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PubMed1997

[A case report of choroid plexus carcinoma].

Choroid plexus carcinoma (CPC) is a rare tumor with poor prognosis, whose optimal treatment has not yet been established. We report a case of a one-year-old infant who has been treated with successive combined therapy. The therapy involved two operations for partial removal, interrupted radiotherapy up to 12Gy, 2 cycles of salvage chemotherapy, followed by an operation for total removal, and then a further 3 cycles of chemotherapy. CT scan after the preoperative salvage chemotherapy showed remarkable shrinkage of the residual tumor, which made operative procedure easier. The patient was disease-free for ten months after the last operation. Patients with combined preoperative chemotherapy and total resection seem to enjoy prolonged progression-free survival, so preoperative chemotherapy for choroid plexus carcinoma seems to be of benefit, despite the fact that its optimal recipe has not yet been established.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Choroid plexus papillomas.

Choroid plexus papillomas (CPPs) are rare neoplasms accounting for less than 1% of all intracranial tumours. We present our experience with 13 consecutive cases managed by us between 1981 and 1991. There were eight children and five adults. Five patients had tumours in the 4th ventricle, four in lateral ventricle, one in the 3rd ventricle, two in the cerebellomedullary cistern and one in the cerebellopontine angle. The cerebellomedullary cistern is a rare site for CPPs. Although the 4th ventricle remains the common site for adult CPPs, in our series there was a higher incidence of posterior fossa papillomas even in children. Only six patients out of 13 underwent precraniotomy shunts. All patients had their tumours operated upon and verified histologically. Total excision of the tumour could be achieved in nine patients; only a sub total excision was possible in the remaining four. There were two surgical mortalities in the earlier part of this series. Two patients with subtotal excisions underwent radiation therapy; one of these had regrowth of the tumour and another was lost to follow up. The other nine patients are doing well with a follow-up ranging from 9 to 90 months. Surgical resection with the objective of achieving total excision should be attempted in these tumours.

Adolescent↗

PubMed1999

Choroid plexus epithelium (normal and neoplastic) expresses synaptophysin. A potentially useful aid in differentiating carcinoma of the choroid plexus from metastatic papillary carcinomas.

As an incidental finding in paraffin sections of brain tissue used as positive controls for synaptophysin immunostain, the cytoplasm of choroid plexus epithelium present was found to stain strongly positively for this substance. This was subsequently found to be the case in normal choroid plexuses in autopsy material from infancy to old age, as well as in epithelial cells of papillomas and carcinomas of the choroid plexus. The latter findings may prove useful in differentiating choroid plexus carcinomas from metastatic papillary carcinomas of extracerebral origin with the exception of neuroendocrine carcinomas of various sites that are usually positive for synaptophysin.

Adolescent↗

PubMed2006

Chronic hypernatremia increases the expression of vasopressin and voltage-gated Na channels in the rat choroid plexus.

The choroid plexus (CP) epithelium is one of the extrahypothalamic sources of arginine vasopressin (AVP). However, it is unclear whether the regulation of choroidal AVP synthesis in response to pathophysiological stimuli, such as hyperosmotic stress, is similar to that observed in the hypothalamus. In the present study, rats chronically implanted with cisterna magna cannulas, enabling the collection of cerebrospinal fluid (CSF) in freely moving animals, were subjected to salt loading. CSF osmolality increased from the baseline normonatremic levels ranging between 292 +/- 0.5 and 295 +/- 2 to 309 +/- 4 mosm/kg H(2)O at 2 days of hypernatremia. This elevated CSF osmolality was maintained at a relatively stable level until the end of a 10-day observation period. Changes in choroidal and hypothalamic AVP expression in response to hyperosmotic stress were assessed by semiquantitative reverse-transcriptase polymerase chain reaction. An increase in hypothalamic AVP expression was accompanied by augmented AVP synthesis in the CP. Compared to normonatremia, choroidal levels of AVP mRNA increased 5- and 10-fold at 2 and 5 days of salt loading, respectively. Salt loading also resulted in increased hypothalamic expression of the alpha-II, beta(1), and beta(2) subunits of voltage-gated Na(+) channels. Similarly, the choroidal mRNA levels for the alpha-II and beta(1) subunits increased approximately 2-fold after 5 days of salt loading; however, no changes in the beta(2) subunit expression were found in the CPs of hypernatremic rats. These experiments support the hypothesis that the regulation of choroidal AVP synthesis is similar to that observed in the hypothalamus. It is also suggested that the increased expression of voltage-gated Na(+) channels found in the hypothalamus and CP after salt loading may play a role in the adaptation of AVP-producing cells to chronic hypernatremia.

