1/13. HPV in situ hybridization with catalyzed signal amplification and polymerase chain reaction in establishing cerebellar metastasis of a cervical carcinoma.We report an unusual case of cerebellar metastasis from a cervical adenosquamous carcinoma in which molecular techniques assisted in establishing the correct diagnosis. The patient was a 43-year-old woman with surgically unresectable cervical carcinoma diagnosed 2 years before presenting with neurological symptoms. A magnetic resonance imaging scan showed a large, enhancing cerebellar lesion with significant brain stem compression. The excised cerebellar tumor resembled a small cell carcinoma and was initially not thought to be a metastasis from the cervical adenosquamous carcinoma. in situ hybridization with catalyzed signal amplification and polymerase chain reactions with primers specific for human papilloma virus (HPV) types 16 and 18 were used to determine the relationship between the cervical and the cerebellar neoplasms. A positive signal was present in the nuclei of both neoplasms by in situ hybridization using HPV16/18 dna probes. polymerase chain reaction revealed the presence of HPV-18 DNA sequences in the cervical and cerebellar neoplasms confirming that the cerebellar neoplasm was a metastasis from the cervical primary.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/13. Oncogene amplification in medulloblastoma: analysis of a case by comparative genomic hybridization and fluorescence in situ hybridization.We describe amplification of the MYCC oncogene in a medulloblastoma with aggressive clinical behavior. The patient was a six year old boy who underwent gross total surgical excision of a cerebellar tumor. Despite chemotherapy and total neuraxis radiation, the clinical course was one of relentless progression, with extensive subarachnoid spread and death within eight months of presentation. The pathological features were consistent with the recently described, "large cell variant" of medulloblastoma. Tumor cells exhibited large vesicular nuclei, prominent nucleoli and strong immunoreactivity for synaptophysin. polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) assay revealed no evidence of MYCN amplification or 1p deletion in the tumor. FISH analysis revealed evidence of MYCC amplification in the 20- to 30-fold range. Comparative genomic hybridization (CGH) revealed regions of gains and amplification in three locations, with gains of chromosome 7, amplification of 8q24 (corresponding to the MYCC locus) and gains of the long arm of chromosome 17 (suggestive of isochromosome 17q). While conventional karyotypic analysis was not successful in the present case, CGH provided invaluable information about gene amplification and losses/gains of chromosomes and chromosomal regions. Thus, CGH is a powerful technique applicable to frozen or paraffin-embedded material which helps to ascertain the presence of gene amplification even without prior knowledge of the gene to be tested.- - - - - - - - - - ranking = 1.6666666666667keywords = hybridization (Clic here for more details about this article) |
3/13. Multiple genomic alterations including N-myc amplification in a primary large cell medulloblastoma.The large cell (LC) subtype is a recently described histologic variant of medulloblastoma (Mb) associated with a rapid and aggressive clinical course. We describe the genomic profile of a LC-Mb tumor obtained from a patient who developed recurrent and fulminant disease despite 'good-risk' features at diagnosis and state- of-the-art multidisciplinary therapy. The tumor sample was analyzed using comparative genomic hybridization (CGH) and complementary molecular approaches. CGH revealed amplicons at chromosome bands 2p24-25, 2q12-22, and 17p11; losses of chromosomes 11q and 18; and low-level gains of 3q, 11p, 13q and 14q. Southern blot analysis confirmed N-myc amplification. No evidence of p53 mutation was detected. The genomic profile of this LC-Mb tumor sample revealed a distinctive pattern of genetic alterations including amplification of N-myc and anonymous oncogenes at chromosome bands 2q12-22 and 17p11. These genomic abnormalities are uncommon in other subtypes of Mb.- - - - - - - - - - ranking = 0.16666666666667keywords = hybridization (Clic here for more details about this article) |
4/13. comparative genomic hybridization of medulloblastomas and clinical relevance: eleven new cases and a review of the literature.Medulloblastomas are highly malignant primitive neuroectodermal tumors of the cerebellum that display a wide variety of histopathological patterns. However, these patterns do not provide an accurate prediction of clinical-biological behavior and no satisfactory morphological grading system has ever been presented. Genetic alterations may provide additional diagnostic information and allow clinically relevant subgrouping of primitive neuroectodermal tumors. We examined 10 medulloblastomas and one medulloblastoma cell line. One amplification site on chromosome 8q24 was detected in the cell line corresponding to the known amplification of the c-myc gene in this cell line. The gain of 2p21-24 in two tumors was shown to represent amplification of the N-myc gene by Southern blot hybridization and fluorescence in situ hybridization. The data show that the isochromosome 17 can be recognized using comparative genomic hybridization (CGH) by the typical combination of loss of 17p combined with gain of 17q. No specific pattern of genetic alterations could be linked to the clinical behavior of the tumors. We have compared our results with previous CGH studies on medulloblastomas.- - - - - - - - - - ranking = 1.1666666666667keywords = hybridization (Clic here for more details about this article) |
