Thyroid Cancer: A Comprehensive Guide to Clinical Management

680 Pages·2006·17.468 MB·English

by  Nikolaos Stathatos MD (auth.), Leonard Wartofsky MD, MPH, MACP, Douglas Van Nostrand MD, FACP, FACNP (eds.)

Thyroid Cancer
Thyroid Cancer
A Comprehensive Guide to Clinical Management
Second Edition
Edited by
Leonard Wartofsky, , ,
MD MPH MACP
Douglas Van Nostrand, , ,
MD FACP FACNP
Washington Hospital Center, Washington, DC
Forewords by
E. Chester Ridgway, ,
MD MACP
University of Colorado Health Sciences Medical Center, Denver, CO
and
Ernest L. Mazzaferri, ,
MD MACP
University of Florida, Gainesville, FL
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Library of Congress Cataloging-in-Publication Data
Thyroid cancer : a comprehensive guide to clinical management / edited by Leonard Wartofsky and Douglas Van Nostrand ; forewords
by E. Chester Ridgway and Ernest L. Mazzaferri.— 2nd ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 1-58829-462-5 (alk. paper)
1. Thyroid gland—Cancer—Treatment.
[DNLM: 1. Thyroid Neoplasms. WK 270 T5494 2006] I. Wartofsky, L. II. Van Nostrand, Douglas.
RC280.T6T527 2006
616.99’444—dc22 2005029167
Dedicated to the memory of some of the great thyroidologists who have influenced our lives and careers.
First and foremost, my mentor and friend, Sidney H. Ingbar, and Clark Sawin, Monte Greer, Ralph Cavalieri,
Farahe Maloof, John Dunn, William McConahey, and Robert Volpe.
And to all of our patients who struggle under the cloud of an uncertain future with their malignancies.
LEONARD WARTOFSKY, MD
To my father, Halstead K. Van Nostrand, who paid for the foundation.
DOUGLAS VAN NOSTRAND, MD
Foreword to Second Edition
Cancer remains a major health problem for our soci- presented a wealth of new information on the problem
ety as we enter the new millennium. In 2002 there were of thyroid cancer. One would hope that all new edi-
approximately 550,000 deaths in the United States tions to existing textbooks would bring as much new
from cancer, which remains the second leading cause information to the subject as Dr. Wartofsky has pro-
of mortality in our society behind heart disease. Each vided in his new edition. The number of chapters has
one accounts for approximately 25% of the deaths in increased from 52 to 91. The text is again organized
the United States on an annual basis. The most com- according to thyroid cancer type: papillary carcinoma
mon cancers to appear in 2005 remain prostate, breast, followed by follicular carcinoma, medullary thyroid
lung and colon which will generate between 150,000 carcinoma, thyroid lymphomas, and anaplastic can-
and 250,000 new cases this year. Likewise, the most cers. However, new General Considerations sections
common causes of death from cancer during this same on Thyroid Cancer and, in particular, on Nuclear
period will be lung, colon, breast and prostate which Medicine aspects of thyroid cancer, now introduce
will cause approximately 160,000, 50,000, 40,000, and the entire text with improved organization and wonder-
30,000 deaths, respectively. fully expanded new information on the molecular patho-
In comparison, thyroid cancer is a relatively uncom- genesis, oncogenic determinants and staging of thyroid
mon cancer. In 2005 we expect approximately 26,000 cancer. This new edition could serve as a textbook for
new cases and approximately 1500 thyroid cancer nuclear medicine physicians, with the importance of
deaths will occur in the same period. Interestingly, thy- nuclear medicine in thyroid cancer emphasized and
roid cancer is the eighth most common cancer in expanded with clearly articulated chapters on radiation
women, similar in prevalence to ovarian cancer and exposure, whole-body imaging with iodine isotopes,
melanoma. Moreover, American Cancer Society sta- and on the emergence of important new isotopic imag-
tistics indicate that thyroid cancer is currently the can- ing techniques such as PET scanning of thyroid malig-
cer in women with the greatest rate of increased nancies. More and more we are recognizing that one
incidence. Fortunately, for most thyroid cancers the basic standard dose for radioiodine therapy may not be
five year survival rate has always been outstanding and appropriate for all patients, and hence the chapters on
is continuing to slowly improve. In the 1970s, the five “dosimetry” during either thyroxine withdrawal or
year survival rate for differentiated thyroid cancer was after recombinant human TSH provide convincing
approximately 92% and in 2005 it is expected to be rationale and arguments for this valuable method for
97%. This is to be compared with 99%, 88%, 63%, determining maximal safe radioactive iodine dosing.
