Overview of the 2017 WHO Classification of Pituitary Tumors
TL;DR: 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 tumor aspects and some of the non-neuroendocrine tumors involving the pituitsary gland.
Abstract: 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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Catholic University of the Sacred Heart1, Memorial Sloan Kettering Cancer Center2, International Agency for Research on Cancer3, University Health Network4, University of Lausanne5, Centre Hospitalier Universitaire de Grenoble6, Utrecht University7, Charité8, University of Texas MD Anderson Cancer Center9, Technische Universität München10, Belfast Health and Social Care Trust11, University of Zurich12, University of Nottingham13, Beatson West of Scotland Cancer Centre14, Tohoku University15, University of Verona16, Institut Gustave Roussy17, University of Bologna18, Radboud University Nijmegen19
TL;DR: This work believes 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.
688 citations
TL;DR: A concise review of the clinical and pathological aspects of silent pituitary adenomas was conducted in view of the new World Health Organization classification of pituitaries, which needs to be evaluated to better serve this unique group of patients.
Abstract: Context Silent pituitary adenomas are anterior pituitary tumors with hormone synthesis but without signs or symptoms of hormone hypersecretion. They have been increasingly recognized and represent challenging diagnostic issues. Evidence acquisition A comprehensive literature search was performed using MEDLINE and EMBASE databases from January 2000 to March 2018 with the following key words: (i) pituitary adenoma/tumor and nonfunctioning; or (ii) pituitary adenoma/tumor and silent. All titles and abstracts of the retrieved articles were reviewed, and recent advances in the field of silent pituitary adenomas were summarized. Evidence synthesis The clinical and biochemical picture of pituitary adenomas reflects a continuum between functional and silent adenomas. Although some adenomas are truly silent, others will show some evidence of biochemical hypersecretion or could have subtle clinical signs and, therefore, can be referred to as clinically silent or "whispering" adenomas. Silent tumors seem to be more aggressive than their secreting counterparts, with a greater recurrence rate. Transcription factors for pituitary cell lineages have been introduced into the 2017 World Health Organization guidelines: steroidogenic factor 1 staining for gonadotroph lineage; PIT1 (pituitary-specific positive transcription factor 1) for growth hormone, prolactin, and TSH lineage, and TPIT for the corticotroph lineage. Prospective studies applying these criteria will establish the value of the new classification. Conclusions A concise review of the clinical and pathological aspects of silent pituitary adenomas was conducted in view of the new World Health Organization classification of pituitary adenomas. New classifications, novel prognostics markers, and emerging imaging and therapeutic approaches need to be evaluated to better serve this unique group of patients.
108 citations
TL;DR: This represents one of the largest surgical series of morphologically characterized pituitary tumors reported to date and the first to include the routine use of transcription factors for tumor classification.
101 citations
TL;DR: The pathological diagnosis of pituitary tumors may help the clinician to adapt the post-operative management, including appropriate follow-up and early recognition and treatment of potentially aggressive forms.
Abstract: Adenohypophyseal tumors, which were recently renamed pituitary neuroendocrine tumors (PitNET), are mostly benign, but may present various behaviors: invasive, “aggressive” and malignant with metastases. They are classified into seven morphofunctional types and three lineages: lactotroph, somatotroph and thyrotroph (PIT1 lineage), corticotroph (TPIT lineage) or gonadotroph (SF1 lineage), null cell or immunonegative tumor and plurihormonal tumors. The WHO 2017 classification suggested that subtypes, such as male lactotroph, silent corticotroph and Crooke cell, sparsely granulated somatotroph, and silent plurihormonal PIT1 positive tumors, should be considered as “high risk” tumors. However, the prognostic impact of these subtypes and of each morphologic type remains controversial. In contrast, the French five-tiered classification, taking into account the invasion, the immuno-histochemical (IHC) type, and the proliferative markers (Ki-67 index, mitotic count, p53 positivity), has a prognostic value validated by statistical analysis in 4 independent cohorts. A standardized report for the diagnosis of pituitary tumors, integrating all these parameters, has been proposed by the European Pituitary Pathology Group (EPPG). In 2020, the pituitary pathologist must be considered as a member of the multidisciplinary pituitary team. The pathological diagnosis may help the clinician to adapt the post-operative management, including appropriate follow-up and early recognition and treatment of potentially aggressive forms.
94 citations
TL;DR: DAs still represent the primary therapy for most prolactinomas, but neurosurgery has regained interest, due to progress in surgical techniques and a high success rate in microprolactinoma, as well as to some underestimated side effects of long-term DA treatment, such as impulse control disorders or impaired quality of life.
88 citations
References
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Book•
01 Jan 2007
TL;DR: The current edition of the WHO Classification of Tumours of the Central Nervous System will serve as an indispensable textbook for all of those involved in the diagnosis and management of patients with tumors of the CNS, and will make a valuable addition to libraries in pathology, radiology, oncology, and neurosurgery departments.
