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      Silent Corticotroph and Somatotroph Double Pituitary Adenoma: A Case Report and Review of Literature

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          Abstract

          Clinically silent double pituitary adenomas consisting of corticotroph and somatotroph cells are an exceedingly rare clinical finding. In this report, we present the case of a 28-year-old man with a 1-year history of recurrent headaches. Imaging revealed a 2.1 (anterior-posterior) × 2.2 (transverse) × 1.3 (craniocaudal) cm pituitary adenoma invading into the left cavernous sinus and encasing the left internal carotid artery. Endoscopic transnasal resection was performed without complications. Immunohistochemical staining revealed a double adenoma consisting of distinct sparsely granulated somatotroph and densely granulated corticotroph cells that were positive for growth hormone and adrenocorticotropic hormone, respectively. K i -67 index labeling revealed a level of 6% within the corticotroph adenoma. No increase in serum growth hormone or adrenocorticotropic hormone was found, indicating a clinically silent double adenoma. While transsphenoidal surgery remains a first-line approach for silent adenomas presenting with mass effects, increased rates of proliferative markers, such as the K i -67 index, provide useful insight into the clinical course of such tumors. Determining the K i -67 index of silent pituitary adenomas could be valuable in predicting recurrence after initial surgical resection and identifying tumors that are at an increased risk of needing additional therapeutic interventions or more frequent surveillance imaging.

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          Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67.

          J. Gerdes, H. Lemke, H. Baisch … (1984)
          The monoclonal antibody Ki-67 detects a nuclear antigen that is present only in proliferating cells. The aim of the present investigation was to clarify whether the Ki-67 nuclear antigen is restricted in its expression to certain phases of the cell cycle. All experiments consistently showed that the Ki-67 nuclear antigen is present in S, G2, and M phase, but is absent in G0. However, the results concerning Ki-67 antigen expression in G1 phase varied: cells passing the early events of mitogen triggered transition from G0 to G1, i.e., G1T and first G1A, lacked the Ki-67 nuclear antigen, whereas G1 cells after mitosis were constantly Ki-67-positive. This result suggests that after mitosis cells might not follow the same metabolic pathways as G0 cells do when entering G1 for the first time. Therefore, we suggest that the early stages of mitogen stimulation represent initial sequences of proliferation and not parts of the cell cycle. Because our data show that the Ki-67 nuclear antigen is present throughout the cell cycle, immunostaining with monoclonal antibody Ki-67 provides a reliable means of rapidly evaluating the growth fraction of normal and neoplastic human cell populations.
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            The 2017 World Health Organization classification of tumors of the pituitary gland: a summary.

            M Beatriz S Lopes (2017)
            The 4th edition of the World Health Organization (WHO) classification of endocrine tumors has been recently released. In this new edition, major changes are recommended in several areas of the classification of tumors of the anterior pituitary gland (adenophypophysis). The scope of the present manuscript is to summarize these recommended changes, emphasizing a few significant topics. These changes include the following: (1) a novel approach for classifying pituitary neuroendocrine tumors according to pituitary adenohypophyseal cell lineages; (2) changes to the histological grading of pituitary neuroendocrine tumors with the elimination of the term "atypical adenoma;" and (3) introduction of new entities like the pituitary blastoma and re-definition of old entities like the null-cell adenoma. This new classification is very practical and mostly based on immunohistochemistry for pituitary hormones, pituitary-specific transcription factors, and other immunohistochemical markers commonly used in pathology practice, not requiring routine ultrastructural analysis of the tumors. Evaluation of tumor proliferation potential, by mitotic count and Ki-67 labeling index, and tumor invasion is strongly recommended on individual case basis to identify clinically aggressive adenomas. In addition, the classification offers the treating clinical team information on tumor prognosis by identifying specific variants of adenomas associated with an elevated risk for recurrence. Changes in the classification of non-neuroendocrine tumors are also proposed, in particular those tumors arising in the posterior pituitary including pituicytoma, granular cell tumor of the posterior pituitary, and spindle cell oncocytoma. These changes endorse those previously published in the 2016 WHO classification of CNS tumors. Other tumors arising in the sellar region are also reviewed in detail including craniopharyngiomas, mesenchymal and stromal tumors, germ cell tumors, and hematopoietic tumors. It is hoped that the 2017 WHO classification of pituitary tumors will establish more biologically and clinically uniform groups of tumors, make it possible for practicing pathologists to better diagnose these tumors, and contribute to our understanding of clinical outcomes for patients harboring pituitary tumors.
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              Overview of the 2017 WHO Classification of Pituitary Tumors.

