Adult medulloblastoma: review of 13 cases with emphasis on MRI

Medulloblastomas are generally associated with childhood, but 14–30% occur in adults, accounting for 1% of adult central nervous system tumors. While approximately one third of adult medulloblastomas present as vermian tumors similar to those seen in childhood, the majority differ substantially from the childhood variety. In this series of 13 patients, 5 had lateral, seemingly extra-axial masses in the cerebellopontine angle or at the tentorium, simulating meningiomas or acoustic neuromas, but angiographic hypovascularity in 2 of the latter suggested a diagnosis other than meningioma. Of 4 paramedian tumors, 3 diffusely infiltrated the cerebellar white matter, showed little or no gadolinium enhancement and were not associated with hydrocephalus. Hydrocephalus was present in less than half of our patients; in childhood the reported incidence is 85–100%. A possible association with pregancy was noted.     

Medulloblastoma in adulthood: Prognostic factors influencing survival and recurrence

Summary Thirty adult patients presenting with medulloblastoma between 1974 and 1991 were studied and treated at Puerta de Hierro Clinic. After diagnosis, all patients were treated by surgery followed by radiotherapy and eight of them received adjuvant chemotherapy. We have studied the influence of some factors such as age, sex, location of tumour in the cerebellum, amount of surgical resection and histological variants on survival and recurrence of the disease. Only the histological type has a statistically significant influence on survival and recurrence: we have found that patients presenting classic medulloblastoma have a long survival and a long relapse-free interval.     

Ganglioside mapping of a human medulloblastoma xenograft

Summary The ganglioside patterns of medulloblastomas have never been established; in this study we report the ganglioside profile of the human medulloblastoma cell line TE-671 grown as a xenograft in nude mice. Gangliosides were isolated and structurally analyzed by fast atom bombardment mass spectometry following permethylation. Identification of individual gangliosides was also performed by immunostaining of high-performance thin-layer chromatography-separated bands. Total ganglioside levels of 0.20 mol/g of tissue were obtained, consistent with those reported for human glioma cell lines grown as xenografts; predominant monosialogangliosides of TE-671 xenografts were II³--NeuAc-LacCer (GM3) and II³--NeuAc-GgOse₃ Cer (GM2) but there were also relatively large proportions of IV³--NeuAc-LcOse₄Cer (3-isoLM1), IV³--NeuAc-nLcOse₄Cer (3-LM1) and a further ganglioside of the neolactoseries with an extra lactosamine moiety. The only oligosialoganglioside detected was IV³, II³--NeuAc₂-GgOse₄Cer (GD1a).Abbreviations: The gangliosides have been designated according to Svenerholm [18] GM3 II³--NeuAc-LacCer - GM2 II³--NeuAc-GgOse₃Cer - GM1 II³--NeuAc-GgOse₄Cer - 3-LM1 IV³--NeuAc-nLcOse₄Cer - 3-isoLMI IV³--NeuAc-LcOse₄Cer - Fuc-3-isoLMI IV³--NeuAc, III⁴-Fuc-LcOse₄Cer - GD1a IV³, II³--NeuAc₂-GgOse₄Cer - FAB-MS Fast atom bombardment-mass spectometry - GC-MS gas chromatography-mass spectometry Supported by NC1 RO1 CA11898 to Dr. Bigner and B8803X-00627-24B from the Swedish Medical Research Council to Dr. L. Svennerholm     

Medulloblastoma in children and in adults: a comparative study

Summary We report on the clinical and pathological characters and factors influencing prognosis in a consecutive series of 20 cases of medulloblastoma presenting in childhood and of 20 cases of the tumour presenting in adulthood. The significant differences which emerged were compared with the findings of the largest published series. Medulloblastoma is more often lateral in site and desmoplastic in histology in adults than in children. On our evidence the age at tumour onset not affect survival.     

