Choroid Plexus Papilloma Research Articles

Pathophysiology of the choroid plexus in brain diseases.

The choroid plexus, located in the ventricular system of the central nervous system (CNS), obtains numerous roles critical for the proper development and operating of the CNS. The functions range from the best-known ones of the barrier and cerebrospinal fluid (CSF) producer, through participation in immune answer, 'nourishment, detoxification and reparation of the rest of the CNS. Increase number of studies point out the association between choroid plexus dysfunction, characterized by alterations in secretory, transport and barrier capabilities, and the broad spectrum of clinical conditions, as well as physiological aging. We present a brief overview of pathological states known or speculated to be connected to choroid plexus dysfunction, ranging from neurodevelopmental, to autoimmune and neurodegenerative diseases. We also cover the topic of choroid plexus tumors, as well explained involvement of the choroid plexus in pathogen invasion of the CNS, also referring to the currently actual SARS-CoV-2 infection. Finally, we have also touched conducted studies on the choroid plexus regenerative potential. With the information provided in the review we want to point out the importance and call for further research on the role of the choroid plexus in the sustainability of central nervous system health.

Hydrocephalus Associated with Brain Tumor: Characteristics, Management & Outcomes in a Regional Neurosurgical Centre in Nigeria

Introduction: Brain tumor is a common neurosurgical condition encountered by neurosurgeons in clinical practice. Hydrocephalus could be associated with brain tumor thereby increasing the burden of the disease to the affected patients. Characteristics and outcome of hydrocephalus resulting from brain tumors are almost unknown in our setting. The objectives of this study were to describe the characteristics and outcome of hydrocephalus caused by brain tumor in our center. Methods: A retrospective analysis of all cases of hydrocephalus resulting from brain tumor managed in our center between January 2015 to December 2019. Relevant data extracted from patient’s case files and operation register was analysed. Results: Out of the total sixty-eight cases of brain tumors, thirty (44.1%) cases of hydrocephalus caused by brain tumor were managed over the study period. The mean age of presentation was 14 years ± 2 SD with a slight male preponderance (M: F = 1.07:1). The most common clinical presentations were headache, progressive visual impairment, altered conscious level and ataxia. Posterior fossa tumors were the commonest (21/30), followed by craniopharyngioma (6/30) and one case each for pituitary macroadenoma, pineal region tumor and choroid plexus papilloma respectively. Pediatric age group was the most affected (19/30). All patients had ventriculoperitoneal shunting before definitive surgery. Postoperative outcome was good in the majority of cases (27/30), mortality was recorded in one patient (1/30). Conclusion: Hydrocephalus is a common association in patients with brain tumor in our center. Most cases of brain tumor associated hydrocephalus occur in children and posterior fossa tumor is the commonest aetiology. The outcome of ventriculoperitoneal shunting is relatively good in our setting.

Posterior interhemispheric approach for surgical removal of a choroid plexus papilloma in the ventricular atrium.

A 12 year-old boy with headaches for 2 months. Magnetic resonance imaging of the brain found a small lesion in the atrium of the right lateral ventricle. We show a posterior interhemispheric approach to the ventricular atrium through a corticotomy in the pre-cuneus and the posterior cingulate gyrus. This approach has the advantage of avoiding lesion to the optic radiation. A complete resection of the lesion was performed without complications. Anatomopathological result showed choroid plexus papilloma. This benign tumor corresponds to less than 1% of brain tumors and typically presents with signs of intracranial hypertension with hydrocephalus.

Echovirus-30 Infection Alters Host Proteins in Lipid Rafts at the Cerebrospinal Fluid Barrier In Vitro.

