WHO histologic grade; methylation subgroup	Young age, supratentorial, favorable-risk subgroup (ontology label requiring validation) (hill2024singlenucleusrnaseqdissection pages 1-2)	Defined by DNA methylation profiling rather than unique recurrent driver mutation; part of 3-group epigenetic framework (hill2024singlenucleusrnaseqdissection pages 1-2)	Favorable prognosis relative to pedB (hill2024singlenucleusrnaseqdissection pages 1-2)	Supports risk stratification alongside histology; not a standalone treatment entity (hill2024singlenucleusrnaseqdissection pages 1-2)
Choroid plexus tumor molecular subgroup: pediatric B (pedB)	Not a WHO histologic grade; methylation subgroup	Predominantly pediatric high-risk subgroup; includes many CPCs and some histologically lower-grade CPTs; frequent recurrences (liu2021outcomeandmolecular pages 9-10, hill2024singlenucleusrnaseqdissection pages 1-2)	Frequent chromosomal copy-number alterations; S/G2/M hyperproliferative enrichment on snRNA-seq; methylation-defined high-risk biology (liu2021outcomeandmolecular pages 9-10, hill2024singlenucleusrnaseqdissection pages 3-4, hill2024singlenucleusrnaseqdissection pages 1-2)	Higher risk of recurrence/aggressive course than pedA/adult subgroup, even when histology is not overtly carcinoma (hill2024singlenucleusrnaseqdissection pages 1-2)	Indicates need for closer surveillance and may justify therapy intensification in future stratified protocols (liu2021outcomeandmolecular pages 9-10, hill2024singlenucleusrnaseqdissection pages 1-2)
Choroid plexus tumor molecular subgroup: adult	Not a WHO histologic grade; methylation subgroup	Adult, often infratentorial low-risk subgroup (ontology/site label requiring validation) (hill2024singlenucleusrnaseqdissection pages 1-2)	TERT promoter mutations found in 7/28 adult CPTs and associated with shorter PFS; rare CCDC47-PRKCA fusion described in aggressive adult CPP; adult tumors showed higher macrophage proportion by snRNA-seq (22.4% vs 8.2% in pediatric high-risk tumors) (hill2024singlenucleusrnaseqdissection pages 3-4, hill2024singlenucleusrnaseqdissection pages 1-2)	Usually more favorable than pediatric high-risk subgroup, but adverse molecular lesions can signal worse course (hill2024singlenucleusrnaseqdissection pages 1-2)	Primarily surgical management; molecular profiling may identify adults needing closer follow-up (hill2024singlenucleusrnaseqdissection pages 1-2)

Table: This table summarizes the main choroid plexus neoplasm subtypes and molecular subgroups using only evidence gathered in the conversation. It is useful for quickly comparing histology, demographics, molecular findings, clinical behavior, and management while flagging site/ontology labels that require validation.

1. Disease information

Definition and classification

CPTs are primary intraventricular neoplasms derived from choroid plexus epithelium. Their three histologic entities form a biologic spectrum rather than a single uniform disease:

CPP: WHO grade 1, papillary and generally indolent.
aCPP: WHO grade 2, defined principally by increased mitotic activity and associated with greater recurrence risk.
CPC: WHO grade 3, malignant, invasive, mitotically active, and often necrotic.

A useful direct statement from the 2024 multiomics study is: “Choroid plexus tumors (CPTs) are intraventricular tumors derived from the choroid plexus epithelium and occur frequently in children.” Published June 2024; DOI/URL: https://doi.org/10.1186/s40478-024-01814-y. (choi2024comprehensivemultiomicsanalysis pages 1-2)

Identifiers and synonyms

MONDO umbrella: choroid plexus neoplasm, MONDO:0016717.
MONDO subtype identifiers: choroid plexus papilloma, MONDO:0009837; choroid plexus carcinoma, MONDO:0016718; benign choroid plexus neoplasm, MONDO:0044764. (OpenTargets Search: choroid plexus carcinoma,choroid plexus papilloma-TP53)
Synonyms: choroid plexus tumor/CPT; choroid plexus papilloma/CPP; atypical choroid plexus papilloma/aCPP; choroid plexus carcinoma/CPC; tumor of choroid plexus epithelium.
MeSH: Choroid Plexus Neoplasms is the preferred disease concept; confirm the current MeSH unique identifier in the production terminology release.
ICD: ICD-10-CM coding is site/behavior based rather than disease-specific—e.g., malignant neoplasm of brain/ventricle for CPC and benign neoplasm of brain for CPP. Histology should therefore be retained separately with ICD-O morphology/topography. ICD-11 and ICD-O codes should be release-validated before ingestion.
OMIM/Orphanet: the umbrella sporadic tumor does not behave like a single Mendelian OMIM phenotype. The clinically important inherited entry is LFS/heritable TP53-related cancer syndrome rather than “CPT” itself. Exact Orphanet identifiers were not established from the retrieved evidence and should not be inferred.

The evidence summarized here is predominantly aggregated disease-level literature, registries, prospective trials, and molecular cohorts, not individual EHR data. Two 2023 Brazilian cases are patient-level primary evidence and should not be used alone to estimate population frequencies. (garcia2023genomicprofileof pages 1-2, garcia2023genomicprofileof pages 5-8, garcia2023genomicprofileof pages 2-5)

2. Etiology, risk, and protective factors

Causal and predisposing factors

Most CPTs are sporadic and lack a recurrent point-mutation driver. The clearest causal predisposition is a germline pathogenic TP53 variant, producing autosomal-dominant LFS/heritable TP53-related cancer syndrome; tumorigenesis commonly involves loss of the remaining wild-type allele and genomic instability. In one CPC, germline TP53 c.718A>G (p.Ser240Gly) was accompanied by 17p13.1 loss/LOH and hyperdiploidy. (garcia2023genomicprofileof pages 1-2, garcia2023genomicprofileof pages 5-8)

Published estimates place TP53 alterations in approximately 44–67% of CPCs; the SJYC07 cohort found 7/13 TP53-mutant tumors, including four germline carriers. In the broader 47-CPT series, TP53 mutations occurred in 7/47 tumors (15%), five in children, illustrating that prevalence depends strongly on subtype composition. (liu2021outcomeandmolecular pages 1-2, choi2024comprehensivemultiomicsanalysis pages 1-2, thomas2021thegeneticlandscape pages 1-3)

