Contributed by Kirti Gupta, MD1, Paul Klimo Jr, MD2, Karen D. Wright, MD3
Departments of 1Pathology, 2Neurosurgery and 3Oncology, St. Jude Children's Research Hospital, Memphis, TN
A 2-year-old girl presented with one-month history of dysmetria and ataxia. Computer tomography (CT) of the brain showed a large parietal-occipital mass and marked hydrocephalus, for which she required placement of bilateral ventriculoperitoneal shunts. Magnetic resonance imaging (MRI) of the brain also revealed two nodules within the lateral ventricle (Figs. 1, 2 and 3, axial T1, non-enhanced T2, diffusion weighted imaging, respectively). Spine MRI showed abnormal leptomeningeal enhancement along the cervical spine, with additional enhancement in the thoracic and upper lumbar spine. A metastatic origin was excluded by exhaustive radiologic investigations, including body CT and positron emission tomography. Her disease progressed following completion of 6 months of intravenous and 3 months of oral chemotherapy; MRI showed interval increase in the size of the left temporal lobe ventricular lesions as well as worsening leptomeningeal disease and new parenchymal nodules. The tumor was completely excised and submitted for histopathological examination.
Low magnification microscopy (x4) of H&E staining of the tumor displayed a variable architecture (Fig. 4) consisting of solid sheets, islands (x10, Fig. 5) and interconnecting cords of cells set in a vascularized fibromyxoid stroma (x 10, Fig. 6) interspersed with areas of necrosis and calcification. Ductal differentiation was identified in rare foci within <10% of the tumor mass (x 40 Fig 7). The cells were polymorphic with round to oval, occasionally spindle-shaped nuclei, conspicuous nucleoli and moderate cytoplasm (x 20 Fig. 8). Mitotic figures were readily identified (x40, Fig. 9) with a high level of immunolabeling with Ki-67/MIB-1 immunostain.
The cells demonstrated a divergent immunophenotype with immunoreactivities for S-100 (Fig 10), smooth muscle actin (Fig 11), CAM 5.2 (Fig 12), and EMA (x40, immunoperoxidase, Fig. 13, respectively). Retained immunoreactivity with BAF-47/INI1 (x40, Fig. 14) and BRG-1 were retained within the tumor cells. The cells were immunonegative for GFAP (x40, Fig. 15), pleomorphic adenoma gene 1 (PLAG-1) and germ cell markers including placental alkaline phosphatase (PLAP), Oct 3/4, alpha-feto protein (AFP) and CD30. EWSR1 gene rearrangement was not identified by fluorescent in-situ hybridization. What is your diagnosis?