Idiosyncratic differentiation in medulloblastoma – a report of two exceptional cases

The medulloblastoma (MB), an embryonal tumour of the cerebellum, occurs in both adults and children, but is more prevalent in children; 70% occur in individuals under 16 years of age [1]. In the new World Health Organization (WHO) 2007 classification of nervous system tumours, the following variants of MB are listed: desmoplastic MB, MB with extensive nodularity (MBEN), anaplastic MB and large cell MB. The biological behaviours of the classic MB and these variants are distinct: large cell and anaplastic MBs have a more aggressive behaviour, while the MBEN and desmoplastic variant are associated with a better outcome [2–4]. In addition, certain molecular abnormalities are associated with these variants, such as MYCC and MYCN amplification with anaplastic and large cell MBs [5]. The medullomyoblastoma and melanotic MB, which were listed as variants in the WHO 2000 classification, have been dropped from the WHO 2007 classification, on the basis that rhabdomyoblastic differentiation and the melanotic phenotype can occur across MB variants. Apart from the entities listed under MB in the WHO classification, idiosyncratic variants occur rarely. As an exceptional group, these deserve mention because they are difficult to classify and can shed light on the biological nature of MBs. In this report, we describe two examples. Case 1: A 2.5-year-old boy presented with obstructive hydrocephalus, and magnetic resonance imaging showed a heterogeneously enhancing 4.5-cm mass within the fourth ventricle and cerebellar white matter. At macroscopic examination, the tumour consisted of focally haemorrhagic, soft grey tissue. Microscopic assessment demonstrated groups of undifferentiated neuroepithelial cells with a high nuclear : cytoplasmic ratio and a high mitotic count. This embryonal element was characteristic of a primitive neuroectodermal tumour (PNET), but was admixed with rhabdomyoblastic and melanotic elements (Figure 1). The former was represented by scattered large round cells and sporadic ‘strap’ cells, both of which were immunoreactive for skeletal muscle markers. The latter was represented by foci of epithelioid cells that formed tubules and contained tiny deposits of melanin. The tubules lacked mitotic activity and other cytological features of the tubular structures found in medulloepithelioma. In addition to these unusual phenotypes, there were foci of neurocytic differentiation. There was also focal anaplasia, but its extent was insufficient to place this MB into the anaplastic category. Early in the postoperative period, the patient developed leptomeningeal dissemination. Case 2: A 9-year-old boy underwent a head computerized tomography scan following minor head trauma. This revealed an unsuspected asymptomatic midline posterior fossa mass. At macroscopic examination, the resected mass consisted of gelatinous pink-grey tissue, measuring 9 ¥ 6 ¥ 2 cm in aggregate. Microscopic evaluation revealed a MB with biphasic phenotype. Apart from the usual PNET element, small compact monomorphic cells with dark speckled chromatin formed nodules and irregular islands (Figure 2). The PNET element was characterized by slightly larger cells that exhibited mild to moderate pleomorphism, and by a few foci of anaplasia, which were insufficient to qualify the tumour as an anaplastic variant. Mitotic figures were found among the characteristic PNET cells, but not among the small densely packed monomorphic cells. Critically, desmoplasia was absent from the PNET and smaller monomorphic cell elements. The small dense cells exhibited a neuronal immunophenotype, being strongly reactive for synaptophysin and Neu-N. The PNET element showed weak immunoreactivity for synaptophysin. Expression of P27 was generally confined to the small neurocytic cells. Regional heterogeneity was also seen with Ki-67 antibody staining, which labelled many cells among the PNET population, but none of the smaller neurocytic cells. These two exceptional tumours exemplify the diverse phenotypic range that can characterize MBs. Neither case fits well into the current or prior WHO classifications. By exclusion, they can perhaps be regarded as classic MBs with unusual divergent differentiation.