New diagnostic and management approaches in endocrine pathology.
Subject: Pathology (History)
Pathology (Personalities)
Endocrine gland diseases (Diagnosis)
Endocrine gland diseases (Care and treatment)
Authors: Asa, Sylvia L.
LiVolsi, Virginia A.
Pub Date: 08/01/2008
Publication: Name: Archives of Pathology & Laboratory Medicine Publisher: College of American Pathologists Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2008 College of American Pathologists ISSN: 1543-2165
Issue: Date: August, 2008 Source Volume: 132 Source Issue: 8
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 230246810
Full Text: Endocrine pathology has a long and colorful history, marked by the important discoveries of Askenazy, Cushing, Hashimoto, Hurthle, Langerhans, Sheehan, and others whose names pepper the language of this field. However, the field itself is young, as it has only been in the last 20 years that people have identified themselves as "endocrine pathologists." Even as subspecialization found its way into surgical pathology, the pituitary remained the territory of the neuropathologists, the thyroid and parathyroid have been in the realm of head and neck pathologists, and the adrenal remained a component of genitourinary pathology. Disorders of the endocrine pancreas and endocrine gut comprise a significant element in gastrointestinal pathology, and endocrine lesions of the lung are usually within the sphere of pulmonary pathology. However, the concept of structure-function correlations, particularly hormone production, is a unique challenge that provides a unifying theme to endocrine pathology that has captivated the minds of those who delve into this area. In many centers, the importance of clinicopathologic correlations and the emergence of multidisciplinary site groups have fostered the development of pathologists who have become experts in this complex and fascinating field.

The rapid growth in knowledge of cell and molecular biology has resulted in new approaches to the diagnosis and management of endocrine disorders. In this special section of the Archives, we have asked some of the experts in this field to provide timely updates for pathologists who deal with endocrine pathology. This special section is not intended to be a comprehensive text. Instead, we have identified specific questions that we perceive as common areas of confusion or concern that represent challenges to the practicing pathologist or critical updates that have changed daily practice.

Pituitary pathology represents a challenge to most pathologists. For many, pituitary specimens are rare. These small fragmented tissues are often crushed. The diagnosis is almost always pituitary adenoma with the occasional craniopharyngioma crossing the surgical pathology bench. At first glance, the diagnosis is simple. So why would we offer you an update on practical pituitary pathology? In this new era of targeted therapies, the pituitary too is being subjected to investigation for novel therapies that will alleviate the significant hormonal imbalance that pituitary tumors can cause. Although pituitary adenomas are benign, they can be highly invasive and lethal neoplasms that require aggressive management, and it behooves the pathologist to assist the endocrine oncologists to appropriately classify, prognosticate, and treat these lesions. Moreover, the unusual lesions that arise in the region of the sella turcica can represent a challenge for diagnosis. The importance of clinical information cannot be overemphasized. Appropriate specimen handling is critical and the rational application of ancillary techniques is reviewed. In addition, the autopsy pituitary, although rarely investigated, can be a valuable source of information yet it remains enigmatic to many pathologists.

The Hurthle cell and its lesions have been a source of controversy since the first recognition of this cell. Indeed, what we term "Hurthle cell" is a misnomer because the cell originally described by Dr Hurthle was the nonfollicular C cell. From that somewhat inauspicious beginning, the literature on Hurthle cells has evoked considerable confusion, especially with regard to nodules and neoplasms composed of this element. In addition, some eosinophilic cells in the thyroid without all of the cytologic features of true Hurthle cells have created considerably more confusion. In the article by Montone et al, this entire topic is reviewed and a modern approach to the diagnosis of these lesions and an understanding of their prognosis is given.

The parathyroid glands and the lesions associated with their hyperfunction are discussed by DeLellis et al. They present an overview of the changes in intraoperative management and pathologic assessment of parathyroid glands in the era of preoperative and intraoperative radiolocalization and intraoperative parathyroid hormone assays. They discuss recent genetic alterations identified in rare clinical syndromes associated with hyperparathyroidism that are finding application in the diagnosis of sporadic benign, atypical, and malignant parathyroid lesions.

The adrenal gland is covered in 2 articles. Dr McNicol describes the adrenal cortex, its development, anatomy, and physiology. She reviews rare congenital lesions whose understanding may lead to better diagnostic criteria for sporadic adult lesions. In addition to reviewing the pathology and pathophysiology of hyperplasias, adenomas, and carcinomas, she defines the value of immunohistochemical and molecular markers in the diagnosis and prognosis of these difficult lesions.

Dr Tischler describes the new World Health Organization classification of intra-adrenal pheochromocytomas and extra-adrenal paragangliomas. His article covers the recently recognized frequency and importance of germline mutations in patients with these unusual tumors. The difficult issue of defining malignancy in these lesions, especially in pheochromocytoma, is an area of controversy. The molecular markers that are proving particularly valuable are discussed, as are practical immunohistochemical stains that can distinguish these lesions from other tumors arising in the adrenal.

The neuroendocrine system of the gastrointestinal tract is discussed by Dr Chetty who reviews the terminology of these lesions, the recent World Health Organization classification and grading scheme, and a reporting format that will prove useful for daily practice. He describes a number of immunohistochemical markers that can be applied to better classify these tumors and provide prognostic algorithms.

