Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas

Recently there has been significant progress in our understanding of pituitary development, physiology, and pathology. New information has helped to clarify the classification of pituitary tumors. Epidemiologic analyses have identified a much higher incidence of pituitary tumors than previously thought. We review the pathogenetic factors that have been implicated in pituitary tumorigenesis and the application of novel targeted therapies that underscore the increasingly important role of the pathologist in determining accurate diagnoses and facilitating appropriate treatment of patients with these disorders.

Although the majority of pituitary macroadenomas are clinically nonfunctioning, treatments as well as follow-up strategy for this condition lack evidence from randomized studies. We evaluated the evidence of treatment and follow-up strategies for clinically nonfunctioning adenomas. PubMed was searched for articles on nonfunctioning adenomas in November 2007, and references of selected articles were assessed for potentially relevant articles. All evidence for treatment and follow-up for nonfunctioning adenomas is based on observational studies. The most effective treatment is transsphenoidal surgery, indicated in patients with visual field defects. A wait-and-see approach may be considered in nonfunctioning macroadenomas not reaching to the optic chiasm. Some of these tumors ( approximately 10%) will show spontaneous regression, whereas in approximately 50% there will be progression within 5 yr observation. Postoperative radiotherapy should not be applied to all patients after surgery but can be considered in patients with large postoperative remnants of the tumor. During follow-up careful assessment and replacement of pituitary insufficiencies should be performed. Magnetic resonance imaging is advised with intervals of 1-3 yr and evaluation of visual fields when appropriate. Recurrence rates are reported to be 6-46% after transsphenoidal surgery, whereas after postoperative radiotherapy, recurrence rates of 0-36% are reported. Long-term sequelae of nonfunctioning macroadenomas are hypopituitarism, persistent visual field defects, and decreased quality of life. Whether nonfunctioning macroadenomas are associated with an increased mortality is still a matter of debate. Clinically nonfunctioning pituitary macroadenomas, although benign in nature, need individualized treatment and lifelong radiological and endocrinological follow-up.