Choroid plexus carcinoma in an adolescent male: a case report.

INTRODUCTION/BACKGROUND: Although central nervous system tumors are the most common etiology of malignancies in the pediatric age group, choroid plexus carcinomas are rare, with an annual incidence rate of 0.10 per 100,000 children. CASE PRESENTATION: We report the case of an adolescent male belonging to central India who had presented with a history of persistent headache, projectile vomiting, neck stiffness, and an episode of generalized tonic-clonic seizure. Neurological examination was suggestive of a space-occupying lesion. Further neuroimaging was suggestive of a large left-sided choroid plexus carcinoma, later confirmed on pathological examination. Gross total resection was achieved and followed by radiation therapy. His recovery was satisfactory without any major events despite suffering from such a malignancy with a poor prognosis. CONCLUSION: In the absence of a global consensus on choroid plexus carcinoma management, our patient underwent a successful gross total resection and received postoperative radiotherapy. He made a satisfactory recovery with a further plan to review with gadolinium-enhanced neuroimaging at a later date. We conclude that, when possible, achieving gross total resection is of utmost importance.

Stereotactic Radiosurgery for Choroid Plexus Tumors: A Report of the International Radiosurgery Research Foundation.

BACKGROUND: Choroid plexus tumors (CPT) are rare epithelial tumors of the choroid plexus. Gross total resection (GTR) may be curative, but it is not always possible. OBJECTIVE: To evaluate the role of Gamma Knife stereotactic radiosurgery (GKSRS) as either a primary or adjuvant management option for WHO grade I-III CPT through a multicenter project. METHODS: A total of 32 patients (20 females) with a total of 43 treated tumors were included in the analysis. A total of 25 patients (78%) had undergone initial surgical resection. The median total tumor volume was 2.2 cc, and the median margin and maximum doses were 13 and 25.5 Gy, respectively. RESULTS: Local tumor control was achieved in 69% of cases. Local tumor progression-free survival (PFS) rate for low-grade tumors at 1, 3, and 5 yr was 90%, 77%, 58%, respectively. The actuarial local tumor PFS rate for high-grade tumors at 1, 3, and 5 yr was 77%, 62%, and 62%, respectively. There was no significant difference in local tumor control rates between low- and high-grade CPT (P = .3). Gender, age, and degree of resection were not associated with treated tumor PFS. Distant intracranial spread developed in 6 patients at a median of 22 mo after initial SRS. Actuarial distant brain tumor PFS rate at 1, 2, 5, and 10 yr was 93%, 88%, 78%, and 65%, respectively. Three patients (9%) developed persistent symptomatic adverse radiation effects at a median of 11 mo after the procedure. CONCLUSION: GKSRS represents a minimally invasive alternative management strategy for imaging defined or surgically recurrent low- and high-grade CPT.

Radiation therapy for choroid plexus carcinoma patients with Li-Fraumeni syndrome: advantageous or detrimental?

BACKGROUND: Choroid plexus carcinomas (CPCs) are rare pediatric tumors often associated with Li-Fraumeni Syndrome (LFS), a germline mutation in the TP53 tumor-suppressor gene, predisposing to cancer. MATERIALS AND METHODS: We performed a systemic literature review from 1990-2013 to evaluate the hypothesis that radiation therapy should be avoided in patients with CPC and LFS. Overall survival (OS) was compared using Kaplan-Meier curves and log-rank tests. RESULTS: Twenty-eight patients were documented with CPC and LFS. Eleven out of 17 patients received radiation therapy. The survival of patients receiving radiation was inferior to that of those without radiation [median (±95% confidence interval) 2-year OS=0.18 ± 0.12% versus 0.58 ± 0.12%]. The log-rank tests suggested the difference to be marginally significant (p=0.056). CONCLUSION: This finding provides evidence for pursuing treatment approaches that do not include radiation therapy for patients with LFS.

Metastasis to the choroid plexus from thyroid cancer: case report.