Other genetic risks

Pediatric tumors show recurrent whole-chromosome changes rather than a universal driver: gains of chromosomes 1, 2, and 21q characterize pediatric-B enrichment.
Adult CPTs may harbor TERT promoter mutations: 7/28 adults (25%) in one series, associated with shorter PFS (log-rank P=0.015).
A rare CCDC47–PRKCA fusion caused by a chromosome-17 inversion was found in an aggressive adult CPP.
A 2024 cohort identified mutually exclusive TP53 and EPHA7 point mutations plus chromosome-1 amplification only in CPC, whereas chromosome-9 amplification was CPP-specific; these are cohort-level candidates, not yet universal diagnostic markers. (choi2024comprehensivemultiomicsanalysis pages 1-2, thomas2021thegeneticlandscape pages 1-3)

Environmental, infectious, lifestyle, and protective factors

No reproducible toxin, infection, diet, smoking, alcohol, occupation, or other lifestyle exposure is established as a CPT cause. No validated protective allele, dietary factor, vaccine, or medication prevents CPT. Apparent environmental modifiers of LFS penetrance remain speculative; reviews discuss lifestyle, diet, exposures, telomere length, MDM2/TP53 polymorphisms, and epigenetic modifiers, but individualized gene–environment risk estimates are unavailable. (gargallo2020li–fraumenisyndromeheterogeneity pages 7-8)

For TP53 carriers, avoiding unnecessary ionizing radiation and genotoxic therapy is a risk-reduction principle for subsequent cancers, not proven primary prevention of the index CPT. (frebourg2020guidelinesforthe pages 7-8)

3. Phenotypes

Clinical manifestations principally result from tumor bulk, CSF overproduction or outflow obstruction, hemorrhage/vascularity, invasion, and dissemination.

Phenotype	Type and characteristics	Suggested HPO term
Hydrocephalus/increased intracranial pressure	Common presenting mechanism; progressive or subacute; particularly important in infants	Hydrocephalus HP:0000238; increased intracranial pressure
Headache	Subjective symptom, especially in older children/adults; variable severity	Headache HP:0002315
Nausea/vomiting	Symptom of raised intracranial pressure; vomiting documented in infant CPC	Vomiting HP:0002013; nausea
Bulging fontanelle/macrocephaly	Infant physical sign; reflects raised pressure	Bulging anterior fontanelle; macrocephaly HP:0000256
Papilledema	Ophthalmic sign of raised pressure	Papilledema HP:0001085
Ataxia/gait impairment	Neurologic sign, more likely with fourth-ventricular/posterior-fossa effects	Ataxia HP:0001251; gait disturbance HP:0001288
Cranial-nerve deficit	Focal neurologic sign; depends on location	Cranial nerve abnormality
Seizures	Less common neurologic symptom	Seizure HP:0001250
Developmental delay/cognitive impairment	May arise from hydrocephalus, tumor injury, surgery, chemotherapy, or radiation; important survivorship outcome	Global developmental delay HP:0001263; intellectual disability HP:0001249
Leptomeningeal dissemination	Imaging/pathologic manifestation, concentrated in CPC; may be present at diagnosis or emerge during follow-up	Neoplasm of the meninges/leptomeningeal disease; ontology mapping requires validation

The classic review lists headache, hydrocephalus, papilledema, nausea, vomiting, cranial-nerve deficits, gait impairment, and seizures. A 2023 CPC infant had vomiting, bulging fontanelle, hydrocephalus, and transependymal edema. In the 2024 multiomics cohort, 5/11 CPC patients had leptomeningeal seeding, versus none with CPP; all seeded cases with known follow-up died. (garcia2023genomicprofileof pages 5-8, choi2024comprehensivemultiomicsanalysis pages 1-2, safaee2013choroidplexuspapillomas pages 1-2)

Quality of life. Tumor- and treatment-related hydrocephalus, neurodevelopmental delay, sensory deficits, endocrine effects, and impaired mobility can affect schooling, independence, and caregiver burden. A historical estimate gives 56% 5-year CPC survival, with many survivors experiencing long-term cognitive/developmental deficits. Disease-specific EQ-5D/SF-36 norms and robust per-phenotype frequencies were not identified. (thomas2021thegeneticlandscape pages 1-3)

4. Genetic and molecular information

Principal genes and variants

TP53—HGNC:11998; tumor-suppressor loss of function, usually germline or somatic missense/nonsense/indel with LOH. Germline pathogenic variants establish heritable TP53-related cancer risk; a tumor-only result does not prove germline origin. Open Targets ranks TP53 as the strongest supported disease target for the umbrella CPT and both CPP/CPC. (OpenTargets Search: choroid plexus carcinoma,choroid plexus papilloma-TP53)
TERT promoter—somatic adult-CPT alteration; not a germline CPT cause.
EPHA7—candidate somatic CPC alteration in one 20-patient cohort.
BRD1—one aCPP carried a high-VAF frameshift deletion, classified AMP tier II; it is a case-specific candidate, not an established germline causal gene.
CCDC47–PRKCA—rare somatic fusion in aggressive adult CPP.
TAF12, NFYC, RAD54L—chromosome-1 candidate oncogenes; validation as routine biomarkers is incomplete. (garcia2023genomicprofileof pages 2-5, hill2024singlenucleusrnaseqdissection pages 1-2, choi2024comprehensivemultiomicsanalysis pages 1-2, thomas2021thegeneticlandscape pages 1-3)

Variant interpretation should use ACMG/AMP rules for germline TP53 and AMP/ASCO/CAP somatic tiers for tumor variants. Population frequencies must be checked variant-by-variant in gnomAD; no single carrier frequency applies to sporadic CPT. The Brazilian founder TP53 p.Arg337His allele is geographically enriched—historically reported near 1/300 newborns in southern/southeastern Brazil—but this does not represent global frequency. (bittar2021clinicalandmolecular pages 9-10, giacomazzi2015pediatriccancerand pages 1-2)

Chromosomal and epigenetic abnormalities

CPTs commonly exhibit numerical aneuploidy and whole-chromosome copy-number alterations. Pediatric-B tumors are enriched for gains of chromosomes 1, 2, and 21q; adult tumors for gains of 5 and 9 and loss of 21q. The Brazilian aCPP had gains of 12, 18, and 20 and losses of 13q and 22q; its CPC had a hyperdiploid genome and TP53-locus loss. (garcia2023genomicprofileof pages 1-2, garcia2023genomicprofileof pages 2-5, thomas2021thegeneticlandscape pages 1-3)

DNA methylation resolves three clinically meaningful groups:

Pediatric A: supratentorial pediatric low-risk CPP/aCPP.
Pediatric B: supratentorial pediatric high-risk group containing CPP, aCPP, and CPC.
Adult: predominantly infratentorial low-risk CPP/aCPP.

