Original ArticleAggressive Pituitary Adenomas: The Dark Side of the Moon
Introduction
Although pituitary adenomas are usually believed to be benign lesions, as many as 25%–55% of pituitary adenomas are considered to be invasive,1, 2 and some show a clinically more aggressive behavior.3, 4
The World Health Organization classification for endocrine tumors distinguishes the pituitary tumors, according to various ultrastructural features, as typical, atypical, and pituitary carcinomas, but such classification does not necessarily correlate with clinical behavior. Atypical adenomas are not necessarily invasive nor do they always show recurrence or a clearly aggressive behavior,5, 6 whereas aggressive adenomas, even with a malignant evolution, may often show ultrastructural features of a typical pituitary adenoma.7 Aggressiveness of pituitary adenomas might be related to immunophenotype changing, silent adrenocorticotrophic hormone (ACTH)-secreting adenomas, silent growth hormone (GH)-secreting adenomas, thyroid-stimulating hormone–secreting adenomas, adenomas with a proliferation index of >15%, and so on. There are still some lesions that do not have such immunohistochemical features and still clinically behave aggressively.
This lack of a correlation between immunohistochemistry and clinical behavior is also highlighted by heterogeneous terminology: the term aggressive is often wrongly used as synonymous for invasive, merging 2 different entities, thus limiting the feasibility and the effectiveness of an early diagnosis. Aggressive pituitary tumors require closer clinical and radiologic surveillance and more complex and multidisciplinary management.
As a consequence of the lack of a standard definition, no previous studies have been published reporting data about the management of this subgroup of pituitary adenomas. The few exceptions are small series and case reports, focusing on the role of temozolomide as a salvage therapy in patients unresponsive to conventional treatments.8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19
We report our experience, describing a series of 7 patients harboring an aggressive pituitary adenoma, focusing on the fundamental role of a multidisciplinary approach for this challenging and not yet fully understood disease.
Section snippets
Methods
By reviewing the pertinent literature,6, 20, 21, 22 we identified the most common features typically shown by pituitary tumors with aggressive behavior.
We considered:
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Invasion and/or infiltration of the surrounding structures
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Rapid growth to large size
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Tendency to recur rapidly
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Resistance to conventional treatments.6
Rapid growth and tendency to recur rapidly may be considered as 2 sides of the same coin and for this reason, we decided to retrospectively analyze patients harboring at least 3 of 4 of
Results
From 2007 to 2015, 7 patients (4 women and 3 men; mean age, 44.14 years; range, 35–63 years) affected by an aggressive pituitary adenoma, according to the criteria outlined earlier, were treated at the Multidisciplinary Pituitary Center of the University of Messina (Table 1 and Figure 1, Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, Figure 7, Figure 8 showing illustrative cases from our series).
Two had nonfunctioning pituitary adenomas, 2 had prolactin (PRL)-secreting, 2 had ACTH-secreting,
Discussion
No large series of aggressive pituitary adenomas have been reported in the literature. As a consequence, no reliable markers for aggressiveness (biohumoral, histopathologic, immunohistochemical, molecular or neuroradiologic) are available for early detection of this subgroup of pituitary adenomas. This situation is probably also related to a lack of standardization of terminology.
We analyzed a small subgroup of patients harboring aggressive pituitary adenomas. The disappointing results in the
Conclusions
The so-called aggressive pituitary adenomas are a specific entity, lying between benign adenomas and malignant pituitary carcinomas. They show a rather distinct clinical behavior with massive invasion of surrounding tissues, rapid growth, tendency to recur rapidly, resistance to conventional treatments, and, in some patients, a fatal outcome.
Considering the lack of specific tools available for their early identification, they are often diagnosed late, thus reducing the chances of a good
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Conflict of interest statement: This study was supported in part by the Grant PON02_00643_3604826 from MIUR (Italian Ministry of University and Research).