Thyroid Cancer (Endocrine Updates, 2)

Because of its relative rarity and favorable outcome, it has not been feasible to assess medical interventions for thyroid cancer using randomized prospective trials. The approach to diagnosis and treatment relies to a great extent on information derived from retrospective studies. Overall prognosis and survival rates have been edging upward over the past two decades. This is attributed to a wider acceptance of total thyroidectomy as the primary surgical strategy. The appropriate indication of radioiodine therapy remains controversial, and physicians must be familiar with staging criteria to make educated decisions.
We are now beginning to understand the genetic mechanisms of thyroid tumor initiation and progression. There are still major challenges ahead. Thyroid Cancer provides comprehensive updates on the epidemiology, pathogenesis, diagnosis and treatment of thyroid neoplasms. Although the material should be of particular interest to scholars in the field, the contributors have striven to make it of practical use to physicians who treat patients with thyroid disease.

Thyroid cancer, the most common type of endocrine tumor, has been the subject of intense research and considerable attention in the past decade. At least two reasons may explain why the scientific community has taken a renewed interest in this cancer.

The first reason is the considerable advance in our understanding of the genetic mechanisms underlying the initiation and progression of thyroid cancer. Rearrangement of the RET proto-oncogene (RET/PTC, for papillary thyroid carcinoma) has been linked specifically to the papillary histotype, the most frequent thyroid cancer, and probably represents the initiating event. Other events, such as mutation of ras or abnormal methylation of DNA, have been suggested, but not yet proved, to be necessary for the progression of the malignant phenotype. Both follicular carcinoma and its premalignant lesion, follicular adenoma, are associated with ras mutations, which again may initiate, but not entirely accomplish, the malignant transformation.

Clinically, the end stage of follicular and papillary carcinomas is undifferentiated, or anaplastic, carcinoma. Accumulating evidence indicates that mutations of the p53 tumor-suppressor gene are a common feature, and probably the cause, of these extremely aggressive tumors. Interestingly, mutations of the RET proto-oncogene are also responsible for medullary thyroid cancer, which is a tumor of the calcitonin-secreting cells and does not involve the follicular epithelium. In the hereditary form of medullary thyroid cancer (the form associated with multiple endocrine neoplasia type 2), germ-line point mutations of RET are responsible for the development of the tumor in gene carriers, with a penetrance of nearly 100 percent. For this reason, genetic screening for RET mutations is currently used in clinical practice to identify gene carriers who should receive prophylactic or early treatment with total thyroidectomy. This strategy is a notable example of prophylactic treatment of a human cancer.

The second reason for the renewed interest in thyroid cancer is the outbreak of thyroid cancer among children after the disaster at the Chernobyl nuclear power plant in 1986. Starting in 1990, an almost 100-fold increase in the incidence of thyroid cancer was recorded among children living in contaminated territories of Belarus, Ukraine, and to a lesser extent, the Russian Federation. The event shocked the world and reminded us that contamination by fallout of radioactive iodine causes thyroid cancer, that young children are particularly at risk, and that detrimental effects on health may be seen even far away from the center of the explosion. Molecular studies of thyroid cancers after the Chernobyl disaster have also shown that a particular form of genetic damage (activation of RET/PTC3) is specifically linked to radiation-induced thyroid cancer.

From a clinical point of view, thyroid cancer, at least in its differentiated form, is an indolent tumor with a high rate of cure. Prognostic factors have identified two groups of patients, those at low risk of recurrence or death and those at high risk, and controversy still surrounds treatment approaches for these two groups.

Thyroid Cancer, edited by James A. Fagin, comprehensively discusses all the important issues related to this subject. This book will appeal to a broad spectrum of researchers and practitioners, including endocrinologists, nuclear-medicine specialists, and oncologists. The book begins with chapters devoted to basic aspects of thyroid cancer, including the epidemiology, pathogenesis, and pathologic features of thyroid tumors. Attention to clinical aspects starts with a series of three chapters devoted to the differential diagnosis and management of thyroid nodules. These chapters are particularly important in view of the high prevalence of thyroid nodules, most benign, in the general population. These nodules can generate anxiety and concern in both the patient and the physician about the possibility of cancer. Approaches to the treatment of primary tumors and the diagnosis and treatment of metastatic disease are fully covered, and current controversies are exposed and weighed. Rare forms of thyroid cancer and less common treatments are discussed in the last two chapters. The references are exhaustive and up to date.

This book gives a comprehensive overview of the issues related to thyroid cancer. The reader may use it to gain an understanding of current knowledge and state-of-the-art techniques as well as to guide decision making in clinical practice. As an endocrinologist facing the management of thyroid cancer daily, I enjoyed reading this book and learned from it.

Reviewed by Furio Pacini, M.D.
Copyright © 1999 Massachusetts Medical Society. All rights reserved. The New England Journal of Medicine is a registered trademark of the MMS.