Methylation complements rather than replaces histology. CPC-associated methylation biomarkers include AK1, PER2, and PLSCR4; homozygous TP53-mutant CPCs form a particularly adverse group. (liu2021outcomeandmolecular pages 9-10, hill2024singlenucleusrnaseqdissection pages 1-2, thomas2021thegeneticlandscape pages 1-3)

5. Environmental information

No infectious agent or environmental carcinogen has been causally linked to CPT. Consequently, CTD-style chemical annotations, pathogen taxonomy, lifestyle dose-response associations, and CHEBI preventive-agent annotations are not currently justified. Radiation is clinically relevant mainly as a treatment and as a subsequent-neoplasm hazard in germline TP53 carriers. (frebourg2020guidelinesforthe pages 7-8)

6. Mechanism and pathophysiology

Causal chain

Upstream predisposition: germline or somatic TP53 dysfunction, uncommon adult TERT-promoter activation/fusion events, and/or chromosome-wide dosage imbalance → checkpoint failure and genomic instability → dysregulated cell cycle, replication stress, epithelial–mesenchymal transition, and impaired epithelial differentiation → expansion of choroid plexus epithelial tumor cells → hypervascular intraventricular mass, CSF obstruction/overproduction and hydrocephalus → invasion, leptomeningeal spread, neurologic injury, and developmental morbidity. (nagar2018anewgenetically pages 6-8, choi2024comprehensivemultiomicsanalysis pages 1-2, thomas2021thegeneticlandscape pages 1-3)

Multiciliogenesis and developmental signaling

Normal choroid plexus epithelium contains multiciliated cells. Human CPCs show solitary cilia and reduced GMNC–MCIDAS–FOXJ1 differentiation activity. In mouse systems, NOTCH activation suppresses GMNC/MCIDAS; disrupting the NOTCH complex restores multiciliation and decreases growth, while GMNC/MCIDAS overexpression suppresses tumor-cell proliferation. Combined NOTCH and Sonic Hedgehog defects generated CPC-like tumors. This is mechanistically strong model evidence but not yet a clinically validated therapeutic intervention. (li2022disruptionofgmncmcidas pages 1-2)

Suggested annotations include GO:0007049 cell cycle, GO:0006281 DNA repair, GO:0007059 chromosome segregation, GO:0035082 axoneme assembly, GO:0060271 cilium assembly, GO:0048870 cell motility, GO:0001837 epithelial-to-mesenchymal transition, and GO:0007155 cell adhesion. Relevant cells include choroid plexus epithelial cell, multiciliated epithelial cell, endothelial cell, macrophage, mesenchymal stromal cell, T cell, neuron, and glial cell; exact CL identifiers should be release-validated.

Recent molecular profiling

2024 multiomics. Whole-genome, whole-transcriptome, and methylation sequencing of 20 tumors found CPC enrichment for cell-cycle and epithelial–mesenchymal-transition genes, metastasis/progression programs in disseminated CPC, and broad hypomethylation of LINEs, SINEs, LTRs, and retrotransposons. The authors concluded that loss of epigenetic transposable-element silencing may contribute to CPC tumorigenesis. Cohort composition was 6 CPP, 2 aCPP, 1 mixed CPP/papillary ependymoma, and 11 CPC; mean age was 5.2 years. (choi2024comprehensivemultiomicsanalysis pages 1-2)

2024 single-nucleus RNA-seq. Analysis of 23,906 nuclei from four disease-free choroid plexuses and 11 tumors resolved epithelial, endothelial, mesenchymal, macrophage, neuronal, glial, and T-cell populations. Pediatric-B tumors were enriched for S/G2/M proliferative states; adult tumors had more macrophages (22.4% versus 8.2%, P=0.046), and tumors had fewer mesenchymal cells than normal tissue. The study’s abstract states that it identified “altered macrophage and mesenchymal cell states, as well as changes in extracellular matrix components.” Published October 2024; DOI/URL: https://doi.org/10.1038/s44318-024-00283-2. (hill2024singlenucleusrnaseqdissection pages 3-4, hill2024singlenucleusrnaseqdissection pages 1-2)

Proteomic, metabolomic, lipidomic, spatial-transcriptomic, and large CRISPR-screen signatures are not sufficiently validated for clinical annotation. No established metabolic enzyme deficiency or autoimmune mechanism exists.

7. Anatomical structures affected

Primary organ/system: central nervous system/brain; ventricular system.
Primary tissue: choroid plexus epithelial tissue over vascular stroma.
Sites: lateral ventricles, third ventricle, fourth ventricle; rare cerebellopontine-angle, parenchymal, suprasellar, spinal, or disseminated neuraxial disease.
Age-site pattern: children usually have lateral-ventricular/supratentorial tumors; adults more often have fourth-ventricular/infratentorial CPP. More than 80% of supratentorial CPPs in one review occurred before age 20. Median ages by CPP site were 1.5 years for lateral or third ventricle, 22.5 for fourth ventricle, and 35.5 for cerebellopontine angle. (safaee2013choroidplexuspapillomas pages 1-2)
Secondary structures: meninges/leptomeninges, spinal neuraxis, periventricular white matter affected by edema, and brain parenchyma affected by pressure or invasion.
Subcellular compartments: nucleus/chromatin (TP53, methylation and chromosome instability); centrosome/cilium/axoneme; plasma membrane and extracellular matrix.
Lateralization: no intrinsic left/right disease rule, although older CPP series reported left-lateral-ventricular predominance. Bilateral or multifocal disease is unusual and should prompt evaluation for dissemination or predisposition.

Suggested UBERON concepts: brain, cerebral ventricle, lateral ventricle, third ventricle, fourth ventricle, choroid plexus, cerebrospinal fluid, meninges, and spinal cord; identifiers should be validated against the deployed UBERON release.

