An Old New Friend: Folliculo-Stellate Cells in Pituitary Neuroendocrine Tumors

Abstract

Pituitary neuroendocrine tumors (PitNETs) represent a complex pathology based on numerous incompletely elucidated molecular mechanisms. Beyond tumor cells, analyzing the tumor microenvironment may help identify novel prognostic markers and therapies. A key component of this environment is the folliculo-stellate (FS) cell. We examined FS cells in 77 PitNETs obtained by transsphenoidal surgery, using glial fibrillary acidic protein (GFAP) as an immunohistochemical marker. Immunohistochemistry for anterior pituitary hormones and transcription factors was performed to accurately classify the tumors. Our study included 19 somatotroph, 16 mammosomatotroph, 5 plurihormonal PIT-1 positive, 7 corticotroph, 14 gonadotroph, 11 unusual plurihormonal, and 5 null cell PitNETs. FS cells were observed in 55 of the cases, distributed isolated, in small groups or diffuse networks. A considerable number of tumors immunopositive for more than one hormone (including associations between GH/PRL, but also unusual combinations like GH/ACTH) also contained FS cells (p < 0.01), suggesting their involvement in tumor lineages differentiation. In 27 tumors, GFAP-positive cells clustered in highly vascularized areas. Additionally, in 11 of these cases a direct interaction between endothelial cells and FS cells was noted, sustaining their potential role in tumor angiogenesis. Given their complexity, FS cells may be crucial for understanding tumorigenesis mechanisms.

Keywords: FS cells; GFAP; PitNETs; blood vessels.

Figure 1

Tumoral growth pattern. (a) Acidophilic tumor with diffuse growth pattern; (b) Papillary growth pattern in longitudinal section, loose connective tissue with blood vessels in the center of the papilla; (c) Chromophobe tumor with alveolar growth pattern; (d) Trabecular growth pattern, with thick connective trabeculae inside the tumor.

Figure 2

An example of an unusual plurihormonal PitNET immunopositive for GH, ACTH. (a) positive immunohistochemical reaction for GH; (b) positive immunohistochemical reaction for ACTH.

Figure 3

FS cells—forms of distribution: (a) isolated FC cell; (b) a group of FS cells; (c) diffuse network of FS cells; (d) FS cells forming a follicle.

Figure 4

FS cells and blood vessels interactions. (a) FC cell grouped around blood vessels; (b) FC cell distributed along blood vessel wall; (c) Direct contact between FC cell and endothelial cell (arrow).