and 15% for the five year survival rates of prostate, The Thyroid Nodule section has been expanded to
breast, colon, and lung, respectively. Thus, thyroid emphasize the importance of thyroid ultrasound as a
cancer is important, not only because it is one of the diagnostically critical element for not only the perfor-
top 10 cancers in women, but because it is amenable to mance of fine needle aspiration biopsy, but also for the
early diagnosis, accurate and specific therapies, and diagnosis of thyroid nodules and followup surveillance
excellent survival rates. Despite these salutary charac- of thyroid cancer patients for recurrence in cervical
teristics of thyroid cancer, it is problematic to both lymph nodes. Clearly, the newer ultrasonographic
patients and their physicians because of its high, but modalities and their use by endocrinologists have been
nonfatal, recurrence rates that approximate 30% for one of the reasons why more thyroid nodules are being
differentiated thyroid cancer over a 40 year followup detected, which in turn, results in the higher number of
period. Although not resulting in death, these recur- thyroid cancer cases seen today than five and ten years
rences result in additional interventions for the patient ago. Doubtless, the above-mentioned observed improve-
and the necessity for long-term followup. ments in remission and cure rates must relate to this
In the second edition of Thyroid Cancer, Drs. earlier diagnosis.
Leonard Wartofsky, Douglas Van Nostrand, and their Recombinant human thyrotropin or Thyrogen®, had
skilled and expert group of contributing authors have just been approved for the diagnostic followup of dif-
vii
viii Foreword to Second Edition
ferentiated thyroid cancer in 1999 at the time of the Finally, the new edition ends with some very insight-
first edition of this book. In the intervening five years ful predictions about the future for nuclear medicine as
recombinant thyrotropin has emerged as one of the well as genetic and chemotherapeutic approaches to
most important discoveries leading to improved diag- thyroid cancer. I particularly liked the very informa-
nosis and followup of thyroid cancer. The new text de- tive last new section on resources for patients includ-
tails and expands our collective experiences in the use ing low iodine diets, and the listings of books, multiple
of recombinant thyrotropin as well as illuminates the Internet web sites, and recommendations for patients
promise for this reagent in remnant ablation treatment who have recently been treated with radioactive iodine.
of thyroid cancer, and its dramatic potential for aug- Drs. Wartofsky, Van Nostrand, and their colleagues
menting thyroglobulin testing and even its incremental should be very proud of this new edition and its formi-
value when utilized prior to PET scanning. Ongoing dable amount of new information. The physicians treat-
prospectively designed studies in the United States and ing thyroid cancer will find this text comprehensive and
Europe are providing intriguing results for these indi- accurate. The field of thyroid cancer will be enriched
cations that will likely alter our management algo- and our patients will be the beneficiaries of this new
rithms for diagnosing and treating thyroid cancer in the second edition of Thyroid Cancer.
future.
E. Chester Ridgway, MD, MACP
Foreword to First Edition
As the 20th century draws to a close, it seems like a rates during this same period have dropped signifi-
propitious time to look back upon the advances we have cantly—by almost 21%. In my view this results from
made in understanding thyroid carcinoma, since our the earlier diagnosis of the cancer, which allows the
knowledge today will certainly serve to light the path full impact of effective therapy, and which I believe
of discovery in the next century. Gazing at the world has dramatically altered the clinical course of these
through a small looking glass focused on thyroid carci- tumors.
noma seems an appropriate way to begin thinking about One of the dazzling success stories in medicine in
the clinical management of this group of diseases. What the last half of this century is that with medullary thy-
are the important things that we have learned in recent roid carcinoma, a truly orphan tumor afflicting rela-
years that form the basis of our current clinical knowl- tively few people. First identified in 1959 as a discrete
edge? How can we best use that information in the entity, this tumor was identified before calcitonin was
care of our patients? Dr. Leonard Wartofsky’s new known to exist and before the mystery of the multiple
and sharply focused text, Thyroid Cancer, promises to endocrine neoplasia syndromes had been completely
answer this hypothetical set of questions in a succinct unraveled. The pieces of the puzzle fell together at
and clinically relevant way. lightning speed over a few decades. The Ret proto-
It sometimes seems that thyroid carcinoma is a neglected oncogene mutations recently identified in this tumor
orphan among human cancers, which is at the root of will serve as the portal to our eventual complete under-
some important issues. Thyroid carcinomas comprise standing of its biology and are already the keystone to
a diverse group of malignancies ranging from indolent its diagnosis in members of afflicted kindreds. Now
microscopic papillary carcinomas that pose no threat children with this genetic defect can be identified with
to survival to anaplastic carcinomas that are the most molecular testing well before medullary thyroid carci-
vicious carcinomas afflicting humans. Yet, because noma becomes clinically manifest or is identifiable by
of its low incidence, there have been no prospective any other test, resulting in thyroidectomy that cures the
randomized clinical trials of the treatment of thyroid disease. What a wondrous group of developments to
carcinoma. Furthermore, none are likely to be done, pass on to the patients and physicians of the next cen-
given the prolonged survival and relatively low mor- tury! This work serves as a model for the scientific
tality rates associated with the majority of these can- investigation of malignant tumors.