8. Temporal development

CPTs are predominantly pediatric and may be congenital; CPP has been detected in utero. Median CPP diagnosis is about 3.5 years, while CPC is concentrated in infancy/early childhood. Symptoms may develop subacutely or progressively as hydrocephalus increases. (liu2021outcomeandmolecular pages 1-2, safaee2013choroidplexuspapillomas pages 1-2)

There is no AJCC-style stage system. Clinically useful dimensions are histologic grade, localized versus disseminated disease, extent of resection, TP53 status, and methylation class. CPP may remain stable after complete resection; aCPP can recur, with one review reporting an approximately fivefold greater 5-year recurrence risk than grade-1 CPP; CPC may progress rapidly, recur, and metastasize through CSF. Treatment-induced remission is common after gross-total CPP resection and possible in CPC with multimodal therapy. Spontaneous durable remission is not a recognized management strategy. (liu2021outcomeandmolecular pages 1-2, safaee2013choroidplexuspapillomas pages 1-2)

9. Inheritance and population

Epidemiology

CPTs represent <1% of all brain tumors, but approximately 10–20% of first-year brain tumors. CPP incidence is approximately 0.3 per million person-years, constitutes about 0.3–0.6% of intracranial tumors, and historically outnumbers CPC about 5:1. CPC incidence has likewise been estimated near 0.3 per million annually in childhood datasets. (garcia2023genomicprofileof pages 1-2, liu2021outcomeandmolecular pages 1-2, li2022disruptionofgmncmcidas pages 1-2, safaee2013choroidplexuspapillomas pages 1-2)

A historical CPP male:female ratio was 1.2:1; no consistent ethnicity-specific CPT excess is established. Geographic variation in inherited risk is relevant in southern/southeastern Brazil because of TP53 p.Arg337His. (giacomazzi2015pediatriccancerand pages 1-2, safaee2013choroidplexuspapillomas pages 1-2)

Inheritance

Sporadic CPT is not inherited. LFS-associated predisposition is autosomal dominant, with variable, age-dependent penetrance and expressivity. De novo and constitutional mosaic TP53 variants occur; no anticipation, consanguinity effect, or general CPT carrier frequency is established. In a 2024 analysis of 146 TP53-positive families/4,028 individuals, cumulative risk of any cancer by age 50 was 92.4% in females and 59.7% in males. These figures describe TP53 carriers—not CPT penetrance specifically. (fortuno2024cancerrisksassociated pages 1-2)

10. Diagnostics

Clinical and imaging work-up

Neurologic and developmental examination, head circumference/fontanelle assessment in infants, and fundoscopy when feasible.
Contrast-enhanced brain MRI: typically an intraventricular, lobulated/frond-like, intensely enhancing, highly vascular mass; assess hydrocephalus, edema, hemorrhage, invasion, and residual disease.
For suspected CPC/aCPP, obtain spine MRI and CSF staging when safe because of dissemination risk.
CT may show calcification or acute hemorrhage but adds radiation; MRI is preferred, especially in TP53 carriers.
Routine blood/CSF laboratory tests are nonspecific. No validated circulating protein or metabolite biomarker exists.

Histopathology

CPP has orderly papillary fronds lined by relatively uniform cuboidal/columnar epithelium. aCPP shows increased mitoses; ancillary findings may include increased cellularity, pleomorphism, architectural blurring, and necrosis. CPC exhibits overt malignancy—high cellularity, loss of papillary architecture, brisk mitoses, pleomorphism, necrosis, and invasion. One review describes CPC as having at least four of these malignant features. Cytokeratin positivity supports epithelial differentiation; Ki-67 and p53 staining assist grading/risk assessment but do not replace sequencing. (garcia2023genomicprofileof pages 5-8, garcia2023genomicprofileof pages 2-5, safaee2013choroidplexuspapillomas pages 1-2)

Differential diagnoses include ependymoma, papillary tumor of the pineal region, papillary meningioma/intraventricular meningioma, metastatic papillary carcinoma, atypical teratoid/rhabdoid tumor, medulloblastoma/embryonal tumor, and choroid plexus hyperplasia. Diagnosis should integrate morphology, immunohistochemistry, imaging/site, and methylation classification.

Molecular and genetic testing

Perform tumor sequencing with TP53, copy-number analysis, and preferably DNA-methylation classification in CPC, diagnostically ambiguous tumors, aggressive aCPP, and recurrence.
Perform paired germline TP53 testing with genetic counseling for every child with CPC, irrespective of family history; tumor-only testing can miss or misclassify constitutional disease.
A pediatric CNS predisposition panel or WES/WGS is reasonable when phenotype/family history is broader or TP53 testing is negative. WGS adds structural-variant and copy-number resolution; WES is useful for coding variants but may miss promoter, methylation, and some structural events.
CMA/SNP array can define aneuploidy/LOH. Karyotype and FISH are not routine first-line tests but may validate selected structural findings. Mitochondrial and repeat-expansion tests are not indicated.
RNA-seq can detect fusions; methylation arrays can resolve pedA/pedB/adult classes. Liquid biopsy/CSF cell-free tumor DNA remains investigational.

11. Outcome and prognosis

CPP generally has excellent long-term control after gross-total resection. aCPP recurrence risk is intermediate and affected by resection completeness and molecular class. CPC historically has approximately 56% 5-year survival, with substantial neurodevelopmental morbidity among survivors. (thomas2021thegeneticlandscape pages 1-3)

In SJYC07, 13 children younger than three years received maximal surgery plus high-dose-methotrexate-containing therapy: 5-year PFS was 61.5% ±13.5% and overall survival 68.4% ±13.1%. Five progressed and died; eight—including five initially high-risk patients—remained progression-free. TP53 status was the only significant prognostic variable: 5-year PFS was 100% wild type versus 28.6% ±17.1% mutant, P=0.012. Extent of resection, metastatic status, and radiotherapy were not statistically significant in this very small cohort and should not be interpreted as proof that they are clinically irrelevant. (liu2021outcomeandmolecular pages 1-2)

Adverse indicators include CPC histology, TP53 mutation—especially biallelic dysfunction—pediatric-B methylation class, dissemination, incomplete local control, TERT-promoter mutation in adults, and selected high-risk copy-number/genomic patterns. Morbidity includes hydrocephalus, neurologic deficits, developmental/cognitive impairment, hearing loss and organ toxicity from chemotherapy, endocrine/vascular effects of radiation, and subsequent cancers in TP53 carriers.

12. Treatment and current applications

Standard strategy

Maximal safe surgical resection is the cornerstone for all CPTs (NCIt: Surgical Resection; Gross Total Resection). Preoperative planning must account for extreme vascularity, blood volume in infants, and possible staged/second-look surgery.
CPP: observation after complete resection; reoperate for accessible recurrence/residual disease. Radiotherapy or chemotherapy is reserved for unusual unresectable, recurrent, or disseminated disease.
aCPP: surgery first. After complete resection, close MRI surveillance is often favored; adjuvant treatment is individualized for residual, recurrent, disseminated, or molecularly high-risk disease.
CPC: maximal surgery plus multiagent chemotherapy. Regimens commonly include platinum, etoposide, vincristine, cyclophosphamide, and/or high-dose methotrexate; no single universally accepted regimen exists because trials are small.
Radiotherapy: consider age, dissemination, residual disease, response, and genotype. Avoid or minimize where feasible in germline TP53 carriers because of secondary-cancer risk; proton therapy may reduce integral dose but does not abolish mutagenic risk. (liu2021outcomeandmolecular pages 9-10, liu2021outcomeandmolecular pages 1-2, frebourg2020guidelinesforthe pages 7-8)

