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Current Therapy of Thyroid Nodules
Symposium on Endocrine Surgery
Current Therapy of Thyroid Nodules Hastings K. Wright, M.D.,* Gerard N. Burrow, M.D.,** Stephen Spaulding, M.D.,t and Daniel G. Sheahan, MB., B.Ch.!
Opinion on the correct treatment of thyroid nodules is currently at a crossroads. One senses an increasingly conservative trend combining both medical and surgical treatment which has not yet been prominently displayed in the surgical literature except in the writings of George Crile, Jr.2 Discussions with a large number of community surgeons and physicians who manage the vast majority of thyroid nodules in this country indicate that this conservative approach is now both common practice and very successful. Nevertheless, there remains a contrary opinion, emanating primarily from some large regional referral cancer centers, which declares that initial diagnosis and management of thyroid nodules should be surgical. The following suggested method of treatment of patients with thyroid nodules is based on our own experience as a combined group of endocrinologists, surgeons, and pathologists in managing a large group of such patients over the past 8 years. To our knowledge, this approach has failed to provide necessary surgical treatment for those thyroid nodules which are malignant only when patients both failed to take prescribed medication and to return for scheduled follow-up.
TO OPERATE OR NOT TO OPERATE The basic problem for the clinician is to decide whether or not to operate, and this decision first requires answers to some basic questions about thyroid neoplasia, both benign and malignant. How large is the group of people in the population with thyroid nodules? Recent autopsy studies on unselected patients who had been hospitalized indicate that almost half the adult autopsy population has one or more thyroid nodules, most of which are not palpable prior to autopsy From the Departments of Medicine, Pathology, and Surgery, Yale University School of Medicine, New Haven, Connecticut :::Professor of Surgery :::::'Associate Professor of Medicine t Assistant Professor of Medicine t Assistant Professor of Pathology Surgical Clinics of North America - VoL 54, No.2, April 1974
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because they are in the interior or posterior part of the gland. The nonpalpable group escapes detection, and therefore the question of surgery never arises. The risk of these nodules in life is clearly minimal, since only 2 to 5 per cent of these undetected nodules are even histologically cancer. Furthermore, the fact that there are fewer than 1000 deaths per year from thyroid cancer in the United States indicates that most of these histologically diagnosed cancers have no true "cancer potential." Obviously, then, the mere discovery of a thyroid nodule because it happens to lie in the palpable portion of the thyroid does not mandate surgery. If the risk of cancer in thyroid nodules in general is only 2 to 5 per cent, are there specific kinds of thyroid nodules which carry a higher risk of malignancy? AGE. It has been estimated that approximately 50 per cent of isolated thyroid nodules appearing in children are malignant. However, multinodularity increases with age, even in patients with only one palpable nodule, and the incidence of cancer in a single palpable nodule therefore decreases with age. PAST HISTORY. A past history of neck or mediastinal irradiation in a patient with a thyroid nodule is very significant. Three-fourths of children with papillary cancer of the thyroid have a history of irradiation. THE ISOLATED NODULE. The reported incidence of thyroid cancer in isolated thyroid nodules is reported to be from 4 to 33 per cent in the literature. The higher values invariably come from surgical series, not autopsy series, and clearly reflect case selection after failure of the nodule to regress spontaneously or to disappear on thyroid medication. MALE OR FEMALE? Thyroid disease is more common in females than in males, including nodules and malignancy. Multinodularity is also more common in females. Thus, an isolated thyroid nodule occurring in a male, particularly a young male, is more likely to be cancer. PHYSICAL EXAMINATION. Physical examination can be helpful in deciding whether or not to operate, particularly if it discloses multinodularity in a thyroid gland originally thought to have only one nodule. Consistency of the nodule on palpation is helpful, since a stony hard character increases the risk of malignancy. Other physical signs, such as adherence to adjacent structures, presence of cervical lymph nodes, or vocal cord paralysis, are signs of an advanced state of malignancy, and demand surgery. LABORATORY AIDS. An important aid in differentiating nodules which require surgery from those which do not is a scan of the uptake of a radioisotope in the thyroid gland. Cancers are less able to concentrate either 131 Iodine or 99m Pertechnetate, and perhaps one-tenth of such "cold" nodules which are removed surgically are malignant. An attempt is now being made to differentiate cold malignant nodules from cold benign nodules, but this is not yet possible at a clinical level. At the biochemical level, studies have shown that cold nodules which do not trap iodine usually still respond to TSH stimulation, and can incorporate phospholipid and produce colloid droplets. Some nodules even show hyperactive adenyl cyclase activity in response to TSH. There may be qualitative differences in such biochemical properties which could distinguish benign nodules from cancers. As of now, the develop-
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CURRENT THERAPY OF THYROID NODULES
ment of scanning techniques testing biochemical properties of nodules is still at an experimental stage. Thyroiditis may present a clinical picture which resembles malignancy. The measurement of thyroid antibodies may be helpful in the differential diagnosis of such patients if antibodies are present in high titers. Needle biopsy may be helpful if titers are borderline.
TREATMENT OF THYROID NODULES
SURGERY ON MULTIPLE NODULES
Multiple Nodules Present in the Gland Patients with nontoxic goiter may present either with multiple discrete nodules or with multiple lobules which are soft and nondiscrete (Table 1). Occasionally, the thyroid gland is huge and unsightly, although rarely symptomatic. A second group of similar patients presents with one large thyroid lobe containing a palpable nodule which does not account for the entire asymmetry of the thyroid gland. Radioactive scanning usually shows other cold areas within this lobe, strongly suggesting multinodularity. In general, these patients can also be treated safely without surgery. Suppression with large doses of thyroid can be tried in all the above patients. However, in our experience, the nodules seldom totally disappear unless the patient was previously hypothyroid. Even if they do not do so, surgery is still not usually indicated unless there is suspicious Table 1. Treatment of Thyroid Nodules A. Multiple Nodules Patient Hyperthyroid ~
Treat hyperthyroidism.
