Medulloblastoma, WHO Grade IV, with divergent differentiation including myoblastic, glial, osteoblastic and chondroblastic differentiation
Medulloblastomas (MB) are the most common malignant CNS tumors of childhood (1). But only 1% of all adult CNS tumors are MBs (3). In the WHO classification, medulloblastomas are classified into four categories including classic, desmoplastic/nodular, medulloblastoma with extensive nodularity, large cell and anaplastic (2). The medullomyoblastoma and melanotic MB, which were listed as variants in the WHO 2000 classification, have been removed from the WHO 2007 classification, on the basis that rhabdomyoblastic differentiation and the melanotic phenotype can occur in other variants. Regarding the origin of the myoblastic and melanotic element of MB, it is suggested that either primitive neuroectodermal cells may undergo differentiation into these elements or these may be part of malignant teratoma or teratoid tumor (5). Apart from the entities listed under MB in the WHO classification, other divergent differentiations occur rarely (4). These deserve mention because they are difficult to classify and can shed light on the biological nature of MBs. In the index case undifferentiated spindle cells showed positivity for synaptophysin and muscle markers. Spindle cell areas were morphologically and immunohistochemically similar to classic MB whereas these show muscle differentiation on immunohistochemistry. No discernible cross striations were recognized however. There was clear cut osseous and chondroid metaplasia in addition to glial differentiation. MIB-1 (Ki-67) showed regional heterogeneity which labeled many spindle cells but none of the glial cells and osseous or cartilaginous areas.
Differential diagnosis of medulloblastoma with divergent differentiation, ependymoma, high grade glioma/gliosarcoma, primary sarcoma, atypical teratoid/rhabdoid (ATRT) tumor or malignant teratoma was considered. Ependymoma was ruled out as undifferentiated spindle cells were negative for EMA and S-100. No characteristic rosettes were identified. GFAP expression was not seen in malignant cells however only intermixed fibrillary areas were positive. ATRT occurs in pediatric age group below 5 years and beyond that it practically never exists. We prefer to regard this tumor as example of unusually divergent differentiation in a MB. True teratomas typically occur at other sites in the CNS, such as the pineal gland, and must contain elements derived from all three germ cell layers. By exclusion, this can be regarded as MB with unusual divergent differentiation. Although this exceptional tumor typifies the varied phenotypic range of MB, it does not fit well into the current or prior WHO classifications. However such divergent differentiation has prompted discussion of the relationship between MB and teratoma. Our report adds to the literature on the phenotypic diversity of MB.
Contributed by Deepali Jain, MD, DNB, Subimal Roy, MD, PhD, Sunita Bhalla, MD, Veer Singh Mehta, MS, Mch