Atypical Choroid Plexus Papilloma Research Articles

Expression of Collagen VI, Anticollagenase, Laminin, MM9, Claudins 1 and 5, N and E Cadherins in Choroid Plexus Tumors

Background: CPTs are rare intraventricular papillary neoplasms derived from the choroid plexus epithelium. Anti-collagenase and extracellular matrix which have not been expressed in brain tumors. Objective: The purpose of this study was to investigate the expression levels of collagen type VI, anti-collagenase, laminin, MM9, claudins 1 and 5, N and E cadherins, and collagen VII, tejido, and collagen degradation enzyme complexes in choroid plexus tumors. Materials and methods: We studied the expression of adhesion molecules, extracellular matrix, and anticollagenase with an immunohistochemistry approach and electron microscopy analysis in 42 choroid plexus tumors. Results: 28(67%) were choroid plexus papillomas, 8 (19%) were atypical choroid plexus papillomas and 6 (14%) were choroid plexus carcinomas. The Ki67-li and MVD increased from CPC to ACPP, being the highest in malignant tumors as well as a strong immunoexpression of anti-collagenase and were inverse correlation with claudin 5, E, and N cadherin and collagen IV immunoexpressions which added further significant information to the prognosis and varied according to the histologic classification. By ultrastructure, the loss of basal membrane and cilia, disorganization, and proliferation of ECM were observed in CPC. Cerebral homeostasis largely results from the ability of both the Blood–Brain Barrier (BBB) at the brain microvascular endothelium and the Blood–Cerebrospinal Fluid Barrier (BCSFB) at the epithelium of the Choroid Plexuses (CPs), to control the composition of the CSF and cerebral extracellular fluid. Under expression of the tight junction proteins occludin, claudin-1 and claudin-5 are key molecular abnormalities responsible for the increased permeability of tumor endothelial tight junctions. Conclusion: The loss of basement membrane and ECM overexpression could be considered as a poor prognosis predictor in CPT. Anti-collagenase and MMP9 overexpression could be related to basal membrane and BBB plasticity in CPTs.

Choroid plexus tumors: A spectrum from benign to malignant

Choroid plexus tumors (CPT) are believed to originate from outgrowths of the choroid plexus. Despite their broad spectrum of symptoms, invasive nature, and prognosis, most CPTs typically exhibit similar presentations due to their relationship with the cerebral ventricles, as well as the mechanical obstruction and mass effect associated with their growth. In addition, these tumors mainly affect the pediatric population, further complicating the differentiation between benign and malignant subtypes. The World Health Organization classifies CPTs into three grades, namely, grades I, II, or III, based on their mitotic activity, which determine the benign or malignant nature of the tumors. CPTs classified by the World Health Organization (WHO) include choroid plexus papillomas (CPP), atypical CPPs (aCPP), and malignant choroid plexus carcinomas (CPC). Choroid plexus adenomas represent an additional category of benign CPTs not officially classified by the WHO. Despite the variations in histology, immunohistochemistry, imaging, treatment, and prognosis, CPTs cannot be reliably distinguished based solely on clinical presentation. Therefore, in this review, we aim to provide a comprehensive overview of each tumor subtype, along with the current management approach and emerging treatments.

Rare Case of Hemorrhagic Atypical Choroid Plexus Papilloma of Fourth Ventricle in Adult: A Diagnostic Dilemma

Choroid plexus papillomas are highly vascular tumors, and such tumors causing subarachnoid hemorrhage have been reported in literature. Similarly, few articles have reported atypical fourth ventricular choroid plexus tumors in adults. However, such an atypical tumor presenting with grossly hemorrhagic transformation without any acute symptoms could not be found in the literature.

Genomic profile of two Brazilian choroid plexus tumors by whole-exome sequencing.