Patient Hypo- or Euthyroid J, Try thyroid before surgery. J, Remove thyroid subtotally only if symptoms develop or one nodule is suspicious.
B. Single Nodule
"Hot" Scan J, Give RAI or resect. Otherwise follow indefinitely.
"Cold" Scan
~n ch~Otherwise, try
Operate and when suspicious on physical examination in males.
suppressive doses of desiccated thyroid for 4 to 6 months. ,/
\.
If nodule disappears,
If nodule
continue on thyroid indefinitely.
does not disappear or enlarges, operate.
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WRIGHT, BURROW, SPAULDING, AND SHEAHAN
hardness of one or more of the, nodules or evidence of continued enlargement over a period of months. If surgery is performed, most surgeons simply remove all the nodules and then place the patient on suppressive doses of thyroid. Total thyroidectomy is not indicated. Single Nodule Pr~.sent in the Gland "HOT" NODULES. While cancers have been found histologically in nodules which were "hot" on radioactive scan, these are rare indeed. Thus, surgery to rule out cancer is an unnecessary step in most of these patients. Hyperthyroidism may not be present when these nodules are first discovered. Indeed, on occasion the "hyperfunctioning" nodule may be the only thyroid tissue. These possibilities should be investigated before considering surgery by thyroid suppression or TSH stimulation followed by a second scan. The hot nodule may undergo necrosis and involution, often after several years of activity. If this happens, the patient could potentially become hypothyroid. Thus, treatment of a hot nodule is usually indicated unless· both the physician and the patient are willing to have repeated evaluations of thyroid function performed on a longterm basis. Radioactive iodine is effective, but surgical rerrioval of the nodule is simple and a safe alternative method of treatment. COLD NODULES. Colloid Cysts. Colloid cysts would not require surgery if this diagnosis could be made by any other means. Since such cysts have almost no metabolic activity, it should be possible to differen" tiate them from cancers which do have metabolic activity. Several radioisotope scanning techniques have been tried, including selenomethionine, gallium, cesium, and mercury. Unfortunately, the quality of resolution obtained with present equipment is not good; furthermore, one cannot totally rule out a cystic component in a cancer by these techniques. In addition, isotopic techniques may show false cold areas in focal thyroiditis. Other technical developments which may offer eventual help in diagnosing cysts include ultrasonic scanning with or without needle biopsy of apparent cystic lesions. However, these techniques are not yet as accurate as surgery, and removal of the cold nodule is usually necessary as a diagnostic step. Medullary Cancer. Another new technical development appears to have special prOInise for the early identification of medullary cancer. This tumor commonly produces excessive secretion of thyrocalcitonin, and sensitive radioimmunoassays of this hormone in blood are now available. Treatment of this thyroid cancer is the proper subject for another treatise, and only an outline will be presented here. The diagnosis should be apparent preoperatively. Associated endocrine tumors should be removed first. An aggressive surgical approach seems warranted, including total thyroidectomy and en bloc excision of adjacent lymph nodes. If total resection is impossible, as much of the tumor should be removed as possible, even in the presence of known metastatic disease, to treat the
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281
secondary effects of thYTocalcitonin secretion on the gastrointestinal tract and cardiovascular system. These tumors do not respond to TSH and do not concentrate iodine. Consequently, treatment with thyroid should not be effective. Finally, as in other endocrine cancer, longterm survival even with metastases is common. TRIAL OF THERAPY WITH THYROID HORMONE. In most instances, no test is yet available to distinguish between benign and cancerous single cold nodules. Children, males with suspicious nodules, and patients with suggestive evidence of extrathYToidal disease should therefore undergo immediate surgery because of the high risk of cancer in such nodules. The remainder of patients with cold nodules which are not suspicious on physical examination can safely be treated with suppressive doses of thyroid hormone (full doses of 3 gr of desiccated thYToid daily) in an attempt to cause regression of the nodule. The nodule disappears in the majority of such patients on thyroid medication in 4 to 6 months because of suppression by exogenous thyroid of TSH which is stimulating thYToid tissue. There are other nodules which are not TSH dependent, but which appear because of hemorrhage into a cyst. These nodules often regress despite thYToid medication. The use of thyroid suppression is based on excellent theoretical grounds. Most nodules are known to be influenced by TSH, and nontoxic nodular goiter is thought to be caused by repeated cycles of TSH stimulation, resulting in hypertrophy of parts of the thYToid. Exogenous thyroid hormone in adequate doses inhibits TSH secretion, preventing further stimulation of the thYToid gland, and promoting involution. The pathogenesis of thYToid cancers, particularly papillary cancers, may also be related to that of multinodular goiters. Chronically elevated TSH levels can cause thyroid cancer in animals, especially when acting on goiters caused by administration of goitrogens, iodine deficiency, or partial destruction of the gland by irradiation. Elimination of TSH stimulation may prevent eventual cancer development, and the use of exogenous thYToid therefore may become indicated in the prophylaxis of cancer development in patients with similar problems. One theoretical worry is that thyroid suppression therapy in patients with isolated cold nodules could cause only partial or temporary regression of a thyroid cancer. This may be particularly true with papillary cancer, which is frequently very sensitive to TSH and may indeed be totally hormone-dependent. Some of these tumors undoubtedly regress with hormone suppression alone, and stay suppressed as long as the patient remains on adequate doses of exogenous thyroid. We have not seen extrathyroidal papillary cancer of the thyroid develop in any patient whose thYToid nodule has completely regressed on treatment which is continued thereafter for the rest of his life. If a thyroid nodule does not regress completely after 4 to 6 months of thyroid suppression, surgery is indicated. Conversely, if a nodule grows significantly in size on suppressive doses of thyroid, surgery is indicated when this response is determined. Partial regression of the nodule in this time period should not be considered an indication for further medication unless the nodule now concentrates iodine. The patients whose nodules
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have disappeared should be followed on thyroid suppression for the indefinite future.
