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

Introduction Standards for chemotherapy against choroid plexus tumors (CPT) have not yet been established. Methods CPT-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. Results 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). 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. Conclusions Chemotherapy for Choroid Plexus Carcinoma is feasible and effective. CarbEV is superior to CycEV. A subset of CPC can be cured without irradiation.

Case Report : Li-Fraumeni Syndrome with Central Nervous System Tumors in Two Siblings

Background Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome caused by germline TP53 gene mutations. It is characterized by high risk of early-onset cancer, and has been confirmed as associated with multiple tumors clinically. So pediatricians should be more alert to LFS in children with tumors. Choroid plexus carcinoma (CPC) is a rare, malignant tumor which account for less than 1% of all central nervous system (CNS) tumors. However, when such tumorigenesis occurs, it is important to be vigilant for the presence of LFS. Case presentation The first patient is a 32-month-old boy admitted for convulsions and then was found intracranial space-occupying lesion. Underwent operation, he was diagnosis as choroid plexus carcinoma (WHO Grade III). After 5 months, his elder sister, a 13-year-old girl, was brought to emergency department for confusion and intermittent convulsions. Surgery was performed immediately after head CT examination found the lesion. The pathology result indicated glioblastoma. Because the siblings of the same family have successively suffered from malignant tumors, we performed genetic testing on this family. TP53 gene mutation occurred in both children of these two cases from their father, and their other brother was not spared either. So the two siblings both met the diagnostic criteria of LFS. Then they all received systematic anti-tumor therapy, and follow-up hitherto. Conclusion Here we reported a rare LFS case that two siblings were inherited the same TP53 germline mutations from their father. They suffered from choroid plexus carcinoma and glioblastoma and were finally diagnosed with LFS. In this LFS family, the primary tumors of the two children were both central nervous system tumors, which were not reported in the previous literature. It is suggested that clinicians should be alert to LFS related tumors, which is helpful for early diagnosis. Timely detection of TP53 gene is an important way for early diagnosis of LFS, especially in children with tumor. The incidence of secondary tumor in LFS patients is significantly higher, and other family members of the LFS patient also have an increased risk of suffering from the tumors. Therefore, early diagnosis and timely tumor surveillance can obtain better therapeutic effect and prognosis for both proband and their family.

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 (<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.

Choroid Plexus Carcinoma with Rhabdoid Features: A Case Report

The case of a patient under 2 years of age with acute vomiting, fever and seizures. MR imaging of the brain revealed a right lateral intraventricular mass and mild hydrocephalus. Surgery achieved gross total tumor resection, but tumor histology revealed choroid plexus carcinoma with heavy stratification and atypical “rhabdoid” cells.

Extraventricular Choroid Plexus Carcinoma with Spinal Metastasis: A Case Report

We report a case of extraventricular choroid plexus carcinoma (CPC) accompanied by spinal metastasis in a pediatric patient. A 15-year-old female patient presented with chronic progressive headache and blurry vision. Magnetic resonance imaging (MRI) revealed an intra-axial mass in the left frontal lobe. A gross total resection was performed, and the histopathological examination revealed the diagnosis of CPC, confirmed with immunohistochemical (IHC) analysis of GFAP, S100, EM, P53 and Ki67. Eleven months later, MRI result identified another mass in the left frontal lobe. Spinal MRI showed drop metastasis to the spine, accompanied by leptomeningeal seeding. This case demonstrated the importance of IHC and spinal MRI in the management of CPC. This case report may provide more insight into extraventricular CPC cases, which is important for the adequate management of patients with CPC in the future.