5/13. Large cell/anaplastic medulloblastomas and medullomyoblastomas: clinicopathological and genetic features.OBJECT: medulloblastoma is the most common malignant central nervous system neoplasm found in children. A distinct variant designated large cell/anaplastic (LC/A) medulloblastoma is characterized by frequent dissemination of cerebrospinal fluid (CSF) at presentation and a more aggressive clinical course. The authors report on their examination of the clinicopathological and genetic features of seven such cases encountered at their institution. methods: Eighty cases of medulloblastomas were reviewed and seven (8.8%) of these were believed to fit the histological and immunohistochemical criteria for LC/A medulloblastoma. In three cases (43%) either desmoplastic or classic medulloblastoma was the underlying subtype, and in two cases (28%) the LC/A tumor was found within the setting of medullomyoblastoma. fluorescence in situ hybridization was used in six of the seven cases to characterize the presence of isochromosome 17q, deletion of chromosome 22q (a deletion characteristically found in atypical teratoid/rhabdoid tumors), and c-myc amplification. The patients' clinical histories revealed CSF dissemination in all cases and lymph node metastasis in one case. Isochromosome 17q was found in five (83%) of six cases. Evidence of chromosomal gains indicated aneuploidy in three tumors (50%), and amplification of c-myc was found in three tumors (50%). No 22q deletions were encountered. CONCLUSIONS: A high percentage of LC/A medulloblastomas arise within a background of typical medulloblastomas or medullomyoblastomas. As is the case in conventional medulloblastomas, the presence of 17q is a common early tumorigenic event; however, in a significant percentage of specimens there is also evidence of aneuploidy and/or amplification of c-myc. These findings indicate that LC/A morphological characteristics reflect a more advanced tumor stage than that found in pure medulloblastomas or in typical medullomyoblastomas.- - - - - - - - - - ranking = 0.16666666666667keywords = hybridization (Clic here for more details about this article) |
6/13. Trilateral retinoblastoma variant indicative of the relevance of the retinoblastoma tumor-suppressor pathway to medulloblastomas in humans.Results of recent studies have led investigators to suggest that the retinoblastoma tumor-suppressor (rb) gene plays an underappreciated role in the genesis of brain tumors. Such tumors cause significant rates of mortality in children suffering from hereditary retinoblastoma. It has been assumed that the pineal gland, which is ontogenetically related to the retina, accounts for the intracranial origin of these trilateral neoplasms. To address this issue, the authors describe an unusual trilateral retinoblastoma variant. The authors provide a detailed clinicopathological correlation by describing the case of a child with bilateral retinoblastoma who died of a medulloblastoma. The intraocular and intracranial neoplasms were characterized by performing detailed imaging, histopathological, and postmortem studies. karyotype analysis and fluorescence in situ hybridization were used to define the chromosomal defect carried by the patient and members of her family. An insertion of the q12.3q21.3 segment of chromosome 13 into chromosome 18 at band q23 was identified in members of the patient's family. This translocation was unbalanced in the proband. The intraocular and cerebellar neoplasms were found to be separate primary neoplasms. Furthermore, the pineal gland was normal and the cerebellar neoplasm arose within the vermis as a medulloblastoma. Finally, the two neoplasms had different and characteristically identifiable cytolological and immunohistochemical profiles. The findings of the present study, taken together with those of recent molecular and transgenic studies, support the emerging concept that rb inactivation is not restricted to central nervous system regions of photoreceptor lineage and that inactivation of this tumor suppressor pathway may be relevant to the determination of etiological factors leading to medulloblastoma in humans.- - - - - - - - - - ranking = 0.16666666666667keywords = hybridization (Clic here for more details about this article) |
7/13. Clinical and molecular analysis of disseminated hemangioblastomatosis of the central nervous system in patients without von hippel-lindau disease. Report of four cases.Hemangioblastomas of the central nervous system (CNS) may occur sporadically or in association with von Hippel-Lindau (VHL) syndrome. The authors present four patients with no family history or clinical evidence of VHL syndrome in whom extensive, progressive, en plaque coating of the brainstem and spinal cord with hemangioblastomas developed 1 to 8 years after complete resection of a solitary cerebellar hemangioblastoma. Analysis included detailed physical, biochemical, radiological, and pathological examinations in all four patients, combined with family pedigree analysis. In addition, a detailed investigation of the VHL gene was undertaken. Allelic loss, comparative genomic hybridization (CGH), single-stranded conformational polymorphism screening, CpG island methylation status, and x chromosome inactivation clonality analyses were performed. Although there was no evidence of germline alterations in the VHL gene on clinical and radiological examination or in the family history (all four patients) or analysis of peripheral blood (three patients), somatic deletion of one copy of the VHL gene occurred in these tumors. These