Abstract: Representing the first volume in the fourth edition series of the World Health Organization (WHO) Classification of Tumours, this book provides a welcome mix of old and new. Similar to prior versions, it opens with a summary of the recently revised WHO Classification of Tumours of the Central Nervous System (CNS), the remainder of the book being dedicated to a comprehensive yet succinct presentation of the most current knowledge relative to each individual tumor and familial tumor syndrome. The 73 contributing authors have likewise adopted a familiar standardized format with the following subheadings: definition, grading, incidence, age and sex distribution, localization, clinical features, neuroimaging, macroscopy, histopathology, proliferation, genetic susceptibility, genetics, histogenesis, and prognostic and predictive factors. Although a fair number of images have been recycled from previous editions, the majority is new and includes more than 400 full-color photomicrographs and macroscopic images, as well as numerous neuroimages, informative diagrams and charts. A number of tumor entities new to this version of the WHO Classification are explored in detail, including pilomyxoid astrocytoma, atypical choroid plexus papilloma, angiocentric glioma, extraventricular neurocytoma, papillary glioneuronal tumor, rosetteforming glioneuronal tumor of the fourth ventricle, papillary tumor of the pineal region, pituicytoma, and spindle cell oncocytoma of the adenohypophysis. Perhaps the most noticeable improvement comes by way of a voluminous expansion in the genetics sections of the majority of tumor categories. This update parallels the recent explosion of research utilizing high-resolution genome screening and other molecular techniques. The authors have done an outstanding job in distilling the information housed in over 2,500 cited references into a readerfriendly authoritative reference of CNS neoplasia. In summation, the current edition of the WHO Classification of Tumours of the Central Nervous System will serve as an indispensable textbook for all of those involved in the diagnosis and management of patients with tumors of the CNS, and will make a valuable addition to libraries in pathology, radiology, oncology, and neurosurgery departments.
5,018 citations
Book•
01 Jan 2004
TL;DR: Pathology and Genetics of Tumours of Endocrine OrgansMolecular Pathology of Breast CancerWho Classification of TUMoursPathology & Genetics of Surgical Tissues, Haematopoietic and Lymphoid Tissues and Soft Tissue Pathology.
Abstract: Pathology and Genetics of Tumours of Endocrine OrgansMolecular Pathology of Breast CancerWho Classification of Tumours of the Lung, Pleura, Thymus and HeartPathology and Genetics of Tumours of the Nervous SystemWHO Classification of Skin TumoursThe Molecular Basis of CancerMolecular Genetics of Lung CancerPathology and Genetics of Tumours of the Digestive SystemPathology and Genetics of Tumours of Head and Neck TumoursFemale Genital Tumours: Who Classification of TumoursPathology & Genetics of Tumours of Haematopoietic and Lymphoid TissuesModern Soft Tissue PathologyPathology and Genetics of Tumours of Endocrine OrgansWHO Classification of Tumours of the Digestive SystemPathology and Genetics of Tumours of the SkinWHO Classification of Tumours of the Urinary System and Male Genital OrgansWHO Classification of Tumours of the Central Nervous SystemPathology and Genetics of Tumours of the Breast and Female Genital OrgansWHO Classification of Tumours of Haematopoietic and Lymphoid TissuesWHO Classification of Tumours of Female Reproductive OrgansWHO Classification of Head and Neck TumoursPathology and Genetics of Tumours of the Nervous SystemPathology and Genetics of Tumours of Haematopoietic and Lymphoid TissuesPathology and Genetics of Tumours of the Nervous SystemWHO Classification of Tumours of Soft Tissue and BonePathology and Genetics of Tumours of the Urinary System and Male Genital OrgansSoft Tissue
1,622 citations
Additional excerpts
...In the previous WHO edition (2004) [8], the pituitary neuroendocrine tumors were divided into typical adenoma, atypical adenoma, and carcinoma....
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TL;DR: A subset of growth hormone-secreting human pituitary tumours carries somatic mutations that inhibit GTPase activity of a G protein α chain, αs, which results in the activation of adenylyl cyclase, which bypasses the cells' normal requirement for trophic hormone.
Abstract: A subset of growth hormone-secreting human pituitary tumours carries somatic mutations that inhibit GTPase activity of a G protein alpha chain, alpha(s) The resulting activation of adenylyl cyclase bypasses the cells' normal requirement for trophic hormone Amino acids substituted in the putative gsp oncogene identify a domain of G protein alpha-chains required for intrinsic ability to hydrolyse GTP This domain may serve as a built-in counter-part of the separate GTPase-activating proteins required for GTP hydrolysis by small GTP-binding proteins such as p21ras
1,342 citations
"Overview of the 2017 WHO Classifica..." refers background in this paper
...resulting in upregulation of the cAMP pathway [116, 117]; the GNAS gene mutation is however rarely identified in other pituitary neuroendocrine tumor subtypes [117]....
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TL;DR: The prevalence of pituitary adenomas in the study population (one case in 1064 individuals) was more than 3.5-5 times that previously reported, which may have important implications when prioritizing funding for research and treatment of Pituitary Adenomas.
Abstract: Context: Prevalence data are important for assessing the burden of disease on the health care system; data on pituitary adenoma prevalence are very scarce. Objective: The objective of the study was to measure the prevalence of clinically relevant pituitary adenomas in a well-defined population. Design: This was a cross-sectional, intensive, case-finding study performed in three regions of the province of Liege, Belgium, to measure pituitary adenoma prevalence as of September 30, 2005. Setting: The study was conducted in specialist and general medical practitioner patient populations, referral hospitals, and investigational centers. Methods: Three demographically and geographically distinct districts of the province of Liege 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 demogr...
860 citations
TL;DR: Pituitary tumours are common and show a range of hormonal and proliferative behaviours that provide a model for the study of neoplasia mechanisms, although there are many differences in disease pathogenesis between mice and humans.
Abstract: Recently there has been significant progress in our understanding of pituitary development, physiology, and pathology. New information has helped to clarify the classification of pituitary tumors. Epidemiologic analyses have identified a much higher incidence of pituitary tumors than previously thought. We review the pathogenetic factors that have been implicated in pituitary tumorigenesis and the application of novel targeted therapies that underscore the increasingly important role of the pathologist in determining accurate diagnoses and facilitating appropriate treatment of patients with these disorders.
417 citations