RARE-17. HIGH-THROUGHPUT SCREEN IDENTIFIES POTENTIAL CHEMOTHERAPIES FOR CHOROID PLEXUS CARCINOMA TREATMENT USING INTRAARTERIAL STRATEGY

Choroid plexus carcinoma is a rare infantile brain tumor with an aggressive clinical course.1 There is no optimal treatment and survival is poor. Gross total surgical removal is the single most important predictor of survival.1 Gross total surgical removal rates are inconsistent and associated with significant morbidity owing to the hemorrhagic nature of these tumors compounded by a small circulating blood volume. Neoadjuvant systemic chemotherapy with “second look surgery” helps to achieve gross total surgical removal2 but has an inefficient pharmacokinetic profile and exposes children to dose- limiting toxic side effects. Hence, there is a strong need to identify and develop new agents and strategies to improve current choroid plexus carcinoma (CPC) treatment. Here, we report a high-throughput drug screening using a CPC cancer tissue-originated from a 7-year-old male patient and procured (Children’s Cancer Hospital Egypt) to identify new potent drugs. The selected candidates have been used as single agent and combination agent chemotherapy to propose a relevant study (e.g pharmacokinetics, toxicity, biodistribution, anticancer efficacy) for improving CPC treatment using a pre-existing intraarterial chemotherapy. A genetically engineered model has been developed by Shannon et al by breeding RosamTmG with Nestin-Cre to generate Nestin-cre/Rosa mTmG reporter mice overexpressing c-Myc, which provides a fully penetrant model of CPC in the lateral ventricle CP and 4th ventricle CP.3 This mice model will be used to explore in vivo the newly discovered drug combinations to treat the CPC tumor. 1. Hosmann, A. et al. Management of choroid plexus tumors—an institutional experience. Acta Neurochir. (Wien). 161, 745–754 (2019) 2. Schneider, C. et al. Neoadjuvant chemotherapy reduces blood loss during the resection of pediatric choroid plexus carcinomas *christian. J. Neurosurg. Pediatr. Pediatr. 16, 126–133 (2015) 3. Shannon, M. L. et al. Mice Expressing Myc in Neural Precursors Develop Choroid Plexus and Ciliary Body Tumors. Am. J. Pathol. 188, 1334–1344 (2018)

Choroid plexus carcinoma with leptomeningeal spread in an adult: a case report and review of the literature

Background Choroid plexus carcinoma is an intraventricular neoplasm originating from the choroid plexus epithelium and is of rare occurrence in adults. However, owing to the low prevalence of choroid plexus carcinoma, there is very limited information about the disease entity and treatment. Here we report a rare case of choroid plexus carcinoma in an adult patient. Case presentation A 46-year-old South Korean (East Asian) male presented with low back pain, headache, and diplopia. Magnetic resonance imaging demonstrated enhancing mass lesion in the left trigone, cerebellar with leptomeningeal spread. Surgery was performed via left parietal craniotomy, and the lesion was histologically confirmed to be choroid plexus carcinoma. The patient received adjuvant craniospinal irradiation for remnant mass and leptomeningeal spread. Magnetic resonance imaging performed immediately after completion of the treatment revealed a partial decrease in the size of the tumor. However, the patient expired died as a result of acute respiratory distress syndrome before follow-up of long-term outcome. Conclusion Choroid plexus carcinoma with leptomeningeal spread in adults is very important for rapid diagnosis and treatment. In the case of the presence of leptomeningeal spread, craniospinal irradiation can be considered as a treatment method, but may have serious complications. Hence, the technique should be applied with care.

Preoperative Devascularization of Choroid Plexus Tumors: Specific Issues about Anatomy and Embolization Technique

(1) Background: Surgical treatment of choroid plexus tumors is challenging, burdened by a notable risk of bleeding. Neoadjuvant chemotherapy and preoperative embolization have been attempted, with encouraging results; however, the consensus on these procedures is lacking. (2) Methods: We present a case of a 10-month-old girl who underwent preoperative embolization of a hemorrhagic choroid plexus carcinoma of the lateral ventricle via the anterior choroidal artery, followed by total resection. (3) Results: The endovascular procedure was successfully completed, despite the rectification of the anterior choroidal artery associated with the absence of flow proximal to the plexal point. Minimal bleeding was observed during resection and the patient remained neurologically intact. (4) Conclusions: The time from entrance to exit in the anterior choroidal artery should be monitored and regarded as a potential ‘occlusion time’ in this specific group of patients. Nevertheless, our case supports the feasibility and effectiveness of preoperative embolization of a choroid plexus carcinoma of the lateral ventricle via the anterior choroidal artery, without complications. Furthermore, we suggest the use of a fast-embolic agent, such as N-butyl cyanoacrylate glue, as the preferred agent for this specific pathology and patient population.