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      Pituitary Adenoma in Pediatric and Adolescent Populations

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          Abstract

          Pituitary adenomas are rare in children and adolescents and although mostly benign, they can sometimes be challenging to manage due to their locally invasive nature. In this study, we examined the clinicopathologic features of 42 pituitary adenomas in patients ≤21 years of age. The youngest patient was 8 years old (median age: 18 years), and the female-to-male ratio was 1.8:1. Five patients had recurrence after resection. There was no obvious difference between the recurrent rates in the typical (11.7%) and atypical adenomas (12.5%) based on the 2004 WHO classification. However, the recurrence rate was much higher in adenomas with an elevated proliferation index of ≥3% (20.8%) or with evidence of local invasion (18.2%). Adenomas with combination of an elevated proliferation index of ≥3% and imaging evidence of local invasion had the highest recurrence rate of 25%. In summary, pituitary adenomas are more frequent in adolescents as compared with children and are more common in girls. An elevated proliferation index of ≥3% and evidence of local invasion on imaging seem to correlate with a high probability of recurrence. Furthermore, we observe rarity of α-thalassemia/mental retardation syndrome X-linked (ATRX) protein loss (surrogate to ATRX mutation) in these tumors without any connotation on prognosis.

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          Most cited references26

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          A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal

          The classification of neuroendocrine neoplasms (NENs) differs between organ systems and currently causes considerable confusion. A uniform classification framework for NENs at any anatomical location may reduce inconsistencies and contradictions among the various systems currently in use. The classification suggested here is intended to allow pathologists and clinicians to manage their patients with NENs consistently, while acknowledging organ-specific differences in classification criteria, tumor biology, and prognostic factors. The classification suggested is based on a consensus conference held at the International Agency for Research on Cancer (IARC) in November 2017 and subsequent discussion with additional experts. The key feature of the new classification is a distinction between differentiated neuroendocrine tumors (NETs), also designated carcinoid tumors in some systems, and poorly differentiated NECs, as they both share common expression of neuroendocrine markers. This dichotomous morphological subdivision into NETs and NECs is supported by genetic evidence at specific anatomic sites as well as clinical, epidemiologic, histologic, and prognostic differences. In many organ systems, NETs are graded as G1, G2, or G3 based on mitotic count and/or Ki-67 labeling index, and/or the presence of necrosis; NECs are considered high grade by definition. We believe this conceptual approach can form the basis for the next generation of NEN classifications and will allow more consistent taxonomy to understand how neoplasms from different organ systems inter-relate clinically and genetically.
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            The prevalence of pituitary adenomas: a systematic review.

            Pituitary adenomas display an array of hormonal and proliferative activity. Once primarily classified according to size (microadenomas, or = 1 cm), these tumors are now further classified according to immunohistochemistry and functional status. With these additional classifications in mind, the goals of the current study were to determine the prevalence of pituitary adenomas and to explore the clinical relevance of the findings. The authors conducted a metaanalysis of all existing English-language articles in MEDLINE. They used the search string (pituitary adenoma or pituitary tumor) and prevalence and selected relevant autopsy and imaging evaluation studies for inclusion. The authors found an overall estimated prevalence of pituitary adenomas of 16.7% (14.4% in autopsy studies and 22.5% in radiologic studies). Given the high frequency of pituitary adenomas and their potential for causing clinical pathologies, the findings of the current study suggest that early diagnosis and treatment of pituitary adenomas should have far-reaching benefits.
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              A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up.

              Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.
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                Author and article information

                Journal
                J Neuropathol Exp Neurol
                J. Neuropathol. Exp. Neurol
                jnen
                Journal of Neuropathology and Experimental Neurology
                Oxford University Press
                0022-3069
                1554-6578
                July 2019
                26 April 2019
                26 April 2019
                : 78
                : 7
                : 626-632
                Affiliations
                Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110
                Author notes
                Send correspondence to: Sonika Dahiya, MD, Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110; E-mail: sdahiya@ 123456wustl.edu
                Author information
                http://orcid.org/0000-0002-5585-0964
                Article
                nlz040
                10.1093/jnen/nlz040
                6581558
                31115468
                c7f14491-5872-45c1-9c5c-d9c753a99904
                © 2019 American Association of Neuropathologists, Inc.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contactjournals.permissions@oup.com

                History
                Page count
                Pages: 7
                Funding
                Funded by: Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine
                Categories
                Original Articles

                atrx,atypical,clinicopathologic features,invasive,pediatric,pituitary neuroendocrine neoplasm,prognosis,who classification

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