Book review
	By Prof.Ian D. Hay, M.D., Ph.D, F.A.C.E, F.A.C.P., F.R.C.P.(E,G & L). Dr. Wartofsky, past president of the American Thyroid Association, has dedicated this new textbook to "all our patients who struggle under the cloud of an uncertain future with their malignancies". It is his hope that his comprehensive guide will serve the "needs of practicing physicians for clinically relevant information about thyroid cancer", a disease which Dr. Mazzaferri, in his extensive foreword, describes as "a neglected orphan among human cancers". Dr. Wartofsky has assembled a cast of 22 American authors, 13 from Washington D.C., to produce 52 chapters, organized into nine parts, of which 6 are de-voted to the specific histotypes of thyroid malignancy, with papillary thyroid cancer taking the lion's share at 82 pages. The first part of the book considers the thyroid nodule from the viewpoint of the endocrinologist, nuclear medicine specialist, cytologist or histopa-thologist, and endocrine surgeon. From the standpoint of these three latter disciplines, Wartofsky has been fortunate to have enlisted the expertise of Yolanda and James Oertel, and Orlo Clark, whose contributions are collectively responsible for 25% of the chapters in the text. The main body of the text (269 pages) is devoted to the specific tumor types, and the individual parts for the papillary (PTC) and follicular cancers (FTC) are similarly organized, with chapters devoted to clinical aspects by the editor, followed by considerations from pathology, pediatrics, surgery, nuclear medicine, medical oncology, and radiation therapy. Under "general considerations", and preceding the chapters on the differentiated tumors, is a section that takes up more than a quarter of the whole text, and en-compasses molecular pathogenesis, epidemiology, and radiation effects, but also includes a timely contribution from Matt Ringel on rhTSH, and perhaps a less clinically relevant contribution on immunologic aspects of follicular neoplasms from Jim Baker. The text concludes with a "future directions" section, which includes 6 paragraphs devoted to new approaches to chemotherapy and radiotherapy, but consists principally of a 35 page scholarly review on DNA ploidy, tumor markers, and cancer-causing genes, accompa-nied by an "exhaustive" list of 236 references. The lack of current relevance of 34 of these pages to "practicing physicians who are managing patients with thyroid cancer" does not seem lost on Dr. McDermott, who readily admits in his concluding remarks that such studies of oncogenes and tumor suppressor genes have provided "extremely valuable insights into pathophysiology", and optimistically hopes that "many of these discoveries have or will soon have important clinical applications". In the meanwhile, the practicing physician, who is strapped for time, might want in this overlong chapter to concentrate on the final section devoted to possible clinical applications! Although the text has a publica-tion date of 2000, it is disappointing to note that most of the recent references seem to be from the 1996-98 period, many abstracts are cited from presentations at international meetings during 1996, and only a handful of references in the entire book are derived from the literature published during 1999. In his foreword, Mazzaferri describes that "thirty years ago the main diagnostic tests to identify a malignant nodule were thyroid hormone suppression and radionuclide, imaging". It seemed therefore quite remarkable that the first figure (page 8) in this text written for the 21 st century, was a suggested algorithm for nodule evaluation that included both of these ancient techniques. Frustratingly, the relevant text to accompany this algorithm consisted of only one sentence on page 5, and the interested reader has to wait until the summary on page 44 in Chapter 4 to learn more about Dr. Wartofsky's justification for this proposed algorithm. By contrast, Dr. Blum's contribution on nonisotopic imaging is authoritative and well illustrated, while Dr. Oertel's guide to FNAB is concise, practical, and reflects her extensive personal experience in performing aspirations, including her use of an ice cube for mild anesthesia. In Dr. Clark's initial chapter on surgical management of thyroid nodules and cancer risk, he summarizes his reasons for favoring total thyroidectomy, and makes the point that in removing a thyroid cancer adequately, a surgeon should remove all nodes in the central compartment, and consider modified radical neck dissection in