Choroid plexus tumors (CPTs) are rare intracranial neoplasms, representing <1% of all brain tumors, yet they represent 20% of first-year pediatric brain tumors. Although these tumors have been linked to TP53 germline mutations in the context of Li-Fraumeni syndrome, their somatic driver alterations remain poorly understood. In this study, we report two cases of lateral ventricle tumors: 3-yr-old male diagnosed with an atypical choroid plexus papilloma (aCPP), and a 6-mo-old female diagnosed with a choroid plexus carcinoma (CPC). We performed whole-exome sequencing of paired blood and tumor tissue in both patients, categorized somatic variants, and determined copy-number alterations. Our analysis revealed a tier II variant (Association for Molecular Pathology [AMP] criteria) in BRD1, a H3 and TP53 acetylation agent, in the aCPP. In addition, we detected copy-number gains on Chromosomes 12, 18, and 20 and copy-number losses on Chromosomes 13q and 22q (BRD1 locus) in this tumor. 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. The CPC patient presented loss of heterozygosity (LoH) of TP53 loci and hyperdiploid genome. Both tumors were microsatellite-stable. This is the first study performing whole-exome sequencing in Brazilian choroid plexus tumors, and in line with the literature, we corroborate the absence of recurrent somatic mutations in these tumors. Further studies with larger sample sizes are necessary to confirm our findings and better understand the underlying biology of these tumors.

A Prospective Study of Conventionally Fractionated Dose Constraints for Reirradiation of Primary Brain Tumors in Adults

Dose constraints for reirradiation of recurrent primary brain tumors are not well-established. This study was conducted to prospectively evaluate composite dose constraints for conventionally fractionated brain reirradiation. A single-institution, prospective study of adults with previously irradiated, recurrent brain tumors was performed. For 95% of patients, electronic dosimetry records from the first course of radiation (RT1) were obtained and deformed onto the simulation computed tomography for the second course of radiation (RT2). Conventionally fractionated treatment plans for RT2 were developed that met protocol-assigned dose constraints for RT2 alone and the composite dose of RT1+RT2. Prospective composite dose constraints were based on histology, interval since RT1, and concurrent bevacizumab. Patients were followed with magnetic resonance imaging including spectroscopy and perfusion studies. Primary endpoint was the rate of symptomatic brain necrosis at 6 months after RT2. Patients were enrolled from March 2017 to May 2018; 20 were evaluable. Eighteen had glioma, 1 had atypical choroid plexus papilloma, and 1 had hemangiopericytoma. Nineteen patients were treated with volumetric modulated arc therapy, and one was treated with protons. Median RT1 dose was 57 Gy (range, 50-60 Gy). Median RT1-RT2 interval was 49 months (range, 9-141 months). Median RT2 dose was 42.4 Gy (range, 36-60 Gy). Median planning target volume was 186 cc (range, 8-468 cc). Nineteen of 20 patients (95%) were free of grade 3+ central nervous system necrosis. One patient had grade 3+ necrosis 2 months after RT2; the patient recovered fully and lived another 18 months until dying of disease progression. Median overall survival from RT2 start for all patients was 13.3 months (95% credible interval, 6.3-20.7); for patients with glioblastoma, 11.5 months (95% credible interval, 6.1-20.1). Brain reirradiation can be safely performed with conventionally fractionated regimens tailored to previous dose distributions. The prospective composite dose constraints described here are a starting point for future studies of conventionally fractionated reirradiation.

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

There are limited data available on incidence and survival of patients with choroid plexus tumors (CPT). This study provides the most current epidemiological analysis of choroid plexus tumors from 2004 to 2017 in the United States. Data on 2013 patients with CPT were acquired from the Central Brain Tumor Registry of the United States in collaboration with the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute, from 2004 to 2017. CPT cases were classified by the following pathological subtypes: choroid plexus papilloma (CPP), atypical choroid plexus papilloma (aCPP), and choroid plexus carcinoma (CPC). Frequencies and age-adjusted incidence rates (AAIR) per 100 000 and rate ratios per 100 000 (IRR) were reported for age, sex, race, and ethnicity for each pathological subtype with 95% confidence intervals (95% CI). Using CDC's National Program of Cancer Registries survival database, survival curves and hazard ratios (HRs) evaluated overall survival from 2001 to 2016. 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). 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. 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). This analysis is the most current and comprehensive study in the US on the incidence and survival for CPT. Population based statistics provide critical information in understanding disease characteristics, which impact patient care and prognosis.

