Correlation between choroid plexus carcinoma and Li-Fraumeni syndrome: implications of TP53 mutations and management strategies-a case-based narrative review.

BACKGROUND: Choroid plexus carcinomas (CPCs) are rare, aggressive grade 3 tumors of the central nervous system associated with Li-Fraumeni syndrome (LFS) in a notable percentage of cases due to TP53 germline mutations. Understanding the correlation between CPCs and LFS is crucial for tailored management strategies. However, distinguishing CPCs from benign choroid plexus papillomas (CPPs) remains challenging, relying largely on histologic features. This study aimed to explore the association between CPCs and LFS, emphasizing the impact of TP53 mutations on diagnosis, treatment, and clinical outcomes. MATERIALS AND METHODS: Scientific databases such as PubMed, Scopus, and Web of Science were systematically searched up to January 2024 using keywords related to CPCs, LFS, TP53 mutation, and central nervous system tumors. Selection criteria included studies investigating the link between CPCs and LFS, their management approaches, and genetic implications of TP53 mutations. Ten relevant studies were selected for analysis after screening titles, abstracts, and full-text articles. Data extraction focused on clinical, genetic, and management factors related to CPCs associated with LFS. RESULTS: The review highlighted the strong association (36%) between CPCs and LFS, primarily due to TP53 germline mutations. Studies emphasized the need for genetic testing in patients with CPCs, especially in pediatric cases, to identify LFS implications. Furthermore, the impact of TP53 mutations on treatment strategies was emphasized, recommending irradiation-sparing therapies due to inferior survival rates associated with radiotherapy in LFS patients with CPCs. Cases illustrated the challenges in diagnosing CPCs and the importance of immunohistochemistry and genetic testing for TP53 mutations. CONCLUSION: CPCs pose challenges in diagnosis and management, particularly in distinguishing them from benign tumors. The association with LFS, often due to TP53 germline mutations, underscores the importance of genetic testing for early detection and tailored treatment strategies. Irradiation-sparing therapies are recommended for LFS-associated CPCs to mitigate the risk of secondary malignancies. Comprehensive profiling of CPC patients, especially in pediatric cases, is crucial for early detection and management of potential secondary cancers associated with LFS.

Paediatric choroid plexus carcinoma: a retrospective case series from Karachi.

The objective of this study is to report clinical, radiological, and histopathological characteristics of three paediatric patients diagnosed as Choroid plexus carcinoma seen at our hospital, between 2015 and 2020. Three patients were diagnosed with choroid plexus carcinomas between 2015 and 2018. The mean age at diagnosis was 1.3 years (range 8 months to 1.5 years). All the three patients had subtotal resection and received adjuvant chemotherapy. One patient also received adjuvant radiotherapy. Despite these treatment measures, residual disease was noted in all three patients and two patients were subsequently treated on palliative care grounds. The average duration of follow-up after the first surgery for all three patients was approximately 33 months. Attaining satisfactory outcome in patients with CPC is challenging. Our case series reflects the difficulty in achieving gross total resection and ensuring that the disease does not recur.

Tumors of Choroid Plexus and Other Ventricular Tumors.

Tumors arising inside the ventricular system are rare but represent a difficult diagnostic and therapeutic challenge. They usually are diagnosed when reaching a big volume and tend to affect young children. There is a wide broad of differential diagnoses with significant variability in anatomical aspects and tumor type. Differential diagnosis in tumor type includes choroid plexus tumors (papillomas and carcinomas), ependymomas, subependymomas, subependymal giant cell astrocytomas (SEGAs), central neurocytomas, meningiomas, and metastases. Choroid plexus tumors, ependymomas of the posterior fossa, and SEGAs are more likely to appear in childhood, whereas subependymomas, central neurocytomas, intraventricular meningiomas, and metastases are more frequent in adults. This chapter is predominantly focused on choroid plexus tumors and radiological and histological differential diagnosis. Treatment is discussed in the light of the modern acquisition in genetics and epigenetics of brain tumors.

Case Report: Reversible Hyperglycemia Following Rapamycin Treatment for Atypical Choroid Plexus Papilloma in an Infant.

In this study, atypical choroid plexus papilloma was treated with high-dose rapamycin for 17 days preoperatively in an infant. Rapamycin significantly reduced the blood supply to the tumor while reducing the tumor volume, and most of the tumor was resected successfully. However, the infant developed hyperglycemia related to the rapamycin dose, which was effectively controlled by adjusting the dose and applying insulin.

Paediatric atypical choroid plexus papilloma: is adjuvant therapy necessary?

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Molecular insights into malignant progression of atypical choroid plexus papilloma.