SURGERY ON THE ISOLATED COLD NODULE
Once a decision is made to perform surgery for an isolated, cold nodule, the operation should be performed by a surgeon prepared to safely perform total thyroidectomy and, possibly, radical dissection of the anterior neck. Neither procedure is usually necessary, but when required they are best performed at the initial surgery. The first step should be total exposure of both thyroid lobes even though a nodule is palpable preoperatively only in one gland. This step requires division of the lateral and inferior veins of each lobe, a procedure which then allows bidigital palpation of each lobe. Single Nodule Preoperatively, but Multiple Nodules at Surgery In our experience, multiple nodules are discovered at surgery in 60 per cent of patients after a diagnosis of a single nodule by careful preoperative palpation and thyroid scan. The unrecognized nodules are usually posterior in the gland, and palpable only after mobilization of both lobes. If multinodularity is discovered, the risk of cancer in the nodule previously thought to be single significantly decreases. All nodular tissue should be removed, leaving the posterior capsules of each thyroid lobe intact. Total thyroidectomy is not indicated because of the significant risk of recurrent nerve injury and/or hypoparathyroidism even in expert hands-a risk that should be taken only in treating diffuse undifferentiated or medullary thyroid cancer. In the rare case where suspicious signs of cancer are present with multinodularity (enlarged perithyroid lymph nodes, adherence of the thyroid to adjacent structures), a histologic diagnosis must be obtained on frozen section and further surgical dissection carried out according to the nature of the lesion, as outlined below in the discussion of treatment of thyroid cancer. Single Nodule Preoperatively and at Surgery If a single nodule alone is discovered on complete palpation of both lobes, and there are no suspicious signs of extrathyroid involvement or of cancer in the mass itself (one warning sign of probable cancer is the demonstration of abnormal vasculature in the nodule, commonly a hemangiomatous venous pattern), our current practice where possible is to first remove the mass itself with its capsule and 1.0 cm of surrounding normal thyroid tissue and submit this specimen to the pathologist for immediate frozen section examination before continuing the operation. Many other surgeons do not agree, and consider extracapsular lobectomy on the side ofthe lesion to be the minimum acceptable initial step in operative diagnosis. However, at least four out of five, and probably more, of these isolated lesions are benign, and no operation beyond simple removal of the mass is necessary. If the pathologist finds cancer, a more radical operation can easily be performed, and we have not seen seeding of the
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283
cancer from the initial conservative resection outlined above followed by extracapsular lobectomy or subtotal thyroidectomy.
CRITICAL ROLE OF THE PATHOLOGIST
After initial removal of the isolated nodule, either by excisional biopsy or by lobectomy, the pathologist assumes the critical role in deciding on further surgical maneuvers. This is a difficult assignment, for the conclusions which are reached on gross examination and frozen section histologic examination of the nodule largely dictate what the surgeon should do in the operating room. In the treatment of cancer of most other organs, a diagnosis of "cancer" on frozen section is sufficient to guide the surgeon. However, the malignant potential of the several types of thyroid cancer is not equal, and a specific diagnosis of the type of thyroid cancer is necessary to guide surgical treatment. Fortunately, the commonly accepted criteria now used by pathologists for diagnosing and classifying thyroid cancers are clinically useful to the surgeon. The surgeon and the pathologist must learn to use this common language instead of relying on a diagnosis of "benign" or "malignant" on frozen section analysis of submitted tissue. Classification of Thyroid Cancers The most widely used classification is that described in Table 2. It is based on the histologic appearances of thyroid malignant neoplasms, and the order of listing roughly indicates the degree of malignancy with papillary cancer being the least and giant cell undifferentiated cancer the most malignant. However, direct spread of tumor into adjacent neck structures significantly worsens the prognosis irrespective of the tumor type involved. Gross Appearance of the Several Thyroid Cancers The gross appearances of thyroid cancer are of little diagnostic value in small lesions. Even those showing apparent encapsulation require extensive microscopic study. However, the invasive nature of most larger lesions is usually readily evident, particularly if extrathyroidal tissue is Table 2.
Histologic Classification of Thyroid Cancer Papillary cancer Follicular cancer Clear cell Oxyphil Medullary cancer Undifferentiated cancer Small cell Giant cell Metastatic cancer Other Lymphoma Sarcoma
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WRIGHT, BURROW, SPAULDING, AND SHEAHAN
involved in the mass. The following gross features are sometimes helpful to the surgeon and the pathologist in the operating room: PAPILLARY CANCER. Small lesions may be indistinguishable from minute scars. Because their malignant character is recognized only at microscopic examination, they are called occult sclerosing cancers. Larger tumors are often cystic with irregular borders and may be indistinguishable from degenerating colloid nodules in that the cystic contents may show recent or altered blood and fibrosis; dystrophic calcification and occasionally ossification are seen. Direct spread into adjacent structures is not common. Metastatic spread to adjacent lymph nodes may be found at surgery, making the diagnosis obvious. FOLLICULAR CANCER. Lesions which show only microscopic invasion are grossly indistinguishable from follicular adenomas. Grossly invasive lesions are rare, but are more likely than papillary cancers to extend beyond the confines of the thyroid gland into adjacent structures. These tumors are usually fleshy with central fibrosis and focal areas of hemorrhage and necrosis, and are usually well encapsulated in one lobe alone. Gross vascular invasion may be evident. MEDULLARY CANCER. This tumor is usually a single, solid, hard, gray white mass which appears well encapsulated and without a central fibrosis scar. Vascular invasion may be evident. UNDIFFERENTIATED CANCER. These tumors are usually firm, white, and of irregular outline. Invasion into adjacent structures is usual at the time of diagnosis. Areas of hemorrhage and necrosis are not common.