Animals↗

PubMed2001

Brain drug delivery, drug metabolism, and multidrug resistance at the choroid plexus.

The choroid plexuses (CPs) have the capability to modulate drug delivery to the cerebrospinal fluid (CSF) and to participate in the overall cerebral biodisposition of drugs. The specific morphological properties of the choroidal epithelium and the existence of a CSF pathway for drug distribution to different targets in the central nervous system suggest that the CP-CSF route is more significant than previously thought for brain drug delivery. In contrast to its role in CSF penetration of drugs, CP is also involved in brain protection in that it has the capacity to clear the CSF from numerous potentially harmful CSF-borne exogenous and endogenous organic compounds into the blood. Furthermore, CP harbors a large panel of drug-metabolizing enzymes as well as transport proteins of the multidrug resistance phenotype, which modulate the cerebral bioavailability of drugs and toxins. The use of an in vitro model of the choroidal epithelium suitable for drug transport studies has allowed the demonstration of the choroidal epithelium acting as an effective metabolic blood-CSF barrier toward some xenobiotics, and that a vectorial, blood-facing efflux of conjugated metabolites occurs at the choroidal epithelium. This efflux involves a specific transporter with characteristics similar to those of the multidrug resistance associated protein (MRP) family members. Indeed, at least one member, MRP1, is largely expressed at the CP epithelium, and localizes at the basolateral membrane. These metabolic and transport features of the choroidal epithelium point out the CP as a major detoxification site within the brain.

ATP-Binding Cassette Transporters↗

PubMed2002

Establishment and characterization of an immortalized Z310 choroidal epithelial cell line from murine choroid plexus.

The choroid plexus plays a wide range of roles in brain development, maturation, aging process, endocrine regulation, and pathogenesis of certain neurodegenerative diseases. To facilitate in vitro study, we have used a gene transfection technique to immortalize murine choroidal epithelial cells. A viral plasmid (pSV3neo) was inserted into the host genome of primary choroidal epithelia by calcium phosphate precipitation. The transfected epithelial cells, i.e., Z310 cells, that survived from cytotoxic selection expressed SV40 large-T antigen throughout the life span, suggesting a successful gene transfection. The cells displayed the same polygonal epithelial morphology as the starting cells by light microscopy. Immunocytochemical studies demonstrate the presence of transthyretin (TTR), a thyroxine transport protein known to be exclusively produced by the choroidal epithelia in the CNS, in both transfected and starting cells. Western blot analyses further confirm the production and secretion of TTR by these cells. The mRNAs encoding transferrin receptor (TfR) were identified by Northern blot analyses. The cells grow at a steady rate, currently in the 110th passage with a population doubling time of 20-22 h in the established culture. When Z310 cells were cultured onto a Trans-well apparatus, the cells formed an epithelial monolayer similar to primary choroidal cells, possessing features such as an uneven fluid level between inner and outer chambers and an electrical resistance approximately 150-200 omega-cm(2). These results indicate that immortalized Z310 cells possess the characteristics of choroidal epithelia and may have the potential for application in blood-CSF barrier (BCB) research.

Animals↗

PubMed2006

Genetics of choroid plexus tumors.

Choroid plexus tumors consist of papillomas and carcinomas. A variety of germline and somatic genetic changes have been demonstrated for each of these subtypes. In this paper, the authors summarize the current knowledge of the genetic bases of these tumors.

