Contributed by Nancy McLaughlin, MD, PhD, FRCSC1, Justin Dye, MD1, Négar Khanlou, MD2, William H. Yong, MD2, Neil A. Martin, MD1
Departments of 1Neurosurgery and 2Pathology and Laboratory Medicine - Neuropathology
David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA
A 26 year-old female initially noted blurry vision when looking towards the right. Three months later, she noted diplopia when looking towards the right side. Right abducens nerve palsy was documented by her ophthalmologist. Initial brain MRI performed four months after the onset of blurry vision showed a 4mm (AP) X3mm(transverse)X5mm (craniocaudal) area of enhancement anterior to the pons on the right side (Figure 1). Neurology coordinated an extensive serum screening for inflammatory, infectious, and metabolic causes, all of which came back negative. Two to three months later, she started experiencing daily pressure headaches felt mostly in the occipital and suboccipital regions. The follow-up brain MRI showed the presence of a prepontine/premedullary mass, measuring 23mm (AP) X34mm (transverse) X29mm (craniocaudal) (Figure 2). This mass was mostly solid but presented some cystic necrotic areas. The lesion, believed to be extra-axial, exerted mass effect on the pons and medulla without causing abnormal signal within the brainstem. The mass also caused asymmetry of the fourth ventricle without evidence of obstructive hydrocephalus. At the time of consultation with neurosurgery, approximately 7 months after the onset of her blurry vision, the patient reported difficulty swallowing solids for the last two weeks. Other than abducens nerve palsy, the rest of her physical exam was unremarkable. After review of the images with neuroradiology, the suspected diagnosis was a malignant nerve sheet tumor, most probably arising from the abducens cranial nerve. The investigation was completed with a spine MRI which demonstrated the presence of three subcentimetric enhancing nodules, interpreted as possible schwannomas or meningiomas (Figure 3). A catheter angiogram did not reveal any direct arterial feeder that could be embolized.
The patient underwent an extended right retrosigmoid craniotomy for microsurgical biopsy and resection of the prepontine and premedullary mass. The cerebellopontine angle was inspected under microscopic visualization. A reddish purple tumor could be seen between the trigeminal nerve and the 7th and 8th cranial nerve complex as well as between this complex and the region of the lower cranial nerves (Figure 4). Intra-operative frozen section analysis indicated a highly vascular and malignant appearing neoplasm. Because of its rapid growth rate, maximal safe debulking of the soft tumor was performed, realizing satisfactory decompression. All cranial nerves from trochlear to hypoglossal were seen during surgery, except the abducens nerve. A small amount of residual tumor was left, adherent to the 7th and 8th cranial nerve complex and the ventrolateral surface of the pons.
Standard hematoxylin and eosin studies showed a neoplasm of high cellularity with marked nuclear atypia, hyperchromasia, and high nuclear/cytoplasmic ratio (Figures 5 and 6). A focus of spindled muscle fibers was also present within the neoplasm (Figure 7). Immunohistochemistry using antibodies to synaptophysin showed patchy immunoreactivity in tumor cells (Figure 8). Desmin immunoreactivity was evident in many areas (Figure 9). MIB-1 immunohistochemistry showed an elevated labeling index estimated to approximately 30%-40% of positive tumor nuclei (Figure 10). Fluorescence in situ hybridization (FISH) studies using the probes to MYC-N (Chromosome 2 - centromere 2/2p24.1), MYC-C (break apart - 8q24), and EWSR1 (break apart - 22q12) showed no aberrations in the tumor nuclei (300 tumor nuclei/probe). What is the diagnosis?