Paediatric medulloblastoma: Atypical CT features at presentation in the SIOP II trial

Summary A review of cranial CT studies of 233 patients for the Second Medulloblastoma Trial of the International Society of Paediatric Oncology showed typical CT appearances in only 30% of patients. The varied appearances encountered are described with particular emphasis on atypical CT features.A shorter version of this paper was published in the Proceedings of the XIV Symposium Neuroradiologicum (Neuroradiology (1991) 33 [Suppl]: 516–517)     

Second cancers after medulloblastoma: population-based results from the United States and Sweden

Medulloblastoma, one of the most common central nervous system(CNS)tumors in children, requires aggressive multimodality therapy including surgery, radiation therapy, and occasionally chemotherapy. Given its intensive treatment regimen and improved survival during the past 20 years, it is likely that a cohort of survivors will result who may incur consequences of therapy, including a second cancer. We used population-based data from the United States and Sweden to estimate risks of second neo plasms in patients with histologically confirmed medulloblastoma (n = 1,262).Overall, there was a 5.4-fold excess of second neoplasms (95 percent confidence interval = 3.3-8.4) based on 20 observed and 3.7 expected cancers. The second cancers occurred eight to 432 months after initial diagnosis(median, 73 months) with significantly elevated ratios for all intervals examined except for less than one year after initial diagnosis. Significantly elevated risks were seen for cancers of the salivary glands, cervix uteri, brain and CNS, thyroid gland, and acute lymphoblastic leukemia. Of the 15second cancers with treatment data, seven occurred in the radiation field or within areas of scatter while two others may have been radiation-related. Although based on small numbers of second cancers, the results suggest that as survival increases, some patients with medulloblastoma will have an increased risk of a second cancer, particularly a radiation-related cancer. Thus, as survival improves, late-occurring consequences of diagnosis and treatment will need to be carefully assessed. Identification of patients hypersensitive to radiation therapy, such as those with Gorlin Syndrome, should also be attempted in order to reduce the sequelae from intensive radiation exposure. This revised version was published online in July 2006 with corrections to the Cover Date.     

MYCN AMPLIFICATION IN MEDULLOBLASTOMA

Prominent neuronal differentiation and MYCN amplification occur only in a small percentage of medulloblastomas (primitive neuroectodermal tumor of the cerebellum). In this article, we describe two medulloblastomas that showed a striking degree of neuronal differentiation with islands of mature neurons associated with abundant neuropil. In these differentiated foci, there were no mitoses or atypia, and the histology was reminiscent of a malformative or hamartomatous lesion. Both tumors were assessed for MYCN amplification by the novel technique of differential polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH). In case 1, MYCN amplification was in the 10 - fold range determined by differential PCR, while in case 2 the level of amplification was marked, with 20 - 30 copies compared with diploid controls. FISH analysis also confirmed the presence of MYCN amplification in both tumors. These two cases are of great interest, especially as they show MYCN amplification in medulloblastomas with marked degree of neuronal differentiation. Furthermore, in both cases, there was evidence of a slower and more indolent clinical course, suggesting a more favorable outcome in medulloblastoma with this degree of neuronal differentiation.     

Medulloblastoma in an adult suggestive of external granule cells as its origin: A histological and immunohistochemical study

We describe a rare case of medulloblastoma in an adult woman with histological findings suggesting an origin for this neoplasm in the external granular layer or its remnants. The patient presented with cerebellar dysfunction, and neuroimaging revealed a right cerebellar mass lesion. Pathological examination of the operative specimen revealed a medulloblastoma with occasional areas of neuronal or glial differentiation. Zic protein was also detected immunohistochemically in the tumor cells. The tumor cells were mainly distributed in the subarachnoid space and extended to the cerebellar parenchyma through the perivascular space to form tumor nodules. A suggestive finding, as concerns the origin of this neoplasm, was that the tumor cells were also spread evenly along the subpial zone of the molecular layer, reminiscent of the cellular architecture of the fetal external granular layer.     

Silencing of DNA repair sensitizes pediatric brain tumor cells to γ-irradiation using gold nanoparticles

We present a nanoparticle (NP)-mediated delivery vehicle that effectively carries and protects siRNA in pediatric ependymoma (EP) and medulloblastoma (MB) cells. The delivery vehicle consists of gold NPs coated with a polymeric shell comprising polyethylene glycol (PG), chitosan and polyethyleneimine (Au-CP-PEI). NPs loaded with siRNA knocked down Ape1 expression by over 75% in both MB and EP cells. Further, this reduction in Ape1 expression is associated with an increase in DNA damage after irradiation. The results indicate that NP-associated delivery of siApe1 is a feasible approach to circumventing pediatric brain tumor resistance to radiation therapy.