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      The evolution in pituitary tumour classification: a clinical perspective

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          Abstract

          Objective

          Pituitary tumours comprise a pathologically and clinically diverse group of neoplasms. Classification frameworks have changed dramatically in the past two decades, reflecting improving understanding of tumour biology. This narrative review examines the evolution of pituitary tumour classification, from a clinical perspective.

          Results

          In 2004, pituitary tumours were classified as ‘typical’ or ‘atypical’, based on the presence of markers of proliferation, Ki67, mitotic count and p53. In 2017, the new WHO marked a major paradigm shift, with a new focus on lineage-based classification, determined by transcription factor and hormonal immunohistochemistry. The terms ‘typical’ and ‘atypical’ were omitted, though the importance of proliferative markers Ki67 and mitotic count was acknowledged. The recent WHO 2022 classification incorporates further refinements, specifically recognising some less common types that may represent less well-differentiated tumours. Whilst ‘high risk’ tumour types have been identified, further work is still required to improve prognostication.

          Conclusions

          Recent WHO classifications have marked significant progress in the diagnostic evaluation of pituitary tumours, though shortcomings and challenges remain for both clinicians and pathologists in managing these tumours.

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          Most cited references72

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          Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK).

          Pituitary adenomas (PAs) are associated with increased morbidity and mortality. The optimal delivery of services and the provision of care for patients with PAs require distribution of the resources proportionate to the impact of these conditions on the community. Currently, the resource allocation for PAs in the health care system is lacking a reliable and an up-to-date epidemiological background that would reflect the recent advances in the diagnostic technologies, leading to the earlier recognition of these tumours. To determine the prevalence, the diagnostic delay and the characteristics of patients with PA in a well-defined geographical area of the UK (Banbury, Oxfordshire). Sixteen general practitioner (GP) surgeries covering the area of Banbury and a total population of 89 334 inhabitants were asked to participate in the study (data confirmed on 31 July 2006). Fourteen surgeries with a total of 81,449 inhabitants (91% of the study population) agreed to take part. All cases of PAs were found following an exhaustive computer database search of agreed terms by the staff of each Practice and data on age, gender, presenting manifestations and their duration, imaging features at diagnosis, history of multiple endocrine neoplasia type 1 and family history of PA were collected. A total of 63 patients with PA were identified amongst the study population of 81,149, with a prevalence of 77.6 PA cases/100,000 inhabitants (prolactinomas; PRLoma: 44.4, nonfunctioning PAs: 22.2, acromegaly; ACRO: 8.6, corticotroph adenoma: 1.2 and unknown functional status; UFS: 1.2/100,000 inhabitants). The distribution of each PA subtype was for PRLoma 57%, nonfunctioning PAs 28%, ACRO 11%, corticotroph adenoma 2% and UFS 2%. The median age at diagnosis and the duration of symptoms until diagnosis (in years) were for PRLoma 32.0 and 1.5, nonfunctioning PAs 51.5 and 0.8, ACRO 47 and 4.5 and corticotroph adenoma 57 and 7, respectively. PRLoma was the most frequent PA diagnosed up to the age of 60 years (0-20 years: 75% and 20-60 years: 61% of PAs) and nonfunctioning PA after the age of 60 years (60% of PAs). Nonfunctioning PAs dominated in men (57% of all men with PA) and PRLoma in women (76% of all women with PA). Five patients (7.9%) presented with classical pituitary apoplexy, with a prevalence of 6.2 cases/100,000 inhabitants. Based on a well-defined population in Banbury (Oxfordshire, UK), we have shown that PAs have a fourfold increased prevalence than previously thought; our data confirm that PAs have a higher burden on the Health Care System and optimal resource distribution for both clinical care and research activities aiming to improve the outcome of these patients are needed.
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            High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium.