Echovirus-30 (E-30) is a non-polio enterovirus responsible for meningitis outbreaks in children worldwide. To gain access to the central nervous system (CNS), E-30 first has to cross the blood-brain barrier (BBB) or the blood-cerebrospinal fluid barrier (BCSFB). E-30 may use lipid rafts of the host cells to interact with and to invade the BCSFB. To study enteroviral infection of the BCSFB, an established in vitro model based on human immortalized brain choroid plexus papilloma (HIBCPP) cells has been used. Here, we investigated the impact of E-30 infection on the protein content of the lipid rafts at the BCSFB in vitro. Mass spectrometry analysis following E-30 infection versus uninfected conditions revealed differential abundancy in proteins implicated in cellular adhesion, cytoskeleton remodeling, and endocytosis/vesicle budding. Further, we evaluated the blocking of endocytosis via clathrin/dynamin blocking and its consequences for E-30 induced barrier disruption. Interestingly, blocking of endocytosis had no impact on the capacity of E-30 to induce loss of barrier properties in HIBCPP cells. Altogether, these data highlight the impact of E-30 on HIBCPP cells microdomain as an important factor for host cell alteration.

MODL-30. DISSECTING THE ROLE OF MULTI-CILIOGENESIS NETWORK IN CHOROID PLEXUS TUMOR

The choroid plexus (CP) in brain ventricles consists of a fibro-vascular core encapsulated by epithelial cells that possess clusters of primary cilia on cell surface. CP tumors are rare primary brain neoplasms that most commonly occur in young children. Compared to the benign CP papilloma, choroid plexus carcinoma (CPC) is poorly understood and highly lethal with few treatments available. Molecular, cytogenetics and genomics studies uncovered complex alterations in CPC including frequent chromosomal loss and recurrent focal aberrations, whereas abnormal NOTCH signaling is observed in many CP tumors. We showed that activation of both NOTCH and Sonic Hedgehog (SHH) signaling in mice drives the formation of aggressive CP tumor. Molecular and histology analyses demonstrated that these murine CP tumors closely resemble their human counterparts, which also display aberrant SHH and NOTCH signaling, suggesting they may represent potential therapeutic avenues. Indeed, treatment with vismodegib, an FDA-approved SHH pathway inhibitor, suppresses CP tumor growth. Unlike multi-ciliated CP epithelial cells, tumor cells in these animal models are characterized by a solitary primary cilium. Though key genes of the multi-ciliogenesis circuit driven by Geminin coiled-coil domain-containing protein 1 (GEMC1) are expressed in CP epithelium, GEMC1-dependent transcriptional program is suppressed in NOTCH-driven CP tumors. Importantly, CPCs in humans consist of tumor cells with a solitary primary cilium and exhibit profound defects multi-ciliogenesis program. Together, these results indicate that a solitary primary cilium is crucial for CPC development, whereas multi-ciliogenesis circuit possesses tumor suppressive functions and may represent a novel therapeutic target in CPC.

RARE-26. RETROSPECTIVE ANALYSIS OF PEDIATRIC CHOROID PLEXUS TUMORS

BACKGROUNDChoroid plexus tumors (CPT) include choroid plexus papilloma (CPP), atypical choroid plexus papilloma (aCPP), and choroid plexus carcinoma (CPC). Because of their rarity, limited data are available on the current status of treatment and outcomes for pediatric CPTs.METHODWe retrospectively reviewed clinical information on patients with CPT patients aged between 0 and 30 years at diagnosis and were treated in 8 institutions in Japan.RESULTSOf forty-two cases initially diagnosed as CPT, 18 cases were reviewed by central pathologists. As a result, the diagnosis of CPC or aCPP in five cases were changed to other tumors including AT/RT and astroblastoma. The remaining 37 cases were subjected to analysis. Median age at diagnosis was two years (0 to 25) and the mean follow-up period was seven years. All 26 patients with CPP (n=20) or aCPP (n=6) underwent gross-total resection without adjuvant therapy. Of them 24 patients are alive without recurrence. Four patients of patients with CPC (n=11) died of cancer. Five patients including three patients experienced local relapse, achieved complete remission after resection of tumor plus chemoradiotherapy. All three patients with dissemination of CPC at diagnosis or relapse died of the disease. At least three patients were diagnosed with Li-Fraumeni syndrome: one died of medulloblastoma and one patient developed osteosarcoma.CONCLUSIONCompared with the excellent prognosis of CPP, the survival rates for CPC, especially disseminated CPC are unsatisfactory. Our results also underline the importance of considering genetic testing of TP53 for patients with CPC.

