Spindle Cell Oncocytomas and Granular Cell Tumors of the Pituitary Are Variants of Pituicytoma
Ozgur Mete, M Beatriz Lopes, Sylvia L Asa. University Health Network, Toronto, ON, Canada; University of Virginia Health System, Charlottesville, VA
Background: Sustentacular cells of the neurohypophysis, pituicytes, are specialized glia that have five distinct ultrastructural variants: light, dark, granular, ependymal and oncocytic. Pituicytomas are rare neoplasms arising from pituicytes. Granular cell tumors of the sella are unique neoplasms of the neurohypophysis that have also been suggested to arise from pituicytes. Spindle cell oncocytomas of the pituitary are considered to arise from folliculostellate cells, sustentacular cells of the adenohypophysis. Recent data, however, suggest that while pituicytes, pituicytomas, spindle cell oncocytomas and granular cell tumors are positive for TTF-1, folliculostellate cells are negative for TTF-1. We investigated the genetic, proteomic, and ultrastructural features of these neoplasms in order to refine the classification of these neoplasms.
Design: We collected 7 spindle cell oncocytomas, 4 pituicytomas and 3 granular cell tumors. Tumors were stained for GFAP, S100, olig2, IDH1, NF, vimentin, galectin-3, CD56, chromogranin-A, EMA, CAM5.2, CD68 and bcl-2. Five nontumorous adenohypophysial and five neurohypophysial tissues were also stained for TTF-1. The status of BRAFV600E mutation and BRAF-KIAA fusion was investigated in 12 cases using PCR with sequencing and FISH techniques, respectively. The ultrastructural features of 2 granular cell tumors, 2 pituicytomas and 4 spindle cell oncocytomas were also reviewed.
Results: TTF-1 was negative in all adenohypophysial tissues and was positive in pituicytes. All tumors were positive for TTF-1 and were negative for CAM5.2, IDH1 and NF. Vimentin, S100, galectin-3, EMA and CD68 were variably positive in the majority of these tumors. Olig2 was only positive in one pituicytoma. GFAP expression was seen in some granular cell tumors and pituicytomas. While granular cell tumors were negative for bcl-2 and CD56, pituicytomas and spindle cell oncocytomas showed variable positivity. No BRAFV600E mutation or BRAF-KIAA fusion was detected. The ultrastructural features of granular cell tumors and spindle cell oncocytomas revealed similarities with granular and oncocytic pituicytes, respectively.
Conclusions: Diffuse TTF-1 expression in pituicytes, pituicytomas, spindle cell oncocytomas and granular cell tumors indicates a common pituicyte-lineage. The ultrastructural variants of pituicytes are reflected in morphological variants of tumors arising from these cells. We propose the terminology “oncocytic pituicytomas” and “granular cell pituicytomas” to refine the classification of these lesions.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 65, Wednesday Afternoon