LINC-24. Survival and genetic evaluation of patients diagnosed with choroid plexus tumor treated at a Brazilian institution

INTRODUCTION: Choroid plexus tumors (CPT) are rare intraventricular neoplasms of epithelial origin. They usually occur in the 2nd year of life, corresponding to 0.4-0.6% of intracranial tumors in this age group. They are classified, according to WHO 2021: choroid plexus carcinoma (CPC), atypical choroid plexus papilloma (ACPP) and choroid plexus papilloma (CPP). Li-Fraumeni syndrome (LFS) is present in 50% of patients with CPC. In Brazil, the TP53p.R337H mutation affects 0.3% of the population in the South/Southeast. OBJECTIVE: Evaluate the genetic assessment and overall-survival (OS) of patients with CPT treated at IOP/GRAACC/UNIFESP. PATIENTS/METHODS: Between 1995-2021, 48 patients were diagnosed with CPT in our institution, 27 CPC, 18 CPP and 3 ACPP. From 2012-2021 patients were referred for genetic evaluation, 16 of which had CPC (2 had previously CPP). Family history for neoplasms was present in 87.5%, 37.5% compatible with Li-Fraumeni Syndrome (LFS) of which 50% with positive mutations. The molecular investigation of TP53 gene in patients with CPC was performed and positive in 62,5%:R337H(6 patients), R110C*, R158H*, H179R*, R196* (*1 patient each). For those with R337H, p53 protein immunohistochemistry resulted in 90-100% positivity. Treatment strategies consisted of surgery with gross total resection being achieve in all ACPP, 94,4% CPP and 55,5% CPC. Chemotherapy was performed in only 1 case of ACPP and all CPC with a variety of schemas, including high dose of chemotherapy and autologous bone marrow transplant for slow responders or recurrent disease. The three- and five-years OS for CPC was 72.5% and 61.7%, respectively. For CPP and ACPP 5y OS was 100%. CONCLUSION: The present study is in agreement with the literature showing an excellent survival for CPP and ACPP but an inferior outcome for patients with CPC and TP53 mutation despite being assisted by a well-prepared multidisciplinary team with an adequate treatment.

RARE-27. Treatment and outcomes in atypical choroid plexus papilloma: a single institution experience

BACKGROUND: Atypical choroid plexus papillomas (aCPP) are rare central nervous system (CNS) tumors often occurring in very young children. While surgical resection has been a mainstay of therapy, there is no consensus and limited data on the treatment of relapsed or metastatic tumors. METHODS: Retrospective review of the treatment and outcome of patients diagnosed with aCPP since 2011 was performed. RESULTS: Of the seven patients, 4 were male and 3 were female with a median age of 3 years at diagnosis (range: antenatal to 18 years old). All non-metastatic patients (six) were treated with surgery and all achieved gross total resection. Two patients had diffuse leptomeningeal contrast enhancement on diagnosis MRI that resolved after resection of primary tumor alone. One patient developed local relapse underwent re-resection with a GTR then was treated with 4 cycles of chemotherapy based on CPT-SIOP-2000 protocol (carboplatin, etoposide) and has not had further relapse in 24 months. One patient had metastatic disease at the time of diagnosis. They were treated with adjuvant chemotherapy, which stabilized disease for 36 months until they had progression. Additional four cycles were given and has again stabilized disease now 8 months from completion of that therapy. One non-metastatic patient died of unknown causes 28 months from diagnosis. CONCLUSIONS: Surgical resection remains the standard of care for patients with aCPP. However, chemotherapy based on the SIOP backbone may be useful to reduce the need for or to delay radiation therapy in select patients in the relapsed or metastatic setting.