RARE-18. GENETIC EVALUATION IN PATIENTS WITH CHOROID PLEXUS TUMORS

INTRODUCTIONChoroid 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 sub classified, according to WHO 2016, in 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 TP53 p.R337H mutation affects 0.3% of the population in the South/Southeast.OBJECTIVEEvaluate the incidence of genetic mutations in patients with choroid plexus tumors and therefore the importance of genetic evaluation.PATIENTS AND METHODSBetween 1992–2019, 38 patients were diagnosed with CPT in our institution, 23 with CPC. From 2012, 21 patients were referred for genetic evaluation, 16 of which had CPC (2 had previously CPP). Positive family history for neoplasms was present in 87.5%; 37.5% compatible with LFS, 50% of them with mutations. All the patients with positive, but unspecific, family history of neoplasms, had pathogenic mutation. The molecular investigation of the TP53 gene in patients with CPC was performed and positive in 56.2%: R337H (5 patients), R110C, R158H, H179R, R196* (1 patient each). Of those with R337H, p53 protein immunohistochemistry resulted in 90–100% positivity. One of the patients with CPP that evolved to CCP had the H179R mutation. Clinical course was similar among them, and with those without mutations.CONCLUSIONThese results confirm the need for genetic evaluation in patients with choroid plexus tumors for adequate therapeutic management and long-term follow-up.

RARE-39. MOLECULARLY CONFIRMED ATYPICAL CHOROID PLEXUS PAPILLOMA WITH INTRACRANIAL DISSEMINATION

INTRODUCTIONAmong choroid plexus tumors (CPTs), metastasis occurs more frequently as pathological grading increases. There could be an underestimation of pathological diagnosis if disseminated CPTs are diagnosed with lower grade tumors such as choroid plexus papilloma (CPP) or atypical choroid plexus papilloma (aCPP). Thus, molecular diagnosis using genome-wide DNA methylation profiling may be useful to clarify malignant potential among thetumor entity. Here, we report about a case of aCPP with intracranial dissemination that was molecularly diagnosed by methylation profiling. CASE DESCRIPTION: A 2-year-old girl presented with a history of vomiting. Brain magnetic resonance imaging showed a large tumor mass in the right lateral ventricle and diffuse enhancement surrounding her brainstem, which suggested dissemination. Gross total resection of the mass was performed. Intraoperative findings revealed multiple spot metastatic lesions on the inner wall of lateral ventricle. The pathological diagnosis was aCPP owing to the presence of a glandular structure with a papillary pattern suggesting a neoplasm of epithelial origin, increased cellularity, several necrotic areas, and an intermediate number of mitoses. The CPT-SIOP-2000 treatment protocol was followed without radiation therapy, and the disseminated lesion was disappeared during the chemotherapy. Methylation data of the current case was entered into a recently published classifier, and the tumor was classified as methylation class “plexus tumor, subclass pediatric A” with high confidence (calibrated score 0.96), which includes cases diagnosed as CPP and aCPPs.CONCLUSIONOur case indicates the clinical significance of molecular confirmation of diagnosis among CPTs, particularly lower grade tumors with dissemination.