Pitfalls in Frozen Section Diagnosis of Thyroid Nodules While the infiltrative nature of large thyroid cancers is easily established grossly at surgery, histologic examination of non infiltrating and small lesions is the sole means of establishing malignancy. If the surgeon and pathologist are at all suspicious on examination of the gross lesion in situ or after excisional biopsy, a frozen section histologic examination should be done before proceeding further with the operation. A description of the histologic criteria used to diagnose the several thyroid cancers is beyond the scope of this paper. However, it should be emphasized that a correct diagnosis is helpful during the operation, since different thyroid cancers require different operations. Unfortunately, correct conclusions are not always reached on examination of only one or more frozen section slides from a lesion, and the true nature of the nodule may only become apparent after extensive examination of multiple permanent slides one or more days after the surgical procedure. FALSE POSITIVE DIAGNOSES FROM FROZEN SECTIONS. False positive diagnoses of cancer can be made. Atypical epithelial cells with marked pleomorphism can be seen in hyperthyroidism, thyroiditis, and adenomatous goiter, and may suggest cancer to the unwary. However, if the clinical history is known to the pathologist, this problem should rarely occur, since these bizarre cells do not show mitotic activity and are presumably only degenerative in nature in these conditions. DIFFERENTIATION OF FOLLICULAR CANCER FROM ADENOMA. This problem commonly arises in examining solitary nodules showing a follicular pattern. Follicular cancers can be so well differentiated as to resem-
CURRENT THERAPY OF THYROID NODULES
285
ble normal thyroid acini, and their metastases can show a similar pattern. Unless capsular, adjacent thyroid tissue, or vascular invasion is identified, cancer cannot be diagnosed. This usually requires multiple sections of the nodule, a process which is most suitably done on permanent section after surgery. If the pathologist finds himself in this difficulty, he should so inform the surgeon so that a total lobectomy can be performed on the side of the lesion. DIFFERENTIATION OF PAPILLARY CANCER FROM PAPILLARY HYPERPLASIA. Distinction between papillary neoplasia and hyperplasia may be especially difficult, particularly in adenomatous goiter. Some nodules of adenomatous goiter may show hyperplastic papillary foci in cystic areas, and the intense hyperplasia of Graves' disease showing intrafollicular papillae may suggest cancer to the unwary. Again, because of the paucity of cellular pleomorphism and mitotic activity in both neoplastic and hyperplastic papillary lesions, the criteria of malignancy are capsular or vascular invasion. The presence of psammoma bodies is of considerable value because they are rarely seen in nonneoplastic lesions. Benign papillary adenomas are relatively rare, and it is emphasized that such a frozen section diagnosis should not be rendered to the surgeon until exhaustive examination of multiple tissue blocks has excluded capsular and vascular invasion. If a problem in diagnosis exists, the surgeon is best advised to proceed with a conservative operation for papillary cancer. UNDIFFERENTIATED TUMORS. Undifferentiated tumors less commonly present diagnostic difficulties. The small cell variant, in its diffuse form, may be confused with a lymphocytic or lymphoblastic lymphoma and, in its compact form, with medullary thyroid cancer or metastatic breast cancer. The giant cell variant may be misdiagnosed as a sarcoma though the latter are distinctly rare tumors of the thyroid. Examination of numerous tissue blocks may be required before focal areas of recognizable follicular or papillary cancer clearly indicate the primary thyroid epithelial origin of the tumor. METASTATIC TUMORS. Metastatic spread to the thyroid from malignant melanoma or from primary renal, bronchogenic, or breast cancer is not uncommon. Such lesions, however, rarely present as apparent primary neoplasms of the thyroid, and an adequate preoperative work-up should prevent the problem of deciding the cell type of the lesion in the operating suite. As with undifferentiated tumors, most lesions can be appropriately diagnosed if multiple tissue blocks are extensively examined after surgery~ NODULE CALLED BENIGN ON FROZEN SECTION, BUT CANCER ON PERMANENT SECTION AFTER SURGERY COMPLETED. Occasionally, a frozen section diagnosis of benign nodule is changed to a diagnosis of cancer one or more days after surgery when multiple permanent sections are read. This is unavoidable and should cause no consternation if the surgeon and pathologist have consulted and hedged their bets at the operating table. If the final diagnosis is papillary cancer, and the surgeon has performed a lobectomy on the side of the gross lesion, in our opinion nothing more need be done except to place the patient on suppressive
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WRIGHT, BURROW, SPAULDING, AND SHEAHAN
doses of desiccated thyroid. However, if only the nodule itself has been removed at surgery, most surgeons believe that subsequent subtotal thyroidectomy is indicated. If the final diagnosis is follicular cancer, and the surgeon has performed a lobectomy on the side of the gross lesion, an adequate operation has been done unless metastatic disease develops. We have not seen a mistake made on undifferentiated cancer; the diagnosis is usually obvious grossly, and the lesion is usually unresectable. If an operation has been done on the thyroid for some other reason than to rule out cancer, but microscopic foci of cancer are found on permanent section analysis, nothing more need be done. In our experience, the patient is "cured" by whatever operation has been performed, even subtotal lobectomy. These "cancers" must therefore have a low malignant potential. We have placed all such patients on desiccated thyroid.
