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PubMed1982

Intracellular plasma proteins in human fetal choroid plexus during development. I. Developmental stages in relation to the number of epithelial cells which contain albumin in telencephalic, diencephalic and myelencephalic choroid plexus.

The developmental stages of telencephalic, diencephalic and myelencephalic choroid plexuses in the human fetus and the morphology of choroid plexus epithelial cells in the various plexuses in different development stages were described on basis of PAS- and toluidine blue-stained material. Six different cell types were identified in various combinations in 4 different stages (I-IV). The number and distribution of albumin-containing epithelial cells in various plexuses in the different stages of development were investigated by indirect immunoperoxidase technique. Albumin-containing cells did not belong to a single cell type. The telencephalic plexus exhibited a staining pattern for albumin which was different from that of the diencephalic and myelencephalic plexuses. In the telencephalic plexus positive epithelial cells were frequent in stage I, whereas only a few positive cells were present in stage II and III. In contrast, 30-40% of the epithelial cells in both diencephalic and myelencephalic plexuses in stage I, II and III showed a positive staining reaction. Later in gestation less than 10% were positive. It is suggested that a main function of the diencephalic and myelencephalic plexuses early in gestation is associated with protein transport rather than with glycogen synthesis and storage which might be a major function of the telencephalic plexus.

Cell Differentiation↗
PubMed1999

Pediatric choroid plexus neoplasms.

PURPOSE: Choroid plexus tumors (CPT) are rare childhood neoplasms. The relatively small number of reported cases and the controversies surrounding the clinical and pathological classification of these tumors have made it difficult to define a standard of care for these patients. Our intention is to contribute to the body of knowledge of these tumors and further define the role of adjuvant therapy. METHODS AND MATERIALS: We performed a retrospective review of 14 children with choroid plexus neoplasms referred to St. Jude Children's Research Hospital between October 1985 and December 1987. Ten patients had choroid plexus carcinoma (CPC) based on pathologic criteria and evidence of brain invasion at surgery or leptomeningeal disease (M+); 4 patients had choroid plexus papilloma (CPP). Patients with CPP were initially treated with surgery alone whereas patients with CPC were generally treated with postoperative therapy that included chemotherapy (CT) and/or craniospinal irradiation (CSI) with a focal boost to the primary site. For most patients CT consisted of combinations of cyclophosphamide, etoposide, vincristine, and a platinum agent. The median CSI dose was 35.2 Gy (range 24-46.2 Gy). The median primary site dose was 55.2 Gy (range 49.6-64 Gy). RESULTS: Seven of the 10 CPC cases presented with leptomeningeal dissemination; two of these patients have succumbed to disease. Of the 3 patients with M0 status, all are alive with no evidence of disease (NED). The medial time to relapse from the time of surgery was 5.3 mo (range 3-25 mo). Seven CPC patients were treated with gross total resection (GTR). Three of these patients (2 M0, 1 M+) received CT without CSI and are currently NED (27, 69, and 60 mo respectively). One M+ patient progressed on CT and has stable disease after CSI (6 mo), one (M0) received CT and CSI and is NED (120 mo), one (M+) is currently on CT with objective response (3 mo) and one (M+) died of progressive disease (24.5 mo) despite CT and CSI. Three patients with CPC had subtotal resection (STR). One of these patients (M+) received CT and CSI and is NED (23 mo), one (M0) had an elective second resection GTR alone and is currently NED (153 mo), and one (M+) developed progressive disease (13.5 mo) while on CT and died despite CSI. Among the 4 CPP patients, GTR was performed in two; both were NED at 54 and 81 mo. Two patients with CPP (one with focal atypia) were treated with STR initially; both transformed to CPC at 7 and 27 mo, respectively. Both were currently NED following salvage with (1) GTR and CSI alone (98 mo) or (2) STR, CT, and CSI (62 mo). Six of the 12 survivors in this series had significant neuropsychological sequelae. CONCLUSION: The prognosis of CPP is good for patients treated with GTR. Malignant transformation occurred in 2 CPP patients with less than GTR. Patients with localized CPC who undergo GTR have had a favorable outcome with the addition of chemotherapy or irradiation. CSI may not be routinely indicated in M0 children following GTR. There is evidence that salvage with radiation therapy may be successful following progression on chemotherapy. For patients treated with STR, the use of CT and CSI appears to be necessary.

Adolescent↗
PubMed1989

The clinical significance of prenatally diagnosed choroid plexus cysts.