              Ozgur Mete, M Lopes (2017)
              This review focuses on discussing the main changes on the upcoming fourth edition of the WHO Classification of Tumors of the Pituitary Gland emphasizing histopathological and molecular genetics aspects of pituitary neuroendocrine (i.e., pituitary adenomas) and some of the non-neuroendocrine tumors involving the pituitary gland. Instead of a formal review, we introduced the highlights of the new WHO classification by answering select questions relevant to practising pathologists. The revised classification of pituitary adenomas, in addition to hormone immunohistochemistry, recognizes the role of other immunohistochemical markers including but not limited to pituitary transcription factors. Recognizing this novel approach, the fourth edition of the WHO classification has abandoned the concept of "a hormone-producing pituitary adenoma" and adopted a pituitary adenohypophyseal cell lineage designation of the adenomas with subsequent categorization of histological variants according to hormone content and specific histological and immunohistochemical features. This new classification does not require a routine ultrastructural examination of these tumors. The new definition of the Null cell adenoma requires the demonstration of immunonegativity for pituitary transcription factors and adenohypophyseal hormones Moreover, the term of atypical pituitary adenoma is no longer recommended. In addition to the accurate tumor subtyping, assessment of the tumor proliferative potential by mitotic count and Ki-67 index, and other clinical parameters such as tumor invasion, is strongly recommended in individual cases for consideration of clinically aggressive adenomas. This classification also recognizes some subtypes of pituitary neuroendocrine tumors as "high-risk pituitary adenomas" due to the clinical aggressive behavior; these include the sparsely granulated somatotroph adenoma, the lactotroph adenoma in men, the Crooke's cell adenoma, the silent corticotroph adenoma, and the newly introduced plurihormonal Pit-1-positive adenoma (previously known as silent subtype III pituitary adenoma). An additional novel aspect of the new WHO classification was also the definition of the spectrum of thyroid transcription factor-1 expressing pituitary tumors of the posterior lobe as representing a morphological spectrum of a single nosological entity. These tumors include the pituicytoma, the spindle cell oncocytoma, the granular cell tumor of the neurohypophysis, and the sellar ependymoma.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Neurol Surg Rep
                Journal ID (iso-abbrev): J Neurol Surg Rep
                Journal ID (doi): 10.1055/s-00000182
                Title: Journal of Neurological Surgery Reports
                Publisher: Georg Thieme Verlag KG (Rüdigerstraße 14, 70469 Stuttgart, Germany )
                ISSN (Print): 2193-6358
                ISSN (Electronic): 2193-6366
                Publication date Collection: April 2022
                Publication date (Electronic): 27 May 2022
                Publication date PMC-release: 1 May 2022
                Volume: 83
                Issue: 2
                Pages: e33-e38
                Affiliations
                [1 ]Department of Neurological Surgery, Albert Einstein College of Medicine, Bronx, New York, United States
                [2 ]Department of Neurological Surgery, Montefiore Medical Center, Bronx, New York, United States
                [3 ]Department of Endocrinology, Albert Einstein College of Medicine, Bronx, New York, United States
                [4 ]Department of Endocrinology, Montefiore Medical Center, Bronx, New York, United States
                [5 ]Department of Anatomic and Clinical Pathology, Albert Einstein College of Medicine, Bronx, New York, United States
                [6 ]Department of Anatomic and Clinical Pathology, Montefiore Medical Center, Bronx, New York, United States
                Author notes
                Address for correspondence Isabella L. Pecorari, MS Montefiore Medical Center, The University Hospital for the Albert Einstein College of Medicine 3316 Rochambeau Avenue, Bronx, New York 10467United States isabella.pecorari@ 123456einsteinmed.org
                Author information
                http://orcid.org/0000-0002-1474-2553
                Article
                Publisher ID: 210029
                DOI: 10.1055/s-0042-1749389
                PMC ID: 9142216
                PubMed ID: 35646510
                SO-VID: a0d6a38c-cbb6-4103-963d-5cb6dc46a544
                Copyright © The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ )
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License, which permits unrestricted reproduction and distribution, for non-commercial purposes only; and use and reproduction, but not distribution, of adapted material for non-commercial purposes only, provided the original work is properly cited.

                History
                Date received : 17 November 2021
                Date accepted : 29 March 2022
                Funding
                Funding None.
                Categories
                Subject: Case Report

                Keywords: double pituitary adenoma,somatotroph,corticotroph, k i -67
                Data availability:
                Keywords: double pituitary adenoma, somatotroph, corticotroph, k i -67

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