Choroid plexus tumors are rare pediatric neoplasms ranging from low-grade papillomas to overtly malignant carcinomas. They are commonly associated with Li-Fraumeni syndrome and germline TP53 mutations. Choroid plexus carcinomas associated with Li-Fraumeni syndrome are less responsive to chemotherapy, and there is a need to avoid radiation therapy leading to poorer outcomes and survival. Malignant progression from choroid plexus papillomas to carcinomas is exceedingly rare with only a handful of cases reported, and the molecular mechanisms of this progression remain elusive. We report a case of malignant transformation of choroid plexus papilloma to carcinoma in a 7-yr-old male with a germline TP53 mutation in which we present an analysis of molecular changes that might have led to the progression based on the next-generation genetic sequencing of both the original choroid plexus papilloma and the subsequent choroid plexus carcinoma. Chromosomal aneuploidy was significant in both lesions with mostly gains present in the papilloma and additional significant losses in the carcinoma. The chromosomal loss that occurred, in particular loss of Chromosome 13, resulted in the losses of two critical tumor suppressor genes, RB1 and BRCA2, which might play a possible role in the observed malignant transformation.

Intraventricular choroid plexus tumors: clinical characteristics and impact of current management on survival.

INTRODUCTION: Choroid plexus tumors (CPTs) represent one of the most common intraventricular tumors. Although most are benign, they often reach considerable sizes before clinical manifestation, challenging their surgical management. We aim to describe the clinical characteristics and the impact of current management on the survival of patients harboring intraventricular CPT. METHODS: The National Cancer Database (NCDB) was queried to identify biopsy-proven intraventricular CPT patients (2004-2015). Demographic and patterns of care were described, the log-rank method was used to independently analyze survival according to age, WHO grade and extent of resection (EOR). Multivariate analysis was performed to investigate the impact of prognostic factors on overall survival (OS). RESULTS: A total of 439 CPT patients with known WHO grade were included. WHO grade I tumors were more frequent in adults, while WHO grade III tumors were more common in pediatric population. Most CPTs were benign, with a median tumor size of 3-4 cm. Mean tumor size in pediatric population was greater than in adult population (4.39 cm vs. 2.7 cm; p < 0.01). Frequency was similar between males and females (51.7% vs. 48.3%; p > 0.0.5). Five- and ten-year OS among all patients was 87% and 84%, respectively. EOR was not associated with survival for any WHO grade. On multivariable analysis, only patient age (p = 0.022), WHO grade (p = 0.003) and medical comorbidity scores (p = 0.002) were independently associated with OS after diagnosis. CONCLUSION: Patients with CPTs present at different stages of life, with sizable tumor burden and distinct WHO grade prevalence. Considering their favorable survival, efforts to improve tumor control should be meticulously weighed against the long-term risk associated with surgery, radiation, and chemotherapy.

Late recurrence of choroid plexus carcinoma.

BACKGROUND: Choroid plexus carcinomas (CPC) are rare malignant brain tumours arising from the choroid plexus epithelium. CPC are most common in the paediatric population, particularly those under 2 years of age. Common presentations include headache, diplopia and signs of increased intracranial pressure such as nausea and vomiting. Infants may present with increased head circumference, bulging fontanelles, splayed cranial sutures and/or neurological delay. Diagnosis is made via radiological and histological analysis. MANAGEMENT AND PROGNOSIS: Gross total resection (GTR) is the preferred treatment and infers the best survival rate, but despite this, prognosis remains poor. The utility of chemotherapy and/or radiation in CPC management remains controversial, and an optimal treatment regimen has not been identified. Even with GTR, recurrence is common and usually occurs within months after resection. Delayed recurrence is exquisitely rare and has been reported very few times to date. CASE PRESENTATION: Here, we present a rare case of delayed CPC recurrence 10 years after initial presentation. A 2-month-old male was diagnosed with CPC and received GTR, chemotherapy and stem cell transplant. The patient presented with a recurrent CPC 10 years after the initial diagnosis. CONCLUSIONS: This case demonstrates the importance of long-term surveillance and raises questions regarding the natural history, recurrence patterns and factors contributing to long-term relapse in CPC. Further research should be targeted at identifying patient factors contributing to increased risk of late recurrence and whether adjuvant treatments play any role in decreasing this.

Epigenetics impacts upon prognosis and clinical management of choroid plexus tumors.

