Abstract
PubMed, Scopus, and Web of Science Core Collection databases were systematically searched for studies reporting synchronous double or multiple pituitary adenomas (MPA), a rare clinical condition, with a vague pathogenesis. Multiple adenomas of the pituitary gland are referred to as morphologically and/or immunocytochemically distinct tumors that are frequently small-sized and hormonally non-functional, to account for the low detection rate. There is no general agreement on how to classify MPA, various criteria, such as tumor contiguity, immunoreactivity, and clonality analysis are being used. Among the component tumors, prolactin (PRL)-immunopositive adenomas are highly prevalent, albeit mute in the majority of cases. The most frequent clinical presentation of MPA is Cushing’s syndrome, given the fact that in more than 50% of reported cases at least one lesion stains for adrenocorticotrophic hormone (ACTH). Plurihormonal hyperactivity may be diagnosed in a patient with MPA when more than one tumor is clinically active (e.g., ACTH and PRL) or in cases with at least one composite tumor (e.g., GH and PRL), to complicate the clinical scenario. Specific challenges associated with MPA include high surgical failure rates, enforcing second-look surgery in certain cases, and difficult preoperative neuroradiological imaging evaluation, with an overall sensitivity of only 25% for magnetic resonance imaging to detect distinct multiple tumors. Alternatively, minor pituitary imaging abnormalities may raise suspicion, as these are not uncommon. Postoperative immunohistochemistry is mandatory and in conjunction to electron microscopy scanning and testing for transcription factors (i.e., Pit-1, T-pit, and SF-1) accurately define and classify the distinct cytodifferentiation of MPA.
Highlights
Up to 10–20% of people harbor a pituitary tumor, mostly in the form of a benign, sporadic, or familial [1], monoclonal, and slow-growing micro- or macroadenoma while aggressive or true malignant tumors constitute a rare finding [2]
A systematic search of the literature was performed in United States National Library of Medicine PubMed, Scopus, and Web of Science Core Collection databases with “multiple pituitary adenoma/tumor,” “double pituitary adenoma/tumor,” “pituitary magnetic resonance imaging,” and “pituitary immunohistochemistry” as key words
Based on tumor immunoreactivity profile and assigned clonality, multiple pituitary adenomas (MPA) should be classified into three main patterns [9]: [1] GH-PRL-TSH-secreting adenomas combined with FSH-LHsecreting tumors; [2] GH-PRL-TSH producing adenomas combined with adrenocorticotrophic hormone (ACTH)-secreting tumors; and [3] ACTH-secreting adenomas combined with FSH-LH-producing tumors, with the first two subgroups being identified as the most prevalent ones (Table 3)
Summary
Up to 10–20% of people harbor a pituitary tumor, mostly in the form of a benign, sporadic, or familial [1], monoclonal, and slow-growing micro- or macroadenoma while aggressive or true malignant tumors constitute a rare finding [2]. Multiple Pituitary Adenomas (MPA) represent simultaneous, but otherwise morphologically and IHC distinct masses of the pituitary gland [5] and need to be distinguished from mixt, multihormone-secreting tumors as such term a single pituitary lesion expressing two or several hormones at IHC. Albeit rare in the clinical setting, MPA are increasingly suspected when there is an incidental finding upon preoperative magnetic resonance imaging (MRI) evaluation of the pituitary gland. As they may pose a challenging clinical scenario with regard to imaging localization and optimal first-choice approach, occasionally enforcing thorough surgical exploration of the pituitary gland to achieve complete removal of functional adenomatous tissue, MPA deserve attention as a distinctive pituitary pathology.
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