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      Unusual Course of an Aggressive Pituitary Prolactinoma: Case Report and Review of the Literature

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          Abstract

          Pituitary carcinomas are rare tumors with heterogeneous behaviors. Their carcinogenesis is still unknown. Consequently, treatment is multimodal and not standardized. Dopamine (DA) agonists are used as first-line treatments, while radiotherapy and surgery may be used for local control of invasive tumors. We describe the case of a 35-year-old male who presented with an invasive prolactinoma, managed initially with a transsphenoidal resection, postsurgical radiotherapy and DA agonists. The patient posteriorly presented a sole metastatic lesion to the lumbar spine that was later managed with local radiotherapy. Due to pituitary recurrence of the lesion, multiple surgical resections were needed until further treatment was declined. The clinical course in this patient was unusual. He lived for 13 years after initial diagnosis, with a very invasive tumor without systemic chemotherapy. Radiotherapy is used in pituitary tumors in which surgery fails; we hypothesize that it contributed to the malignant transformation and the late resistance to DA agonists in our patient. Several biomarkers in tumoral tissue have been evaluated regarding their association with malignancy and aggressive behaviors, although more studies are still needed. Therapeutic strategies are limited, without evidence on the impact on overall survival and prognosis. Risk factors associated with early malignancy in pituitary prolactinomas include recurrent behavior, increase in prolactin levels with a stable sellar mass, and secondary development of DA agonist resistance. However, there are still no conclusive answers as to whether physicians should rigorously follow up these patients or provide direct therapy with aggressive approaches.

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          Most cited references19

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          Clinical review: Pituitary carcinoma: difficult diagnosis and treatment.

          Although pituitary tumors are common, pituitary carcinoma is very rare and is only diagnosed when pituitary tumor noncontiguous with the sellar region is demonstrated. Diagnosis is difficult, resulting in delays that may adversely effect outcome that is traditionally poor. Barriers to earlier diagnosis and management strategies for pituitary carcinoma are discussed. PubMed was employed to identify relevant studies, a review of the literature was conducted, and data were summarized and integrated from the author's perspective. The available data highlight the difficulties in diagnosis and management and practical challenges in conducting clinical trials in this rare condition. They suggest that earlier diagnosis with aggressive multimodal therapy may be advantageous in some cases. Although pituitary carcinoma remains difficult to diagnose and treat, recent developments have led to improved outcomes in selected cases. With broader use of molecular markers, efforts to modify current histopathological criteria for pituitary carcinoma diagnosis may now be possible. This would assist earlier diagnosis and, in combination with targeted therapies, potentially improve long-term survival.
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            Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients.

            Dopamine agonist resistance in prolactinoma is an infrequent phenomenon. Doses of cabergoline (CAB) of up to 2.0 mg/week are usually effective in controlling prolactin (PRL) secretion and reducing tumor size in prolactinomas. The clinical presentation, management, and outcome of patients that are not well controlled by such commonly used doses of CAB-resistant patients are poorly understood.
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              Biomarkers of aggressive pituitary adenomas.

              Pituitary adenomas exhibit a wide range of behaviors. The prediction of aggressive or malignant behavior in pituitary adenomas remains challenging; however, the utility of biomarkers is rapidly evolving. In this review, we discuss potential biomarkers as they relate to aggressive behavior in pituitary adenomas. While detailed histological subtyping remains the best independent predictor of aggressive behavior in the majority of cases, evidence suggests that the additional analyses of FGFR4, MMP, PTTG, Ki-67, p53, and deletions in chromosome 11 may contribute to decisions concerning management of aggressive pituitary adenomas.
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                Author and article information

                Journal
                CRN
                CRN
                10.1159/issn.1662-680X
                Case Reports in Neurology
                S. Karger AG
                1662-680X
                2019
                January – April 2019
                30 April 2019
                : 11
                : 1
                : 148-156
                Affiliations
                [_a] aSchool of Medicine, Universidad de los Andes, Bogotá, Colombia
                [_b] bEndocrinology Section, Department of Internal Medicine, Fundación Santa Fe de Bogotá, Bogotá, Colombia
                [_c] cDepartment of Pathology, Fundación Santa Fe de Bogotá, Bogotá, Colombia
                [_d] dDepartment of Neurosurgery, Fundación Santa Fe de Bogotá, Bogotá, Colombia
                Author notes
                *Deyanira González-Devia, Endocrinology Section, Department of Internal Medicine, Fundación Santa Fe de Bogotá, Calle 119 Nº 7–75, Bogotá D.C. 110111 (Colombia), E-Mail deyaniragonzalezdevia@yahoo.com
                Author information
                https://orcid.org/0000-0001-7277-7482
                Article
                499702 PMC6616046 Case Rep Neurol 2019;11:148–156
                10.1159/000499702
                PMC6616046
                31320875
                23fbeb50-9d6c-461b-9110-dba5c85ea917
                © 2019 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 22 February 2019
                : 18 March 2019
                Page count
                Figures: 4, Pages: 9
                Categories
                Case Report

                Geriatric medicine,Neurology,Cardiovascular Medicine,Neurosciences,Clinical Psychology & Psychiatry,Public health
                Prolactinoma,Brain tumor,Pituitary carcinoma,Radiotherapy,Dopamine agonist

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