Cerebral Ventricle Neoplasms↗

PubMed1989

The role of radiotherapy in the management of choroid plexus neoplasms.

Choroid plexus papillomas are very rarely reported neoplasms in both the surgical and radiological literature. The authors present their series of 7 papillomas and 1 carcinoma. They review the recent and former literature with the aim of demonstrating the role and usefulness of radiotherapy.

Adult↗

PubMed1983

[Ultrastructural study of papillomas of the choroid plexus].

The choroid plexus papillomas are rare neoplasms. They constitute about 0.5 per 100 of all intracranial tumors. From a histological point of view they are generally benign tumors. However they give a high mortality rate due to their location near vital structures, the rapid production of intracranial hypertension, and the rich vascularity making risky the surgical treatment.

Cerebral Ventricle Neoplasms↗

PubMed1983

Third ventricle choroid plexus papillomas.

Choroid plexus papillomas are only infrequently located in the third ventricle. Two infants with such lesions are presented and the diagnosis by computed tomography described. The transcallosal approach to the third ventricle was employed in both cases and led to successful excision. This approach is recommended for lesions in the anterior third ventricle in children, and the occurrence of subdural effusions as a complication is pointed out.

Cerebral Ventricle Neoplasms↗

PubMed1999

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.

Antineoplastic Agents↗

PubMed1977

A morphological and chemical study of calcification of the choroid plexus.

Human choroid plexus was submitted to low temperature ashing (LTA) in order to isolate the calcification. The ashing residue was then subjected to morphological, chemical and structural studies using technics such as scanning electron microscopy, flame and flameless atomic absorption spectrometry, infrared spectrometry and X-ray diffraction. Morphologically, the calcification consisted of wound-up fibers forming granules with a diameter of 0.05 to 0.15 mm. The concretions were identified as cristalline Ca3(PO4)2 and hydroxylapatite. The content of trace elements was high, but within the limits found in other biological apatites. In some cases, however, the Fe content exceeded these limit values.

Calcinosis↗

PubMed2003

Differential expression of fibroblast growth factor receptors in the developing murine choroid plexus.

The choroid plexuses (CPs) are specialised secretory organs situated within the ventricles of the brain involved in the production of cerebrospinal fluid (CSF) and the maintenance of the blood-CSF barrier. Abnormal function of the CPs can lead to hydrocephalus and raised intracranial pressure, pathologies frequently observed in certain craniofacial syndromes caused by single point mutations in fibroblast growth factor receptors (FGFRs). At present, relatively little is known about the embryonic CPs in terms of gene or protein expression, function as the brain develops or on the potential role of FGFRs within this context. Given the limited information available on the regulation of FGFRs during development of the CPs and periventricular tissues, we have carried out a detailed analysis of the localisation of FGFR1, 2, 3 and 4 proteins in these regions of the murine embryo from the time of formation of the CP in the third ventricle at E12.5 throughout the second half of gestation, and examined the expression of different FGFR isoforms at E12.5 by RT-PCR. We show here that FGFR1 and FGFR4 are expressed in murine CPs at E12.5 but not at E15.5 or E18.5, suggesting a role for the signaling pathways transduced by these receptors at early stages of CP development. In contrast, FGFR2 expression is maintained throughout CP development, indicating that this receptor may play a role in the function of immature and mature CP. Also FGFR3 is detected at each developmental stage studied, but surprisingly its expression appears confined to the nuclei of CP cells, suggesting that FGFR3 in the CP does not respond to extracellular FGFs but may act in intracrine fashion.

Animals↗

PubMed1995

Clinical significance of fetal choroid plexus cysts.