cers. Nonetheless, patients often suffer greatly from We are also acquiring a clearer view of the molecu-
this disease: many have serious recurrences and some lar biology of well-differentiated—papillary and folli-
die from relentlessly progressive and untreatable can- cular—thyroid carcinomas. Ret rearrangements found
cer. This is a disease that knows no boundaries, strik- in papillary carcinomas of humans have been shown to
ing young and old alike. Unfortunately, management produce the tumor in transgenic mice, underscoring the
paradigms derive from retrospective studies, and few central role of Retin the pathogenesis of papillary carci-
new drugs have been added to our therapeutic arma- noma. Study of familial papillary thyroid carcinoma—
mentarium. One would thus anticipate a deep void in now recognized to occur in a small but important subset
our understanding of these tumors. Despite these short- of patients in whom it may be transmitted as an autoso-
comings, the 20th century has seen major advances in mal dominant trait—undoubtedly will provide impor-
our understanding of their etiology, pathophysiology, tant new information. These and other exciting
and management. The good news is that the advances discoveries, such as the identification of the sodium-
have been rapidly translated into improved outcomes iodide symporter in laboratory animals and humans,
for many patients with thyroid carcinoma. For example, portend more basic discoveries that will generate cur-
data from the National Cancer Institute shows that, rently unimaginable diagnostic and therapeutic tools.
although the incidence of thyroid carcinoma has The latest example of this success in the laboratory is
increased significantly—almost 28%—since the early recombinant human TSH, which was recently intro-
1970s in the United States, cancer-specific mortality duced into clinical practice and already is dramatically
ix
x Foreword to First Edition
improving and simplifying the care of patients with dif- ring with increasing frequency. While we were busy
ferentiated thyroid carcinoma. discovering thyroid lymphoma, the incidence of anaplas-
During the past 50 years we have learned much tic thyroid carcinoma has been quietly declining, prob-
about the important etiologic role of ionizing radiation ably as a result of early diagnosis and treatment of
in thyroid carcinoma. Introduced at the turn of the 20th well-differentiated tumors that often serve as its fore-
century by Roentgen, external radiation soon became runner. All of us breathe a quiet sigh of relief at this
routine practice in the United States for many benign improvement. Now it is well appreciated that a tumor’s
clinical conditions ranging from “statushymico- prognosis cannot be fully assessed until its final histol-
lymphaticus” to acne. It took over 50 years, however, ogy has been carefully studied, sometimes both histo-
to understand that the thyroid gland of children is logically and immunochemically, to uncover the dark
extremely sensitive to the carcinogenic effects of ion- secrets of its origin. This has therapeutic implications.
izing radiation and that this therapy itself caused papil- I think much of our success in reducing mortality
lary thyroid carcinoma, often decades after the from thyroid carcinoma stems from early diagnosis.
exposure. Studies of the Japanese survivors of the Thirty years ago the main diagnostic tests to identify a
atomic bombings of Nagasaki and Hiroshima first malignant nodule were thyroid hormone suppression
documented thyroid carcinoma as a consequence of and radionuclide imaging. Now the standard of care in
radioactive fallout. Nonetheless, the notion was long a clinically euthyroid patient is to perform a fine-needle
held that internal radiation of the thyroid from ingested aspiration biopsy of the nodule before any other tests
radioactive iodine was not a thyroid carcinogen. The are done. Though it remains a less than perfect test, the
outbreak of papillary thyroid carcinoma among chil- study of fine-needle cytology has prevented unneces-
dren exposed to radioactive iodine fallout from the sary surgery in many patients while increasing the yield
nuclear reactor accident in Chernobyl, however, abruptly of carcinoma among those undergoing thyroidectomy.
closed the door on this notion. This accident placed a I think fine-needle aspiration of nodules has saved
deadly exclamation mark after the statement that small more lives than is generally acknowledged—by pre-
doses of radioiodine indeed are carcinogenic to the thy- venting long periods of thyroid hormone suppression—
roid glands of infants and children, and sparked renewed while malignant nodules sometimes became wildly
concerns about the above-ground nuclear weapons test- metastatic. There is evidence that long delays in
ing program in Nevada between 1950 and 1960, during therapy significantly increase cancer-specific mortal-
which radioactive iodine fallout rained down on nearly ity rates of papillary and follicular thyroid carcinoma.