RARE-22. GERMLINE PATHOGENIC VARIANT c.1552G>A;p.E518K IN DGCR8 CONFERS SUSCEPTIBILITY FOR SCHWANNOMATOSIS AND THYROID TUMORS

Germline mutations in DICER1 cause a pleiotropic susceptibility syndrome characterized by the development of pediatric or early-onset tumors including pleuropulmonary blastoma, Wilms tumors, pineoblastomas, multinodular goiter (MNG) and thyroid cancers. Somatic mutations in the other two microprocessors DROSHA and DGCR8 have been found in Wilms Tumors and pineoblastomas. We present here two families with peripheral schwannomatosis and thyroid tumors carrying a germline variant c.1552G>A;p.E518K in DGCR8. Family one had six affected members with early-onset MNG and five of them developed schwannomatosis. All five members were heterozygous for the variant. One of the carriers had also been diagnosed with a choroid plexus papilloma at 7 years old. The common second event in all tumors tested was the loss of chromosome 22 at the somatic level. In family two, a 35-year-old male was diagnosed with a peripheral schwannoma at the age of 12. Since then, he has developed seven extra peripheral schwannomas (one of which was an ancient schwannoma) and papillary thyroid cancer. DGCR8 lies on chromosome 22q, adjacent to the three schwannoma genes: LZTR1, SMARCB1 and NF2. The variant, c.1552G>A;p.E518K localizes to the first RNA-binding domain of DGCR8 and structural modelling predicts that it abolishes proper binding of RNA. It is also a hotspot somatic mutation in Wilms tumors. Using miRNA profiling, we show that this variant disrupts global microRNA production and DGCR8 mutated tumors show a specific miRNA profile different from DGCR8 wild type tumors. These findings reinforce DGCR8 as a novel susceptibility gene for schwannomatosis and thyroid tumors.

RARE-49. CHOROID PLEXUS ADENOMA WITHOUT ASSOCIATED HYDROCEPHALUS PRESENTING AS PRECOCIOUS PUBERTY

Precocious puberty (PP) is a rare presentation of intracranial pathology unrelated to the pituitary. PP in this setting is considered a paraneoplastic phenomenon, achieved through synthesis of sex-hormones by the tumor itself or via alterations in the release of gonadotrophins from the pituitary. The latter has been described with masses adjacent to the pituitary or with those which cause hydrocephalus. We describe a case of a choroid plexus papilloma (CPP) without hydrocephalus presenting as precocious puberty. An 18 month-old female presented with 4-months of weight loss, bilateral galactorrhea and constipation. Her weight decreased from the 15th to below the 1st percentile. CBC, celiac and thyroid studies were normal. Prolactin was at the upper limit of normal (25.8;ref 3.3–26.3). Breast ultrasound demonstrated symmetric breast tissue development. She was referred to pediatric gastroenterology for constipation and failure to thrive. Caloric supplementation, bowel regimen and barium enema were recommended. One week later, she was admitted with dehydration, painful constipation and further weight loss in the setting of an acute febrile illness. MRI revealed a normal pituitary and an intraventricular mass without hydrocephalus. She underwent gross total resection of the mass, later determined to be a choroid plexus papilloma. The patient’s galactorrhea resolved abruptly following resection. Because of her galactorrhea, our patient underwent neuroimaging revealing an incidental mass without associated hydrocephalus. To our knowledge, precocious puberty and hyperprolactinemia have not been described in neoplasms distant from the pituitary. Thus, these lesions should be recognized as a potential etiology of precocious puberty and hyperprolactinemia.

LINC-20. INFANT BRAIN TUMOURS IN HONG KONG

OBJECTIVESTo review the clinical features, pathology and survivals of infants with brain tumours.METHODSA retrospective review of the clinical findings, pathology, treatment and survival outcome in infants with brain tumours.RESULTSFrom 1999 to 2018, there were 507 children (<18 years) who were diagnosed to have brain tumours in Hong Kong. The patients were treated in five public hospitals. The clinical data were collected by the Hong Kong Paediatric Haematology and Oncology Study Group, and were cross-checked with the data of the Hong Kong Cancer Registry. In this group of patients, there were 36 infants (birth to 365 days of age) i.e. 7.1% of the whole group. Both benign and malignant brain tumours were included, while non-neoplastic lesions were excluded. On average, there was 1.89 cases per year. The pathology of the tumours were astrocytoma (n= 8), medulloblastoma (n=6), germ cell tumour (n=6), PNET (n=5), ATRT (n=4), choroid plexus tumours (n=3), ependymoma (n=2), craniopharyngioma (n= 1) and ganglioglioma (n= 1). These infants were treated according to their clinical conditions and prognosis, with operation, chemotherapy or both. Radiotherapy was withheld or postponed to older age. Some patients only received palliative care due to the poor neurological status or prognosis. The overall survivals of children younger than 18 years old vs infants were 67.3% (±2.3) vs 50.5%(±9.2) respectively, while the event free survivals were 64.4% (±2.4) and 43.5% (±8.8) at 10-years respectively.CONCLUSIONInfants with brain tumours have different pathology and inferior outcome.

