Contributed by Marwah M Abdulkader, MD1, Isaac C Wu, MD2, James C Miller, MD3, Don-John Summerlin, DMD1, Eyas M Hattab, MD1
1Department of Pathology and Laboratory Medicine; 2Department of Radiology; 3Department of Neurological Surgery
Indiana University School of Medicine, Indianapolis, Indiana, USA
CLINICAL HISTORY AND IMAGING
A 36-year-old man presented with a large nasal tumor following a long history of multiple meningiomas. At the age of 13, the patient underwent surgical resection and received a single course of radiation therapy for a left optic meningioma. He did well until age 33, when he was found to have multiple meningiomas in three new locations: falcine (Figure 1a), right petroclival and right anterior foramen magnum. These were surgically resected but no additional radiation was administered. Three years later, the patient presented with nasal symptoms, headaches, and seizures. Imaging studies revealed a large mass with intracranial and nasopharyngeal component measuring 4.1 x 5.4 x 6.8 cm in greatest dimensions and causing right frontal lobe compression (Figures 1b and 1c). A systemic workup, including PET CT, for other malignancies was unremarkable. A two-stage surgical resection was performed. The mass was initially biopsied by transsphenoidal endoscopic approach and then partially resected by bifrontal craniotomy, frontal sinus obliteration, en bloc ethmoidectomy, and nasal cavity resection.
Pathologic examination revealed a high-grade malignant neoplasm that appeared primitive. Architecturally, the tumor consisted of patternless sheets of tumor cells interrupted by abundant glandular, trabecular, and rosette-like arrangements (Figure 2a). The latter mostly resembled Flexner-Wintersteiner rosettes as they exhibited central canals, while scattered ones mimicked Homer Wright rosettes (Figures 2b and 2c). Occasional lumina with mucinous-like material were observed. A finely vacuolated, neuropil-like background was evident on close examination. The neoplastic cells showed a variable degree of pleomorphism, with hyperchromatic nuclei and coarse salt and pepper chromatin and small nucleoli. Mitotic figures were readily identified and apoptotic bodies were abundant (Figure 2d). Extensive hemorrhage and necrosis was present. Periodic acid Schiff (PAS) stain showed the epithelial tumor cells with PAS-rich contents. Immunohistochemical stains were performed and showed immunoreactivity for AE1/AE3 in many of the tumor cells, particularly in the areas showing glandular differentiation (Figures 3a and 3b). Chromogranin showed faint diffuse immunoreactivity, while synaptophysin was focally immunoreactive (Figure 3c). NeuN immunohistochemical stain elicited a striking pattern of immunoreactivity with abundant intense vesicular staining in an apical fashion in most of the epithelial areas (Figure 3d). CD99, GFAP, SALL4, and WT1 were not immunoreactive. INI1 was expressed by the neoplastic cells. Genetic analysis revealed no rearrangement of the EWSR1 gene. What is your diagnosis?