patients with palpable nodes in the lateral neck. His initial discussion of the surgery of follicular cell-derived cancers is so comprehensive that one wondered what more would be said later for the individual histotypes, a point to which this reviewer will return. In the "general considerations" section, there are three chapters by James Figge and his collaborators. The chapter on epidemiology is concise and well written, while that on molecular pathogenesis could well have been abbreviated from its 19 pages and 118 references. The chapter on radiation consists of two parts: the first, devoted to 1949-85, is comprehensive but readable, while the second, devoted to Chernobyl, is perhaps more detailed than the practicing clinician requires, with its accompanying 95 references. The Oertels' chapter on classification of thyroid cancer is derived from the 1988 WHO Mono-graph and the 1992 AFIP Fascicle. Given that widely accepted classification, it is somewhat surprising to find medullary thyroid carcinoma (MTC) treated in this text under "un-differentiated cancers", taking its place after anaplastic carcinoma, and lymphoma. The Oertels make clear what they consider to be "miscellaneous and unusual cancers of the thyroid", and describe their pathology in Chapter 48. It seems unfortunate that, in the accompanying clinical aspects chapter, the atypical histologic variants (tall cell, columnar cell, solid, and diffuse sclerosing) of PTC are not considered under that heading, and even more extraordinary that Hurthle cell carcinoma (HCC), instead of being considered in the FTC section, finds itself relegated to the end of Chapter 49, after embryologic thyroid remnants and metastatic cancers in the thyroid gland. The two chapters by Johnston and Sweeney on radioiodine therapy seem to this reader inappropriately placed in the text at this point. It would seem unusual to consider arguments for routine remnant ablation even before one has read about the presentation and initial operative therapy of PTC and FTC. A similar argument might be made about the present position in the text of the sec-ond chapter, which lists all possible short- and long-term radiation side effects and complications. As noted above, the PTC section, encompassing Chapters 16 through 26, represents almost 20% of the text, and the quality of its content varies considerably. Chapter 17 by the Oertels is an authoritative, well illustrated "gem". By contrast, Clark's Chapter 18 on the surgical approach to PTC, gives new meaning to the term "rampant redundancy", since all but 2 sentences in this chapter are identical to the 6 paragraphs previously published on pages 51-53 in Chapter 5! I personally was delighted to read about the pTNM system of staging in PTC in Dr. Wartofsky's clinical aspects chapter, but was saddened to see that, for patients aged 45 years and older, stages II and III are wrongly described. Stage II should include both T2 and T3 node-negative cases, while stage III implies either T4NOM0 or Any T,NlM0 disease. In contrast to most other contemporary references on this subject, there was no mention of AGES, AMES, or even EORTC prognostic systems. Dr. Wartolsky inaccurately describes recurrences at nodal, distant, and local sites as "three varieties of presentation that reflect a different prognostic category", and states that these factors have been incorporated into the "MACIS" scoring system, which is certainly not the case. The chapters devoted to I-131 therapy, external irradiation, and chemotherapy in PTC are informative, as is Dr. Burch's chapter on Tg monitoring in follow-up. Chapter 24 on Dr. Wartofsky's approach to the whole body scan-negative, Tg-positive patient will be familiar to readers of the previously published and non-referenced JCEM 83: 4195-4203 of 1998. In my opinion, the chapter devoted to prognosis in PTC is inadequate. Much is quoted from a 1990 report from the Mayo Clinic on 1,500 consecutively treated PTC patients, but, like Wartofsky's chapter 16, there is no mention of the many prognostic scoring and risk-group schemes that have been derived since 1987 from large multivariate analyses. This is an unfortunate omission in a text that is claiming to be a comprehensive guide for the practicing physician. Lastly, with regard to the PTC section, the approach to pediatric cases advised by Dr. Poth, in terms of routine administration of 80 to 150 mCi of I-131 for remnant ablation, seems remarkably aggressive, and perhaps foolhardy in view of the potential for long-term morbidity, and even