The choroid plexus cyst is one of many malformations of the central nervous system that can be detected in utero by ultrasonography. Choroid plexus cysts occur in 2.3% of fetuses. Because previous reports have shown an association between choroid plexus cysts and chromosomal anomalies, we analyzed 82 prenatally diagnosed cases, 65 of whom had chromosome analysis performed. Of the group, 6.2% had chromosomal anomalies of the trisomy 18 type. The remaining 17 cases were clinically normal at birth. These cases of trisomy 18 were also associated with multiple structural anomalies. Therefore, we suggest that after the diagnosis of choroid plexus cysts is made, a complete ultrasonographic survey of the fetal anatomy be performed. Fetal karyotype determination may be offered to patients, especially in the presence of structural anomalies.

Abnormalities, Multiple↗
PubMed1993

The AgNOR technique, PCNA immunohistochemistry, and DNA ploidy in the evaluation of choroid plexus biopsy specimens.

The histologic distinctions between normal choroid plexus and choroid plexus papilloma and between choroid plexus papilloma and choroid plexus carcinoma are sometimes difficult. The authors performed the silver nucleolar organizer region (AgNOR) technique, immunohistochemistry for proliferating cell nuclear antigen (PCNA), and DNA ploidy analysis by flow cytometry on 9 samples of normal choroid plexus, 8 papillomas, and 13 carcinomas to evaluate whether these techniques can aid in these differential diagnoses. Significant differences were found in the mean AgNOR count between normal choroid plexus (1.35 +/- 0.11) and choroid plexus papillomas (2.42 +/- 0.81) (P < 0.001), but not between choroid plexus papillomas and carcinomas. In the normal choroid plexus, AgNORs were smooth and round; in the papillomas and carcinomas, however, they varied in size and shape. Compound AgNORs were commonly present in the tumors but were essentially absent in controls. Antibody to PCNA did not stain normal choroid plexus cells (except for focal staining in one sample of normal choroid plexus adjacent to a carcinoma) but stained many papilloma and carcinoma cells. DNA ploidy analysis demonstrated aneuploidy in some papillomas and carcinomas but could not be used for the distinction of normal choroid plexus from papillomas. These results suggested that the AgNOR technique and PCNA immunohistochemistry could be used to distinguish normal choroid plexus from choroid plexus papilloma in small, diagnostically difficult biopsy specimens.

Antigens, Neoplasm↗
PubMed2002

Chromosomal imbalances in choroid plexus tumors.

We studied 49 choroid plexus tumors by comparative genomic hybridization. Chromosomal imbalances were found in 32 of 34 choroid plexus papillomas and 15 of 15 choroid plexus carcinomas. Choroid plexus papillomas frequently showed +7q (65%), +5q (62%), +7p (59%), +5p (56%), +9p (50%), +9q (41%), +12p, +12q (38%), and +8q (35%) as well as -10q (56%), -10p, and -22q (47%); choroid plexus carcinomas mainly showed +12p, +12q, +20p (60%), +1, +4q, +20q (53%), +4p (47%), +8q, +14q (40%), +7q, +9p, +21 (33%) as well as -22q (73%), -5q (40%), -5p, and -18q (33%). Several chromosomal imbalance differences could be found that were characteristic for a tumor entity or age group. In choroid plexus papillomas +5q, +6q, +7q, +9q, +15q, +18q, and -21q were significantly more common whereas choroid plexus carcinomas were characterized by +1, +4q, +10, +14q, +20q, +21q, -5q, -9p, -11, -15q, and -18q. Among choroid plexus papillomas, children more often showed +8q, +14q, +12, and +20q; adults mainly presented with +5q, +6q, +15q, +18q, and -22q. Although the number of aberrations overall as well as of gains and losses on their own bore no significance on survival among choroid plexus tumors, a significantly longer survival among patients with choroid plexus carcinomas was associated with +9p and -10q. Our results show that aberrations differ between choroid plexus papillomas and choroid plexus carcinomas as well as between pediatric and adult choroid plexus papillomas, supporting the notion of different genetic pathways. Furthermore, gain of 9p and loss of 10q seem to be correlated with a more favorable prognosis in choroid plexus carcinomas.

Adult↗
PubMed1996

Hyperdiploid karyotype in a choroid plexus papilloma.

A choroid plexus papilloma from a 23-month-old child was found to have a hyperdiploid karyotype. This karyotype is compared with that of other choroid plexus papillomas. Our results are also compared with flow cytometry results and the karyotypes of choroid plexus carcinomas.