Thyroid cancer is not a common primary cancer causing intracranial metastasis. Here we report a 74-year-old woman with magnetic resonance imaging (MRI) demonstrating a 4 cm round, heterogeneously enhancing mass in the trigone of the right lateral ventricle. Systemic screening by computed tomography (CT) examination detected a 20 mm nodule with calcification in the thyroid, multiple well circumscribed nodules in bilateral lung filed, and a bone metastasis to the right dorsal rib. Cerebral angiography demonstrated a hypervascular mass fed from anterior and posterior choroidal arteries. Tumor biopsy via parietal transcortical approach confirmed a thyroid carcinoma metastasis to the choroid plexus. Of the 33 reported cases of choroid plexus metastasis, 14 (42%) are from kidney and 3 (9%) from thyroid cancer, which appears to be overrepresented considering their prevalence among all brain metastasis. There may be seed-and-soil relationship between thyroid cancer and choroid plexus.

Infant brain tumors: incidence, survival, and the role of radiation based on Surveillance, Epidemiology, and End Results (SEER) Data.

PURPOSE: To evaluate the incidence of infant brain tumors and survival outcomes by disease and treatment variables. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results (SEER) Program November 2008 submission database provided age-adjusted incidence rates and individual case information for primary brain tumors diagnosed between 1973 and 2006 in infants less than 12 months of age. RESULTS: Between 1973 and 1986, the incidence of infant brain tumors increased from 16 to 40 cases per million (CPM), and from 1986 to 2006, the annual incidence rate averaged 35 CPM. Leading histologies by annual incidence in CPM were gliomas (13.8), medulloblastoma and primitive neuroectodermal tumors (6.6), and ependymomas (3.6). The annual incidence was higher in whites than in blacks (35.0 vs. 21.3 CPM). Infants with low-grade gliomas had the highest observed survival, and those with atypical teratoid rhabdoid tumors (ATRTs) or primary rhabdoid tumors of the brain had the lowest. Between 1979 and 1993, the annual rate of cases treated with radiation within the first 4 months from diagnosis declined from 20.5 CPM to <2 CPM. For infants with medulloblastoma, desmoplastic histology and treatment with both surgery and upfront radiation were associated with improved survival, but on multivariate regression, only combined surgery and radiation remained associated with improved survival, with a hazard ratio for death of 0.17 compared with surgery alone (p = 0.005). For ATRTs, those treated with surgery and upfront radiation had a 12-month survival of 100% compared with 24.4% for those treated with surgery alone (p = 0.016). For ependymomas survival was higher in patients treated in more recent decades (p = 0.001). CONCLUSION: The incidence of infant brain tumors has been stable since 1986. Survival outcomes varied markedly by histology. For infants with medulloblastoma and ATRTs, improved survival was observed in patients treated with both surgery and early radiation compared with those treated with surgery alone.

MGMT promoter methylation and temozolomide response in choroid plexus carcinoma.

Choroid plexus carcinoma (CPC) is a malignant tumor with a strong tendency to spread along the cerebrospinal fluid pathway. There is no standardized chemotherapy protocol for this rare tumor. We report a 38-year-old man with CPC in the lateral ventricle with obstructive hydrocephalus. Because of the poor demarcation between thalamus and fornix, subtotal tumor resection was performed. Postoperative spine magnetic resonance (MR) image revealed whole spinal axis dissemination. After diagnosis of CPC, the patient was treated with whole ventricular and spine radiation concomitant with temozolomide chemotherapy, although the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter was found to be unmethylated. Although MR images revealed transient stable disease during adjuvant therapy, tumor progression was depicted after four cycles of temozolomide therapy. We discuss the ineffectiveness of adjuvant temozolomide therapy for CPC in connection with O(6)-methylguanine-DNA methyltransferase promoter methylation.

The impact of radiotherapy fields in the treatment of patients with choroid plexus carcinoma.

