bromochloroacetic-acid and Choroid-Plexus-Neoplasms

Atypical teratoid/rhabdoid tumor (ATRT) and choroid plexus tumors (CPT) represent, so far, 2 well defined types of CNS neoplasm on the basis of their histological features and clinical presentation (10). While CPTs are intraventricular epithelial tumors arising from choroid plexus epithelium, the cellular origin of ATRTs is still unknown. Inactivating mutations of the hSNF5/INI-1 gene located in the chromosomal region 22q11.2 are regarded as a crucial step in the molecular pathogenesis of ATRTs; the genetic changes associated with CPTs are largely unknown. However, the recent finding of inactivation of hSNF5/INI-1 in choroid plexus carcinomas and papillomas (9, 18) points to a closer relationship between these 2 entities. This is supported by the occurence of choroid plexus carcinomas (CPC) in the setting of families with rhabdoid predisposition syndrome (RPS), (19) caused by germ line inactivation of the INI1 gene.

Topics: Central Nervous System Neoplasms; Choroid Plexus Neoplasms; Chromosomal Proteins, Non-Histone; DNA-Binding Proteins; Gene Silencing; Humans; Keratins; Mutation; Rhabdoid Tumor; Sequence Analysis, DNA; SMARCB1 Protein; Teratoma; Transcription Factors

Choroid plexus tumors are rare intraventricular papillary neoplasms derived from choroid plexus epithelium, which account for only between 0.4-0.6% of all intracranial and 2-3% of pediatric neoplasms. Plexus papillomas outnumber choroid plexus carcinomas by a ratio of 5:1 and around 80% of choroid plexus carcinomas arise in children. Plexus tumors are most common in the lateral and fourth ventricles; while 80% of lateral ventricle tumors present in children, fourth ventricle tumors are evenly distributed in all age groups. Clinically, choroid plexus tumors tend to cause hydrocephalus and increased intracranial pressure. Histologically, choroid plexus papillomas correspond to WHO grade I, choroid plexus carcinomas to WHO grade III. Immunohistochemically, cytokeratins and vimentin are expressed by virtually all choroid plexus papillomas and most choroid plexus carcinomas while transthyretin and S-100 protein are present in 80-90% of cases, less frequently, though, in choroid plexus carcinomas. Glial fibrillary acidic protein can be found focally in about 25-55% of choroid plexus papillomas and 20% of choroid plexus carcinomas. The mean Ki67/MIB1 labeling index for choroid plexus papillomas is 1.9%, for choroid plexus carcinomas 13. 8%. Choroid plexus papillomas typically show hyperdiploidy with gains particularly on chromosomes 7, 9, 12, 15, 17, and 18 while one choroid plexus carcinoma showed rearrangements of chromosomes 7p11-12, 9q11-12, 15q22, and 19q13.4. Choroid plexus papillomas can usually be cured by surgery alone with a 5-year survival rate of up to 100% with occasional recurrences while choroid plexus carcinomas grow more rapidly and have a less favorable outcome with a 5-year survival rate of 26-40%.

Topics: Animals; Choroid Plexus Neoplasms; Chromosome Aberrations; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Papilloma

Immunohistochemical analysis of 9 choroid plexus papillomas (CPPs) and 3 choroid plexus carcinomas (CPCs) using a panel of antibodies against glial fibrillary acidic protein (GFAP), cytokeratin (CK), epithelial membrane antigen (EMA), S-100 protein, vimentin (vim), and neuron specific enolase (NSE) is presented. Focal positivity was observed for GFAP in 11, vimentin in 7, cytokeratin in 2 and EMA in 3 cases. Diffuse and intense immunoreactivity for S-100 protein was seen in all papillomas, however, unreactive areas were noted in carcinomas. All cases exhibited focal to diffuse NSE positivity. Location and type of the tumour and age of the patient did not influence the staining pattern except for predominant S-100 positivity in papillomas. The significance of these findings is discussed in relation to the differential diagnosis or immunoreactivity patterns of these tumours.

