LAUSR

In this special issue, eminent international experts and collaborators from several continents appraise the present landscape regarding aggressive pituitary tumors, from epidemiology and diagnosis to imaging and specific forms of treatment. Most pituitary adenomas grow slowly and even with enlargement, are quite demarcated from normal pituitary and rarely produce symptoms [1]. They arise from any of the five differentiated cell types within the pituitary gland, are benign and function based on their specific lineage, and are associated with typical endocrine syndromes [2]. Interestingly, microadenomas (defined arbitrarily as < 1 cm in size) appear to stop growing; what specifically limits this ability to proliferate remains unknown. The large majority of pituitary adenomas change little in size over many years; a few are very aggressive and recur more frequently even after successful treatment [3, 4]. Here, Leandro Kauski and Gerald Raverot discuss what should be considered an aggressive tumor in “Definition and Diagnosis of Aggressive Pituitary Tumors” and Olaf M. Dekkers, Niki Karavitaki, and Alberto M Pereira review incidence and prevalence in “The Epidemiology of Aggressive Pituitary Tumors (and its challenges).” Most pituitary adenomas are sporadic and non-familial. However, certain genetic defects confer a more aggressive behavior; particularly in young patients with giant prolactinomas and somatotropinomas (multiple endocrine neoplasia type 1; MEN1, aryl hydrocarbon receptor interacting protein; AIP gene mutations, and G proteincoupled receptor 101; GPR 101 duplication) [5–7]. Hereditary pituitary adenomas are more aggressive, occur in younger patients, which allows for prospective screening. However, comprise only 5% of all pituitary adenomas. Christina Tatsi and Constantine Stratakis detail the particularities of these tumors at two ends of the age spectrum in “Aggressive Pituitary Tumors in the Young and Elderly.” A comparatively small proportion of sporadic pituitary adenomas behave more aggressively presenting through inappropriate hormone secretion, [8] are resistant to standard therapies and exhibit rapid growth and invasion of surrounding structures [9–11]. Genomic and epigenetic landscape studies in aggressive pituitary tumors have not yielded any positive results... yet! A new comprehensive clinical classification of these pituitary tumors, a five-tiered classification includes; invasion, immuno-phenotype, and proliferation markers (Ki67 index, mitotic count, and p53 positivity) and should enable earlier tumor management. Fertility is usually affected in both women and men, and there are some advancements in the area, reviewed here by Júlia Vieira Oberger Marques and Cesar Luiz Boguszewski in “Fertility Issues in Aggressive Pituitary Tumors.” While striving to perform less magnetic resonance imaging in the follow-up of smaller pituitary adenomas, [12] imaging plays an important role in defining invasion and Jean-François Bonneville, Julia Potorac and Albert Beckers illustrate several important pearls in “Neuroimaging of Aggressive Pituitary Tumors.” Pathology remains essential in defining the characteristics and trophic activity of all pituitary adenomas, which are discussed in detail in “Are Aggressive Tumors and Carcinomas Two Sides of the Same Coin? Pathologists reply to Clinician’s Questions” by Jacquelline Trouillas, Marie-Lise Jaffrain-Rea; Alexandre Vasiljevic, Olaf Dekkers, Vera Popovic, Anne Wierinckx, Ann McCormack,Pia Burman, Gérald Raverot, and Chiara Villa. The best outcome for treatment of aggressive tumors is observed when patients are treated in multidisciplinary Pituitary Center of Excellence [13]. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11154-020-09561-w) contains supplementary material, which is available to authorized users.