RARE-26. Evaluating the clinical utility of DNA methylation profiling for choroid plexus tumors

INTRODUCTION: Choroid plexus tumors (CPT) are rare, potentially aggressive CNS tumors with defined histologic criteria for grading. In recent years, several patients within our practice have demonstrated discordance between histological diagnosis and clinical behavior. DNA methylation profiling has emerged as a potential diagnostic adjunct for aiding clinical planning and treatment approach. In this study, we sought to retrospectively evaluate the clinical utility of DNA methylation profiling within our cohort of patients with CPT. METHODS: We performed a retrospective chart review of all patients with choroid plexus tumors treated at Dana-Farber / Boston’s Children’s Cancer and Blood Disorder Center between 1990-2021, evaluating the histology, treatment approach, and clinical outcome. Available tissue samples were sent to the National Institute of Health for DNA methylation profiling. RESULTS: Seventeen patients with CPT were identified. Median age at diagnosis was 1.8 years (range: 0.4-27.7). Histologic diagnosis included choroid plexus papilloma (CPP; n=4), atypical choroid plexus papilloma (aCPP; n=5), and choroid plexus carcinoma (CPC, n=8). DNA methylation in an initial subset placed these tumors with the pediatric type A (n=5), pediatric type B (n=6), and adult (n=1) subgroups. For one patient, methylation profiling returned as unclassifiable (possibly representing an alternative diagnosis). Discrepancies with the histologic grade were noted in several cases: one patient diagnosed with CPP grouped with pediatric type B CPT on methylation analysis, had rapid recurrence, and a diagnosis of CPC was made on a re-resection specimen; another patient with aCPP with concerning features was classified as pediatric type A by methylation, and is without evidence of disease after initial complete resection. Survival outcomes based on histologic diagnosis and molecular subgroups are compared and reported. CONCLUSION: DNA methylation profiling is a useful tool for the diagnosis of CPT and may have the potential to guide clinical planning and management.

Choroid plexus carcinoma in a dog—Case report

AbstractObtaining a conclusive definitive diagnosis for an intra‐ventricular tumour in a dog can be challenging. In doing so, all differential diagnoses should be considered. Differentiation between choroid plexus tumours (CPTs) (a choroid plexus papilloma, atypical choroid plexus papilloma or choroid plexus carcinoma) and gliomas, including ependymoma, oligodendroglioma and astrocytoma should be considered. Histopathologic features and immunohistochemistry are essential in the differentiation between intra‐ventricular tumours. A 4‐year‐old Boerboel dog presented with a left head tilt and a wide range of nonspecific clinical abnormalities not limited to weight loss, depression and marked bradycardia. MRI proved useful in providing a diagnosis of an intra‐ventricular tumour and demonstrated the potential of choroid plexus carcinomas (CPCs) to metastasize. In this case, the histological features displayed malignancy with invasion into the neuroparenchyma, drop metastasis and immunohistochemistry with E‐cadherin‐positive result that assisted with differentiation of CPC from other tumours.

Disruption of GMNC-MCIDAS multiciliogenesis program is critical in choroid plexus carcinoma development

Multiciliated cells (MCCs) in the brain reside in the ependyma and the choroid plexus (CP) epithelia. The CP secretes cerebrospinal fluid that circulates within the ventricular system, driven by ependymal cilia movement. Tumors of the CP are rare primary brain neoplasms mostly found in children. CP tumors exist in three forms: CP papilloma (CPP), atypical CPP, and CP carcinoma (CPC). 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. 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. GMNC and MCIDAS are early transcriptional regulators of MCC fate differentiation in diverse tissues. Consistently, components of the GMNC-MCIDAS transcriptional program are expressed during CP development and required for multiciliation in the CP, while CPC driven by deletion of Trp53 and Rb1 in mice exhibits multiciliation defects consequent to deficiencies in the GMNC-MCIDAS program. Previous studies revealed that abnormal NOTCH pathway activation leads to CPP. Here we show that combined defects in NOTCH and Sonic Hedgehog signaling in mice generates tumors that are similar to CPC in humans. NOTCH-driven CP tumors are monociliated, and disruption of the NOTCH complex restores multiciliation and decreases tumor growth. NOTCH suppresses multiciliation in tumor cells by inhibiting the expression of GMNC and MCIDAS, while Gmnc-Mcidas overexpression rescues multiciliation defects and suppresses tumor cell proliferation. Taken together, these findings indicate that reactivation of the GMNC-MCIDAS multiciliogenesis program is critical for inhibiting tumorigenesis in the CP, and it may have therapeutic implications for the treatment of CPC.