PURPOSE: Choroid plexus tumors comprise of choroid plexus papilloma (CPP, WHO grade I), atypical choroid plexus papilloma (aCPP, WHO grade II) and choroid plexus carcinoma (CPC, WHO grade III). Molecular events driving the majority of choroid plexus tumors remain poorly understood. Recently, DNA methylation profiling has revealed different epigenetic subgroups. METHODS: Comprehensive review of epigenetic profiles of choroid plexus tumors in the context of histopathological, genetic, and clinical features. DNA methylation profiling segregates choroid plexus tumors into three distinct epigenetic subgroups: supratentorial pediatric low-risk choroid plexus tumors (CPP and aCPP), infratentorial adult low-risk choroid plexus tumors (CPP and aCPP), and supratentorial pediatric high-risk choroid plexus tumors (CPP and aCPP and CPC). Epigenetic subgrouping provides additional prognostic information in comparison to histopathological grading. CONCLUSIONS: Epigenetic profiling of choroid plexus tumors can be used for the identification of patients at risk of recurrence and is expected to play a role for treatment stratification and patient management in the context of future clinical trials.

Clinical Outcomes in Patients with Renal Cell Carcinoma Metastases to the Choroid Plexus.

OBJECTIVE: Intraventricular metastatic brain tumors account for a small, but challenging, fraction of metastatic brain tumors (0.9%-4.5%). Metastases from renal cell carcinoma (RCC) account for a large portion of these intraventricular tumors. Although patient outcomes have been assumed to be poor, these have not been reported in a modern series with a multimodality treatment paradigm of radiotherapy (RT), resection, and cerebrospinal fluid (CSF) diversion. We have presented the first case series of patients with intraventricular metastatic tumors from RCC. METHODS: We performed a single-institution retrospective review of patients with intraventricular RCC metastases treated from January 2003 to January 2019. Volumetric analysis was used to delineate the tumor size and the Kaplan-Meier method to evaluate the survival data. RESULTS: A total of 22 intraventricular RCC metastases were identified in 19 patients with 61.3 patient-years of follow-up. The median patient age was 64 years, and the median tumor volume was 2.2 cm3. Overall, 19 metastases had been treated initially with RT. Of these, 16 had received stereotactic body RT and 3 had received whole brain RT. Three tumors were surgically excised and had received adjuvant stereotactic body RT in the upfront setting. Although 5 patients had presented with obstructive hydrocephalus, none had required CSF diversion. After treatment, 5 metastases had progressed, resulting in 1- and 3-year progression-free survival rates of 81.6% and 68%, respectively. The median overall survival was 2.8 years, with 1- and 5-year overall survival rates of 76.7% and 28.3%, respectively. Leptomeningeal carcinomatosis was not observed. CONCLUSIONS: Despite the relatively limited overall survival for this population with metastatic cancer, comparable to contemporary parenchymal brain metastasis cohorts, reasonable local central nervous system control was achieved in most patients using a paradigm of focal RT and resection, where indicated. Finally, CSF diversion was not required even in patients presenting with hydrocephalus.

Solitary Metastasis of Adenocarcinoma of Submandibular Gland to Choroid Plexus in Cerebellopontine Angle: First Case Reported in Literature.

BACKGROUND: Adenocarcinoma of the salivary gland (AdCASG) is a rare and malignant tumor of the salivary glands. Albeit, metastatic lesions occur anecdotally in the choroid plexus and most rarely in the cerebellopontine angle (CPA). We report the first case of metastatic AdCASG to the choroid plexus of the lateral recess of the fourth ventricle located in CPA, emphasizing the clinical presentation and neuroradiologic findings. CASE DESCRIPTION: A 40-year-old man was referred with signs of increased intracranial pressure and a unilateral hearing problem. Magnetic resonance imaging showed a pear-shaped, vividly enhancing tumor in the left CPA. The tumor was a metastatic AdCASG. Gross total resection of the lesion was followed by a conventional radiotherapy lead in a 5-year tumor-free control interval. CONCLUSIONS: Metastatic lesions to the choroid plexus may show a pedunculated shape in magnetic resonance imaging. It is hypothesized that tumor seeding may occur through the veins, lymphatics, and nerve sheaths in the skull base region. Tissue specimen is necessary to confirm such rare pathology.

Secondary Diffuse Choroid Plexus B-Cell Lymphoma: Case Report and Review of Literature.

