The Predictive Value of Pathologic Features in Pituitary Adenoma and Correlation with Pituitary Adenoma Recurrence

Abstract

BackgroundThe 2004 World Health Organization classification introduced atypical pituitary adenoma (aPA), which was equivocally defined as invasion with increased mitotic activity that had a Ki-67 labeling index (LI) greater than 3%, and extensive p53 immunoreactivity. However, aPAs that exhibit all of these features are rare and the predictive value for recurrence in pituitary adenomas (PAs) remains uncertain. Thus, we sought to characterize pathological features of PAs that correlated with recurrence.MethodsOne hundred and sixty-seven cases of surgically resected PA or aPA were retrieved from 2011 to 2013 in Seoul St. Mary’s Hospital. Among them, 28 cases were confirmed to be recurrent, based on pathologic or radiologic examination. The pathologic characteristics including mitosis, invasion, Ki-67 LI and p53 immunoreactivity were analyzed in relation to recurrence.ResultsAnalysis of the pathologic features indicated that only Ki-67 LI over 3% was significantly associated with tumor recurrence (p = .02). The cases with at least one pathologic feature showed significantly higher recurrence rates (p < .01). Analysis indicated that cases with two pathologic features, Ki-67 LI over 3% and extensive p53 immunoreactivity 20% or more, were significantly associated with tumor recurrence (p < .01).ConclusionsBased on these results, PA tumor recurrence can be predicted by using mitosis, invasion, Ki-67 LI (3%), or extensive p53 immunoreactivity (≥ 20%). Assessment of these features is recommended for PA diagnosis for more accurate prediction of recurrence.

Both invasiveness and proliferation criteria predict recurrence of non-functioning pituitary macroadenomas after surgery: a retrospective analysis of a monocentric cohort of 120 patients

“…The first two factors have already been reported in several studies (13,22,24,28,33). In particular, Kim and coworkers showed that young age and postoperative residue were the two main predictors of recurrence of non-functioning pituitary adenomas (13), and a recent Australian study showed a 4.2-fold greater risk of regrowth or relapse of the tumor in patients younger than 41 years of age (28). Interestingly, we demonstrate for the first time that the proliferative (atypical) character of non-functioning pituitary macroadenoma confers an additional risk of recurrence/progression, with an odds ratio of 4.8, independent of other well-established predictive factors.…”

“…We also demonstrated that a younger age, the presence of a postoperative residual tumor and the proliferative nature of the tumor were all independent factors predicting recurrence or progression of NFMA. The first two factors have already been reported in several studies (13,22,24,28,33). In particular, Kim and coworkers showed that young age and postoperative residue were the two main predictors of recurrence of non-functioning pituitary adenomas (13), and a recent Australian study showed a 4.2-fold greater risk of regrowth or relapse of the tumor in patients younger than 41 years of age (28).…”

“…It is therefore not surprising that the reported incidence of atypical adenoma was highly variable, ranging from 2.9% (11) to 18.7% (12). Although the criteria previously described are difficult to apply, it is however essential to identify those lesions of uncertain potential, which are at higher risk of recurrence or progression (4,13).…”

Residual Tumor Confers a 10-Fold Increased Risk of Regrowth in Clinically Nonfunctioning Pituitary Tumors

“…A study in 39 patients reported that pituitary adenomas with progression (regrowth within 5 years after initial surgery) had a higher mean proliferation index (3.66% ± 3.00%; n = 12) than tumors without progression (1.89% ± 1.25%; n = 27; P < 0.05) [13]. Other studies have suggested a Ki-67 LI > 3% to be associated with tumor recurrence [14], but others report that although this Ki-67 LI threshold of 3% has a high specificity (89.5%), its sensitivity is comparatively poor (53.8%) [15]. Our study shows that Ki-67 as a standalone parameter is unreliable, in that most of our tumors with high Ki-67 could be fully resected with no visible tumor 3 months after surgery and, therefore, low risk of recurrence.…”

Comparative Proteomic Study Shows the Expression of Hint-1 in Pituitary Adenomas

“…Furthermore, suprasellar extension and/or cavernous sinus invasion are also not associated with tumor recurrence and, although larger tumors are found to recur more frequently, no statistically significant differences were found. [ 47 ].…”