Disseminated atypical choroid plexus papilloma in late young adulthood – A case report

Atypical choroid plexus papillomas (CPPs) are a rare variant of choroid plexus papillomas, extra-axial tumours that arise from the neuroepithelial lining of the choroid plexus. The latest WHO Classification defines as atypical CPPs as those choroid plexus papillomas that have increased mitotic activity, that is, at least 1 mitosis per mm2. Other features may include hypercellularity, cytological atypia, and necrosis. Atypical CPPs typically occur in the paediatric population.

Embolization of a third ventricular choroid plexus papilloma: illustrative case.

BACKGROUNDChoroid plexus tumors are rare neoplasms that are typically found in the lateral ventricles. They have infrequently been reported in the third ventricle, and treatment strategies have varied.OBSERVATIONSThe authors described a 6-month-old patient who presented with irritability and hypotonia. The patient was found to have a large tumor in the third ventricle with obstructive hydrocephalus. Preoperative angiography revealed a feeding artery from the right medial posterior choroidal artery (MPChA). The feeding artery was effectively embolized, and the patient subsequently received open resection of the tumor. Pathology revealed features consistent with atypical choroid plexus papilloma (CPP).LESSONSChoroid plexus tumors are often hypervascular, which can often make gross total resection (GTR) difficult. Preoperative angiography of tumors identifies feeding vessels, and embolization has the potential to decrease perioperative blood loss and allow for a higher GTR rate. Third ventricular CPPs appear to invariably receive vascular supply from the MPChA, arising from the right posterior cerebral artery. Embolization followed by resection of a choroid plexus tumor in the third ventricle is an effective treatment strategy.

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

IntroductionStandards for chemotherapy against choroid plexus tumors (CPT) have not yet been established.MethodsCPT-SIOP-2000 (NCT00500890) was an international registry for all CPT nesting a chemotherapy randomization for high-risk CPT with Carboplatin/Etoposide/Vincristine (CarbEV) versus Cyclophosphamide/Etoposide/Vincristine (CycEV). 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. High risk was defined as choroid plexus carcinoma (CPC), incompletely resected APP, and all metastatic CPT. From 2000 until 2010, 158 CPT patients from 23 countries were enrolled.ResultsFor 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). 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. Without irradiation, 12 out of 33 patients with CPC younger than three years were alive for a median of 8.52 years. Extent of surgery and metastases were not independent prognosticators.ConclusionsChemotherapy for Choroid Plexus Carcinoma is feasible and effective. CarbEV is superior to CycEV. A subset of CPC can be cured without irradiation.

Choroid plexus papilloma and atypical choroid plexus papilloma in children: treatment results

Choroid plexus tumors (CPTs) are rare intraventricular tumors, accounting 2–5% of brain tumors in children. Choroid plexus papilloma (CPP) classified by the World Health Organization (WHO) on the basis of histological criteria as benign tumor (WHO grade I), CPPs accounts for 10–20% of brain tumors during the first year of life, the median age of patients with CPP at the time of diagnosis – 3.5 years. Atypical choroid plexus papilloma (APP) is an intermediate (WHO grade II) tumor which was officially included in the WHO classification in 2007. Median age 0,63 years. In this work, for the first time in the Russian literature, we present the outcomes of CPP and APP therapy in a large cohort of patients. The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI. In our study from January 1, 2009 to December 31, 2019, 83 CPP and 37 APP were histologically verified. For all patients, surgical removal of the tumor was the first stage of treatment. In 79 (95.2%) patients with CPP and in 32 (86.5%) children with APP, radical resection was performed at the first stage. In 73.5% of children with CPP and 62.2% of children with APP there was no intra- and postoperative complications. In both CPP and APP, the 5-year EFS in patients with complete resection was statistically significantly higher compared to subtotal tumor resection (100% and 33 ± 27% in CPP, 94 ± 4% and 25 ± 22% for APP) (p &lt; 0.001). Chemoradiation therapy was given to 1 patient with CPP, 4 patients with APP with tumor recurrence/progression. 

