Atypical Pituitary Adenoma: A Clinicopathologic Case Series

Object: In 2004 the World Health Organization (WHO) classified atypical pituitary adenoma as a distinct adenoma subtype. However, the clinical significance of this distinction remains undetermined. We sought to define patient characteristics, tumor features, and treatment outcomes associated with atypical pituitary adenoma.

Methods: We reviewed records of patients undergoing resection of pituitary adenoma at our institution from 2007–2014. Per institutional protocol, adenomas exhibiting mitotic activity underwent evaluation for all 3 markers of atypicality (mitotic index, extensive p53 staining, and MIB index >3%). Statistical analyses were performed using chi-square, Fisher’s exact test, t-test, and log rank.

Results: From 2007 to 2014, a total of 701 patients underwent resection for pituitary adenoma. Of these adenomas, 122 exhibited mitotic activity and therefore underwent evaluation for all 3 markers of atypicality, with 36 tumors (5%) proving to be atypical. There were 21 female patients (58%) and 15 male patients (42%) in the atypical cohort, and 313 female patients (47%) and 352 male patients (53%) in the non-atypical cohort (p = 0.231, Fisher’s exact test). The mean age of atypical patients was 37 years (range 10–65 years), significantly lower than the mean of 49 years (range 10–93 years) seen for non-atypical patients (p < 0.001). The most common presenting symptoms for patients with atypical adenomas were headaches (42%) and visual changes (33%). Atypical adenomas ranged from 0.2 cm to 7.3 cm, and non-atypical adenomas ranged from 0.2 to 7.1 cm. Atypical adenomas were more likely to be functional (78%) than non-atypical adenomas (42%) (p < 0.001). Functional atypical adenomas were significantly larger than functional non-atypical adenomas (mean diameter 2.2 cm versus 1.5 cm, p = 0.008), as were nonfunctional atypical adenomas and nonfunctional non-atypical adenomas (mean diameter 3.3 cm versus 2.3 cm, p = 0.01). Among the entire adenoma cohort, larger presenting tumor size was associated with cavernous sinus invasion (p < 0.001, t-test). The median time until recurrence was 56 months for atypical adenomas, 129 months for functional non-atypical adenomas, and 204 months for nonfunctional non-atypical adenomas (p < 0.001). Functional atypical adenomas recurred significantly earlier than functional non-atypical adenomas (p < 0.001). When accounting for extent of resection, cavernous sinus invasion, size, age, gender, and functional subtype, atypicality remained a significant predictor of earlier recurrence among functional adenomas (p = 0.002).

Conclusion: When compared with non-atypical pituitary adenoma, atypical adenomas are more likely to present in younger patients at a larger size, are more often hormonally hypersecreting, and are associated with earlier recurrence. These features help distinguish atypical pituitary adenoma as a distinct clinical entity in addition to a discrete pathological diagnosis.