Differentiation of Glioma Stem Cells and Progenitor Cells into Local Host Cell-Like Cells: A Study Based on Choroidcarcinoma Differentiation of Choroid Plexus of GFP Transgenic Nude Mouse.

The idea of multiple differentiation capacity of glioma stem cells and progentior cells (GSCPs) has been accepted by most of the researchers, but the effect of local environment on the differentiation of GSCPs is unclear. GSCPs SU2 and CM-Dil-stained C6 cells (C6-Dil) were injected into the brain of GFP transgenic nude mice. The xenografts were sectioned. Morphological changes of tumor cells that resided in the choroid plexus, molecular markers expression, and the relationship between the original tumor cells and host cells were studied carefully. The tumorigenicity rate was 40/40 (100%) in all of the inoculated nude mice. Cell morphology and molecular expression of neoplasm settled in the choroid plexus showed that choroidcarcinoma derived from GSCPs was developed. These results showed that GSCPs may have the multiple differentiation capacity, which can be induced by the local environment of host brain as NSCs, and cell fusion may play an important role in the transformation.

Atypical teratoid/rhabdoid tumors may show morphological and immunohistochemical features seen in choroid plexus tumors.

Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive embryonal tumors having a poor prognosis and are associated with mutations in the tumor suppressor gene hSNF5/SMARCB1/INI1. Differential diagnosis includes choroid plexus carcinoma which has occasionally been attributed as showing an inactivation of INI1/SMARCB1 nuclear staining in immunohistochemistry. However, these findings have been challenged by others. We therefore examined eight AT/RTs from six patients by immunohistochemistry for membranous expression of the inward rectifier potassium channel Kir7.1, which was in the central nervous system so far considered specific for choroid plexus tumors and normal choroid plexus epithelium. Two AT/RT cases exhibited membranous staining of Kir7.1, indicating a plexus epithelial differentiation of these tumors. The implications of these results on tumor diagnosis are discussed.

TP53 alterations determine clinical subgroups and survival of patients with choroid plexus tumors.

PURPOSE Choroid plexus carcinomas are pediatric tumors with poor survival rates and a strong, but poorly understood, association with Li-Fraumeni syndrome (LFS). Currently, with lack of biologic predictors, most children are treated with aggressive chemoradiation protocols. PATIENTS AND METHODS We established a multi-institutional tissue and clinical database, which enabled the analysis of specific alterations of the TP53 tumor suppressor and its modifiers in choroid plexus tumors (CPTs). We conducted high-resolution copy-number analysis to correlate these genetic parameters with family history and outcome. Results We studied 64 patients with CPTs. All individuals with germline TP53 mutations fulfilled LFS criteria, whereas all patients not meeting these criteria harbored wild-type TP53 (P < .001). TP53 mutations were found in 50% of choroid plexus carcinomas (CPCs). Additionally, two sequence variants known to confer TP53 dysfunction, TP53 codon72 and MDM2 SNP309, coexisted in the majority of TP53 wild-type CPCs (92%) and not in TP53 mutated CPC (P = .04), which suggests a complementary mechanism of TP53 dysfunction in the absence of a TP53 mutation. High-resolution single nucleotide polymorphism (SNP) array analysis revealed extremely high total structural variation (TSV) in TP53-mutated CPC tumor genomes compared with TP53 wild-type tumors and choroid plexus papillomas (CPPs; P = .006 and .004, respectively). Moreover, high TSV was associated with significant risk of progression (P < .001). Five-year survival rates for patients with TP53-immunopositive and -immunonegative CPCs were 0% and 82 (+/- 9%), respectively (P < .001). Furthermore, 14 of 16 patients with TP53 wild-type CPCs are alive without having received radiation therapy. CONCLUSION Patients with CPC who have low tumor TSV and absence of TP53 dysfunction have a favorable prognosis and can be successfully treated without radiation therapy.

Jugular foramen chordoid meningioma.

Chordoid meningioma (CM) is a rare histological variant of meningioma and is classified as an atypical meningioma on pattern alone. Herein is described the first case of CM occurring in the jugular foramen. The patient was a 45-year-old woman with a 2 year history of progressive right hearing loss. Magnetic resonance imaging (MRI) demonstrated a large, dumbbell-shaped, homogenously gadolinium-enhanced mass in the right jugular foramen, extending medially to the cerebellopontine angle and caudally into the upper carotid space. Angiographic findings supported a diagnosis of schwannoma. Intraoperatively, the tumor appeared to involve the right glossopharyngeal nerve completely and the vagus nerve incompletely, and was incompletely resected. Microscopically, the tumor consisted predominantly of cords and nests of medium-sized cells with bland cytological features, surrounded by a pale basophilic mucin. Immunohistochemically, the tumor cells demonstrated reactivity for epithelial membrane antigen (membranous) and vimentin, with negative staining for S-100 protein, cytokeratin, CD34, glial fibrillary acidic protein (GFAP), synaptophysin, and chromogranin A. Based on the chordoid histology, an organoid lobular arrangement of the tumor cells, and the location of the tumor (jugular foramen), the differential diagnosis included not only a chordoma but also a paraganglioma (glomus jugulare tumor). Histological identification of typical meningotheliomatous areas, plus selective immunohistochemical panel, is important to establish the correct diagnosis.