findings indicate that the multiple, separate deposits of tumors were likely derived from a single clone. Results of CGH indicate that one or several additional genes are probably involved in the malignant behavior of the hemangioblastomas in these patients. Furthermore, the malignant biological and clinical behavior of these tumors, in which multiple sites of subarachnoid dissemination developed 1 to 8 years after initial complete resection, followed by progressive tumor growth and death of the patients, occurred despite a histological appearance typical of benign hemangioblastomas. Malignant hemangioblastomatosis developed 1 to 8 years after resection of an isolated cerebellar hemangioblastoma. Alterations of the VHL gene may be permissive in this setting, but other genes are likely to be the source of the novel biological and clinical presentation of the disseminated hemangioblastomas in these patients. This appears to represent a novel condition in which the product of one or more mutations in several genes permits malignant tumor behavior despite retention of a benign histological picture, a circumstance previously not recognized in CNS tumors.- - - - - - - - - - ranking = 0.16666666666667keywords = hybridization (Clic here for more details about this article) |
8/13. Development of brain metastasis 5 years before the appearance of the primary lung cancer: "messenger metachronous metastasis".We report a patient with a brain metastasis that presented 5 years before the primary adenocarcinoma of the lung from which it originated. The metastasis and the primary tumor were removed. To confirm their common origin, we used comparative genomic hybridization. We have named this type of metastasis "messenger metachronous metastasis." The patient remains well 79 months after the brain metastasectomy and 18 months after the lung surgery.- - - - - - - - - - ranking = 0.16666666666667keywords = hybridization (Clic here for more details about this article) |
9/13. Primitive neuroectodermal tumor in the cerebellopontine angle with isochromosome 17q presenting as meningioma in a woman 26 years of age.An unusual posterior fossa neoplasm in a 26-year-old woman with short history of the cerebellar symptoms is presented. CT and MR images showed the tumor within the cerebellopontine angle, suspected as meningioma. At surgery, the tumor was dura-attached and did not infiltrate the arachnoid. Histologically, the neoplasm was a small blue cell tumor with solid and microcystic pattern, consistent with primitive neuroectodermal tumor (PNET). Immunohistochemically the cells were strongly positive for NCAM and GFAP. fluorescence in situ hybridization (FISH) was performed with the cosmids G9 and F7 (flanking EWSR1/22q12 region) dna probes and dual-color spectrum-orange LSI HER-2/neu (17q11.2)/spectrum green CEP17 (17p11.1-q11.1) DNA probe. The presence of isochromosome 17q within neoplastic cells was found. The tumor was classified as a medulloblastoma. We demonstrate the utility of a multidisciplinary approach to nervous system tumor diagnosis. The clinical features together with histological, immunohistochemical, and characteristic molecular alteration allowed classification of the presented case.- - - - - - - - - - ranking = 0.16666666666667keywords = hybridization (Clic here for more details about this article) |
10/13. Epstein-Barr virus-associated primary B-cell lymphoproliferative disorder of the cerebellum in an immune competent man.BACKGROUND. The role of the Epstein-Barr virus (EBV) in lymphoproliferative lesions has been widely accepted. Most of these lesions occur in patients who have deficiencies in their immune status. lymphomatoid granulomatosis (LG) is a lymphoproliferative disorder originally characterized as an angiocentric, necrotizing, pleomorphic infiltrate of mononuclear cells. The etiology of LG is unknown. It was originally hypothesized that LG may represent an unusual lymphoid response to an infective organism, possibly EBV. methods. tissues from a previously healthy 60-year-old, healthy white man with primary cerebellar lymphomatoid granulomatosis were examined for the presence of EBV by nucleic acid hybridization. RESULTS. The original LG lesion was a polyclonal B-cell proliferation that contained detectable amounts of EBV. Peripheral blood leukocytes were negative for EBV by the same assay. After an 18-month remission, a tumor reappeared near the site of the primary lesion, which had the histologic appearance of a lymphoma. The cells showed restricted clonality and contained a similar amount of EBV-related DNA as the original lesion. Peripheral blood leukocytes at the time of recurrence were negative for EBV. The patient died approximately 2 months after the recurrent tumor was detected. CONCLUSIONS. This case demonstrated the development of a primary cerebellar B-cell lymphoproliferative disorder, histologically identical to lymphomatoid granulomatosis, that transformed into a lymphoma. The original tumor and the subsequent lymphoma contained, on average, several copies of EBV-related DNA per cell. Despite an extensive survey of the patient, no immune deficit was detected. Interpretation of the literature with the results of this case suggest that this instance of primary cerebellar LG arose as a consequence of an unusual EBV-associated B-cell lymphoproliferation. It is suggested that EBV may be a significant factor in the initiation of the abnormal proliferations of T-cells or B-cells reported in this disorder.- - - - - - - - - - ranking = 0.16666666666667keywords = hybridization (Clic here for more details about this article) |
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