BACKGROUND: Central nervous system (CNS) relapse is an uncommon complication of diffuse large B cell lymphoma and is associated with significant mortality and morbidity. It is becoming a more prevalent pathologic entity in the rituximab era. Our case provides insight into the pathophysiology, diagnosis, prevention, and management of secondary intraventricular CNS lymphomas. CASE DESCRIPTION: We report an unusual case of a 64-year-old man who presented with an isolated secondary CNS lymphoma involving the choroid plexus in a diffuse pattern. He initially presented with obstructive hydrocephalus from diffuse choroid plexus lesions and was commenced on systemic therapy after confirmation of diagnosis via samples obtained from an open biopsy. CONCLUSIONS: This case highlights the lack of high-quality evidence behind the use of high-dose intravenous methotrexate as CNS prophylaxis. The case provides additional insight into the pathophysiology of intraventricular CNS lymphomas and the importance of establishing a histopathologic diagnosis via an open biopsy before the administration of high-dose steroids.

Successful Treatment of Recurrent Li-Fraumeni Syndrome-related Choroid Plexus Carcinoma.

The management of choroid plexus carcinoma (CPC) is challenging and multifaceted. Here, we discuss a 3-year-old girl with CPC and Li-Fraumeni syndrome who achieved full remission after surgery and chemotherapy, with radiation therapy spared. At recurrence, we used a novel, standard-dose cytotoxic chemotherapy regimen, focal proton radiation therapy, and targeted agents based on morphoproteomic analysis to achieve long-term survival. We highlight the rationale for our therapy at recurrence, as well as the risk-benefit analyses necessary in decision making for these patients. Our strategy may be effective in managing other patients with recurrent CPC and Li-Fraumeni syndrome.

A French retrospective study on clinical outcome in 102 choroid plexus tumors in children.

The aim of this study was to review and describe therapeutic approaches in children with choroid plexus tumor (CPT) based on a nationwide series. The World Health Organization classification subdivides these rare tumors into three histological subtypes corresponding to three grades of malignancy: low grade (grade I) choroid plexus papilloma (CPP), intermediate grade (grade II) atypical choroid plexus papilloma (aCPP) and high grade (grade III) choroid plexus carcinoma (CPC). This retrospective study included 102 French children younger than 18 years, treated from 2000 to 2012: 54 CPP, 26 aCPP and 22 CPC. The 5 year overall survival was 100% in CPP, 96.2% in aCPP and 64.7% in CPC. In patients with localized disease, complete surgical resection was achieved in 48/52 CPP, 20/26 aCPP and 7/14 CPC. In this group, patients with complete surgical resection had better event free survival than patients with partial resection (88.9 vs. 41.6%). 28 patients (1 CPP, 6 aCPP and 22 CPC) had adjuvant chemotherapy. 2 aCPP and 9 CPC had radiotherapy. We underlined the need for a central histological review to accurately analyze clinical data; we reported a much higher overall survival for CPC than in most previous CPT series probably including atypical teratoid rhabdoid tumors. In our series, the 5 years overall survival in CPC (64.7%) was higher than event free survival (25.2%) and could be interpreted as a clue for the efficiency of adjuvant/salvage therapy even if the heterogeneity of applied treatments in this retrospective series does not allow for meaningful statistical comparisons.

Choroid plexus tumors in adult and pediatric populations: the Cleveland Clinic and University Hospitals experience.

Choroid plexus tumors (CPT) are rare neoplasms accounting for 1-4% of all pediatric brain tumors. They are divided into choroid plexus papilloma (CPP), atypical choroid plexus papilloma (APP) and choroid plexus carcinoma (CPC). CPTs are known to primarily affect children less than 2 years of age. Gross total resection is the most important predictor of survival especially in CPC. Although small case series have been published, limited clinical data are available to describe treatment and outcome of CPTs. More clinical data would be necessary to complete the picture, particularly in populations that are not age limited. Here we share data from the two major hospitals in Cleveland to describe treatment and outcome of adult and pediatric patients. We performed a retrospective analysis of patients with CPT seen in Cleveland Clinic from 1990 to 2015 and at University Hospitals from 1994 to 2015. Results were compared to previously published historical controls. We identified 30 cases with CPT, including 22 pediatric and eight adult cases; 11 females and 19 males. The mean age at presentation was 12.4 years with a median age of 4.5 years (range 2 months-51 years). Gross total surgical resection was achieved in 22, subtotal resection in four, partial resection in two and unknown in two. The histology was CPP in 23 patients, two of whom developed recurrence requiring repeat resection and adjuvant therapy. Median event free survival (EFS) for CPP patients was 7.6 years. The histology was CPC in seven patients. All CPC patients were treated with adjuvant therapy. Median EFS of CPC patients was 4.4 years. Overall survival of all CPT patients was 100% with a median follow up of 7 years. A systematic literature review identified 1012 CPT patients treated from 1989 to 2013. The mean and median age of CPT patients was 13 and 3 years respectively. The median survival of 541 CPP patients was undefined vs. 2.7 years for the 452 CPC patients. The difference between the two populations was highly significant (p < 0.001). Kaplan-Meier survival curves comparing CPTs at Cleveland Clinic and University Hospitals versus a systematic literature review showed a statistically significant advancement in overall survival among the patients treated at Cleveland Clinic and University Hospitals. Our data are consistent with the literature review regarding epidemiology, clinical presentation, and treatment modalities but differed in regards to survival. Differences in survival may be related to different methods of data collection or details in patient care.

