|Contributed by Azzam Ismail MD1, Jayne M. Lamont, PhD3, Deborah A. Tweddle, MBChB, PhD2,3, Andrew D. Pearson, MD2,3, Steven C. Clifford, PhD2,3, David W. Ellison, MD, PhD1,2,3.|
|Departments of Neuropathology1 and Child Health2, Newcastle-upon-Tyne Hospitals Trust and Northern Institute for Cancer Research3, University of Newcastle, Newcastle-upon-Tyne, UK..|
|Published on line in January 2005|
A boy aged 7 years was investigated for dizziness, diplopia and occasional visual hallucinations over a period of three months. Examination revealed mild nystagmus and left-sided cerebellar signs, including ataxia and dysdiadochokinesis. A mass arising from the roof of the fourth ventricle was demonstrated on MRI (Fig. 1). No other radiologic abnormalities were present within the neuraxis. Serum AFP was 1KU/L, and HCG was < 1 IU/L. The tumor was removed via a posterior fossa craniotomy. The child received craniospinal radiotherapy and cisplatin-based chemotherapy, and remains well 44 months post-surgery.
Macroscopic examination revealed pieces of tumor measuring 27mm across altogether, and were characterized by firm gray and soft pink elements.
Microscopy revealed that the tumor had two principal components. The first consisted of undifferentiated small cells with mildly pleomorphic oval nuclei and a high nuclear:cytoplasmic ratio (Fig. 2). This component was characterized by a high mitotic count and abundant apoptotic bodies. The second was composed of mature tissues differentiating along neuroectodermal, mesodermal and endodermal lines. Most of the mature tissue appeared neuroglial (Fig. 3); ganglion cells (Fig. 4), cells with a glial nuclear morphology and occasional ependymal rosettes were scattered throughout a GFAP immunopositive fibrillary background. Ganglion cells were positive with Neu-N immunohistochemistry (Fig. 5). However, the following elements were admixed with the neuroglial component in one region of the tumor: smooth (Fig. 6) and striated muscle (Fig. 7), cartilage (Fig. 8), and tubular / glandular structures (Figs. 9 and 10). These mature tissues showed the expected immunophenotypes, including cytokeratin and epithelial membrane antigen reactivities in the tubular structures (Fig.11) and labeling of smooth muscle cells with anti-smooth muscle actin antibody (Fig. 6). The small cell component showed focal immunoreactivity for synaptophysin, but no labeling with antibodies to GFAP, epithelial membrane antigen, cytokeratin or smooth muscle actin. The growth fraction of this component was very high; Ki-67 immunolabeling exceeded 80% in some areas, whereas it was virtually zero in the mature tissues..
Imbalance on chromosome 17 was assessed in both components of the tumor using fluorescence in situ hybridization (FISH) on both microdissected preparations of whole nuclei and paraffin tissue sections. Loss of 17p (Fig. 12) was combined with gain of 17q (Fig. 13) in both the primitive small cell and mature components.