Fig.20.5 ).Mitoticactivityusuallyisscanty.Thecytoplasmoftheconstituentcellsmaybeacidophilic,basophilic,orchromophobic,dependingonthetypeandamountofsecretoryproductwithinthecell,butitisfairlyuniformthroughouttheneoplasm.Thefunctionalstatusoftheadenomacannotbepredictedfromitshistologicappearance.AdenomasthatharborTP53 mutationsoftendemonstratebriskmitoticactivityandhigherproliferationratesandaredesignatedatypicaladenomasbecauseoftheirpotentialforaggressivebehavior.
Fig.20.4Pituitaryadenoma.Thismassive,nonfunctioningadenomahasgrownfarbeyondtheconfinesofthesellaturcicaandhasdistortedtheoverlyingbrain.Nonfunctioningadenomastendtobelargeratthetimeofdiagnosisthanthosethatsecreteahormone.
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Fig.20.5Pituitaryadenoma.Themonomorphismofthesecellscontrastswiththeadmixtureofcellsseeninthenormalanteriorpituitaryglandin
Fig.20.1 .Notealsotheabsenceofthereticulinnetwork.
Themostcommoncauseofhyperpituitarismisananteriorlobepituitaryadenoma.
Pituitaryadenomascanbemacroadenomas(>1cmindiameter)ormicroadenomas(<1cmacross),andonclinicalevaluation,theycanbefunctionalornonfunctioning.
Macroadenomasmaypotentiallyleadtomasseffects,includingvisualdisturbances.
Functioningadenomasareassociatedwithdistinctendocrinesignsandsymptoms.
MutationoftheGNAS gene,whichresultsinconstitutiveactivationofastimulatoryGprotein,isoneofthemorecommongeneticalterations.
Thetwodistinctivemorphologicfeaturesofmostadenomasaretheircellularmonomorphismandabsenceofareticulinnetwork.
Adenomas arising from different pituitary cells produce hormones characteristic of that cell type and cause clinical syndromes that reflect the activity of the hormones.
Prolactin-secreting lactotroph adenomas are the most frequent type of hyperfunctioning pituitary adenoma, accounting for about 30% of all clinically recognized cases. They range in size from microadenomas to large, expansile tumors associated with considerable mass effect. Prolactin is demonstrable within the cytoplasm of the neoplastic cells by immunohistochemical techniques. Prolactin secretion by lactotroph adenomas is highly efficient, such that even microadenomas can secrete sufficient hormone to induce systemic symptoms.
Hyperprolactinemia causes amenorrhea, galactorrhea, loss of libido, and infertility. Because manifestations of hyperprolactinemia (e.g., amenorrhea) are obvious in premenopausal women, prolactinomas are diagnosed at an earlier stage in women of reproductive age than in others with these tumors. By contrast, the effects of hyperprolactinemia are subtle in men and older women, in whom the tumor may reach a large size before coming to clinical attention. Hyperprolactinemia also is a feature of other conditions, including pregnancy, high-dose estrogen therapy, renal failure, hypothyroidism, hypothalamic lesions, and dopamine-inhibiting drugs (e.g., reserpine). In addition, any mass in the suprasellar compartment may disturb the normal inhibitory influence of hypothalamus on prolactin secretion, resulting in hyperprolactinemia—a mechanism known as the stalk effect. Thus, mild elevations of serum prolactin (<200 µg/L) in a patient with a pituitary adenoma do not necessarily indicate a prolactin-secreting neoplasm.