RARE-52. RB1 GENE DELETIONS ARE THE NOVEL MECHANISM OF CHOROID PLEXUS TUMORS (CPT) ONCOGENESIS

BACKGROUNDCPTs are known to be rare TP53-dependent neoplasms, while major molecular alterations underlying tumor progression, especially in TP53-wild type cases, are still unclear.METHODS18 primary CPT, including 16 choroid plexus carcinomas (CPC) and two atypical choroid plexus papillomas (CPP), were evaluated for copy number status of 87 major oncogenes and tumor suppressor genes by nCounter Cancer CNV assay by Nanostring and TP53 and RB1 by MLPA. Germline TP53 nucleotide substitutions were analyzed by Sanger sequencing.RESULTSPathogenic germline TP53 variants were present in 4 cases confirming Li-Fraumeni syndrome (LFS). Two patients have somatic TP53 substitutions. Only one patient with LFS harbored somatic TP53 deletion. In 7 patients, heterozygous deletions of RB1 involving from 3 exons to the whole coding sequence detected by MLPA were discovered. All these findings were validated by nCounter CNV assay. Additionally, four patients have WT1 deletions, two patients – BRCA2, and in 1 case - NF1, concomitant with RB1 deletions in 3 cases. Interestingly, in one patient who faced a progression of CPP to CPC germline, RB1 deletion was detected, and in both subsequent tumors, the length of the deleted region progressively increased. Notably, that RB1 deletions are mostly mutually exclusive to TP53 substitutions. 3 of 4 patients with RB1 deletions having follow-up period >1 year faced with tumor-related adverse events.CONCLUSIONSSomatic or uncommon germline RB1 heterozygous deletions have been unraveled as a novel mechanism of aggressive CPT and could be implemented in prognosis definition schemes.

EPID-10. EPIDEMIOLOGY STUDY OF UNCOMMON CHILDHOOD BRAIN TUMOURS IN ASIAN CHILDREN

Our local registry identified 656 brain tumours from Jan 1999 to Dec 2018, (incidence: 29.8/yr/million). Other from Glioma, Medulloblastoma/PNET, Germ Cell tumours, Ependymoma, the remaining rarer tumours accounted for 18% (n=118). The 7 more common groups are: craniopharyngioma(n=28); ATRT(n=18); choroid plexus papilloma/CA(n=12); Ganglioglioma(n=11); ETMR(n=7); DNET(n=7); meningioma(n=6). Their respective incidences are 1.27; 0.81; 0.55; 0.5; 0.32; 0.32 0.27/yr/million. For craniopharyngioma, M:F=15:13 and median age was 7.4yrs (2mons-16.5yrs). 12/28 children had surgery alone and 13/28 had focal RT post-surgery with better outcome. 3 underwent intra-cystic interferon-beta also stable. For ATRT, M:F=7:8 and median age was 2.3yrs (4mos-14.2yrs). 2 had metastatic disease and 7/18 patients remained alive. For choroid plexus tumours, there were 7 papilloma, 2 atypia and 3 carcinoma. M:F=5:6 and median age was 1.5yrs (4mos-14yrs). All papilloma, 1/2 atypia and 1/3 carcinoma survived. For ganglioglioma, M:F=7:4 with median age of 5.5yrs (5mos-13.2yrs). They commonly presented with seizure and only one died (brainstem primary). The ETMR includes ependymoblastoma and medulloepithelioma, they had quite different clinical characteristics and outcome. 6/7 DNET had convulsion and M:F=6:1. Median age was 11.5yrs (2.66-14yrs). They all survived even if incompletely resected. For meningioma, 1/6 had germline mutation of NF-2 gene. M:F=3:3 and onset was >8yrs except the NF-2 patient. All survived but the NF-2 had multiple recurrences. 4 patients developed secondary meningioma due to irradiation but they were >18yrs so excluded. In summary, rarer forms of childhood brain tumours only accounted for <20% of all brain tumours and they had diverse presenting features and outcome.