Choroid plexus (CP) cysts are commonly detected on routine mid-trimester ultrasound scan. When associated anomalies are detected, the risk is sufficient to justify an invasive diagnostic test such as amniocentesis. However, the risk when no associated anomalies are detected is much less well defined. This information is required to determine the appropriate management in cases of apparently isolated CP cysts. We thought the only way to resolve the difficulties in counselling prospective parents was to conduct a prospective study in a large unselected population. A registry of fetal CP cysts detected over 3 years in the Yorkshire Region was compiled and we identified 524 CP cysts. These cases were then amalgamated and analysed with 1361 cases from prospective studies reported in the world English literature and a further 71 unpublished cases identified from a 2 year prospective series from Ninewells Hospital, Dundee. The risk of chromosomal abnormalities was 1 in 150 (95% CI 1 in 85, 1 in 261) when no fetal anatomic abnormalities, apart from the CP cysts themselves, were detected antenatally. The risk increased to approximately 1 in 3 if any other associated ultrasound abnormalities were detected antenatally. The risk did not appear to be related to whether or not cyst size diminished as gestation progresses, whether they were unilateral or bilateral, and whether they were small or large in size (60-80% < 10 mm). 76% of aneuploidic cases were trisomy 18 and 17% were trisomy 21. The risk of Down's syndrome in fetuses with CP cysts but no other anomalies detected antenatally is 1 in 880. The probability of a chromosomal abnormality is high when CP cysts are associated with any other antenatally detected anomaly, indicating a clear need to offering amniocentesis. The predictive value is much lower when no other anomalies are detected. In such cases, it is probably advisable to regard CP cysts as an indication for detailed ultrasound assessment, rather than invasive testing.

Brain Diseases↗

PubMed1996

[The indications for the management of fetuses with choroid plexus cysts].

Choroid plexus cysts (CPC) in the fetus are still the subject of considerable debate in the literature. Because of their association with aneuploidy, and especially with trisomy 18, of which they are an ultrasonographic marker, the detection of fetal CPC now poses the problem of how these cases should be managed, since most occur in young women (there being no correlation between CPC and age), and since the incidence among the general population is fairly high (around 1%). With the aim of contributing further to the debate, a retrospective study was performed of all cases of fetal CPC diagnosed in our Centre between January 1984 and August 1994, together with a review of the relevant literature. There were 95 cases of fetal CPC with complete neonatal and necroptic data available. These cases included women recruited in the course of routine screening for congenital malformations carried out in our Centre at 14 and 21 weeks gestation, women referred to us from other Centres, and women recruited in the course of amniocentesis indicated for those aged over 35. In all cases in which fetal CPC was detected, a careful ultrasonographic examination was performed to exclude the presence of even the smallest morphologic anomaly. Whenever the fetus was found to have an anomaly karyotyping was done. If the CPC was not associated with any morphologic anomaly, karyotyping was proposed only to those women at risk of aneuploidy because of their age. There were 11 cases of trisomy 18, all of which presented morphologic anomalies associated with CPC. Some of these anomalies where "minor", however, and therefore difficult to assess even when a careful ultrasonographic examination was performed by an experienced operator (Intra ventricular septal defect, single umbilical artery). In 2 cases, CPC was associated with trisomy 21. Both women were aged over 35. All the other cases of CPC not associated with morphologic anomaly were normal on postnatal examination. From a meta-analysis of the literature, two distinct management protocols emerge for the problem of "isolated CPC detected at ultrasonographic examination". One group of authors recommends karyotyping for all women with fetal CPC, considering the presence of CPC in itself a risk factor for aneuploidy. The second group, to which we ourselves belong, believes it is sufficient to perform a careful ultrasonographic examination so as to exclude the presence of other morphologic anomalies associated with the CPC. Karyotyping should be proposed only to women at risk of aneuploidy because of their age (> 35). A review of the biggest series reported in the literature shows that, of a total of 1670 fetuses with CPC, 94 were trisomy 18. None of the cases of CPC "in isolation" emerged as being associated with this aneuploidy. However, numerous cases of trisomy 18 have been described in which CPC is associated with "minor" morphologic anomalies in the fetus which may be difficult to detect. It is therefore essential to perform a careful ultrasonographic examination in all cases of CPC, preferably in a Centre with specialist knowledge of ultrasonography. If this option is not available, then karyotyping of all women with fetal CPC is clearly advisable.