REQUIRED OPERATION AFTER SPECIFIC HISTOLOGIC DIAGNOSIS OF CANCER ON FROZEN SECTION
Papillary Cancer Opinions differ in this country on the correct operation for papillary cancer, but a large number of surgeons now utilize conservative operations in treating this cancer. If no extrathyroidal extension is apparent on careful inspection of the neck and histologic examination of suspicious lymph nodes, we have performed a total lobectomy on the side of the gross lesion. Up to 85 per cent of such glands have microscopic foci of cancer in the other lobe, but they are rarely palpable. We have preferred to perform a subtotal lobectomy on the contralateral side, leaving the posterior capsule and approximately 25 per cent of the posterior of this lobe intact. Even more conservative treatment may be correct, especially in children and in women under the age of 40, and in patients with a history of neck irradiation. Recurrence in the contralateral lobe after simple lobectomy on the side of the lesion is uncommon in such patients maintained on suppressive doses of thyroid for the remainder of their lives. We have seen none ourselves. If papillary cancer is found outside the thyroid gland, particularly in adjacent lymph nodes, we have utilized a modified radical neck operation similar to that described by Block and Wilson. 1 This operation leaves the sternocleidomastoid muscle intact, preserves the jugular vein except in the rare instances where it is involved, and utilizes no disfiguring vertical cervical incisions. However, in all other respects a standard neck dissection is carried out to include a total lobectomy on the side of the lesion and a near total lobectomy on the opposite side. Enlarged posterior lymph nodes are taken by simple excision and are not included in the block dissection. Recurrence is rare after apparent removal of all cancer in the neck by this operation if the patient is maintained on thyroid suppression. However, mediastinal recurrences have been reported. Where follicular and papillary elements are found in the same specimen, with no undifferentiated areas, treatment should be as for papillary cancer alone (Fig. 1). Survival after conservative operations for these
CURRENT THERAPY OF THYROID NODULES
287
Figure 1. Mixed pattern of papillary and follicular elements in a thyroid cancer. Since survival after surgery is similar to that for papillary cancer alone, treatment of such a lesion should be as for papillary cancer. Postoperative care should include suppressive doses of thyroid hormone.
lesions followed by desiccated thyroid medication is similar to that for papillary cancer alone. However, if undifferentiated areas are found, usually in patients over 50, total thyroidectomy seems indicated because of the extremely malignant nature of these tumors.
Follicular Cancer Follicular cancer alone is not common, is usually encapsulated, and is usually found only in one lobe. Total lobectomy is an adequate operation unless the isthmus must be removed to obtain sufficient margin around the tumor, or unless known metastases are present. Lymph node dissections are not necessary, as these tumors metastasize via the blood stream to lung and bone. Completion thyroidectomy at a later date should be reserved for those few instances where radio-iodine treatment of distant metastases is planned. Undifferentiated Cancer These tumors grow rapidly, and are usually attached to vital neck organs which cannot be sacrificed at operation. In our experience, neck recurrence has been universal after supposedly curative total thyroidectomy unless the tumor was inadvertently discovered as a microscopic foci at operation for another indication. Removal of the isthmus to preserve airway patency is all that can be accomplished in most instances. Radiation therapy can then be tried, particularly for the small cell variant, although the results are poor.
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REFERENCES 1. Block, G. E., and Wilson, S. M.: A modified neck dissection for carcinoma of the thyroid. SURG. CLIN. N. AMER., 51: 139, 1971. 2. Crile, G., Jr.: Changing end results in patients with papillary carcinoma of the thyroid. Surg., Gynec. Obstet., 132:460, 1971. Department of Surgery Yale University School of Medicine 333 Cedar Street New Haven, Connecticut 06510
Current Therapy of Thyroid Nodules Hastings K. Wright, M.D.,* Gerard N. Burrow, M.D.,** Stephen Spaulding, M.D.,t and Daniel G. Sheahan, MB., B.Ch.!
Opinion on the correct treatment of thyroid nodules is currently at a crossroads. One senses an increasingly conservative trend combining both medical and surgical treatment which has not yet been prominently displayed in the surgical literature except in the writings of George Crile, Jr.2 Discussions with a large number of community surgeons and physicians who manage the vast majority of thyroid nodules in this country indicate that this conservative approach is now both common practice and very successful. Nevertheless, there remains a contrary opinion, emanating primarily from some large regional referral cancer centers, which declares that initial diagnosis and management of thyroid nodules should be surgical. The following suggested method of treatment of patients with thyroid nodules is based on our own experience as a combined group of endocrinologists, surgeons, and pathologists in managing a large group of such patients over the past 8 years. To our knowledge, this approach has failed to provide necessary surgical treatment for those thyroid nodules which are malignant only when patients both failed to take prescribed medication and to return for scheduled follow-up.