SJYC07 demonstrates a real-world protocol: high-dose methotrexate-containing induction, focal irradiation for localized intermediate-risk disease, additional chemotherapy for metastatic disease, and oral antiangiogenic maintenance. Its results support non-myeloablative therapy as a potentially less toxic curative approach for some young children. (liu2021outcomeandmolecular pages 1-2)

Experimental and precision approaches

A molecularly guided case targeting mTOR, PDGFRB, FGF2, and HDAC pathways with sirolimus, thalidomide, sunitinib, and vorinostat achieved a reported 92% tumor reduction. This is a single case, not a standard regimen.
NCT04994977 tested intra-arterial melphalan/carboplatin/topotecan before second-look surgery. It enrolled one patient and terminated for low accrual; efficacy cannot be inferred. https://clinicaltrials.gov/study/NCT04994977. (NCT04994977 chunk 1)
NCT03500991, HER2-specific locoregional CAR-T for HER2-positive recurrent pediatric CNS tumors including CPC, enrolled ten and is active but not recruiting. https://clinicaltrials.gov/study/NCT03500991. (NCT03500991 chunk 1)
NCT04185038, B7-H3-specific locoregional CAR-T, includes recurrent/refractory CPC within a broader CNS basket; estimated enrollment is 90. CPC-specific efficacy is unproven. https://clinicaltrials.gov/study/NCT04185038. (NCT04185038 chunk 1)
NCT03173950, phase II nivolumab for recurrent rare adult CNS tumors including all CPT subtypes, completed with 133 total basket participants; subtype-specific benefit was not available in the retrieved record. https://clinicaltrials.gov/study/NCT03173950. (NCT03173950 chunk 1)

No approved CPT-specific gene therapy, RNA therapy, CAR-T product, checkpoint inhibitor, or pharmacogenomic dosing rule exists. Suggested NCIt intervention terms include Surgical Resection, Chemotherapy, Radiation Therapy, Proton Beam Radiation Therapy, Methotrexate, Carboplatin, Etoposide, Vincristine, Cyclophosphamide, Topotecan, Melphalan, Nivolumab, and Chimeric Antigen Receptor T-Cell Therapy.

Supportive care includes CSF diversion when required, seizure treatment, transfusion/hemostatic planning, antiemetics, infection prophylaxis, nutrition, audiology, neuropsychology, physical/occupational/speech therapy, school support, and long-term endocrine/second-cancer surveillance.

13. Prevention and screening

There is no population screening, vaccine, lifestyle prevention, or chemoprophylaxis for sporadic CPT. Secondary prevention is targeted to TP53 carriers and relatives:

genetic counseling, confirmatory germline testing, and cascade testing;
annual whole-body and brain MRI beginning in childhood for variants associated with childhood cancer, plus clinical examination and abdominal ultrasound every six months under European TP53 guidance;
minimize diagnostic and therapeutic ionizing radiation where clinically reasonable;
discuss reproductive options, including prenatal or preimplantation genetic testing, non-directively.

These measures seek early detection of multiple LFS-spectrum cancers, not merely recurrent CPT. (fortuno2024cancerrisksassociated pages 1-2, frebourg2020guidelinesforthe pages 7-8)

Tertiary prevention comprises complete local control where safe, neuraxis surveillance for CPC/high-risk aCPP, treatment of hydrocephalus, rehabilitation, neurocognitive monitoring, and avoidance of unnecessary radiation in TP53 carriers.

14. Other species and natural disease

Naturally occurring CPP/CPC has been reported in dogs (Canis lupus familiaris, NCBI Taxon 9615), cats (Felis catus, 9685), and rarely horses (Equus caballus, 9796). Canine CPC can shed malignant cells into CSF and canine high-grade tumors show microvascular proliferation, desmoplasia, and high proliferative indices. Evidence is primarily case reports and small pathology series; breed predisposition, VBO mappings, incidence, and validated ortholog-specific variants are not established in the retrieved material. There is no transmission or zoonotic potential because CPT is neoplastic, not infectious.

Relevant orthologs include canine/feline/equine TP53, MYC, RB1, GMNC, and MCIDAS, but NCBI Gene IDs should be obtained directly from current NCBI orthology records before database loading.

15. Model organisms

Genetically engineered mouse models

Conditional stabilized MycT58A expression plus Trp53 deletion in newborn Otx2-lineage/choroid plexus epithelial cells produced CPC with 100% penetrance; half of mice died by 100 days and all by 150 days, mainly from hydrocephalus. Tumors reproduced human CPC hypercellularity, pleomorphism, vascularity, mitotic activity, and choroid plexus lineage identity. They also showed replication stress, DNA-repair/checkpoint dysregulation, and upregulated AurA and Plk1, providing a preclinical therapeutic platform. Published February 2018; DOI/URL: https://doi.org/10.1016/j.bbrc.2017.11.192. (nagar2018anewgenetically pages 3-4, nagar2018anewgenetically pages 6-8)

Conditional Trp53/Rb1 loss and NOTCH/SHH perturbation models reproduce monociliation and GMNC–MCIDAS suppression. Restoring GMNC/MCIDAS reduced proliferation, supporting a differentiation-suppressor mechanism. (li2022disruptionofgmncmcidas pages 1-2)

Other models and limitations

SV40 large-T-antigen, E2F1, and retinoblastoma-pathway models can generate choroid plexus tumors; Xenopus CRISPR disruption of retinoblastoma-family genes also produces choroid plexus lesions. Cell lines and primary tumor cultures permit drug/pathway studies, but validated patient-derived organoid and xenograft resources remain scarce.

Limitations include engineered lesions that are not universal in humans, compressed latency, species-specific ventricular development and immunity, and incomplete modeling of leptomeningeal dissemination, treatment toxicity, and human developmental outcomes. Models should therefore support—not substitute for—human methylation, genomic, and clinical evidence.