Choroid Plexus Neoplasms↗
PubMed1956

The electron microscopy of the choroid plexus.

1. The choroid plexus of the rat has been studied in detail by electron microscopy. Samples from the frog, rabbit, and cat have also been examined without noting significant differences. 2. The surface of the ependymal epithelium is covered by pedicels of variable size. There is reason for thinking of these structures as labile. They may actually pinch off and contribute to the secretory product. In any case, the surface area is vastly increased by their presence. Polypoid border seems an apt term to apply to this type of surface. 3. There is also a great expansion of the basal surface of ependymal cells. In the vicinity of cell junctions this surface is deeply infolded, and continuous with elaborate interdigitations of the lateral intercellular surfaces. Analogous infolding of the basal cell surface is known to exist in other epithelia also noted for their water transport (kidney tubules, salivary gland, and ciliary body). 4. Pretreatment of rats with diamox, an agent known to block cerebro-spinal fluid production, did not produce an important morphological change in the features of the ependyma, or any other part of the choroid plexus. 5. Capillaries of the choroid plexus have a very attenuated endothelium. This is seen to be fenestrated. It is thought this probably represents the condition in life, and is not simply a fixation artefact. 6. Pial cells tend to interpose sheets of cytoplasm between the capillaries and ependyma. The sheets are not continuous, however, and so would not constitute a serious diffusion barrier. These cells belong to the reticuloendothelial system, and undergo shape changes, and probably increase in number, when the system is stimulated by the repeated injection of trypan blue.

Animals↗
PubMed2002

Evaluation of proliferative index and cell cycle protein expression in choroid plexus tumors in children.

Choroid plexus tumors are papillary neoplasms originating from the epithelium of the choroid plexus within the cerebral ventricles. They may be highly proliferative tumors, but detailed studies confirming their proliferative potential are lacking. Accordingly, we performed a clinicopathological correlation study of neoplasms arising from the choroid plexus in children using immunohistochemistry to characterize both their proliferative potential and their degree of cell cycle dysregulation when compared to non-neoplastic choroid epithelium. Twelve children with choroid plexus papillomas (CPPs) and 11 with choroid plexus carcinomas (CPCs) were identified from the time period 1982-1997. The outcome and survival of these children following treatment was determined from the medical record. Immunohistochemical studies were performed on CPPs and CPCs in this patient population and on non-neoplastic choroid epithelium using antibodies to MIB-1, p53, cyclin E, retinoblastoma protein (pRB), p107, and E2F-1. In 5 children with CPCs, tumor tissue was available for immunohistochemistry at a second surgery after cycles of chemotherapy had been given. The mean survival for patients with CPPs was 8.5 years, and with CPCs 5.2 years with a minimum follow-up of 4 years for the group. The expression of cell cycle markers and MIB-1 was greater in CPCs than in CPPs or normal choroid plexus. The expression of MIB-1, p53, pRB, and E2F-1 was significantly lower in patients with CPCs after chemotherapy than before. The MIB-1 labeling index for CPC patients who are alive and well after treatments was 15.19+/-3.2 compared to 22.63+/-3.04 for patients who have died from their disease (P<0.05). We conclude that CPCs in children are characterized by a higher MIB-1 labeling index and greater cell cycle dysregulation than are CPPs. Chemotherapy may work in part on CPCs to decrease their proliferative potential and expression of cell cycle regulatory proteins.

Adolescent↗
PubMed1996

[Papillary carcinoma of the choroid plexus: apropos 3 cases].

Choroid plexus carcinoma are tumors arising from epithelial cells of the choroid plexus. They distinguish from the benign choroid plexus papilloma because of their invasive capacity and cellular pleomorphism. This is a rare neoplasm and only infrequently occurs in adults. We report three cases of choroid plexus carcinoma, two women of 61 and 58 years old and a third one a child of 3 years old. We performed a review of the literature with special attention to the epidemiologic, histologic, clinic and therapeutic issues.

Carcinoma, Papillary↗
PubMed2003

A SCL4A10 gene product maps selectively to the basolateral plasma membrane of choroid plexus epithelial cells.

