Clinicopathological correlates of extrasellar growth patterns in pituitary adenomas

We reviewed clinical, imaging and histopathology details of 297 patients who underwent surgery for pituitary adenomas, with an equal distribution of functional and non-functioning tumors, to examine clinicopathological correlates of extrasellar growth. Knosp grades of 3 and 4 on MRI defined cavernous sinus invasion, Hardy grades of C and D defined significant suprasellar/subfrontal extension, and intraoperative evidence of tumor eroding through the clivus or sellar floor defined infrasellar invasion. Disease status at follow-up was known in 246 patients overall, including 35 patients who were evaluated for progression of residual disease on serial imaging. On univariate analysis, we found several statistically significant associations (p < 0.05) including adenoma size with age, sex and tumor protein p53 reactivity; cavernous sinus invasion with size, non-functional status, increased mitotic activity, an elevated MIB-1 proliferation index and p53 reactivity; suprasellar/subfrontal extension with p53 reactivity; and infrasellar invasion with age and tumor size. When adjusting for confounders with logistic regression, several significant associations were evident including adenoma size with male sex and p53 reactivity; cavernous sinus invasion with size and elevated MIB-1 proliferation index; suprasellar/subfrontal extension with p53 reactivity; and infrasellar invasion with adenoma size alone. Patients with early progression of postoperative residual tumor were younger with a non-significant trend towards higher MIB-1 proliferation indices. Individual patterns of extrasellar growth in pituitary adenomas are associated with unique clinical and immunohistochemical profiles. Younger patients with elevated MIB-1 values are probably at high risk for early recurrence of non-functioning tumors. Definitions of atypia must be standardized before more robust assumptions about tumor biology can be established.