TO OPERATE OR NOT TO OPERATE The basic problem for the clinician is to decide whether or not to operate, and this decision first requires answers to some basic questions about thyroid neoplasia, both benign and malignant. How large is the group of people in the population with thyroid nodules? Recent autopsy studies on unselected patients who had been hospitalized indicate that almost half the adult autopsy population has one or more thyroid nodules, most of which are not palpable prior to autopsy From the Departments of Medicine, Pathology, and Surgery, Yale University School of Medicine, New Haven, Connecticut :::Professor of Surgery :::::'Associate Professor of Medicine t Assistant Professor of Medicine t Assistant Professor of Pathology Surgical Clinics of North America - VoL 54, No.2, April 1974
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because they are in the interior or posterior part of the gland. The nonpalpable group escapes detection, and therefore the question of surgery never arises. The risk of these nodules in life is clearly minimal, since only 2 to 5 per cent of these undetected nodules are even histologically cancer. Furthermore, the fact that there are fewer than 1000 deaths per year from thyroid cancer in the United States indicates that most of these histologically diagnosed cancers have no true "cancer potential." Obviously, then, the mere discovery of a thyroid nodule because it happens to lie in the palpable portion of the thyroid does not mandate surgery. If the risk of cancer in thyroid nodules in general is only 2 to 5 per cent, are there specific kinds of thyroid nodules which carry a higher risk of malignancy? AGE. It has been estimated that approximately 50 per cent of isolated thyroid nodules appearing in children are malignant. However, multinodularity increases with age, even in patients with only one palpable nodule, and the incidence of cancer in a single palpable nodule therefore decreases with age. PAST HISTORY. A past history of neck or mediastinal irradiation in a patient with a thyroid nodule is very significant. Three-fourths of children with papillary cancer of the thyroid have a history of irradiation. THE ISOLATED NODULE. The reported incidence of thyroid cancer in isolated thyroid nodules is reported to be from 4 to 33 per cent in the literature. The higher values invariably come from surgical series, not autopsy series, and clearly reflect case selection after failure of the nodule to regress spontaneously or to disappear on thyroid medication. MALE OR FEMALE? Thyroid disease is more common in females than in males, including nodules and malignancy. Multinodularity is also more common in females. Thus, an isolated thyroid nodule occurring in a male, particularly a young male, is more likely to be cancer. PHYSICAL EXAMINATION. Physical examination can be helpful in deciding whether or not to operate, particularly if it discloses multinodularity in a thyroid gland originally thought to have only one nodule. Consistency of the nodule on palpation is helpful, since a stony hard character increases the risk of malignancy. Other physical signs, such as adherence to adjacent structures, presence of cervical lymph nodes, or vocal cord paralysis, are signs of an advanced state of malignancy, and demand surgery. LABORATORY AIDS. An important aid in differentiating nodules which require surgery from those which do not is a scan of the uptake of a radioisotope in the thyroid gland. Cancers are less able to concentrate either 131 Iodine or 99m Pertechnetate, and perhaps one-tenth of such "cold" nodules which are removed surgically are malignant. An attempt is now being made to differentiate cold malignant nodules from cold benign nodules, but this is not yet possible at a clinical level. At the biochemical level, studies have shown that cold nodules which do not trap iodine usually still respond to TSH stimulation, and can incorporate phospholipid and produce colloid droplets. Some nodules even show hyperactive adenyl cyclase activity in response to TSH. There may be qualitative differences in such biochemical properties which could distinguish benign nodules from cancers. As of now, the develop-
279
CURRENT THERAPY OF THYROID NODULES
ment of scanning techniques testing biochemical properties of nodules is still at an experimental stage. Thyroiditis may present a clinical picture which resembles malignancy. The measurement of thyroid antibodies may be helpful in the differential diagnosis of such patients if antibodies are present in high titers. Needle biopsy may be helpful if titers are borderline.
TREATMENT OF THYROID NODULES
SURGERY ON MULTIPLE NODULES
Multiple Nodules Present in the Gland Patients with nontoxic goiter may present either with multiple discrete nodules or with multiple lobules which are soft and nondiscrete (Table 1). Occasionally, the thyroid gland is huge and unsightly, although rarely symptomatic. A second group of similar patients presents with one large thyroid lobe containing a palpable nodule which does not account for the entire asymmetry of the thyroid gland. Radioactive scanning usually shows other cold areas within this lobe, strongly suggesting multinodularity. In general, these patients can also be treated safely without surgery. Suppression with large doses of thyroid can be tried in all the above patients. However, in our experience, the nodules seldom totally disappear unless the patient was previously hypothyroid. Even if they do not do so, surgery is still not usually indicated unless there is suspicious Table 1. Treatment of Thyroid Nodules A. Multiple Nodules Patient Hyperthyroid ~
Treat hyperthyroidism.
Patient Hypo- or Euthyroid J, Try thyroid before surgery. J, Remove thyroid subtotally only if symptoms develop or one nodule is suspicious.
B. Single Nodule
"Hot" Scan J, Give RAI or resect. Otherwise follow indefinitely.
"Cold" Scan
~n ch~Otherwise, try
Operate and when suspicious on physical examination in males.
suppressive doses of desiccated thyroid for 4 to 6 months. ,/
\.
If nodule disappears,
If nodule
continue on thyroid indefinitely.
does not disappear or enlarges, operate.