PURPOSE: To perform a comprehensive literature review and analysis of cases dealing with choroid plexus carcinoma (CPC) to determine the optimal radiotherapy (RT) treatment field. METHODS AND MATERIALS: A PubMed search of English language articles from 1979 to 2008 was performed, yielding 33 articles with 56 patients who had available data regarding RT treatment field. The median age at diagnosis was 2.7 years (range, 1 month-53 years). Of 54 patients with data regarding type of surgery, 21 (38.9%) had complete resection. Chemotherapy was delivered to 27 (48%) as part of initial therapy. The RT treatment volume was the craniospinal axis in 38 (68%), whole brain in 9 (16%), and tumor/tumor bed in 9 (16%). Median follow-up for surviving patients was 40 months. RESULTS: The 5-year overall survival and progression-free survival (PFS) rates were 59.5% and 37.2%, respectively. Complete resection (p = 0.035) and use of craniospinal irradiation (CSI; p = 0.025) were found to positively affect PFS. The 5-year PFS for patients who had CSI vs. whole brain and tumor/tumor bed RT were 44.2% and 15.3%. For the 19 patients who relapsed, 9 (47%) had a recurrence in the RT field, 6 (32%) had a recurrence outside the RT field, and 4 (21%) had a recurrence inside and outside the irradiated field. CONCLUSION: Patients with CPC who received CSI had better PFS compared with those receiving less than CSI. This study supports the use of CSI in the multimodality management of patients with CPC.

Primary postoperative chemotherapy without radiotherapy for treatment of brain tumours other than ependymoma in children under 3 years: results of the first UKCCSG/SIOP CNS 9204 trial.

BACKGROUND: Radiotherapy is an effective adjuvant treatment for brain tumours arising in very young children, but it has the potential to damage the child's developing nervous system at a crucial time - with a resultant reduction in IQ leading to cognitive impairment, associated endocrinopathy and risk of second malignancy. We aimed to assess the role of a primary chemotherapy strategy in avoiding or delaying radiotherapy in children younger than 3 years with malignant brain tumours other than ependymoma, the results of which have already been published. METHODS: Ninety-seven children were enrolled between March 1993 and July 2003 and, following diagnostic review, comprised: medulloblastoma (n=31), astrocytoma (26), choroid plexus carcinoma [CPC] (15), CNS PNET (11), atypical teratoid/rhabdoid tumours [AT/RT] (6) and ineligible (6). Following maximal surgical resection, chemotherapy was delivered every 14 d for 1 year or until disease progression. Radiotherapy was withheld in the absence of progression. FINDINGS: Over all diagnostic groups the cumulative progression rate was 80.9% at 5 years while the corresponding need-for-radiotherapy rate for progression was 54.6%, but both rates varied by tumour type. There was no clear relationship between chemotherapy dose intensity and outcome. Patients with medulloblastoma presented as a high-risk group, 83.9% having residual disease and/or metastases at diagnosis. For these patients, outcome was related to histology. The 5-year OS for desmoplastic/nodular medulloblastoma was 52.9% (95% confidence interval (CI): 27.6-73.0) and for classic medulloblastoma 33.3% (CI: 4.6-67.6); the 5-year EFS were 35.3% (CI: 14.5-57.0) and 33.3% (CI: 4.6-67.6), respectively. All children with large cell or anaplastic variants of medulloblastoma died within 2 years of diagnosis. The 5-year EFS for non-brainstem high-grade gliomas [HGGs] was 13.0% (CI: 2.2-33.4) and the OS was 30.9% (CI: 11.5-52.8). For CPC the 5-year OS was 26.67% (CI: 8.3-49.6) without RT. This treatment strategy was less effective for AT/RT with 3-year OS of 16.7% (CI: 0.8-51.7) and CNS PNET with 1-year OS of 9.1% (CI: 0.5-33.3). INTERPRETATION: The outcome for very young children with brain tumours is dictated by degree of surgical resection and histological tumour type and underlying biology as an indicator of treatment sensitivity. Overall, the median age at radiotherapy was 3 years and radiotherapy was avoided in 45% of patients. Desmoplastic/nodular sub-type of medulloblastoma has a better prognosis than classic histology, despite traditional adverse clinical features of metastatic disease and incomplete surgical resection. A subgroup with HGG and CPC are long-term survivors without RT. This study highlights the differing therapeutic challenges presented by the malignant brain tumours of early childhood, the importance of surgical approaches and the need to explore individualised brain sparing approaches to the range of malignant brain tumours that present in early childhood.

De novo germline TP53 mutation presenting with synchronous malignancies of the central nervous system.