Topics: Adult; Carcinoma; Child; Child, Preschool; Choroid Plexus Neoplasms; Female; Glial Fibrillary Acidic Protein; Glioma; Humans; Infant; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Mucins; Phosphopyruvate Hydratase; S100 Proteins; Sensitivity and Specificity; Vimentin

Choroid plexus papillomas (CPP) are rare, benign tumors of the central nervous system. They usually occur in the lateral ventricles in children and the fourth ventricle in adults. Extensive seeding along the neural axis is usually associated with malignant transformation of the tumor. We report a rare case of a 74-year-old patient with a fourth ventricle CPP associated with diffuse spinal deposits. Radiological and histological findings are presented and the relevant literature is discussed.

Topics: Aged; Choroid Plexus Neoplasms; Humans; Keratins; Magnetic Resonance Imaging; Male; Papilloma, Choroid Plexus; Spinal Cord Neoplasms

Rhabdoid tumours (RTs) are rare but highly aggressive tumours of childhood. Their rarity and their miscellaneous locations make the diagnosis particularly challenging for pathologists. Central nervous system and peripheral RTs have been associated with biallelic inactivation of the hSNF5/INI1/SMARCB1 (hSNF5/INI1) tumour suppressor gene. Immunohistochemistry (IHC) with a monoclonal anti-hSNF5/INI1 antibody has recently been proposed as an efficient diagnostic tool for RTs. We have conducted a retrospective study of 55 tumours referred to our institution with a suspicion of RT. This analysis included pathological review, IHC with anti-hSNF5/INI1 antibody, and molecular investigation using quantitative DNA fluorescent analysis and sequencing of the nine exons of hSNF5/INI1. The molecular lesion could be detected in 37 of the 39 cases exhibiting negative staining for hSNF5/INI1. In the two discrepant cases, the lack of detection of genetic abnormality was probably owing to the presence of a high number of non-tumour cells in the samples. This indicates that hSNF5/INI1 IHC is very sensitive and highly specific for the detection of hSNF5/INI1 loss-of-function. Among the 38 cases with typical RT histological features, six failed to exhibit hSNF5/INI1 mutation and stained positive for hSNF5/INI1. This strongly supports the evidence of a second genetic locus, distinct from hSNF5/INI1, associated with RT. Conversely, seven tumours with histological features poorly compatible with RT stained negative for hSNF5/INI1; they nevertheless exhibited an age of onset and a clinical behaviour similar to RT. This suggests that hSNF5/INI1 inactivation is not strictly limited to typical RT but characterizes a wider family of hSNF5/INI1-deficient tumours. Consequently, we believe that anti-hSNF5/INI1 IHC should be performed widely, even when the pathological characteristics are not typical. The molecular investigation should be performed in infants when a rhabdoid predisposition syndrome is suspected.

Topics: Adult; Biomarkers, Tumor; Carcinoma; Child, Preschool; Choroid Plexus Neoplasms; Chromosomal Proteins, Non-Histone; DNA Mutational Analysis; DNA-Binding Proteins; Female; Gene Deletion; Genetic Markers; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Infant; Keratins; Kidney Neoplasms; Male; Point Mutation; Retrospective Studies; Rhabdoid Tumor; SMARCB1 Protein; Transcription Factors; Vimentin

Chordoid glioma has been recently described as a slow-growing neoplasm with chordoid appearance, occurring exclusively in the regions of the third ventricle and hypothalamus of middle-aged women. We experienced a case of a 48-year-old woman with a suprasellar tumor composed of chordoid glioma and Rathke's cleft cyst, which was confirmed by histopathological, immunohistochemical and electron microscopic examinations. Histologically, chordoid glioma comprised the major part of the tumor, and the prominent Rathke's cleft cysts were distributed focally in the same tumor tissue without any transitions. Chordoid glioma was immunoreactive for glial fibrillary acidic protein, S-100 protein and vimentin, and focally positive for epithelial membrane antigen and CD34, while cytokeratin highlighted epithelial cells lining Rathke's cleft cysts. Ultrastructural examination of the chordoid glioma revealed short cytoplasmic processes, intermediate filaments, intercellular junctions of zonular adherens type, basal lamina, secretory granules and pinocytic vesicles. The ultrastructural observations of the current case are similar to those of the subcommisural organ, although cell body zonation or microvilli were not evident. The coexistence of chordoid glioma and Rathke's cleft cyst has not been reported previously and may represent a collision tumor.