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hardness of one or more of the, nodules or evidence of continued enlargement over a period of months. If surgery is performed, most surgeons simply remove all the nodules and then place the patient on suppressive doses of thyroid. Total thyroidectomy is not indicated. Single Nodule Pr~.sent in the Gland "HOT" NODULES. While cancers have been found histologically in nodules which were "hot" on radioactive scan, these are rare indeed. Thus, surgery to rule out cancer is an unnecessary step in most of these patients. Hyperthyroidism may not be present when these nodules are first discovered. Indeed, on occasion the "hyperfunctioning" nodule may be the only thyroid tissue. These possibilities should be investigated before considering surgery by thyroid suppression or TSH stimulation followed by a second scan. The hot nodule may undergo necrosis and involution, often after several years of activity. If this happens, the patient could potentially become hypothyroid. Thus, treatment of a hot nodule is usually indicated unless· both the physician and the patient are willing to have repeated evaluations of thyroid function performed on a longterm basis. Radioactive iodine is effective, but surgical rerrioval of the nodule is simple and a safe alternative method of treatment. COLD NODULES. Colloid Cysts. Colloid cysts would not require surgery if this diagnosis could be made by any other means. Since such cysts have almost no metabolic activity, it should be possible to differen" tiate them from cancers which do have metabolic activity. Several radioisotope scanning techniques have been tried, including selenomethionine, gallium, cesium, and mercury. Unfortunately, the quality of resolution obtained with present equipment is not good; furthermore, one cannot totally rule out a cystic component in a cancer by these techniques. In addition, isotopic techniques may show false cold areas in focal thyroiditis. Other technical developments which may offer eventual help in diagnosing cysts include ultrasonic scanning with or without needle biopsy of apparent cystic lesions. However, these techniques are not yet as accurate as surgery, and removal of the cold nodule is usually necessary as a diagnostic step. Medullary Cancer. Another new technical development appears to have special prOInise for the early identification of medullary cancer. This tumor commonly produces excessive secretion of thyrocalcitonin, and sensitive radioimmunoassays of this hormone in blood are now available. Treatment of this thyroid cancer is the proper subject for another treatise, and only an outline will be presented here. The diagnosis should be apparent preoperatively. Associated endocrine tumors should be removed first. An aggressive surgical approach seems warranted, including total thyroidectomy and en bloc excision of adjacent lymph nodes. If total resection is impossible, as much of the tumor should be removed as possible, even in the presence of known metastatic disease, to treat the
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secondary effects of thYTocalcitonin secretion on the gastrointestinal tract and cardiovascular system. These tumors do not respond to TSH and do not concentrate iodine. Consequently, treatment with thyroid should not be effective. Finally, as in other endocrine cancer, longterm survival even with metastases is common. TRIAL OF THERAPY WITH THYROID HORMONE. In most instances, no test is yet available to distinguish between benign and cancerous single cold nodules. Children, males with suspicious nodules, and patients with suggestive evidence of extrathYToidal disease should therefore undergo immediate surgery because of the high risk of cancer in such nodules. The remainder of patients with cold nodules which are not suspicious on physical examination can safely be treated with suppressive doses of thyroid hormone (full doses of 3 gr of desiccated thYToid daily) in an attempt to cause regression of the nodule. The nodule disappears in the majority of such patients on thyroid medication in 4 to 6 months because of suppression by exogenous thyroid of TSH which is stimulating thYToid tissue. There are other nodules which are not TSH dependent, but which appear because of hemorrhage into a cyst. These nodules often regress despite thYToid medication. The use of thyroid suppression is based on excellent theoretical grounds. Most nodules are known to be influenced by TSH, and nontoxic nodular goiter is thought to be caused by repeated cycles of TSH stimulation, resulting in hypertrophy of parts of the thYToid. Exogenous thyroid hormone in adequate doses inhibits TSH secretion, preventing further stimulation of the thYToid gland, and promoting involution. The pathogenesis of thYToid cancers, particularly papillary cancers, may also be related to that of multinodular goiters. Chronically elevated TSH levels can cause thyroid cancer in animals, especially when acting on goiters caused by administration of goitrogens, iodine deficiency, or partial destruction of the gland by irradiation. Elimination of TSH stimulation may prevent eventual cancer development, and the use of exogenous thYToid therefore may become indicated in the prophylaxis of cancer development in patients with similar problems. One theoretical worry is that thyroid suppression therapy in patients with isolated cold nodules could cause only partial or temporary regression of a thyroid cancer. This may be particularly true with papillary cancer, which is frequently very sensitive to TSH and may indeed be totally hormone-dependent. Some of these tumors undoubtedly regress with hormone suppression alone, and stay suppressed as long as the patient remains on adequate doses of exogenous thyroid. We have not seen extrathyroidal papillary cancer of the thyroid develop in any patient whose thYToid nodule has completely regressed on treatment which is continued thereafter for the rest of his life. If a thyroid nodule does not regress completely after 4 to 6 months of thyroid suppression, surgery is indicated. Conversely, if a nodule grows significantly in size on suppressive doses of thyroid, surgery is indicated when this response is determined. Partial regression of the nodule in this time period should not be considered an indication for further medication unless the nodule now concentrates iodine. The patients whose nodules
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have disappeared should be followed on thyroid suppression for the indefinite future.
SURGERY ON THE ISOLATED COLD NODULE
Once a decision is made to perform surgery for an isolated, cold nodule, the operation should be performed by a surgeon prepared to safely perform total thyroidectomy and, possibly, radical dissection of the anterior neck. Neither procedure is usually necessary, but when required they are best performed at the initial surgery. The first step should be total exposure of both thyroid lobes even though a nodule is palpable preoperatively only in one gland. This step requires division of the lateral and inferior veins of each lobe, a procedure which then allows bidigital palpation of each lobe. Single Nodule Preoperatively, but Multiple Nodules at Surgery In our experience, multiple nodules are discovered at surgery in 60 per cent of patients after a diagnosis of a single nodule by careful preoperative palpation and thyroid scan. The unrecognized nodules are usually posterior in the gland, and palpable only after mobilization of both lobes. If multinodularity is discovered, the risk of cancer in the nodule previously thought to be single significantly decreases. All nodular tissue should be removed, leaving the posterior capsules of each thyroid lobe intact. Total thyroidectomy is not indicated because of the significant risk of recurrent nerve injury and/or hypoparathyroidism even in expert hands-a risk that should be taken only in treating diffuse undifferentiated or medullary thyroid cancer. In the rare case where suspicious signs of cancer are present with multinodularity (enlarged perithyroid lymph nodes, adherence of the thyroid to adjacent structures), a histologic diagnosis must be obtained on frozen section and further surgical dissection carried out according to the nature of the lesion, as outlined below in the discussion of treatment of thyroid cancer. Single Nodule Preoperatively and at Surgery If a single nodule alone is discovered on complete palpation of both lobes, and there are no suspicious signs of extrathyroid involvement or of cancer in the mass itself (one warning sign of probable cancer is the demonstration of abnormal vasculature in the nodule, commonly a hemangiomatous venous pattern), our current practice where possible is to first remove the mass itself with its capsule and 1.0 cm of surrounding normal thyroid tissue and submit this specimen to the pathologist for immediate frozen section examination before continuing the operation. Many other surgeons do not agree, and consider extracapsular lobectomy on the side ofthe lesion to be the minimum acceptable initial step in operative diagnosis. However, at least four out of five, and probably more, of these isolated lesions are benign, and no operation beyond simple removal of the mass is necessary. If the pathologist finds cancer, a more radical operation can easily be performed, and we have not seen seeding of the
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cancer from the initial conservative resection outlined above followed by extracapsular lobectomy or subtotal thyroidectomy.
