TTF-1-positive oncocytic sellar tumor with follicle formation/ependymal differentiation: non-adenomatous tumor capable of two different interpretations as a pituicytoma or a spindle cell oncocytoma

Abstract

We describe herein the unique case of a 70-year-old male with a TTF-1-positive non-adenomatous sellar tumor that has unusual morphological and immunohistochemical features. MRI examination detected a 2-cm sellar mass that was enhanced heterogeneously. By histology, the tumor was composed of epithelioid and oncocytic cells arranged in a trabecular pattern with occasional luminal structures. The lesion was diffusely immunopositive for thyroid transcription factor-1 (TTF-1) and vimentin but negative for S100 protein and GFAP. Immunoreactivity for epithelial membrane antigen, low molecular weight cytokeratin (CAM 5.2), and neuronal markers was also observed in the tumor cells. By electron microscopy, the tumor cells were filled with abundant mitochondria and extended microvillous projections into small extracellular and intracellular lumens. TTF-1 is considered to be an excellent marker of pituicytes, specialized glia of the neurohypophysis. This case can be regarded as a variant of pituicytoma, showing both ependymal differentiation and oncocytic changes. However, the immunoprofile was not completely consistent with a pituicyte lineage; the epithelial features suggested a possibility of folliculostellate cell origin. TTF-1-positive sellar neoplasms might therefore have variable morphological and immunohistochemical profiles. For suitable classification of TTF-1 positive sellar neoplasms, their histological features should be carefully re-evaluated.

TTF-1-Expressing Supratentorial Embryonal Tumors (PNET): A Clinicopathologic Study of Two Cases and Literature Review of TTF-1-Positive Primary Brain Tumors

“…Three separate cases of TTF-1 immunopositive mixed pituicytoma, one with classic pituicytoma, spindle cell oncocytoma, and an ependymal component [56], a second with epithelioid oncocytic, follicle formation, and ependymal differentiation [61], and a third with spindle cell oncocytoma and (pituicytic) ependymal differentiation [64], point to unify their derivation. Nuclear TTF-1 expression was documented in the ependymal component [64] (also called "follicle formation/ependymal differentiation" or "follicle-like organotypic differentiation") in the classical pituicytomatous [56,61] and in the spindle cell oncocytomatous component [64]. TTF-1 expression was detected using the monoclonal SPT24 antibody in two different cases [61,64].…”

“…Nuclear TTF-1 expression was documented in the ependymal component [64] (also called "follicle formation/ependymal differentiation" or "follicle-like organotypic differentiation") in the classical pituicytomatous [56,61] and in the spindle cell oncocytomatous component [64]. TTF-1 expression was detected using the monoclonal SPT24 antibody in two different cases [61,64]. In a third case, the antibody used was not specified by the authors (presumably SPT24) [56].…”

“…TTF-1 is considered to be an excellent marker of (both fetal and adult) pituicytes, the specialized glial cells of the neurohypophysis [39], although the matter of a common histogenesis for the entire group of TTF-1 immunopositive sellar/parasellar tumors (i.e., pituicytomas, granular cell tumors of the sellar region, spindle cell oncocytomas, and sellar ependymomas) is still not definitely settled [59][60][61][62][63].…”

Spindle cell oncocytoma of the adenohypophysis: A case with atypical histomorphological features and early recurrence

“…First defined by Roncaroli et al, [1] this tumor was recognized by the World Health Organization (WHO) 2007 classification as a separate entity from other tumors of sellar origin. [2] To date, approximately 26 cases have been reported, with the largest series involving 5 cases. This tumor was first regarded as WHO Grade I, since the initial cases exhibited a benign morphology with no recurrence.…”

The “game” of glial fibrillary acidic and S100 proteins in pituitary adenomas: two players or several?

“…In spindle cell oncocytoma, a discussed pathologic entity, which seems to originate from folliculo-stellate cells, tumour cells are positive for S100 but, surprisingly, negative for GFAP [13][14][15]. Unlike spindle cell oncocytomas and adenomas of the anterior hypophysis, the adamantinomatous type of craniopharyngioma exhibits a positive GFAP reaction, while other tumour types appear to be negative for both S100 protein and GFAP but positive for TTF1 [16,17]. GFAP, a marker of the neuroendocrine system, is strongly expressed in the neurohypophysis, namely by the granular cells and by the filament containing cells belonging to the choristoma, probably due to the fact that both cell types emerge from astrocytes [18].…”