Immunohistochemical Profile of Nonfunctioning Pituitary Adenomas

Background: Nonfunctioning pituitary adenomas (NFPAs) are neuro-endocrine tumors without clinical and laboratory signs of anterior pituitary hormonal hypersecretion. The recent World Health Organization classification is based on the adenohypophyseal cell lineages and requires immunohistochemical evaluation of adenohypophyseal hormones and pituitary transcription factors. There are few data regarding the age and sex prevalence of different cell-types nonfunctioning adenomas and clinical data correlations. Objective: To discover the immunohistochemical profile of large cohort of NFPAs. Materials and Methods: The study includes 100 consecutive cases of endoscopically transsphenoidally removed nonfunctional pituitary adenomas, immunohistochemically assessed for anterior pituitary hormones and transcription factors. Clinical presentation, imaging, laboratory hormonal data and immunohistochemical staining features have been analyzed. All patients (64 women and 36 men) have been divided into four age groups: 20-34 (A) years old, 35-44 (B) years old, 45-59 (C) years old, 60-70 (D) years old. Peculiarities of immunohistochemical profile have been statistically analyzed in those age groups. Results: Most tumors (97%) were macroadenomas with mass effect symptoms. In the groups of silent corticotroph and Pit-1 adenomas most of the patients had subclinical symptoms of hormonal hypersecretion. The proportions of silent gonadotroph adenomas have appeared to be increased with age with predominant prevalence in group D (60%) in women and group C (78, 6%) in men. The proportions of silent Pit-1 adenomas decreased with age with maximum rate in group A (77,8%) in women and in group A (50%) in men. The incidence of silent corticotroph adenomas was different: increasing with age in women with maximum (36,8%) in group C and decreasing from young age (30%-0%) in men age groups B-D respectively. Plurihormonal pituitary adenomas from different cell lineages were found only in women, with maximum incidence rate (17,6%) in group B. The incidence of “null cell” adenomas didn’t differ in men and women in group B and C but was much more higher in men in groups A and D (16,7% vs 0% and 33% vs 6,6% respectively). Conclusions: The different age and sex prevalence of NFPAs, revealed in our study, may be helpful in diagnosing and optimal treatment of NFPAs.

Alterations in CD8+ Tregs, CD56+ Natural Killer Cells and IL-10 Are Associated With Invasiveness of Nonfunctioning Pituitary Adenomas (NFPAs)

Invasive nonfunctioning pituitary adenomas (NFPAs) grow rapidly and the mechanisms are unclear. Among many complex mechanisms, the role of immunity in the development of NFPAs has not been fully explored. Here, we analyzed the clinical features 146 NFPA patients who underwent trans-sphenoidal surgery or craniotomy and examined the effects of immune tolerance in invasiveness of NFPA patients using fluorescence-activated cell sorting and immunohistochemical methods. We found patients with invasive NFPAs had more visual deficits and defective fields, higher tumor size, and lower white blood cell count compared with patients with noninvasive NFPAs. Additionally, compared with patients with noninvasive NFPAs, patients with invasive NFPAs had conspicuously lower CD3−CD56+ natural killer (NK) cells and significantly higher levels of CD3+CD8+CD28-T cells (CD8+ Tregs) and interleukin-10 (IL-10) in peripheral blood. Moreover, patients with invasive NFPAs had lower infiltrated CD56+ cells, less infiltrated CD28+ cells, and significantly greater IL-10 expression. These results demonstrated that low CD56+ cells infiltration and CD28+ cells infiltration, as well as high IL-10 expression in pituitary tumor tissues, were related with increased invasiveness of NFPAs. Levels of CD3−CD56+ NK cells, CD8+ Tregs and IL-10 in the peripheral blood could be feasible diagnostic markers for invasive NFPAs.