We present a case of a 14-year-old male with a germline TP53 mutation who presented with synchronous primitive neuroectodermal tumor and choroid plexus carcinoma. Identification of synchronous brain tumors prompted genetic testing for predisposition to malignancy. Within 5 months of presentation, the child developed widely metastatic alveolar rhabdomyosarcoma. Patient DNA sequencing showed a TP53 allele with a premature stop codon in the oligomerization/nuclear export signal (NES) domain (R342ter). The child's parents, younger brother, paternal grandparents, and maternal grandmother, are without history of malignancy. The patient's brother tested negative for TP53 mutations. This case identifies a rare, de novo, germline TP53 mutation presenting with synchronous CNS malignancies and exhibiting a more fulminant course than typical cases of Li-Fraumeni syndrome.

Chemotherapy improves the survival of patients with choroid plexus carcinoma: a meta-analysis of individual cases with choroid plexus tumors.

BACKGROUND: Choroid plexus carcinomas (CPC) are rare brain tumors with a dismal prognosis. Although the role of surgery has been well established, the question of whether chemotherapy improves the prognosis is still under discussion. METHODS: We created a database of all cases of choroid plexus tumors (CPT) reported in the literature up to the year 2004 to determine prognostic factors and different therapeutic modalities. This database was validated by comparison with an existing database of cases until 1997. RESULTS: Of 857 documented cases of CPT (median patient age at diagnosis, 3 years), 347 were CPC, 15 atypical choroid plexus papilloma (APP), and 495 choroid plexus papilloma (CPP). Histology was a significant prognostic factor (P < .0001; log rank). Within the subgroup of patients with CPC, both surgery and irradiation were linked to a better prognosis (P < .005). The 104 CPC patients who received chemotherapy had a statistically better survival than those without chemotherapy (P = .0004). When subgroups were defined by radiation treatment, chemotherapy remained beneficial in the subgroup of nonirradiated tumors (P = .0001). The benefit of chemotherapy was also significant when the analysis was restricted to the subgroup of patients with less than completely resected CPC (2-year overall survival (OS) 54.8 +/- 7% (standard deviation (SD) vs. 24.4 +/- 7%, P < .0001) and when this subgroup was further divided into smaller subgroups. Likewise, in a multivariate analysis, chemotherapy was highly significantly linked to better prognosis (P = .0001). CONCLUSION: Patients with less than completely resected CPC should receive chemotherapy.

Choroid plexus carcinoma secreting carbohydrate antigen 19-9 in an adult. Case report.

A 53-year-old man presented with a choroid plexus carcinoma in the body of the right lateral ventricle manifesting as gait disturbance due to left mild hemiparesis and papilledema. Subtotal removal of the tumor was performed. Histological examination revealed well-differentiated papillary adenocarcinoma. Immunohistochemical examination showed intense reactivity for carbohydrate antigen 19-9 (CA19-9). The serum level of CA19-9 was significantly high, but decreased rapidly after radiation therapy. Systemic examinations found no malignancy in other organs. This second case of choroid plexus carcinoma producing CA19-9 indicates that CA19-9 may be a useful marker of choroid plexus carcinoma.

[Choroid plexus tumors: report of 7 cases in a single institution].

The management of seven patients with choroid plexus tumors, 4 adults and 3 children (mean age 17.5 years) at our institution was reviewed. There were 4 cases of papilloma and 3 of carcinoma located in the lateral ventricle in 1 case, the third ventricle in 1 case, and the fourth ventricle in 5 cases. Total surgical excision was attempted in all patients. Total resection was achieved in three patients, resulting in no deficit in two and persistence of preoperative dysphagia in one. There was no recurrence after total resection. Subtotal resection was achieved in four patients, one of whom underwent second surgery resulting in total resection, and one patient died of respiratory disturbance after the third operation because of regrowth of the tumor. Complete excision could not be achieved in 3 of the 5 tumors located in the fourth ventricle because of extension to the brainstem. The median survival was 59.5 months for patients with papilloma, and 67.7 months for those with carcinoma. Adjuvant therapy was also required for carcinoma, one patient was treated by radiotherapy, and two by radiotherapy plus chemotherapy. Only one patient with papilloma was treated by radiotherapy plus chemotherapy postoperatively.

[A study of usefulness of chemotherapy in long-term survival choroid plexus carcinoma case of childhood].