Topics: Antigens, CD34; Central Nervous System Cysts; Choroid Plexus Neoplasms; Female; Glial Fibrillary Acidic Protein; Glioma; Humans; Immunohistochemistry; Keratins; Magnetic Resonance Imaging; Microscopy, Electron; Middle Aged; Mucin-1; S100 Proteins; Vimentin

The authors report a case of cystic choroid plexus papilloma that originated in the posterior fossa. No connection with the ventricular system was found intraoperatively. Magnetic resonance (MR) and computerized tomography imaging did not furnish a diagnosis, but findings of pathological examinations were consistent with those of choroid plexus papilloma. The authors describe the different appearances of the tumor on MR images and discuss the differential diagnosis with other tumors of the posterior fossa.

Topics: Choroid Plexus Neoplasms; Cranial Fossa, Posterior; Cyst Fluid; Diagnosis, Differential; Hemangioblastoma; Humans; Keratins; Magnetic Resonance Imaging; Male; Middle Aged; Papilloma, Choroid Plexus; S100 Proteins; Tomography, X-Ray Computed

Tumors derived from choroid plexus epithelium are uncommon and may exhibit a wide variety of histologic patterns. They often are difficult to distinguish from metastatic carcinomas. Previous studies that addressed this issue yielded conflicting results. Recent reports have demonstrated that evaluation of coordinate expression of cytokeratin (CK) 7 and CK20 aids in distinguishing primary from metastatic lesions in a number of anatomic sites and that tumors that commonly are metastatic to the brain retain their CK7/CK20 immunophenotype in this location. We examined 35 choroid plexus tumors with a panel of antibodies to determine their CK7/CK20 immunophenotype. Tumors from 35 patients (7 male, 28 female; mean age, 25 years), including 31 choroid plexus papillomas and 4 atypical papillomas, were evaluated. All tumors were intraventricular or within the cerebellopontine angle and composed predominantly of orderly columnar epithelial cells resting on distinct fibrovascular cores. Atypical papillomas contained combinations of focal loss of architectural pattern, increased mitotic activity, necrosis, and brain parenchymal invasion. No lesion was unequivocally malignant. Twenty-six tumors (74%), including all atypical papillomas, were CK7 positive and CK20 negative. Two tumors stained with both markers, one stained with CK20 only, and six stained with neither marker. Other findings included expression of glial fibrillary acidic protein in 24 tumors, S-100 protein in 19 tumors, transthyretin in 31 tumors, Ber EP4 in 1 tumor, CAM5.2 in 33 tumors, epithelial membrane antigen in 4 tumors, and pancytokeratin in 27 tumors. Our results indicate that the majority of choroid plexus tumors have a CK7-positive/CK20-negative immunophenotype. This finding may be useful in differentiating these lesions from metastatic carcinomas that have differing CK7/CK20 profiles.

Topics: Adolescent; Adult; Aged; Biomarkers; Child; Child, Preschool; Choroid Plexus Neoplasms; Female; Humans; Immunophenotyping; Infant; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Neoplasm Metastasis

Neoplasms of the choroid plexus are very rare in the rat, and few cases have been described. We report on a spontaneously occurring choroid plexus carcinoma arising from the fourth ventricle in a 2-year-old female albino rat. The infiltrative growth was observed in the adjacent brain parenchyma, in the wall of the vessels of the circle of Willis, in the perivascular space of VIRCHOW and ROBIN and in the leptomeninges. Immunohistochemical investigations demonstrated positive staining for cytokeratin (Lu-5) indicating that choroid plexus tumors in the rat express epithelial differentiation. The diagnosis was made on the basis of microscopical and immunohistochemical findings.

