The WHO categorizes pituitary tumours as typical adenomas, atypical adenomas and pituitary carcinomas, although this classification does not cover the entire spectrum of histopathological findings or clinical behaviour
Pituitary adenomas are generally benign, but some display high rates of recurrence and/or resistance to conventional therapies—and are clinically defined as aggressive adenomas
Aggressive pituitary adenomas seem to represent a distinct entity requiring strict follow-up and early multimodal treatment, nonetheless, specific morphological, radiological and molecular diagnostic criteria should be identified
Pituitary carcinomas, by definition, are diagnosed only by demonstration of craniospinal dissemination or systemic metastases, although not all show cytological features of malignancy
Unlike pituitary carcinomas, aggressive pituitary adenomas do not give rise to metastases, but the two classes can share some histological features
Temozolomide might be useful in treating aggressive pituitary adenomas: anti-VEGF therapy, mTOR and tyrosine kinase inhibitors can also be used in selected patients
The WHO categorizes pituitary tumours as typical adenomas, atypical adenomas and pituitary carcinomas, with typical adenomas constituting the major class. However, the WHO classification does not provide an accurate correlation between histopathological findings and clinical behaviour. Tumours lacking typical histological features are classified as atypical, but not all are clinically atypical or exhibit aggressive behaviour. Pituitary carcinomas, by definition, have craniospinal or systemic metastases, although not all display classical cytological features of malignancy. Aggressive pituitary adenomas, defined from a clinical perspective, have earlier and more frequent recurrences and can be resistant to conventional treatments. Specific biomarkers have not yet been identified that can distinguish between clinically aggressive and nonaggressive pituitary adenomas, although the antigen Ki-67 proliferation index might be of value. This Review highlights the need to develop new biomarkers to facilitate the early detection of clinically aggressive pituitary adenomas and discusses emerging markers that hold promise for their identification. Defining aggressiveness is of crucial importance for improving the management of patients by enhancing prognostic predictions and effectiveness of treatment. New drugs, such as temozolomide, have potential use in the management of these patients; anti-VEGF therapy, mTOR and tyrosine kinase inhibitors are also potentially useful in managing selected patients.
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The authors are grateful to the Jarislowsky and Lloyd Carr-Harris Foundations for their generous support.
The authors declare no competing financial interests.
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Di Ieva, A., Rotondo, F., Syro, L. et al. Aggressive pituitary adenomas—diagnosis and emerging treatments. Nat Rev Endocrinol 10, 423–435 (2014). https://doi.org/10.1038/nrendo.2014.64
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