We report a girl who was diagnosed with choroid plexus carcinoma at the age of 7 and has had an active daily life in the 11 years after onset. She underwent two tumor excision operations and received radiotherapy followed by intensive chemotherapy using cisplatin, carboplatin, and etoposide. In general, the prognosis of choroid plexus carcinoma is very poor, especially in the childhood cases, since no optimal treatment for choroid plexus carcinoma has yet been established. However, the results of analyses of the present long-term survival case, and similar long-term survival cases in the literature, strongly suggest the usefulness of chemotherapy in the treatment of choroid plexus carcinoma in children.

Choroid plexus papillomas of the cerebellopontine angle.

The cerebellopontine angle (CPA) is a rare site for the growth of choroid plexus papilloma (CPP). The clinicoradiological diagnosis of this tumor in the CPA is difficult because of the nonspecific clinical presentation and radiological features. Five cases of choriod plexus papilloma (3 males, 2 females) operated upon at this center are reviewed. All the cases were operated upon by retromastoid suboccipital craniectomy. As they all presented with a typical CPA syndrome without any distinctive radiological feature, a clinicoradiological diagnosis of CPP could not be reached in any of these. The diagnosis of CPP could only be suspected at the operation table and established on histopathological examination. Two patients developed recurrences at the primary site following surgery. One patient developed recurrence twice despite gross total excision of tumor in each sitting. Subsequently, this patient remained symptom free for a follow-up period of 1 year. Another patient developed recurrence 2 years following surgery, but he died due to septicemia and aspiration pneumonitis. Therefore definitive surgery could not be performed. Radiotherapy was offered to one of the patients having residual mass post operatively, to render her symptom free for a 4 year follow-up. The remaining two patients have also showed progressive improvement in their symptoms following surgery for 4 years on follow-up. Hydrocephalus was a common feature in all the cases preoperatively, but only one required shunt CSF diversion, because of rapid deterioration in visual equity. In all other cases, hydrocephalus was managed conservatively. Surgery remains the main modality of treatment for CPP, both for primary and recurrent tumors, but radiotherapy may have a role in cases of recurrence, which are quite frequent.

Is there a requirement for adjuvant therapy for choroid plexus carcinoma that has been completely resected?

Choroid plexus carcinomas (CPC) are rare central nervous system malignancies. While attempted surgical resection is imperative, the benefit of adjuvant therapy, particularly in the setting of a gross total resection (GTR), is unclear. We reviewed all pediatric cases of CPC reported in the literature between 1985 and 2000. Seventy-five cases of CPC were identified. Mean age at the time of diagnosis was 26 months. Thirty-seven patients had a GTR and 38 patients had a subtotal resection (STR). Thirty-eight cases (51%) were alive and 37 cases (49%) were deceased at time of publication. For cases with a GTR, survival was 84% compared to an 18% survival for patients with a STR. For patients with a GTR, all forms of adjuvant therapy were statistically equivalent. Our retrospective literature review confirms the importance of GTR in the therapy of CPC, with GTR alone being the single most important predictor of survival. The prognosis is poor for any patient with a STR, with the exception of those patients for whom adjuvant therapy allowed for an eventual GTR. The small number of patients receiving a GTR and no further therapy precluded a statistical comparison of no therapy in the setting of a GTR versus any form of adjuvant therapy. However, all four of these patients are alive, raising the possibility that adjuvant therapy in the setting of a GTR may not be required.

Choroid plexus carcinoma in an adult.

Choroid plexus carcinomas are rare in adults. They can behave aggressively and their optimal management is uncertain. An adult patient with choroid plexus carcinoma who was treated with an incomplete surgical resection and postoperative radiotherapy is reported. Despite an identifiable local response to radiotherapy, disease progression resulted in death 4 years after presentation. This report reviews the current literature and discusses the management issues regarding this uncommon adult malignancy.

Chemotherapy of choroid plexus carcinoma.

Choroid plexus carcinoma is a rare and frequently lethal tumor. Its cure depends primarily on the achievement of gross total resection. The contribution of adjuvant therapies, both irradiation and chemotherapy, in the context of gross total resection is unclear, but where such resection is not possible there may be a role for adjuvant therapy to permit more nearly complete resection. In particular, the limitation on resectability is imposed by the friability and extraordinary degree of vascularity, both of which may be favorably influenced by the use of chemotherapy following an initial biopsy, with deferral of the attempt at definitive resection until the impact of chemotherapy has been realized.