EPID-05. EVALUATION OF THE INCIDENCE OF CENTRAL NERVOUS SYSTEM TUMORS IN A CHILDHOOD CANCER TREATMENT CENTER AND THE CREATION OF A SPECIFIC GROUP

Central Nervous System Tumors (CNST) are the main solid neoplasm of childhood, representing 20% diagnosis. Based on this information, a search was carried out at a reference treatment center for childhood cancer in the state of Sao Paulo, belonging to University of Sao Paulo- ITACI/HCFMUSP, and at between 2017 and 2019, 352 new patients, 116 of which were neoplasm of CNS (32.9%). Aiming at an incidence of new cases, in 2019, an institutional group was created, with a team composed of Pediatric Oncologists, Neurosurgeons, Radiologists, Radiotherapists and Pathologists. In this first year, 31,8% of the 132 new patients were diagnosed with CNS tumor. According to WHO 2016, 15 patients were classified as a group that includes Diffuse Astrocytomas, Oligodendrioglial Tumors and Other Astrocytic Tumors. Among the other patients, 14.2% were Medulloblastomas, 4.7% Embryonic Tumors and 2.3% ART / RT. Patients diagnosed with diffuse brainstem glioma accounted for 11.9% of the total. The institution had a diagnosis of Angiocentric Glioma, Craniopharyngioma, Plexiform Neurofibroma and Anaplastic Ependymoma. Neuronal-glial tumors accounted for 9.5% of cases. Choroid plexus tumors represents 5%. Among them, 4.72% had metastatic tumors: Neuroblastoma and Ewing’s Sarcoma. Of the total of 42 patients, there were 5 deaths, 4 due to disease progression and one due to clinical complications. With the group, the discussions were carried out, allowing us to analyze that the presence of the Radiotherapy, Neurosurgery and Pathology team from the first moment, optimized the beginning of treatment and increased the patients’ survival.

Abstract PO-235: Choroid plexus papilloma: A report of a benign but rare entity

Abstract Choroid plexus papilloma (CPP) accounts for &amp;lt;1% of all the intracranial neoplasms and is a rare benign neoplasm with common sites being the fourth ventricle in adults and lateral ventricle in children. They are occasionally bilateral with associated hydrocephalus. A 28-year-old female with no past medical history presented to the emergency department with a fall and witnessed seizure. On her way to the bathroom, she felt dizzy and missed a step leading her to trip and fall hitting her headfirst. While on the floor she was witnessed a seizure and brought to the emergency department where she had postictal confusion, slow speech, and was unable to recall events after falling. She also complained about fatigue, lack of energy, sleepiness, loss of interest, sad mood, and suicidal thoughts. CT scan demonstrated a 2.6 cm fourth ventricular mass with internal calcifications. Posterior to the mass there was a subtle increased density which was favored as additional calcifications with moderate obstruction of the 4th ventricle and mild ventriculomegaly. Differential diagnosis included subependymoma, ependymoma as well as astrocytoma. Histopathological examination revealed CPP with appropriately controlled stains to be positive for S100 and Ki-67 to be approximately 3% and negative for p63. CPP is derived from neuroectoderm and is designated as Grade I neoplasms by WHO and Grade II is reserved for atypical CPP. The most optimal treatment strategy is resection which is curative with very little chance of recurrence after a gross-total resection in approximately 96% of the cases. One of the management challenges faced is the vascularity of the tumor which is due to the intraventricular location of tumor which has a rich anastomotic supply of choroidal blood vessels. Due to the rich vascularity of the tumor embolization is considered as an adjunct to reduce the intravascular blood loss intraoperatively with the overall mortality ranging from 0-25% and the mortality rate from the blood loss to be approximately 12%. Currently, the patient is doing well without any evidence of metastasis. Hence it is important to be aware of this rare and benign entity and endoscopic removal is recommended despite the intraoperative bleeding it might cause. Citation Format: Hansini Laharwani, Vijay Kumar, James Neill. Choroid plexus papilloma: A report of a benign but rare entity [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-235.

