Pituitary Carcinoma: A Devastating Disease in Need of an Earlier Diagnosis and of Effective Therapies

Pituitary Carcinoma: A Devastating Disease in Need of an Earlier Diagnosis and of Effective Therapies Giulio Maira and Francesco Doglietto Pituitary adenomas represent the third most common intracranial tumor (15) and are therefore the mainstay of our daily practice. Pituitary surgery can be extremely successful, as we are increasingly able to cure devastating disorders such as Cushing disease and acromegaly. Nonetheless, even in the era of endoscopy, neuronavigation, and other technologies that have advanced the boundaries of pituitary surgery, every surgeon is aware of the limits of surgical treatment: interdisciplinary collaboration is indeed part of every center encountering pituitary pathologies. The multidisciplinary approach, which includes at least the endocrinologist and radiotherapist, leads to disease control in many circumstances that cannot be controlled solely by surgery. Unfortunately, however, some situations are still extremely frustrating because young patients, who harbor apparently benign tumors, escape treatment; once the singular aggressivity of the tumor is evident, not infrequently it is also clear that our therapeutic chances are already gone: this is the most frequent case scenario of pituitary carcinomas, a rare condition, with approximately 150 cases reported in the literature. In this issue, Shastri et al. add another patient to the literature. Sometimes the management of pituitary adenomas is indeed complicated by our difficulty in predicting tumor behavior (10, 14). Malignancies of the pituitary are extremely rare with a prevalence of only 0.1%-0.2% of all pituitary tumors (8, 10). At present, the designation “pituitary carcinoma” is predicated on documenting craniospinal spread and/or systemic metastasis (16). Considering the dismal prognosis of these patients, we agree with Scheithauer et al., who consider this clinical definition to be inadequate: “too little, too late” (15). The case presented by Shastri et al. indeed underlines this major limit: even an apparently benign and totally removed adenoma can evolve into a pituitary carcinoma and, as doctors, we frequently find ourselves as spectators of this evolution, bewildered as why a specific patient has evolved to this state. Not infrequently, we regret not using more aggressive therapies at earlier stages of the disease. The natural history of pituitary adenomas indeed varies widely. The typically indolent growth rate of these tumors is juxtaposed with high rates of tumor cell invasion into adjacent dural structures. Macroscopic invasion of adjacent structures, such as the cavernous sinus, is evident in approximately 30% of cases; malignant transformation remains uncommon, but rates of morbidity and mortality are high when aggressive tumor behavior occurs (3). These are the main reasons why there is a strong need for reliable predictors of disease: the authors of two recent reviews have extensively examined them (13, 14). In clinical practice we use the Ki-67 index daily to define those patients who need a stricter follow-up: as with other tumors, this index has indeed a prognostic value (5). Other markers, such as p53, seem to correlate with clinical outcome, and many more are being considered and awaiting validation (13, 14): one of these, as the authors note, is telomerase expression, which has already proven significant for the prognosis of other tumors of the sellar and parasellar areas, such as chordomas (9, 12). With the aim of defining a subpopulation of pituitary adenomas, which needs a closer follow-up, the World Health Organization 2000 Classification of Endocrine Tumors defined an atypical pituitary adenoma as one that exhibits a combination of three invasionassociated criteria and/or exhibits aggressive operative behavior, including increased mitotic activity, a Ki-67 labeling index greater Key words Cancer Co