the entire continental United States. The National Can- The key to fine-needle aspiration diagnosis is to under-
cer Institute estimates that a substantial excess of thy- stand the diagnostic details of the cytology report and
roid carcinomas has probably occurred and perhaps will to act accordingly.
continue to occur as a result of this exposure. How clini- Much of the current debate on thyroid carcinoma has
cians will deal with this information, including what tests revolved around the extent of initial therapy, both sur-
should be done, is under discussion, but national screen- gical and medical, that is necessary for patients with
ing studies are not likely to be done. differentiated thyroid carcinoma. Almost everyone
We also have learned much about the pathology of believes that some differentiated thyroid carcinomas
thyroid carcinoma during the 20th century. The early require minimal therapy, whereas others require more
observations about the prognostic implications of aggressive management. The problem lies in defining
tumor size and invasion through the thyroid capsule are aggressive tumors. Several staging systems and prognos-
now well accepted. In addition, pathologists now rec- tic scoring systems have been devised to discriminate be-
ognize a number of histologic variants of papillary and tween low-risk patients who are anticipated to have a good
follicular carcinoma that have important implications outcome with minimal therapy and higher risk patients
that must be carefully factored into the assessment of who require aggressive therapy to avoid morbidity or
a tumor’s prognosis. Other important advances in our mortality from thyroid carcinoma. However, most of the
understanding of thyroid pathology have occurred in this prognostic systems do not identify the variants of papil-
decade. What was once considered small-cell anaplas- lary and follicular carcinoma that have remarkably differ-
tic thyroid carcinoma is now recognized as thyroid ent behaviors. Most prognostic scoring systems have been
lymphoma—known to be a rare complication of Hashi- created with multiple regression analysis to find predic-
moto’s disease—which nevertheless seems to be occur- tive combinations of factors, but almost none include
Foreword to First Edition xi
therapy in the analysis. Moreover, almost all of them have that what we term recurrence of tumor is actually per-
considered cancer mortality as the endpoint of therapy, sistent disease that previously fell below the radar of
ignoring tumor recurrence or disease-free survival. This our older, less-sensitive detection tools. With newer
becomes problematic in defining risk because patients sensitive tests including, for example, thyroglobulin
under age 40 typically have low cancer mortality rates, measured by messenger RNA, we now have the oppor-
but experience high rates of tumor recurrence. Because tunity to identify and treat thyroid cancers at an earlier
most recurrences are in the neck and are easily treated, and more responsive stage. Perhaps the most vivid
some clinicians regard them as trivial problems—but example of this is the identification of diffuse pulmo-
my patients find this notion incomprehensible. Most nary metastases among patients with high serum thyro-
patients are devastated by a recurrence of tumor, regard- globulin levels and negative diagnostic imaging
less of its site. The greatest utility of prognostic scor- studies, which are only seen on posttherapeutic whole-
ing systems lies in epidemiological studies and as tools body scans done after large therapeutic doses of 131I.
to stratify patients for prospective therapy trials, but Whether this enhances survival continues to be debated,
they are least useful in determining treatment for indi- but I think there are compelling reasons to suggest that
vidual patients. it does improve outcome.
In the past few decades most have come to believe Thus many relatively new observations and manage-
that near-total or total thyroidectomy is the optimal ment tools that have largely been developed in the last
treatment for thyroid carcinomas, even for patients at half of this century are being brought to the bedside to
relatively low risk of mortality from their carcinomas. substantially enhance our ability to improve the out-
The main reason not to do total thyroidectomy is that it come of most patients with thyroid carcinoma. Many
is associated with higher complication rates than those challenges remain, however. More effective therapy is
of lobectomy. However, there is now evidence docu- urgently needed for patients with widely metastatic dis-
menting what most of us have known for a long time: ease that is unresponsive to current therapies. We need
surgeons with the most experience have the lowest to understand more about the molecular predictors of
complication rates, regardless of the extent of the thy- recurrence and death from thyroid cancer. Nonethe-
roidectomy. Given the low frequency of this disease, a less, our present state of knowledge provides clinicians
compelling argument can be made to refer patients to a wide variety of diagnostic and therapeutic modalities
centers with highly experienced surgeons for their ini- to effectively manage this group of cancers. I believe
tial management. the knowledge contained in Thyroid Cancer will give
Follow up of differentiated thyroid carcinomas and the practicing clinician the necessary information to
medullary thyroid carcinoma is greatly facilitated by sen- provide patients with the latest and best diagnostic and
sitive serum tests—thyroglobulin and calcitonin—and therapeutic techniques.
the use of a variety of scanning techniques. I believe
Ernest L. Mazzaferri, MD, MACP