Abnormalities, Multiple↗

PubMed1999

HIV infection of choroid plexus in AIDS and asymptomatic HIV-infected patients suggests that the choroid plexus may be a reservoir of productive infection.

The choroid plexus (CPx) may be an important site of viral dissemination since monocytes and dendritic cells in its stroma are infected with HIV in AIDS patients and since the ratio of CPx to brain infection is more than 2 : 1. In order to see if CPx infection also develops in asymptomatic (ASY) HIV-infected patients, we examined archival formalin-fixed brain and CPx from 14 AIDS and seven ASY cases, using routine histology, immunohistochemistry for HIV gp41, and DNA extraction and gene amplification for HIV DNA. Eight of 14 AIDS (57%) had HIV-positive cells in the CPx and four (29%) had HIV encephalitis. Two of seven ASY cases (29%) had HIV-positive cells in the CPx but none had HIV encephalitis. Extracted DNA from brain, CPx and systemic organs of five ASY cases was amplified by nested PCR with or without Southern blotting for HIV env gene. It was positive in systemic organs in five cases; in CPx in four cases; and in brain in one case. This study shows that the CPx is a site of HIV infection in ASY patients and that the frequency of CPx infection is higher than seen in brain in both AIDS and ASY cases. The results are consistent with the hypothesis that the CPx may be a site for hematogeneous spread and a reservoir for HIV infection during the period of clinical latency.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Tubular (acinar) transformation of the choroid plexus epithelium.

The choroid plexus in the normal state shows a beautiful papillary (or villous) architecture supported by the intricately ramifying, thin fibrovascular stroma. This configuration is retained in benign and malignant neoplasms derived therefrom. The choroid plexus was involved in the pathological process of leukemic cell infiltration in one case reported here and in chronic cryptococcal leptomeningitis in the other case. The epithelial cells of the choroid plexus of the lateral ventricle were arranged extensively in a tubular (acinar) configuration, in association with remarkable stromal fibrosis caused by an infiltration of leukemic or inflammatory cells. In addition, choroid plexus epithelial cells in the first case contained a moderate amount of intracytoplasmic glycogen. These two cases indicate that the non-neoplastic choroid plexus epithelium can undergo transformation into a tubular (acinar) structure as a response or adaptation to the fibrotic processes of the stroma. This finding should be differentiated from metastatic adenocarcinoma. This finding also provides some suggestions as to the pathogenesis of "tubular (acinar) adenoma," a rare variant of benign choroid plexus neoplasm.

Arachnoid↗

PubMed1998

Production and secretion of endothelin-1 by cultured choroid plexus carcinoma cells.

Choroid plexus carcinoma is a rare neoplasm derived from the epithelium of the choroid plexus. The production and secretion of endothelin-1 (ET-1) by cultured human choroid plexus carcinoma cells were studied by radioimmunoassay and Northern blot analysis. Immunoreactive (IR)-ET was detected in the culture medium (2.78 +/- 0.12 fmol/10(5) cells/24 h; n = 5; mean +/- SEM) but not in the unconditioned medium. Reverse-phase high-performance liquid chromatography of the extract of the culture medium showed a single peak eluting in the position of ET-1. Treatment with tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) or a combination of interferon-gamma (IFN-gamma), TNF-alpha, and IL-1 beta caused significant increases in the IR-ET levels in the culture medium. Northern blot analysis of total RNA showed the expression of ET-1 mRNA in choroid plexus carcinoma cells. The expression levels of ET-1 mRNA were increased by treatment with a combination of IFN-gamma, TNF-alpha, and IL-1 beta. The present study has shown the production and secretion of ET-1 by cultured human choroid plexus carcinoma cells and suggests the possibility that ET-1 formation is related to the pathophysiology of this tumor.

Blotting, Northern↗