Imaging of fetal brain tumors.

Congenital brain tumors, defined as those diagnosed prenatally or within the first 2months of age, represent less than 2% of pediatric brain tumors. Their location, prevalence and pathophysiology differ from those of tumors that develop later in life. Imaging plays a crucial role in diagnosis, tumor characterization and treatment planning. The most common lesions diagnosed in utero are teratomas, followed by gliomas, choroid plexus papillomas and craniopharyngiomas. In this review, we summarize the pathogenesis, diagnosis, management and prognosis of the most frequent fetal brain tumors.

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

Choroid plexus tumors (CPTs) are intraventricular brain tumors predominantly arising in children but also affecting adults. In most cases, driver mutations have not been identified, although there are reports of frequent chromosome-wide copy-number alterations and TP53 mutations, especially in choroid plexus carcinomas (CPCs). DNA methylation profiling and RNA-sequencing was performed in a series of 47 CPTs. Samples comprised 35 choroid plexus papillomas (CPPs), 6 atypical choroid plexus papillomas (aCPPs) and 6 CPCs plus three recurrences thereof. Targeted TP53 and TERT promotor sequencing was performed in all samples. Whole exome sequencing (WES) and linked-read whole genome sequencing (WGS) was performed in 25 and 4 samples, respectively. Tumors comprised the molecular subgroups "pediatric A" (N=11), "pediatric B" (N=12) and "adult" (N=27). Copy-number alterations mainly represented whole-chromosomal alterations with subgroup-specific enrichments (gains of Chr1, 2 and 21q in "pediatric B" and gains of Chr5 and 9 and loss of Chr21q in "adult"). RNA sequencing yielded a novel CCDC47-PRKCA fusion transcript in one adult choroid plexus papilloma patient with aggressive clinical course; an underlying Chr17 inversion was demonstrated by linked-read WGS. WES and targeted sequencing showed TP53 mutations in 7/47 CPTs (15%), five of which were children. 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). 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.

PEDT-02 Clinical usage of NCC Oncopanel/FoundationOne CDx for pediatric/AYA patients with recurrent malignant brain tumors

Backgrounds: Analyses of somatic mutations in malignant brain tumors have been used to make effective treatment strategies. NCC Oncopanel and FoundationOne CDx are custom targeted next-generation sequencing (NGS) panels. The cost for this analysis is 560,000 yen covered by National Health Insurance in Japan since June 2019. These methods can be applied for the solid cancers with no established therapies and relapsed after the standard therapies. Following these inclusion criteria, most malignant brain tumors, especially recurrent malignant brain tumors in pediatric/AYA generations, can be included. Object: To report the results of our initial experiences. Methods: In the last one year, we utilized these NGS panels for five patients with recurrent malignant brain tumors in this generations: 2 epithelioid glioblastomas; 1 anaplastic meningioma; 1 diffuse astrocytoma (gliomatosis cerebri); 1 atypical choroid plexus papilloma. Results: Final recommended treatments are as follows: BRAF/MEK inhibitors, bevacizumab, or anti-PD-1 antibody for one epithelioid glioblastoma; MEK inhibitor for another epithelioid glioblastoma previously treated by BRAF inhibitor and bevacizumab; ERK1/2 inhibitors for anaplastic meningioma. The diffuse astrocytoma had IDHR132H mutation. There was no clinical trial using IDH inhibitor for recurrent diffuse astrocytoma; thus, the final recommendation for this case was rechallenge of temozolomide. To date, only one NGS for a choroid plexus papilloma has been reported (Arch Pathol Lab Med, 2017). Our case had multiple actionable gene alterations, including TERT mutation and amplification of various genes. Unfortunately, there was no druggable gene alteration among them. Conclusions: Insurance-covered cancer gene panel tests could represent effective treatment options for some malignant brain tumors in pediatric/AYA generations. If the relapse is local and can be treated by repeat resections, we think the surgery is the first-line choice. But, in another situation, information from NGS panels should be obtained positively. Efforts to increase the utility of off-label use of drugs are encouraged.