Ureaplasma parvum meningitis following atypical choroid plexus papilloma resection in an adult patient: a case report and literature review

BackgroundWhile Ureaplasma parvum has previously been linked to the incidence of chorioamnionitis, abortion, premature birth, and perinatal complications, there have only been rare reports of invasive infections of the central nervous system (CNS) in adults. Owing to its atypical presentation and the fact that it will yield sterile cultures using conventional techniques, diagnosing U. parvum meningitis can be challenging.Case presentationWe describe a case of U. parvum meningitis detected in an adult patient following surgical brain tumor ablation. After operation, the patient experienced epilepsy, meningeal irritation, and fever with unconsciousness. Cerebrospinal fluid (CSF) analysis showed leukocytosis (484 * 106 /L), elevated protein levels (1.92 g/L), and decreased glucose concentrations (0.02 mmol/L). Evidence suggested that the patient was suffering from bacterial meningitis. However, no bacterial pathogens in either CSF or blood were detected by routine culture or serology. The symptoms did not improve with empirical antibiotics. Therefore, we performed metagenomic next-generation sequencing (mNGS) to identify the etiology of the meningitis. Ureaplasma parvum was detected by mNGS in CSF samples. To the best of our knowledge, this case is the first reported instance of U. parvum meningitis in an adult patient in Asian. After diagnosis, the patient underwent successful moxifloxacin treatment and recovered without complications.ConclusionsAs mNGS strategies can enable the simultaneous detection of a diverse array of microbes in a single analysis, they may represent a valuable means of diagnosing the pathogens responsible for CNS infections and other clinical conditions with atypical presentations.

Choroid Plexus Tumors in Children: Long-Term Follow-Up of Consecutive Single-Institutional Series of 59 Patients Treated over a Period of 8 Decades (1939–2020)

To present long-term follow-up of a consecutive single-institutional series of patients treated for choroid plexus tumors over 8 decades. From 1939 to 2020, 59 children were treated for choroid plexus tumors. Median age at diagnosis was 1.7 years. Gross total resection was achieved in 51 patients (86%). Ten patients (17%) underwent >1 resection. During the first 4 decades of the study (1939-1979), 14 patients with plexus papillomas were treated. Operative mortality was 50%, with 6 of the remaining 7 patients experiencing excellent survival with follow-up periods of 41-81 years. In the last 4 decades (1980-2020), 38 patients had low-grade tumors, and all were alive at the latest follow-up (range, 0.5-39 years). Observed 5-year survival in this subgroup was 100% (n= 30), as was observed 10-year survival (n= 26). One of 7 (14%) patients with atypical choroid plexus papilloma and 3 of 31 patients (10%) with choroid plexus papilloma underwent a second resection owing to recurrent tumor. At last follow-up, 47 patients (80%) were alive; 45 (96%) had a Barthel Index score of 100 and 2 had a Barthel Index score of 50. Today 25 patients are adults (20-59 years old); 17 work full-time, 4 work part-time, and 4 are unable to work. Low-grade choroid plexus tumors can be cured with gross total resection alone, with excellent long-term survival and functionality. The vast majority of survivors live independently as adults and work full-time. Recurrences are uncommon (8.7%), appear within the first few years after primary surgery, and can be treated with repeat resections.