Topics: Animals; Carcinoma; Cerebral Ventricles; Choroid Plexus Neoplasms; Female; Immunohistochemistry; Keratins; Rats; Rats, Sprague-Dawley

Intermediate filament and S100 expression was studied in five cases of choroid plexus papilloma. All the cases showed positivity for S100 and Nimentin. Cytokeratin and glial fibrillary protein (GFAP) intermediate filaments were present in 80 pc of the cases. None of the cases expressed epithelial membrane antigen. These results confirm the divergent differentiation of choroid plexus tumours.

Topics: Adolescent; Adult; Cell Transformation, Neoplastic; Child, Preschool; Choroid Plexus Neoplasms; Diagnosis, Differential; Female; Glial Fibrillary Acidic Protein; Glioma; Humans; Immunohistochemistry; Infant; Keratins; Male; S100 Proteins; Vimentin

Clinical and immunophenotypic (IP) data are presented on three children with choroid plexus (CP) tumors. Two children ages 0.2 and 2 years old with histologically proven malignant tumors had subtotal tumor resections and were treated with ten monthly cycles of eight-drugs-in-1-day chemotherapy without radiation therapy (XRT). Both are free of tumor 4 and 7 years later. The literature on survival of children with CP carcinomas after chemotherapy and XRT is reviewed. Monoclonal antibodies to 17 neuroectodermal, neuronal, glial, and leukocytic markers on frozen sections were used to IP the two malignant tumors and a CP papilloma. All tumors expressed two neuroectodermal markers (PI-153/3 and UJ 223.8), cytokeratin 19, and a neural and leukocyte marker (Thy-1). Two of three expressed neurofilament protein (NF-H) and glial fibrillary acidic protein (GFAP) and one expressed NF-M and common leukocyte antigen. None had strong expression for the panneuroectodermal antigen UJ13/A. There was variable expression of the other markers. The most common IP profile for CP tumors (cytokeratin 18+, PI-153/3+, Thy-1+, UJ 223.8+, and GFAP+ and UJ13A-, UJ 127.11-, and NF-L-) is discussed in the context of the current knowledge of the ontogenetic origin of the CP. It was concluded that chemotherapy for malignant CP tumors can be associated with long-term survival in young children and that the unique IP profile of CP tumors with coexpression of three intermediate filaments suggests new and provocative evidence of their cellular complexity and heterogeneity.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Child; Child, Preschool; Choroid Plexus Neoplasms; Female; Follow-Up Studies; Glial Fibrillary Acidic Protein; Humans; Immunophenotyping; Keratins; Male; Neurofilament Proteins; Tomography, X-Ray Computed

An immunohistochemical study of glial fibrillary acidic protein (GFAP), S-100 protein, cytokeratin (CKER), epithelial membrane antigen (EMA), and transthyretin (TTR) was carried out on 11 cases of choroid plexus papilloma (CPP) and 19 of ependymoma, using the peroxidase antiperoxidase technique. Among the 11 cases of CPP, all 11 were positive for CKER, EMA, and TTR, 10 for S-100 protein, and five for GFAP. Most of the GFAP-positive papilloma cells were simultaneously positive for CKER. However, these GFAP-positive cells were negative for TTR. Among the 19 cases of ependymoma, 16 were positive for GFAP, 17 for S-100 protein, three for CKER, eight for EMA, but none for TTR. Some GFAP-positive cells were also stained for CKER. However, TTR was not found in any of the ependymal cells. These findings suggested that CPP cells which show ependymal or glial differentiation lost the ability to synthesize TTR which is known to be synthesized in the epithelial cells of the choroid plexus. The more GFAP-positive cells present in a CPP, fewer TTR-positive cells are present. Though CPPs are usually easily distinguishable from ependymomas, occasional doubt arises concerning the differential diagnosis between CPP and papillary ependymoma. TTR can be a very useful diagnostic marker of CPP.

Topics: Adult; Biomarkers, Tumor; Child; Child, Preschool; Choroid Plexus Neoplasms; Diagnosis, Differential; Ependymoma; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Infant; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Papilloma; Prealbumin; S100 Proteins