Embryonal tumor with abundant neuropil and true rosettes: an autopsy case-based update and review of the literature
A 17-month-old boy was admitted to the Department of Neurosurgery, Children’s University Hospital in Cracow due to aggravating problems with balance. Starting a week earlier, the parents noticed that the boy had a tendency to tilt the head to the right and would choke when drinking. Neurologic examination found the following deficits: cerebellar disturbances of balance illustrated by the boy’s staggering and inability to walk, compulsory tilting of the head to the right, slight right pyramidal hemiparesis, left VI and VII cranial nerve palsies, bulbar signs demonstrated by choking, weak pharyngeal and palatal reflexes, and a suspected lesion in the visual field which could not be confirmed due to the child’s lack of cooperation. Computer tomography (CT) and magnetic resonance imaging (MRI) revealed an enormous tumor (44 × 35 × 45 mm in CT and 35 × 36 × 32 mm in MRI) in the brainstem, mostly in the left pons and medulla oblongata (Fig. ). The tumor was hyperintense in T2 and showed heterogenous contrast enhancement in T1 with narrowing of the fourth ventricle (Fig. ). There were no features of supratentorial hydrocephalus in spite of evidence of elevated pressure in the posterior fossa. The state of the child was unstable and the risk of its marked worsening due to operation was high. Even the biopsy bore a significant risk. As a result, the parents, after meticulous consideration of the pros and cons, did not give consent to neither an operation nor biopsy on assumption that the child would receive chemotherapy, which was immediately introduced. Consecutively, the child was transferred to the Department of Pediatric Hematology and Oncology, Children’s University Hospital in Cracow. Further diagnostics did not reveal any other foci of disease. Based on the clinical picture and neuroimaging, a malignant glioma of the brainstem was tentatively diagnosed and chemotherapy was introduced accordingly with two cycles of cisplatin, etoposide, and vincristine, and one cycle of cyclophosphamide, etoposide, and vincristine. Two months after first admission, the child showed signs of ataxia and decreased muscle tone. Soon, the child’s condition abruptly worsened with severe vomiting and a forced retroflexed position. Repeated MRI revealed enlargement of the tumor (52 × 50 × 54 mm) and supratentorial hydrocephalus due to compression of the cerebral aqueduct with transudation (Fig. ). The hydrocephalus was treated with implantation of a ventriculo-peritoneal shunt, and chemotherapy with irinotecan and carboplatin was introduced. The hydrocephalus remitted but the child relentlessly deteriorated as the tumor continued to enlarge and died 3 months after hospitalization.\nAn autopsy of the brain performed at Department of Pathology, Children’s University Hospital, revealed an enormous tumor inside left cerebellar hemisphere partially occupying the pons and also expanding to the midbrain. The tumor distorted the whole brainstem and cerebellum, pushing aside and compressing the fourth ventricle, but definitely not originating from it (Fig. ). This confirmed the previous MRI findings of a primary brainstem tumor (Fig. ). On cross section, the tumor showed uniform consistency, slightly lower than the normal brain tissue. The tumor had well marked borders with a smooth transition into adjacent apparently normal tissue.\nMicroscopic pictures represented a very conspicuous pattern with relatively paucicellular neuropil-like background with numerous and rather evenly distributed cellular densities populated with small undifferentiated cells (Fig. ). Rosettes formed another characteristic element of the tumor (Fig. ). Neuropil zones, in contrast to the cellular zones, showed immunopositivity to synaptophysin (Fig. ). Both in cellular zones and neuropil zones, there were scattered characteristic rosettes, totally negative to synaptophysin (Fig. ) but strongly positive to vimentin (Fig. ). The rosettes had an “empty,” homogenous core, but frequently with a delicate eosinophilic contouring reminiscent of ependymoblastic rosettes, though somewhat more delicate than those occurring in typical ependymoblastoma (Fig. ). The rosettes were also weakly positive for glial fibrillary acidic protein (GFAP) and for S100 protein (Fig. ). However, in neuropil zones, there were cells present with the immuno- and morphophenotype of astrocytes (GFAP+ and some S100+). Moreover, outside of the rosettes, synaptophysin-positive mature neuron-like cells were noted (Fig. ), and some were even strongly positive for synaptophysin, in spite of resembling astrocytes (Fig. ). Ki-67 expression was high but limited to rosettes (Fig. ) and cellular zones especially around the vessels. No areas of frank necrosis or any “pathological” forms of endothelial proliferation were noted. However delicate vessels were numerous, frequently surrounded by undifferentiated cells that do not conform to the description of “perivascular formations” or pseudorosettes.