Origin of chordoid glioma of the third ventricle.

CONTEXT: Chordoid glioma is a relatively recently described unique glial neoplasm that has been formally codified by the World Health Organization in Pathology and Genetics of Tumours of the Nervous System, in which it is included along with astroblastoma and gliomatosis cerebri under the rubric "Tumors of Uncertain Origin." Many examples of chordoid glioma come to clinical attention only at a relatively large size and occupy a large portion of the third ventricle. Accordingly, the anatomic origin of chordoid glioma has been unclear and debated. OBJECTIVE: To examine the regional anatomic origin of chordoid glioma. DATA SOURCES: The clinical, imaging, histologic, immunophenotypic, and ultrastructural data in previously published case series and individual case reports of chordoid glioma were reviewed in conjunction with the study of a new case of chordoid glioma that presented at a relatively small size, thereby facilitating neuroanatomic localization. CONCLUSIONS: Chordoid glioma exhibits features of specialized ependymal differentiation on ultrastructural examination, and all examples reported in the literature to date have displayed a highly stereotypical suprasellar anatomic localization and an ovoid shape, as seen on neuroimaging studies and gross anatomy. Neuroanatomic, radiologic, and clinical evidence supports an anatomic origin for chordoid glioma from the vicinity of the lamina terminalis.

A case report of a choroid plexus carcinoma spontaneously occurring in the right lateral ventricle of a 14-week-old, female Donryu rat.

We encountered a brain tumor arising in the right lateral ventricle of a 14-week-old, female Donryu rat and investigated its histological and immunohistochemical characteristics. Macroscopically, the tumor appeared as a grayish mass with a size of 10 mm in diameter, present in front of the right hemicerebrum and well circumscribed on the cut surface. Histological examination revealed the tumor to be a hypercellular mass occupying the front part of the right lateral ventricle and expanding into the area in front of the hemicerebrum, continuing to the ependymal area at its edge. The tumor was constituted by columnar- or pleomorphic-shaped, highly atypical cells of epithelial origin surrounding fibrovascular cores as single or multiple cell layers. Growth was papillary with high proliferating activity. Immunohistochemically, the tumor cells proved positive for cytokeratin but negative for vimentin, S100 protein or glial fibrillary acidic protein, a profile characteristic for the epithelial cells of the choroid plexus, whereas the ependymal cells were found to be positive for all 4 items. In conclusion, the present tumor was diagnosed as a rat choroid plexus carcinoma, only the third such case to be reported in the world literature, with particular features.

Choroid plexus carcinoma presented with spinal dysfunction caused by a drop metastasis: a case report.

A 2-year-old girl demonstrating gait disturbance and dysuria was evaluated and showed two large remote tumors at the left lateral ventricle and lower spinal canal. Pathological analysis demonstrated both of the tumors to be choroid plexus carcinoma (CPC) with high MIB-1 labeling index. The enhanced mitotic propensity would have contributed to an early stage of drop metastasis from the primary site to the sacral sac and following accelerated formation of a longitudinal tumor, which had grown in the subarachnoid space conforming to the spinal canal and finally caused the presenting symptoms of spinal dysfunction. This report shows that CPC can develop exophytically in the subarachnoid space as well as in the ventricle simultaneously before appearance of clinical symptoms and confirms the importance of extensive neuroimaging in its evaluation.

Pathological and immunohistochemical studies of choroid plexus carcinoma of the dog.

Choroid plexus carcinomas in four dogs (three male, one female) aged small middle 2.5 to 10 years, were examined by light microscopy and immunohistochemistry. The dogs showed progressive neurological signs including ataxia, seizures, vestibular disease and cranial nerve deficits, lasting for several months in some cases. Primary tumours were localized in the lateral (one case), third (one case), and fourth (two cases) ventricles. Hydrocephalus was evident at post-mortem examination in one case. In two cases the neoplastic cells closely resembled the structure of normal choroid plexus, with a distinct papillary pattern, composed of well-differentiated columnar epithelium. In the other two cases, cellular pleomorphism, nuclear atypia, increased mitotic activity and necrosis were observed. In all cases, dissemination of neoplastic cell clusters was detected within the subarachnoid space or the ventricular cavity. Immunohistochemical examination showed a multifocal labelling pattern for pankeratin and cytokeratin AE1 and diffuse vimentin positivity in poorly differentiated tumours. Well-differentiated choroid plexus carcinomas showed multifocal immunoreactivity for cytokeratin AE3, multifocal to diffuse immunoreactivity for vimentin and occasional positivity for carcinoembryonic antigen. Epithelial membrane antigen, Ber EP4 and S-100 were negative in all cases. Glial fibrillary acidic protein labelling occurred only in a single, poorly differentiated tumour. Occasional reactions for proliferating cell nuclear antigen and MIB-1 were seen in two cases. It was concluded that at least two morphological and possibly phenotypic subtypes (well-differentiated and anaplastic) of choroid plexus carcinoma of the dog could be identified.