            Prevalence data are important for assessing the burden of disease on the health care system; data on pituitary adenoma prevalence are very scarce. The objective of the study was to measure the prevalence of clinically relevant pituitary adenomas in a well-defined population. This was a cross-sectional, intensive, case-finding study performed in three regions of the province of Liège, Belgium, to measure pituitary adenoma prevalence as of September 30, 2005. The study was conducted in specialist and general medical practitioner patient populations, referral hospitals, and investigational centers. Three demographically and geographically distinct districts of the province of Liège were delineated precisely using postal codes. Medical practitioners in these districts were recruited, and patients with pituitary adenomas under their care were identified. Diagnoses were confirmed after retrieval of clinical, hormonal, radiological, and pathological data; full demographic and therapeutic follow-up data were collected in all cases. Sixty-eight patients with clinically relevant pituitary adenomas were identified in a population of 71,972 individuals; the mean (+/- sd) prevalence was 94 +/- 19.3 cases per 100,000 population (95% confidence interval, 72.2 to 115.8). The group was 67.6% female and had a mean age at diagnosis of 40.3 yr; 42.6% had macroadenomas and 55.9% underwent surgery. Prolactinomas comprised 66% of the group, with the rest having nonsecreting tumors (14.7%), somatotropinomas (13.2%), or Cushing's disease (5.9%); 20.6% had hypopituitarism. The prevalence of pituitary adenomas in the study population (one case in 1064 individuals) was more than 3.5-5 times that previously reported. This increased prevalence may have important implications when prioritizing funding for research and treatment of pituitary adenomas.
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              Advances in the treatment of prolactinomas.

              Prolactinomas account for approximately 40% of all pituitary adenomas and are an important cause of hypogonadism and infertility. The ultimate goal of therapy for prolactinomas is restoration or achievement of eugonadism through the normalization of hyperprolactinemia and control of tumor mass. Medical therapy with dopamine agonists is highly effective in the majority of cases and represents the mainstay of therapy. Recent data indicating successful withdrawal of these agents in a subset of patients challenge the previously held concept that medical therapy is a lifelong requirement. Complicated situations, such as those encountered in resistance to dopamine agonists, pregnancy, and giant or malignant prolactinomas, may require multimodal therapy involving surgery, radiotherapy, or both. Progress in elucidating the mechanisms underlying the pathogenesis of prolactinomas may enable future development of novel molecular therapies for treatment-resistant cases. This review provides a critical analysis of the efficacy and safety of the various modes of therapy available for the treatment of patients with prolactinomas with an emphasis on challenging situations, a discussion of the data regarding withdrawal of medical therapy, and a foreshadowing of novel approaches to therapy that may become available in the future.
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                Author and article information

                Journal
                Endocr Oncol
                Endocr Oncol
                eo
                Endocrine Oncology
                Bioscientifica Ltd (Bristol )
                2634-4793
                21 April 2023
                21 April 2023
                01 January 2023
                : 3
                : 1
                : e220079
                Affiliations
                [1 ]Department of Endocrinology , St Vincent’s Hospital, Sydney, NSW, Australia
                [2 ]Garvan Institute of Medical Research , Sydney, NSW, Australia
                [3 ]St Vincent’s Clinical School , University of New South Wales, Sydney, NSW, Australia
                [4 ]Department of Anatomical Pathology and Cytopathology , St Vincent’s Pathology, Sydney, NSW, Australia
                [5 ]Department of Diabetes and Endocrinology , Princess Alexandra Hospital, Brisbane, QLD, Australia
                [6 ]Faculty of Medicine , the University of Queensland, Brisbane, QLD, Australia
                Author notes
                Correspondence should be addressed to N F Lenders: n.lenders@ 123456garvan.org.au
                Author information
                http://orcid.org/0000-0002-6738-0832
                http://orcid.org/0000-0002-2859-5566
                Article
                EO-22-0079
                10.1530/EO-22-0079
                10305559
                37434652
                462d839b-dd2d-4e86-a074-9ce7fc4d50da
                © the author(s)

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 11 April 2023
                : 21 April 2023
                Funding
                Funded by: Pfizer, doi http://dx.doi.org/10.13039/100004319;
                Funded by: Ipsen, doi http://dx.doi.org/10.13039/501100014382;
                Funded by: Novo Nordisk, doi http://dx.doi.org/10.13039/501100004191;
                Funded by: Pfizer, doi http://dx.doi.org/10.13039/100004319;
                Funded by: Ipsen, doi http://dx.doi.org/10.13039/501100014382;
                Funded by: Pfizer, doi http://dx.doi.org/10.13039/100004319;
                Categories
                Review

                pituitary,neuroendocrine tumours,immunohistochemistry,transcription factors

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