This special section of the Archives summarizes practical diagnostic data and new molecular insights into lesions that affect the major endocrine organs. These updates should be helpful to the diagnostic pathologist in daily clinical practice.

Sylvia L. Asa, MD, PhD; Virginia A. LiVolsi, MD

Accepted for publication April 15, 2008.

From the Department of Pathology, University Health Network, Toronto, Ontario (Dr Asa); and the Department of Surgical Pathology, University of Pennsylvania Medical Center, Philadelphia (Dr LiVolsi).

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Sylvia L. Asa, MD, PhD, Department of Pathology, University Health Network, 200 Elizabeth St, 11th Floor, Toronto, Ontario, Canada M5G 2C4 (e-mail: sylvia.asa@uhn.on.ca).

Asa, Continued

Sylvia L. Asa, MD, PhD, Medical Director of Toronto Medical Laboratories and Pathologist-in-Chief at the University Health Network, is a professor in the Department of Laboratory Medicine and Pathobiology at the University of Toronto. She received her medical and postdoctorate degrees from the University of Toronto and completed her internship in internal medicine at Toronto General Hospital and the University of Toronto. She received her residency training in pathology at Mount Sinai Hospital, St Michael's Hospital, and the Toronto General Hospital, all affiliated with the University of Toronto. She subsequently was a research fellow in the Department of Pathology at St Michael's Hospital and the University of Toronto.

Extremely active in endocrine pathology, Dr Asa is affiliated with numerous professional organizations, including the United States and Canadian Academy of Pathology, The Endocrine Society, The Pituitary Society, the Pituitary Pathology Club, and the Endocrine Pathology Society, of which she is a founding member. She has presented more than 300 papers at international meetings and has been an invited lecturer for the National Institutes of Health, the Japan Endocrine Society, the Endocrine Pathology Society, and the International Academy of Pathology, among others. To ensure public knowledge of the role of pathology and to maintain a direct connection with patients, Dr Asa is a consultant to several patient support groups, including the Pituitary Network Association.

Dr Asa is a founding editor of the journal Endocrine Pathology and has served as an editorial board member for several publications, including the Journal ofClinical Endocrinology and Metabolism, Endocrinology, American Journal ofSurgical Pathology, Advances in Anatomic Pathology, Modern Pathology, Laboratory Investigation, Endocrine-Related Cancer, Journal ofClinical Pathology, and Archives ofPathology & Laboratory Medicine. She is a reviewer for 35 major medical journals. Extensively published, Dr Asa has coauthored 300 articles in high-impact journals. She has coauthored 3 books and more than 50 chapters on endocrinology and related pathology and is the author of the Armed Forces Institute of Pathology Atlas of Tumor Pathology third series fascicle Tumors ofthe Pituitary Gland.

She has been the recipient of many awards and honors, including the Arthur Purdy Stout Society of Surgical Pathologists (1998), the Novartis Canada Senior Scientist Award (2001), the Professor C.F.A. Culling Memorial Lecture Award of the National Society for Histotechnology (2004), and several teaching awards from the University of Toronto. She has served as president of the Endocrine Pathology Society (1997-1998) and the United States and Canadian Academy of Pathology (2005-2006).

As head of one of the largest pathology departments in Canada, Dr Asa has made innovative changes to the practice of the discipline, with an emphasis on automation, electronic initiatives, and telepathology. The department takes a highly subspecialized approach to diagnostic activities, education, and research in cytopathology, surgical pathology, and autopsy pathology. The understanding of mechanisms of disease and translation to diagnostic and prognostic information for patient care requires integration of conventional histology with immunohistochemistry, electron microscopy, flow cytometry, cytogenetics, and molecular diagnostics, all of which are used for advanced diagnostic approaches. Her department also embodies strong primary research programs and collaborative clinical research based on tissue procurement with pathologist interpretation.

LiVolsi, Continued

Virginia A. LiVolsi, MD, was born in New York City and attended Columbia University College of Physicians and Surgeons from where she received her MD degree. During her training, she became interested in thyroid diseases and pursued special projects in the area of thyroid pathology. She continued her interest in endocrine and gynecologic pathology throughout her career first at Yale University and later at the University of Pennsylvania.

Dr LiVolsi currently is professor of Pathology and Laboratory Medicine at the University of Pennsylvania. She has published more than 325 original articles, numerous chapters, and several books including Surgical Pathology of the Thyroid and Endocrine Pathology (the latter, coedited with Dr Asa). She serves on several editorial boards of pathology and endocrinology journals.

Dr LiVolsi has won numerous awards and has been invited to deliver several named lectures around the world. The awards include the Mostofi award for service to the United States and Canadian Academy of Pathology, the Master Pathologist award of the American Society of Clinical Pathologists, and the Medal of Honor from the University of Tokyo. She has held important leadership positions in major pathology organizations, including president of the United States and Canadian Academy of Pathology, the Association of Directors of Anatomic and Surgical Pathology, the Arthur Purdy Stout Society of Surgical Pathologists, and the Endocrine Pathology Society. She has served as a member and is currently chair of the Pathology Panel of the Chernobyl Tissue Bank, an international committee that reviews the pathology of the thyroid tumors that have arisen in children and young adults following the nuclear accident in Chernobyl. In 2006, on the anniversary of the disaster, Dr LiVolsi presented the pathologic aspects of these thyroid lesions at a special commemorative meeting at the United Nations in New York City.
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