CSIG-28. REGULATION OF GEMC1 MULTICILIOGENESIS PROGRAM IN CHOROID PLEXUS CARCINOMA

Abstract Tumors of the choroid plexus (CP) are rare primary brain neoplasms mostly found in children. CP tumors exist in three forms: CP papilloma (CPP), atypical CPP, and CP carcinoma (CPC). Though CPP is more benign, CPC is a highly lethal and little understood cancer with poor survival rate and a tendency for recurrence and metastasis. CP tumors are thought to arise from CP epithelial cells that secrets cerebral spinal fluid and generate multiple cilia on their apical surface. Here we show that aberrant NOTCH and Sonic Hedgehog signaling in mice drive tumors that resemble CPC in humans. In contrast to CP epithelial cells with clusters of multiple cilia, NOTCH-driven CP tumors were monociliated, and disruption of the NOTCH complex restored multiciliation and decreased tumor growth. NOTCH suppressed multiciliation in tumor cells by inhibiting the expression of Geminin Coiled-Coil Domain Containing 1 (GEMC1), and multiciliate differentiation and DNA synthesis associated cell cycle protein (MCIDAS), early transcriptional regulators of multiciliated cell (MCC) differentiation. Consistently, Gemc1-Mcidas deficiency led to a lack of MCCs in the CP, and impaired the correction of the multiciliation defect in tumor cells by a NOTCH inhibitor. Disturbances to the GEMC1 program are commonly observed in human CPCs characterized by solitary cilia and frequent somatic TP53 mutations. Accordingly, CPC driven by deletion of tumor suppressors Trp53 and Rb1 in mice exhibits a cilia deficit consequent to loss of Gemc1-Mcidas expression. Taken together, these findings reveal that the GEMC1-MCIDAS multiciliogenesis program in the CP is critical for inhibiting tumorigenesis, whereas a defective multiciliation program promotes CPC and may represent a therapeutic avenue for this cancer.

Choroid plexus papilloma in a free ranging eared dove (Zenaida auriculata)

Choroid plexus tumors (CPT) are rare neoplasms and histologically classified as choroid plexus papilloma (CPP), atypical choroid plexus papilloma (APP), and choroid plexus carcinoma (CPC). These neoplasms have been described in humans, domestic animals (canine, feline, equine, caprine) and some wild animals (cetaceans and Psittacidae birds). To our best knowledge, herein we report the first CCP in a free-ranging eared dove (Columbiformes; Zenaida auriculata, de Murs 1847). Histologically, the ventricle was dilated, with a papillary proliferation (arboriform pattern) in topography of CP. The neoplasm was well-differentiated, composed by a single layer of cuboidal cells, anchored in a delicate fibrovascular stroma. The neoplastic cells exhibited moderate stroma, with well-defined borders and round nuclei, with vesicular chromatin and inconspicuous nucleoli. Mitotic activity was low (&lt;1 mitosis per 10 high-power fields). Immunohistochemistry for cytokeratin markers (AE1/AE3 antibody) were implemented, however, both neoplastic cells and normal epithelial tissues do not show immunoreactivity.

Paediatric atypical choroid plexus papilloma: is adjuvant therapy necessary?

Choroid Plexus Tumours (CPTs) account for 1-4% of all brain tumours in children. Atypical choroid plexus papillomas (aCPPs) are a subset of these tumours, defined over a decade ago, yet no consensus exists on the optimal approach to their management. We conducted a retrospective analysis of all patients treated for CPTs at the Hospital for Sick Children between January 1, 2000, and December 31, 2018, and focused on patients with aCPP. Data extracted from the patient records for analysis included: demographic and clinical features, radiological imaging, surgical and adjuvant therapies, key pathological features, immunohistochemical staining for TP53 and tumour karyotype. Six of seven aCPP samples were profiled using Illumina HumanMethylationEPIC arrays and the top 10,000 most variably methylated probes were visualized using tSNE. Copy number inferencing was also performed. Twenty-nine patients were diagnosed with CPT, seven of whom had a diagnosis of aCPP as confirmed by histological review. Methylation profiling demonstrated that aCPPs clustered with both choroid plexus papillomas (CPPs) and choroid plexus carcinomas (CPCs). Complete resection of the tumour was pursued in all cases of aCPP and no patient received adjuvant therapy. All aCPP patients were alive at last follow up. This limited case series suggests that paediatric aCPP can be successfully managed with surgical resection alone, followed by a 'watch and wait' approach thus avoiding adjuvant therapies. A deeper understanding of the biology of aCPP is required to identify objective markers which can help provide robust risk stratification and inform treatment strategies.