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/anapl astic (LC/A) medulloblastoma is characterized by frequent dissemination of cerebrospinal fluid (CSF) at presentation and a more aggressive clinical co urse. The authors report on their examination of the clinicopathological an d 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 criter ia for LC/A medulloblastoma. In three cases (43%) either desmoplastic or cl assic medulloblastoma was the underlying subtype, and in two cases (28%) th e LC/A tumor was found within the setting of medullomyoblastoma. Fluorescen ce 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 a mplification. The patients' clinical histories revealed CSF dissemination i n all cases and lymph node metastasis in one case. Isochromosome 17q was fo und in five (83%) of six cases. Evidence of chromosomal gains indicated ane uploidy in three tumors (50%), and amplification of c-myc was found in thre e tumors (50%). No 22q deletions were encountered. Conclusions. A high percentage of LC/A medulloblastomas arise within a back ground of typical medulloblastomas or medullomyoblastomas. As is the case i n conventional medulloblastomas, the presence of 17q is a common early tumo rigenic event; however, in a significant percentage of specimens there is a lso evidence of aneuploidy and/or amplification of c-myc. These findings in dicate that LC/A morphological characteristics reflect a more advanced tumo r stage than that found in pure medulloblastomas or in typical medullomyobl astomas.