The choroid plexus epithelium of the brain ventricular system produces the majority of the cerebrospinal fluid and thereby defines the ionic composition of the interstitial fluid in the brain. The transepithelial movement of Na+ and water in the choroid plexus depend on a yet-unidentified basolateral stilbene-sensitive Na+-HCO3- uptake protein. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the expression in the choroid plexus of SLC4A10 mRNA, which encodes a stilbene-sensitive Na+-HCO3- transporter. Anti-COOH-terminal antibodies were developed to determine the specific expression and localization of this Na+-HCO3- transport protein. Immunoblotting demonstrated antibody binding to a 180-kDa protein band from mouse and rat brain preparations enriched with choroid plexus. The immunoreactive band migrated as a 140-kDa protein after N-deglycosylation, consistent with the predicted molecular size of the SLC4A10 gene product. Bright-field immunohistochemistry and immunoelectron microscopy demonstrated strong labeling confined to the basolateral plasma membrane domain of the choroid plexus epithelium. Furthermore, the stilbene-insensitive Na+-HCO3- cotransporter, NBCn1, was also localized to the basolateral plasma membrane domain of the choroid plexus epithelium. Hence, we propose that the SLC4A10 gene product and NBCn1 both function as basolateral HCO3- entry pathways and that the SLC4A10 gene product may be responsible for the stilbene-sensitive Na+-HCO3- uptake that is essential for cerebrospinal fluid production.

Animals↗
PubMed1975

The human choroid plexus and autoimmune nephritis.

The choroid plexus resembles the glomerular basement membrane (GBM) and may be a site of injury or source of antigen in Goodpasture syndrome. Immunohistologic studies were performed on the choroid plexus of a patient with auto-immune nephritis and pulmonary hemorrhage. The studies showed linear deposition of host IgG, IGM, and beta1c. Antibody eluted from the diseased kidney fixed in a linear pattern to normal choroid plexus and could be absorbed by either choroid plexus or GBM. Antibody to choroid plexus fixed to GBM and the linear staining was no longer observed after absorption with GBM or choroid plexus. Antibody to GBM fixed to normal choroid plexus and was obsorbed by both choroid plexus and glomerular basement membrane. The studies suggest an immunologic relationship between choroid plexus and GBM and a role for the choroid plexus in autoimmune nephritis.

Animals↗
PubMed1982

Brain barrier systems in the lamprey. II. Ultrastructure and permeability of the choroid plexus.

The lamprey choroid plexus was studied by electron microscopic techniques and the composition of cerebrospinal fluid and plasma compared as part of a characterization of the lamprey blood-brain barrier. It was shown that the ultrastructure of the lamprey choroid plexus is very similar to that of the mammalian plexus. A blood-cerebrospinal fluid (CSF) barrier to horseradish peroxidase (molecular weight 40,000) and microperoxidase (molecular weight 2000) was localized to apical tight junctions between the choroidal epithelial cells. Pinocytic uptake of the tracers took place particularly at the apical surface of the epithelium (after intravenous and intraventricular administration). Absorbed tracer-molecules were found in vacuoles presumably belonging to the well-developed lysosomal apparatus of the epithelial cells. Extended Golgi-complexes, dense bodies and some multivesicular bodies were reactive for acid phosphatase activity. Measurements of protein, potassium and sodium in plasma and CSF revealed the same concentration differences previously observed in higher vertebrates. The present study lends further support to the view that the lamprey blood-brain barrier is similar to that of higher vertebrates.

Acid Phosphatase↗
PubMed2002

Clinically significant persistence and enlargement of an antenatally diagnosed isolated choroid plexus cyst.

Isolated choroid plexus cysts are usually diagnosed at the time of screening ultrasonography during the second trimester. While they raise the question of underlying chromosomal abnormalities, their clinical course is almost invariably benign with complete resolution often by the third trimester. We report the highly unusual case of a choroid plexus cyst diagnosed at 14 weeks of gestational age with subsequent further enlargement of the cyst, necessitating postpartum neurosurgical intervention.

Adult↗
PubMed2000

Amphibian choroid plexus lipocalin, Cpl1.

Choroid plexus lipocalin 1 (Cpl1) has been isolated from the African clawed toad (Xenopus laevis) and the cane toad (Bufo marinus). Xcpl1 has been used as a marker for studying early neural development. Due to its retinoid binding properties and the fact that it causes dysmorphogenesis when overexpressed in the early embryo, the protein product is considered to be part of the retinoic acid signalling pathway. Later in development and during adulthood, the epithelial cell sheet of the choroid plexus which forms the blood-cerebrospinal fluid barrier expresses cpl1 as the predominant secretory protein. These data, the similarity of Cpl1 to prostaglandin D(2) synthase and its functional homology to transthyretin will be discussed.

Amphibians↗