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.

Choroid plexus papilloma diagnosed by crush cytology.

In a 32-yr-old man, an infratentorial cystic lesion with a mural nodule was interpreted to be either a hemangioblastoma or a cystic astrocytoma on CT scan. Intraoperative crush cytology revealed it to be a choroid plexus papilloma (CPP). The utility of crush cytology in the rapid diagnosis of central nervous system (CNS) tumors and the differential diagnosis of CNS papillary lesions are highlighted in this report.

Choroid plexus papilloma with osseous and adipose metaplasia.

Rare cases of osseous and chondroid metaplasia in choroid plexus papillomas have been described. We report a case of left lateral ventricular choroid plexus papilloma presenting in a 25-year-old man. The tumor demonstrates prominent calcification with associated osseous metaplasia and a region of adipose metaplasia, which has not been previously described in these tumors. There is no evidence of mucin in the papilloma on mucicarmine and alcian blue stains. A MIB-1 labeling index (marker of cell proliferation) of 0.1% was noted. P53 immunoreactivity was not observed in the papilloma. Ann Diagn Pathol 5:43-47, 2001.

Chordoid glioma of the third ventricle: an ultrastructural study of three cases with a histogenetic hypothesis.

Chordoid glioma is a rare neoplasm occurring in the third ventricle and, as the name implies, having a chordoid appearance. It is currently considered a glial neoplasm of uncertain histogenesis with distinct clinicopathologic features. We report three cases of chordoid glioma with a focus on the ultrastructural appearance. The patients were two men and one woman aged, respectively, 34, 40, and 43 years. Immunohistochemically, all tumors showed strong and diffuse reactivity for glial fibrillary acidic protein and vimentin, whereas immunoreactivity for epithelial membrane antigen and cytokeratin was focal. Ultrastructurally, they showed features of ependymal differentiation for the presence of an apical pole with microvilli and a basal pole characterized, as in normal ependyma, by many hemidesmosomelike structures connecting cell membranes to the underlying basal lamina. Constant features were a submicroscopic cell body zonation (i.e., perinuclear, intermediate, subapical, and apical regions) and the presence of secretory granules. These findings were similar to those described for the secretory ependymal cells of the subcommissural organ, a small structure located in a dorsocaudal region of the third ventricle that undergoes regression after birth in humans. Our observations suggest that chordoid glioma may represent a subtype of ependymoma whose cells resemble the highly specialized ependyma of the subcommissural organ.

Primary choroid plexus carcinoma producing carbohydrate antigen 19-9.

An autopsy case of primary choroid plexus adenocarcinoma arising in a 40-year-old female, who was associated with a high serum level of a carbohydrate antigen 19-9 (CA19-9), is herein presented. After a subtotal removal of a tumor in the left lateral ventricle, the serum level of CA19-9 decreased rapidly, and immunohistochemical examinations of tumor tissue specimens obtained at surgery revealed intense reactivity for CA19-9. The present case may be the first example in which a primary choroid plexus carcinoma was shown to produce CA19-9.

Chordoid glioma: a novel tumor of the third ventricle.

Chordoid glioma of the third ventricle is a recently characterized primary neoplasm of the central nervous system. We present a case and discuss the pathologic and radiologic features. We are aware of only 16 other cases documented in the world literature. This radiologic-pathologic correlation alerts pathologists and radiologists to recognize chordoid glioma as a distinct clinicopathologic entity restricted to the third ventricular area of adult patients.

Choroid plexus papilloma: a clinicopathological study of 23 cases.

BACKGROUND: Choroid plexus papillomas (CPPs) are rare, accounting for less than 1% of all intracranial tumors in adults. However, they are relatively more common in childhood and constitute 1.5 to 4% of intracranial tumors. DESCRIPTION: They are most often located in the lateral ventricle, followed by the fourth and third ventricles and, rarely, in the cerebellopontine angle. The radiological appearance of a CPP as a cyst with a mural nodule is a curiosity. Bone formation is rare in CPPs and only 6 cases have been described in the literature. Neuromelanin production is also extremely rare and only 2 cases have been reported to date. CONCLUSION: In the present communication, 23 cases of CPP are analyzed and rare clinical, pathological, and radiological features are described.

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.