Knowledge gaps and evidence cautions

Exact phenotype frequencies, adult natural history, quality-of-life utilities, and comparative treatment effectiveness remain poorly quantified because cohorts are small and retrospective.
Methylation classes and 2024 single-cell/multiomic discoveries are important for stratification but are not yet independent therapeutic indications.
No validated environmental cause, protective factor, circulating biomarker, metabolomic/lipidomic signature, or CPT-specific approved targeted therapy exists.
Trial basket enrollment should not be interpreted as demonstrated CPT efficacy.
PMID numbers were not exposed for several retrieved full texts; DOI links are therefore supplied rather than inventing PMIDs. Key literature includes Choi et al., published June 2024, https://doi.org/10.1186/s40478-024-01814-y; Hill et al., October 2024, https://doi.org/10.1038/s44318-024-00283-2; Garcia et al., February 2023, https://doi.org/10.1101/mcs.a006245; and Thomas et al., 2021, https://doi.org/10.1093/neuonc/noaa267. (garcia2023genomicprofileof pages 1-2, hill2024singlenucleusrnaseqdissection pages 1-2, choi2024comprehensivemultiomicsanalysis pages 1-2, thomas2021thegeneticlandscape pages 1-3)

References

(garcia2023genomicprofileof pages 1-2): Felipe Antonio de Oliveira Garcia, Adriane Feijó Evangelista, Bruna Minniti Mançano, Daniel Antunes Moreno, Gustavo Noriz Berardinelli, Flávia Escremim de Paula, Augusto Perazzolo Antoniazzi, Carlos Almeida Júnior, Ismael Lombardi, Iara Santana, Gustavo Ramos Teixeira, Caio Evangelista Costa, and Rui Manuel Reis. Genomic profile of two brazilian choroid plexus tumors by whole-exome sequencing. Cold Spring Harbor Molecular Case Studies, 9:a006245, Feb 2023. URL: https://doi.org/10.1101/mcs.a006245, doi:10.1101/mcs.a006245. This article has 2 citations and is from a peer-reviewed journal.
(li2022disruptionofgmncmcidas pages 1-2): Qun Li, Zhiyuan Han, Navleen Singh, Berta Terré, Ryann M. Fame, Uzayr Arif, Thomas D. Page, Tasneem Zahran, Ahmed Abdeltawab, Yuan Huang, Ping Cao, Jun Wang, Hao Lu, Hart G. W. Lidov, Kameswaran Surendran, Lizhao Wu, James Q. Virga, Ying-Tao Zhao, Ulrich Schüller, Robert J. Wechsler-Reya, Maria K. Lehtinen, Sudipto Roy, Zhongmin Liu, Travis H. Stracker, and Haotian Zhao. Disruption of gmnc-mcidas multiciliogenesis program is critical in choroid plexus carcinoma development. Cell Death and Differentiation, 29:1596-1610, Mar 2022. URL: https://doi.org/10.1038/s41418-022-00950-z, doi:10.1038/s41418-022-00950-z. This article has 18 citations and is from a domain leading peer-reviewed journal.
(choi2024comprehensivemultiomicsanalysis pages 1-2): Yeonsong Choi, Seung Ah Choi, Eun Jung Koh, Ilsun Yun, Suhyun Park, Sungwon Jeon, Yeonkyung Kim, Sangbeen Park, Donggeon Woo, Ji Hoon Phi, Sung-Hye Park, Dong-Seok Kim, Se Hoon Kim, Jung Won Choi, Ji Won Lee, Tae-Young Jung, Jong Bhak, Semin Lee, and Seung-Ki Kim. Comprehensive multiomics analysis reveals distinct differences between pediatric choroid plexus papilloma and carcinoma. Acta Neuropathologica Communications, Jun 2024. URL: https://doi.org/10.1186/s40478-024-01814-y, doi:10.1186/s40478-024-01814-y. This article has 5 citations and is from a peer-reviewed journal.
(thomas2021thegeneticlandscape pages 1-3): Christian Thomas, Patrick Soschinski, Melissa Zwaig, Spyridon Oikonomopoulos, Konstantin Okonechnikov, Kristian W Pajtler, Martin Sill, Leonille Schweizer, Arend Koch, Julia Neumann, Ulrich Schüller, Felix Sahm, Laurèl Rauschenbach, Kathy Keyvani, Martin Proescholdt, Markus J Riemenschneider, Jochen Segewiß, Christian Ruckert, Oliver Grauer, Camelia-Maria Monoranu, Katrin Lamszus, Annarita Patrizi, Uwe Kordes, Reiner Siebert, Marcel Kool, Jiannis Ragoussis, William D Foulkes, Werner Paulus, Barbara Rivera, and Martin Hasselblatt. The genetic landscape of choroid plexus tumors in children and adults. Neuro-oncology, 23:650-660, Nov 2021. URL: https://doi.org/10.1093/neuonc/noaa267, doi:10.1093/neuonc/noaa267. This article has 66 citations and is from a domain leading peer-reviewed journal.
(liu2021outcomeandmolecular pages 1-2): Anthony P Y Liu, Gang Wu, Brent A Orr, Tong Lin, Jason M Ashford, Johnnie K Bass, Daniel C Bowers, Tim Hassall, Paul G Fisher, Daniel J Indelicato, Paul Klimo, Frederick Boop, Heather Conklin, Arzu Onar-Thomas, Thomas E Merchant, David W Ellison, Amar Gajjar, and Giles W Robinson. Outcome and molecular analysis of young children with choroid plexus carcinoma treated with non-myeloablative therapy: results from the sjyc07 trial. Neuro-oncology Advances, Dec 2021. URL: https://doi.org/10.1093/noajnl/vdaa168, doi:10.1093/noajnl/vdaa168. This article has 28 citations and is from a peer-reviewed journal.
(hill2024singlenucleusrnaseqdissection pages 1-2): Anthony D Hill, Konstantin Okonechnikov, Marla K Herr, Christian Thomas, Supat Thongjuea, Martin Hasselblatt, and Annarita Patrizi. Single-nucleus rna-seq dissection of choroid plexus tumor cell heterogeneity. The EMBO Journal, 43:6766-6791, Oct 2024. URL: https://doi.org/10.1038/s44318-024-00283-2, doi:10.1038/s44318-024-00283-2. This article has 4 citations.
(garcia2023genomicprofileof pages 2-5): Felipe Antonio de Oliveira Garcia, Adriane Feijó Evangelista, Bruna Minniti Mançano, Daniel Antunes Moreno, Gustavo Noriz Berardinelli, Flávia Escremim de Paula, Augusto Perazzolo Antoniazzi, Carlos Almeida Júnior, Ismael Lombardi, Iara Santana, Gustavo Ramos Teixeira, Caio Evangelista Costa, and Rui Manuel Reis. Genomic profile of two brazilian choroid plexus tumors by whole-exome sequencing. Cold Spring Harbor Molecular Case Studies, 9:a006245, Feb 2023. URL: https://doi.org/10.1101/mcs.a006245, doi:10.1101/mcs.a006245. This article has 2 citations and is from a peer-reviewed journal.
(garcia2023genomicprofileof pages 5-8): Felipe Antonio de Oliveira Garcia, Adriane Feijó Evangelista, Bruna Minniti Mançano, Daniel Antunes Moreno, Gustavo Noriz Berardinelli, Flávia Escremim de Paula, Augusto Perazzolo Antoniazzi, Carlos Almeida Júnior, Ismael Lombardi, Iara Santana, Gustavo Ramos Teixeira, Caio Evangelista Costa, and Rui Manuel Reis. Genomic profile of two brazilian choroid plexus tumors by whole-exome sequencing. Cold Spring Harbor Molecular Case Studies, 9:a006245, Feb 2023. URL: https://doi.org/10.1101/mcs.a006245, doi:10.1101/mcs.a006245. This article has 2 citations and is from a peer-reviewed journal.
(fortuno2024cancerrisksassociated pages 1-2): Cristina Fortuno, Bing-Jian Feng, Courtney Carroll, Giovanni Innella, Wendy Kohlmann, Conxi Lázaro, Joan Brunet, Lidia Feliubadaló, Silvia Iglesias, Mireia Menéndez, Alex Teulé, Mandy L. Ballinger, David M. Thomas, Ainsley Campbell, Mike Field, Marion Harris, Judy Kirk, Nicholas Pachter, Nicola Poplawski, Rachel Susman, Kathy Tucker, Mathew Wallis, Rachel Williams, Elisa Cops, David Goldgar, Paul A. James, Amanda B. Spurdle, David Amor, Lesley Andrews, Yoland Antill, Rosemary Balleine, Jonathan Beesley, Ian Bennett, Michael Bogwitz, Simon Bodek, Leon Botes, Meagan Brennan, Melissa Brown, Michael Buckley, Jo Burke, Phyllis Butow, Liz Caldon, Ian Campbell, Michelle Cao, Anannya Chakrabarti, Deepa Chauhan, Manisha Chauhan, Georgia Chenevix-Trench, Alice Christian, Paul Cohen, Alison Colley, Ashley Crook, James Cui, Eliza Courtney, Margaret Cummings, Sarah-Jane Dawson, Anna deFazio, Martin Delatycki, Rebecca Dickson, Joanne Dixon, Ted Edkins, Stacey Edwards, Gelareh Farshid, Andrew Fellows, Georgina Fenton, Michael Field, James Flanagan, Peter Fong, Laura Forrest, Stephen Fox, Juliet French, Michael Friedlander, Clara