15397 Paraneoplastic dermatomyositis in a patient with an oligodendroglioma

A previously healthy 26-year-old white man presented with nausea, headache, and rash. Physical examination disclosed coalescing, erythematous to violaceous macules and patches on the eyelids, periorbital regions, cheeks, upper chest, shoulders, upper back, and posterior neck, and mild periorbital edema. Review of systems was positive for myalgias. Histopathologic examination of a shoulder lesion demonstrated vacuolar interface dermatitis and a sparse, superficial perivascular dermal lymphocytic infiltrate. Colloidal iron staining demonstrated dermal mucinosis. Based on these findings, the diagnosis of dermatomyositis was made. Labs demonstrated elevated serum creatine kinase (673 U/L); tests for rheumatoid factor, anti-nuclear antibodies, anti-SSA and anti-SSB antibodies, immunoglobulin subclasses, and a myomarker panel were within normal limits. A head MRI demonstrated a cystic mass in the right insula; stereotactic biopsy was consistent with an oligodendroglioma. He received a 60 mg oral dose of prednisone, and topical triamcinolone 0.1% and hydrocortisone 2.5% ointment. Within 10 days the rash completely resolved. He underwent a craniotomy for tumor resection several weeks after initial presentation. At follow-up four months later, he showed no recurrence of myalgias or rash. Ovarian, lung, and gastrointestinal cancers are most commonly associated with dermatomyositis in the Western world. To our knowledge, only 2 previous cases of dermatomyositis associated with an intracranial neoplasm have been reported: in a 39-year-old man following dendritic cell immunotherapy for an oligoastrocytoma and in a seven-year-old girl with a choroid plexus papilloma. Our case adds oligodendroglioma to the list of potential neoplasms to be considered when assessing a patient with dermatomyositis.

Spinal drop of atypical choroid plexus papilloma in an adult patient: A case report and literature review

Background: Choroid plexus papillomas (CPPs) are benign extra-axial tumors that originate from the choroid plexus; these tumors rarely have metastases, being at the spinal level the location with few reported cases.Case Description: We report the case of a 48-year-old man with a history of atypical fourth ventricular CPP and gross total resection (GTR) in 2008. In 2015, he presented with radicular pain, decreased strength, and paresthesia in the left leg. Magnetic resonance imaging revealed a well-defined intradural ovoid lesion in the vertebral canal at the level of the L3-L4 intersomatic space. Subtotal resection of the tumor was performed. The patient recovered well, with relief of pain and no neurological deficit. A literature research few cases of CPP metastasis in adults. We describe here a fifth-decade male patient with a lumbar neoplasm, which according to the histopathologic characteristics and location is the first case of an atypical papilloma implant of the choroid plexus at this spinal level.Conclusion: GTR of primary lesions and associated implants remains the gold standard for surgical treatment of CPP. Radiotherapy, stereotactic radiosurgery, and chemotherapy are adjuvant therapies for CPP but there is no definitive protocol for the management of implants. Proper follow-up of these patients is essential since spinal drop can appear many years after the initial presentation of CPP.