[Choroid plexus tumours in childhood: Experience in Sant Joan de Déu hospital]. / Tumores de plexo coroideo en la infancia: experiencia en el hospital Sant Joan de Déu.

Choroid plexus tumours are rare, with a peak incidence in the first two years of life. The most common location is the lateral ventricle in children, while in adults it is the fourth ventricle. The most common clinical manifestation is the signs and symptoms of intracranial hypertension. They are histologically classified as plexus papilloma, atypical plexus papilloma, and plexus carcinoma. A review is presented on choroid plexus tumours treated in the Hospital Sant Joan de Déu between 1980 and 2014. A total of 18 patients have been treated. An analysis was made of the demographic, clinical, histological data, treatment, and recurrences. The treatment of choice is complete resection, accompanied by adjuvant therapy in carcinomas. In atypical papillomas, the use of adjuvant therapies is controversial, reserving radiation therapy for recurrences. Papillomas have a good outcome, whereas atypical papillomas and carcinomas outcome is poor.

[Choroid plexus tumour treatment at Hospital Infantil Niño Jesús in Madrid: Our experience over the last three decades]. / Tratamiento de los tumores de plexos coroideos en el Hospital Infantil Niño Jesús de Madrid: nuestra experiencia en las últimas tres décadas.

OBJECTIVE: To review childhood patients with choroid plexus tumors (CPT) who underwent surgery at Hospital Infantil Niño Jesús of Madrid since January 1981 to September 2014. MATERIAL AND METHODS: Registered charts were analyzed based on the epidemiology, tumor grade, clinical profile, location, dissemination characteristics, therapy, prognosis and complications. RESULTS: Seventeen childhood patients were recorded with CPT. Cases were distributed so that 9 cases were choroid plexus-papilloma (CPP) (52.9%), 2 cases atypical CPP (11.7%) and 6 cases choroid plexus-carcinoma (CPC) (35.2%). Age at diagnosis was less than 2 years in 14 of the 17 patients (82.3%) and the incidence was higher in males (82.3% of the cases). Gross total resection was performed in 16 patients (94.1%). Adjuvant treatment was used in 6 patients (all this cases with CPC) (35.2%). Two of the 17 patients died (11.7%), showing an incidence density of 0.01 deaths/year. CONCLUSIONS: Our case series is consistent with previous published in scientific literature regarding epidemiology, tumor grade, clinical presentation, radiological features and therapeutic approach. Gross total resection is considered the therapeutic gold standard for choroid plexus tumors. Chemotherapy and radiotherapy should be used as adjuvant treatment in CPC and recurrent or remaining atypical CPP.

Choroid plexus carcinoma in children: the Head Start experience.

BACKGROUND: Choroid plexus carcinoma (CPC) is a rare aggressive intracranial neoplasm with a predilection for young children and a historically poor outcome. Currently, no defined optimal therapeutic strategy exists. The Head Start (HS) regimens have included irradiation-avoiding strategies in young children with malignant brain tumors using high dose chemotherapy to improve survival and minimize neurocognitive sequelae. PROCEDURE: Three sequential HS studies have been conducted from 1991 to 2009. HS treatment strategy has consisted of maximal surgical resection followed by five cycles of intensive induction followed by consolidation myeloablative chemotherapy with autologous hematopoietic stem cell rescue (AuHCR). Irradiation was given following recovery from consolidation based on the patient's age and evidence of residual disease. RESULTS: Twelve children with CPC (median age of 19.5 months) have been treated with HS regimens. Ten patients had >95% resection. Three patients had disseminated disease at diagnosis. Ten patients completed consolidation of whom five are alive, irradiation and disease free at 29, 43, 61, 66 and 89 months from diagnosis. Seven patients experienced tumor recurrence/progression at a median time of 13 months (range 2-43 months). Five patients received irradiation, one for residual disease and four upon progression or recurrence, of whom one is alive at 61 months. The 3- and 5-year progression-free survivals are 58% and 38% and overall survivals 83% and 62% respectively. Late deaths from disease beyond 5 years were also noted. CONCLUSION: Head Start strategies may produce long-term remission in young children with newly diagnosed CPC with avoidance of cranial irradiation.