mortality, con-sequent to such an approach. The section devoted to FTC, like that on PTC, varies in quality. The Oertels are again right on target with their chapter on pathology. Dr. Clark does address the problems he encounters both with follicular and Hurthle cell cancers (HCC), and suggests that in his particular surgical setting frozen section is "a waste of time and money". Some might differ from him in his personal interpretation of "minimally, regular, and widely" invasive in terms of involvement of the thyroid capsule. Again, the chapter on prognosis in FTC seems suboptimal, and the table of poor prognostic factors incomplete by the exclusion of older patient age, which is the first factor mentioned in the accompanying text. Incidentally, the inclusion of age would make the tables for PTC and FTC identical, which probably represents an over- simplification, which would be clarified by consideration of the plentiful data derived from many multivariate analyses in series of both histotypes. The clinical aspects chapter again has some unusual features, some irritating, and others misleading. The first reference cited in Chapter 27 is numbered 15, and it transpires that references 1 through 14 are contained in the summary, which consists of the last 2 paragraphs of the chapter. The chapter talks of staging and prognostic indicators, but the data cited refers to patients with PTC, not FTC. Two paragraphs are devoted by Wartofsky to the particular problems faced by patients with HCC, but as noted above, the reader has to wait another 158 pages of the text to get to the real HCC section! Dr. Poth does have 5 paragraphs devoted to pediatric FTC, although in her first sentence she freely admits to "an almost total lack of definitive data". This presumably underscores Dr. Wartofsky's stated intent "to present evidence-based recommendations where possible, and to indicate clearly where evidence is lacking". In contrast to the PTC and FTC sections, the parts V through VIII, devoted to "undifferentiated cancers", and miscellaneous unusual cancers, are of generally high standard. The four pathology chapters are very well presented and illustrated. Dr. Sherman has done an excellent job with both anaplastic carcinoma and thyroid lymphoma. His contribution on prognosis in anaplastic cancer is appropriately short, bot adequate. The chapter by Donglas Ball on medullary thyroid cancer (MTC) is of a high standard, but I have a problem with his discussion of initial clinical stage. The cited work of Bergholm in Sweden used the internationally accepted pTNM stages, which I think should have been shown in his table 2. Instead, he shows a system attributed to the NTCTCS group, which considers stage I as being only C-cell hyperplasia, in contrast to pTNM where stage I would be in-trathyroid microcancer (T1N0M0). Lastly, although I believe that the PTC variants, and both insular and HCC should have been considered under the PTC and FTC sections, respectively, I think that Ringel and associates are to be complimented for the way that they have identified from the literature 45 cases of squamous cell cancer, 228 insular cancers, 163 tall cell variants, 24 columnar cells, 63 diffuse sclerosing variants, and 31 mucoepidermoid cancers. Moreover, they have given the reader accurate references with one exception! In their tables 2 and 3, they refer to data "adapted from Burman and Ringel (ref. 210) with permission". However, their list of references stops at number 188! For those who want to read more about these unusual tumors, I would guess that the reference is by Burman, Ringel, and Wartofsky from the Endocrinology and Metabolism Clinics of North America 25:49-68 in March of 1996. Well, would I recommend that individual clinicians go out to purchase a personal copy of this rather expensive text? No, I would rather they spend the money on a more general endocrine text, or maintain their dues to their respective thyroid association. However, I do think that this book should grace the library shelves of every significant Division of Endocrinology. It is not an easy task to attempt to create a timely and comprehensive guide for managing thyroid cancer, and Dr. Wartofsky should be applauded for his making such an attempt. In concluding, I am sure that this important text will provide a resource for many years to come for our clinical and lab-based colleagues, who, like myself, have an interest in trying to provide answers for relevant questions posed by concerned patients with differentiated thyroid cancer.