Predictors of Aggressive Clinical Phenotype among Immunohistochemically Confirmed Atypical Adenomas

Object: In 2004, the World Health Organization (WHO) described a new category of pituitary adenomas, known as atypical adenomas, to distinguish lesions with a high propensity for local recurrence and metastasis. These served as an intermediary between commonly encountered benign pituitary adenomas and rare pituitary carcinomas. Despite this pathological diagnosis, not all atypical pituitary adenomas display clinically aggressive behavior, including local recurrence, despite medical, surgical, or radiosurgical treatment. We set out to determine which factors predict a clinically aggressive phenotype among a cohort of atypical pituitary adenomas.

Methods: Medical records from Brigham and Women’s Hospital (BWH) were retrospectively reviewed from April 2008 to July 2015 for all 47 patients surgically treated for atypical pituitary adenomas as defined by the WHO criteria. All variables, including demographic data, past medical history (PMH), endocrine outcomes, preoperative and postoperative Magnetic Resonance Imaging (MRI) findings, clinic notes and intraoperative findings, were collected. Clinically aggressive adenomas were defined as occurring in those patients who necessitated additional therapeutic intervention after the index surgery, including additional surgery, medical therapy, or radiosurgery.

Results: Forty-seven patients with immunohistochemically confirmed atypical adenomas were identified and of these, 23 were noted to have a clinically aggressive course. Among the remaining 24 patients, the disease remained silent after the index surgery. The two groups were well matched with regard to age, gender, preoperative symptoms and past medical history (P > 0.10). On univariate analysis, clinically aggressive lesions were more likely to have a larger axial diameter on MRI (2.9 ± 1.9 versus 1.9 ± 0.7, p = 0.02), greater incidence of cavernous sinus invasion (65% versus 20.8%, p < 0.01), and greater incidence of clival extension (60.9% versus 0%, p < 0.01) on preoperative imaging. The two groups were equivalent with regard to immunohistochemical staining of ACTH, HGH, LH, FSH, PRL, and TSH. Clinically aggressive lesions, however, had a higher average MIB-1 proliferative index (7.7 ± 4.9 versus 5.3 ± 2.9, p = 0.03). On multivariate analysis, the MIB-1 proliferative index trended toward statistical significance (p = 0.06) as an independent predictor of clinical aggressiveness.

Conclusion: Atypical pituitary adenomas demonstrate increased numbers of mitotic figures on histopathology, but not all necessarily demonstrate an aggressive clinical phenotype. Here, we identify other perioperative features that may predict a demonstrated aggressive clinical course.