High-risk pituitary adenomas are aggressive. They show clinical and
imaging features similar to those of carcinomas, including infiltration
of the surrounding brain structures, but lack cerebrospinal or systemic
metastases. In addition, they display distinct behavior, including
tendency for fast growth and frequent recurrences, which are difficult
to control. The term “high-risk” adenoma was first introduced in the
4th edition of the World Health Organization Classification of Endocrine
Tumors in 2017. Five defined adenoma types belong to this category,
including sparsely granulated somatotroph, lactotroph in men, Crooke
cell, silent corticotroph, and plurihormonal PIT-1 positive adenomas.
The morphological and immunohistochemical characteristics of high-risk
adenomas are herein described in detail. In addition, the clinical
features and the treatment options are presented. This review focuses on
predictive markers assessed by immunohistochemistry, which help
clinicians to design the appropriate treatment strategies for high-risk
adenomas. Somatostatin receptor status predicts effectiveness of
postsurgical treatment with somatostatin analogs, and MGMT expression
predicts response to treatment with temozolomide. This comprehensive
review presents the clinical and pathological features of high-risk
pituitary adenomas, underlines the contribution of immunohistochemistry,
and emphasizes the leading role of pathology in the design of optimal
clinical management