Pituitary Adenoma Behavior

When compared with normal tumors, the behavior of pituitary adenomas is extremely unusual. Clinical follow-up of patients with pituitary tumors indicates that the majority of pituitary tumors grow slowly and predictably, with a prolonged and often increasing doubling time. As a consequence, in the majority of cases, pituitary tumors remain trophically stable and show little evidence of overall growth over years. Surgical debulking is a perfectly adequate primary treatment in most cases, and strenuous efforts to remove every vestige of pituitary adenoma for fear that rapid recurrence will negate the benefit of decompression or allow remnant tissue to metastasize is rarely considered or required. For the same reason, the routine use of adjuvant radiotherapy at debulking has become a management strategy of the past.

Perhaps the most unique and unexpected characteristic of pituitary adenomas is the tendency for microprolactinomas to resolve of their own accord (4-7). Whether part of this behavior is the result of epiphenomena such as impaired induction of tumor microvasculature with microhemorrhagic destruction or silent infarction, is not known, but the composite achievement of modest growth through the summation of discrete hemorrhagic or ischemic events superimposed on faster turnover or spontaneous resolution through neat and otherwise asymptomatic infarction is intuitively unlikely. Pituitary adenomas display one further remarkable and mechanistically eloquent feature: in a minority of cases of unequivocal Cushing's disease, removal of histologically entirely normal tissue results in unambiguous cure of the disease (8). Specifically, in a retrospective audit of 57 patients with Cushing's disease, the macroscopically abnormal tissue removed was histologically indistinguishable from normal pituitary gland in 27% of patients, but the cure rate was nevertheless 82% (8).

A central question is how to equate these familiar but nevertheless rather extraordinary behavioral characteristics with mechanisms that, when present in most tumors in most other organ systems, give rise to lesions characterized by inexorable growth, progressive genomic instability, metastatic spread, and, ulti-

Fig. 2. Coronal and saggital MRI of an acromegalic patient with a somatotroph adenoma that had spread extensively prior to presentation. Modest debulking surgery and radiotherapy prevented further tumor growth and the patient remians well at the time of writing, 5 yr after the MRI.

mately, the death of the patient. In other words, what kind of oncogene implicated in the pathogenesis of pituitary adenomas would be so modest in its malignant aspirations that it would allow for these lesions to remain trophically stable for decades or resolve of their own accord? In the case of the Cushing's disease cases noted, what kind of intrinsic defect in an expansion of pituitary cells would be so affected by removal of adjacent normal pituitary tissue that it would regress or at least resume entirely normal trophic and functional activity?

There are exceptions, of course, and the pituitary adenomas that are most taxing clinically are relatively aggressive lesions, often corticotroph, silent corticotroph, or somatotroph adenomas, that have either infiltrated surrounding structures at the time of initial presentation or rapidly recur after debulking, but these form a minority of tumors that come to clinical attention and a small proportion of pituitary adenomas as a whole (Fig. 2). Thus, using behavior as a guide, classic irreversible mechanisms of tumor formation, such as gene mutation or allelic loss of tumor suppressors, can hardly be the whole story.

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  • ricky
    Do pituitary adenomas resolve on own?
    8 years ago

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