Contributed by Ashley R. Perkins, DO, MS1; Robert J.B. Macaulay, MD2; Marilyn M. Bui, MD, PhD2; Julia A. Bridge, MD2,3; Arnold B. Etame, MD, PhD4
1Department of Pathology and Cell Biology, University of South Florida, Tampa; FL
2Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL
3Department of Pathology/Microbiology, University of Nebraska Medical Center, Omaha, Nebraska
4Department of Neuro-Oncology, Moffitt Cancer Center, Tampa, FL
A 63-year old male presented to a neurosurgeon with a firm, immobile, non-tender mass of his right supraorbital forehead. The patient endorsed remote (x 40 years) trauma to the area with subsequent bony irregularity, with recent (x 3 months) subtle enlargement. There was no associated neurologic symptom and his physical exam was negative for neurologic deficits. Imaging revealed a 3.9-centimeter dural-based lesion with osseous extension involving both inner and outer table; there was a dural tail with enhancement, but not bulky intracranial extension. A frontal craniotomy with tumor resection including wide dural excision was performed at an outside institution. The pathologic diagnosis rendered was meningioma; there was disagreement regarding whether to classify the neoplasm as 'atypical'. No adjuvant therapy was administered. Three years later the lesion recurred in the midline, adjacent to the resection site (Figure 1A, Axial T1-weighted MRI with contrast enhancement), and the patient presented to Moffitt Cancer Center for further neurosurgical management. The tumor was resected and the diagnosis was unchanged at that time. The tumor recurred and was re-excised two years later, prompting re-evaluation of the case. A fourth operation was undertaken the following year, six years after the initial presentation; histomorphology was unchanged.
GROSS AND MICROSCOPIC PATHOLOGY
Grossly, the mass was smooth-contoured, convex, tan-white, firm, and contained embedded calcifications. Microscopic examination revealed a moderately cellular, spindle cell neoplasm arranged in interlacing bundles with irregular spicules of bone, focally mimicking fibrous dysplasia (Figure 1B). Conspicuously absent were meningothelial whorls, psammoma bodies or syncytial nests. Individual spindle cells featured pale, eosinophilic cytoplasm with indiscernible cell borders, and open, oval nuclei with occasional nucleoli but no pseudoinclusion (Figure 1C). There was pericellular reticulin staining. Tumor cells were immunoreactive for vimentin, CDK4 and MDM2 with scattered p53 positivity, and were negative for STAT6, S100, EMA, CD34, and SSTR2a. Ki-67 proliferation index was 15%. The morphology and immunohistochemistry were identical seen in the original resection, which was retrieved for review. Co-amplification of MDM2 (orange signals) and CEP12 (green signals) was detected by FISH (Figure 1D). Occasional scattered cells exhibited slightly higher average MDM2 copy number than CEP12 copy number (Figure 1E). There was no amplification or altered copy number of the ETV6 locus (two copies of adjacent, non-rearranged orange/green signals) (Figure 1F).
Next generation sequencing was notable for gene amplification of: CDK4, KRAS, CCND2, MDM2, FGF23, FGF6, and FRS2; a GNAS1 mutation was not detected. What is your diagnosis?