Gaff, Mike Gattas, Peter George, Sian Greening, Marion Harris, Stewart Hart, Nick Hayward, John Hopper, Cass Hoskins, Clare Hunt, Paul James, Mark Jenkins, Alexa Kidd, Judy Kirk, Jessica Koehler, James Kollias, Sunil Lakhani, Mitchell Lawrence, Jason Lee, Shuai Li, Geoff Lindeman, Jocelyn Lippey, Lara Lipton, Liz Lobb, Sherene Loi, Graham Mann, Deborah Marsh, Sue Anne McLachlan, Bettina Meiser, Roger Milne, Sophie Nightingale, Shona O'Connell, Sarah O'Sullivan, David Gallego Ortega, Nick Pachter, Jia-Min Pang, Gargi Pathak, Briony Patterson, Amy Pearn, Kelly Phillips, Ellen Pieper, Susan Ramus, Edwina Rickard, Bridget Robinson, Mona Saleh, Anita Skandarajah, Elizabeth Salisbury, Christobel Saunders, Jodi Saunus, Peter Savas, Rodney Scott, Clare Scott, Adrienne Sexton, Joanne Shaw, Andrew Shelling, Shweta Srinivasa, Peter Simpson, Melissa Southey, Amanda Spurdle, Jessica Taylor, Renea Taylor, Heather Thorne, Alison Trainer, Kathy Tucker, Jane Visvader, Logan Walker, Rachael Williams, Ingrid Winship, Mary Ann Young, and Milita Zaheed. Cancer risks associated with tp53 pathogenic variants: maximum likelihood analysis of extended pedigrees for diagnosis of first cancers beyond the li-fraumeni syndrome spectrum. JCO Precision Oncology, Feb 2024. URL: https://doi.org/10.1200/po.23.00453, doi:10.1200/po.23.00453. This article has 38 citations and is from a peer-reviewed journal.
(liu2021outcomeandmolecular pages 9-10): Anthony P Y Liu, Gang Wu, Brent A Orr, Tong Lin, Jason M Ashford, Johnnie K Bass, Daniel C Bowers, Tim Hassall, Paul G Fisher, Daniel J Indelicato, Paul Klimo, Frederick Boop, Heather Conklin, Arzu Onar-Thomas, Thomas E Merchant, David W Ellison, Amar Gajjar, and Giles W Robinson. Outcome and molecular analysis of young children with choroid plexus carcinoma treated with non-myeloablative therapy: results from the sjyc07 trial. Neuro-oncology Advances, Dec 2021. URL: https://doi.org/10.1093/noajnl/vdaa168, doi:10.1093/noajnl/vdaa168. This article has 28 citations and is from a peer-reviewed journal.
(frebourg2020guidelinesforthe pages 7-8): T. Frébourg, Svetlana Bajalica Lagercrantz, Carla Oliveira, R. Mágenheim, D. Evans, Nicoline Marjolijn Marleen Rianne Rolf Gareth Emma Marc Eam Hoogerbrugge Ligtenberg Kets Oostenbrink Sijmons E, N. Hoogerbrugge, M. Ligtenberg, M. Kets, R. Oostenbrink, R. Sijmons, G. Evans, E. Woodward, M. Tischkowitz, E. Maher, R. Ferner, S. Aretz, I. Spier, V. Steinke-Lange, E. Holinski-Feder, E. Schröck, T. Frébourg, C. Houdayer, C. Colas, P. Wolkenstein, V. Bours, E. Legius, B. Poppe, K. Claes, R. de Putter, I. Guillermo, G. Capellá, J. B. Vidal, C. Lázaro, J. Balmaña, H. S. Hernández, Carla Oliveira, M. Teixeira, S. Bajalica-Lagercrantz, E. Tham, J. Lubiński, K. Ertmańska, B. Melegh, M. Krajc, A. Blatnik, S. Peltonen, and M. Hietala. Guidelines for the li–fraumeni and heritable tp53-related cancer syndromes. European Journal of Human Genetics, 28:1379-1386, May 2020. URL: https://doi.org/10.1038/s41431-020-0638-4, doi:10.1038/s41431-020-0638-4. This article has 405 citations and is from a domain leading peer-reviewed journal.
(hill2024singlenucleusrnaseqdissection pages 3-4): Anthony D Hill, Konstantin Okonechnikov, Marla K Herr, Christian Thomas, Supat Thongjuea, Martin Hasselblatt, and Annarita Patrizi. Single-nucleus rna-seq dissection of choroid plexus tumor cell heterogeneity. The EMBO Journal, 43:6766-6791, Oct 2024. URL: https://doi.org/10.1038/s44318-024-00283-2, doi:10.1038/s44318-024-00283-2. This article has 4 citations.
(OpenTargets Search: choroid plexus carcinoma,choroid plexus papilloma-TP53): Open Targets Query (choroid plexus carcinoma,choroid plexus papilloma-TP53, 16 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(gargallo2020li–fraumenisyndromeheterogeneity pages 7-8): P. Gargallo, Y. Yáñez, V. Segura, A. Juan, B. Torres, J. Balaguer, S. Oltra, V. Castel, and A. Cañete. Li–fraumeni syndrome heterogeneity. Clinical and Translational Oncology, 22:978-988, Nov 2020. URL: https://doi.org/10.1007/s12094-019-02236-2, doi:10.1007/s12094-019-02236-2. This article has 52 citations and is from a peer-reviewed journal.
(safaee2013choroidplexuspapillomas pages 1-2): Michael Safaee, Michael C. Oh, Orin Bloch, Matthew Z. Sun, Gurvinder Kaur, Kurtis I. Auguste, Tarik Tihan, and Andrew T. Parsa. Choroid plexus papillomas: advances in molecular biology and understanding of tumorigenesis. Neuro-oncology, 15 3:255-67, Mar 2013. URL: https://doi.org/10.1093/neuonc/nos289, doi:10.1093/neuonc/nos289. This article has 108 citations and is from a domain leading peer-reviewed journal.
(bittar2021clinicalandmolecular pages 9-10): Camila Matzenbacher Bittar, Yasminne Marinho de Araújo Rocha, Igor Araujo Vieira, Clévia Rosset, Tiago Finger Andreis, Ivaine Tais Sauthier Sartor, Osvaldo Artigalás, Cristina B. O. Netto, Barbara Alemar, Gabriel S. Macedo, and Patricia Ashton-Prolla. Clinical and molecular characterization of patients fulfilling chompret criteria for li-fraumeni syndrome in southern brazil. PLoS ONE, 16:e0251639, Sep 2021. URL: https://doi.org/10.1371/journal.pone.0251639, doi:10.1371/journal.pone.0251639. This article has 10 citations and is from a peer-reviewed journal.
(giacomazzi2015pediatriccancerand pages 1-2): Cristina Rossi Giacomazzi, Juliana Giacomazzi, Cristina B.O. Netto, Patricia Santos-Silva, Simone Geiger Selistre, Ana Luiza Maia, Viviane Ziebell de Oliveira, Suzi Alves Camey, José Roberto Goldim, and Patricia Ashton-Prolla. Pediatric cancer and li-fraumeni/li-fraumeni-like syndromes: a review for the pediatrician. Revista da Associacao Medica Brasileira, 61 3:282-9, Jun 2015. URL: https://doi.org/10.1590/1806-9282.61.03.282, doi:10.1590/1806-9282.61.03.282. This article has 29 citations.
(nagar2018anewgenetically pages 6-8): Salsabiel El Nagar, Frederique Zindy, Charlotte Moens, Luc Martin, Damien Plassard, Martine F. Roussel, Thomas Lamonerie, and Nathalie Billon. A new genetically engineered mouse model of choroid plexus carcinoma. Biochemical and biophysical research communications, 496 2:568-574, Feb 2018. URL: https://doi.org/10.1016/j.bbrc.2017.11.192, doi:10.1016/j.bbrc.2017.11.192. This article has 14 citations and is from a peer-reviewed journal.
(NCT04994977 chunk 1): Intra-Arterial Chemotherapy for Newly Diagnosed, Residual, or Recurrent Atypical Choroid Plexus Papilloma and Choroid Plexus Carcinoma Prior to Second-Look Surgery. Weill Medical College of Cornell University. 2023. ClinicalTrials.gov Identifier: NCT04994977
(NCT03500991 chunk 1): Colleen Annesley. HER2-specific CAR T Cell Locoregional Immunotherapy for HER2-positive Recurrent/Refractory Pediatric CNS Tumors. Seattle Children's Hospital. 2018. ClinicalTrials.gov Identifier: NCT03500991
(NCT04185038 chunk 1): Colleen Annesley. Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors. Seattle Children's Hospital. 2019. ClinicalTrials.gov Identifier: NCT04185038
(NCT03173950 chunk 1): Immune Checkpoint Inhibitor Nivolumab in People With Recurrent Select Rare CNS Cancers. National Cancer Institute (NCI). 2017. ClinicalTrials.gov Identifier: NCT03173950
(nagar2018anewgenetically pages 3-4): Salsabiel El Nagar, Frederique Zindy, Charlotte Moens, Luc Martin, Damien Plassard, Martine F. Roussel, Thomas Lamonerie, and Nathalie Billon. A new genetically engineered mouse model of choroid plexus carcinoma. Biochemical and biophysical research communications, 496 2:568-574, Feb 2018. URL: https://doi.org/10.1016/j.bbrc.2017.11.192, doi:10.1016/j.bbrc.2017.11.192. This article has 14 citations and is from a peer-reviewed journal.

Artifacts

Edison artifact artifact-00

Ask OpenScientist

OpenScientist Report

Classifications

Mappings

Inheritance

Subtypes

Discussions and Knowledge Gaps

Pathophysiology

Histopathology

Pathograph

Phenotypes

Genetic Associations

Medical Actions

Environmental Factors

Biochemical Markers

Differential Diagnoses

Clinical Trials

Source YAML

References & Deep Research

References

Deep Research

Choroid Plexus Neoplasm: Disease-Characteristics Research Report

Executive summary

1. Disease information

Definition and classification

Identifiers and synonyms

2. Etiology, risk, and protective factors

Causal and predisposing factors

Other genetic risks

Environmental, infectious, lifestyle, and protective factors

3. Phenotypes

4. Genetic and molecular information

Principal genes and variants

Chromosomal and epigenetic abnormalities

5. Environmental information

6. Mechanism and pathophysiology

Causal chain

Multiciliogenesis and developmental signaling

Recent molecular profiling

7. Anatomical structures affected

8. Temporal development

9. Inheritance and population

Epidemiology

Inheritance

10. Diagnostics

Clinical and imaging work-up

Histopathology

Molecular and genetic testing

11. Outcome and prognosis

12. Treatment and current applications

Standard strategy

Experimental and precision approaches

13. Prevention and screening

14. Other species and natural disease

15. Model organisms

Genetically engineered mouse models

Other models and limitations

Knowledge gaps and evidence cautions

Artifacts