CRITICAL ROLE OF THE PATHOLOGIST
After initial removal of the isolated nodule, either by excisional biopsy or by lobectomy, the pathologist assumes the critical role in deciding on further surgical maneuvers. This is a difficult assignment, for the conclusions which are reached on gross examination and frozen section histologic examination of the nodule largely dictate what the surgeon should do in the operating room. In the treatment of cancer of most other organs, a diagnosis of "cancer" on frozen section is sufficient to guide the surgeon. However, the malignant potential of the several types of thyroid cancer is not equal, and a specific diagnosis of the type of thyroid cancer is necessary to guide surgical treatment. Fortunately, the commonly accepted criteria now used by pathologists for diagnosing and classifying thyroid cancers are clinically useful to the surgeon. The surgeon and the pathologist must learn to use this common language instead of relying on a diagnosis of "benign" or "malignant" on frozen section analysis of submitted tissue. Classification of Thyroid Cancers The most widely used classification is that described in Table 2. It is based on the histologic appearances of thyroid malignant neoplasms, and the order of listing roughly indicates the degree of malignancy with papillary cancer being the least and giant cell undifferentiated cancer the most malignant. However, direct spread of tumor into adjacent neck structures significantly worsens the prognosis irrespective of the tumor type involved. Gross Appearance of the Several Thyroid Cancers The gross appearances of thyroid cancer are of little diagnostic value in small lesions. Even those showing apparent encapsulation require extensive microscopic study. However, the invasive nature of most larger lesions is usually readily evident, particularly if extrathyroidal tissue is Table 2.
Histologic Classification of Thyroid Cancer Papillary cancer Follicular cancer Clear cell Oxyphil Medullary cancer Undifferentiated cancer Small cell Giant cell Metastatic cancer Other Lymphoma Sarcoma
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involved in the mass. The following gross features are sometimes helpful to the surgeon and the pathologist in the operating room: PAPILLARY CANCER. Small lesions may be indistinguishable from minute scars. Because their malignant character is recognized only at microscopic examination, they are called occult sclerosing cancers. Larger tumors are often cystic with irregular borders and may be indistinguishable from degenerating colloid nodules in that the cystic contents may show recent or altered blood and fibrosis; dystrophic calcification and occasionally ossification are seen. Direct spread into adjacent structures is not common. Metastatic spread to adjacent lymph nodes may be found at surgery, making the diagnosis obvious. FOLLICULAR CANCER. Lesions which show only microscopic invasion are grossly indistinguishable from follicular adenomas. Grossly invasive lesions are rare, but are more likely than papillary cancers to extend beyond the confines of the thyroid gland into adjacent structures. These tumors are usually fleshy with central fibrosis and focal areas of hemorrhage and necrosis, and are usually well encapsulated in one lobe alone. Gross vascular invasion may be evident. MEDULLARY CANCER. This tumor is usually a single, solid, hard, gray white mass which appears well encapsulated and without a central fibrosis scar. Vascular invasion may be evident. UNDIFFERENTIATED CANCER. These tumors are usually firm, white, and of irregular outline. Invasion into adjacent structures is usual at the time of diagnosis. Areas of hemorrhage and necrosis are not common.
Pitfalls in Frozen Section Diagnosis of Thyroid Nodules While the infiltrative nature of large thyroid cancers is easily established grossly at surgery, histologic examination of non infiltrating and small lesions is the sole means of establishing malignancy. If the surgeon and pathologist are at all suspicious on examination of the gross lesion in situ or after excisional biopsy, a frozen section histologic examination should be done before proceeding further with the operation. A description of the histologic criteria used to diagnose the several thyroid cancers is beyond the scope of this paper. However, it should be emphasized that a correct diagnosis is helpful during the operation, since different thyroid cancers require different operations. Unfortunately, correct conclusions are not always reached on examination of only one or more frozen section slides from a lesion, and the true nature of the nodule may only become apparent after extensive examination of multiple permanent slides one or more days after the surgical procedure. FALSE POSITIVE DIAGNOSES FROM FROZEN SECTIONS. False positive diagnoses of cancer can be made. Atypical epithelial cells with marked pleomorphism can be seen in hyperthyroidism, thyroiditis, and adenomatous goiter, and may suggest cancer to the unwary. However, if the clinical history is known to the pathologist, this problem should rarely occur, since these bizarre cells do not show mitotic activity and are presumably only degenerative in nature in these conditions. DIFFERENTIATION OF FOLLICULAR CANCER FROM ADENOMA. This problem commonly arises in examining solitary nodules showing a follicular pattern. Follicular cancers can be so well differentiated as to resem-
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ble normal thyroid acini, and their metastases can show a similar pattern. Unless capsular, adjacent thyroid tissue, or vascular invasion is identified, cancer cannot be diagnosed. This usually requires multiple sections of the nodule, a process which is most suitably done on permanent section after surgery. If the pathologist finds himself in this difficulty, he should so inform the surgeon so that a total lobectomy can be performed on the side of the lesion. DIFFERENTIATION OF PAPILLARY CANCER FROM PAPILLARY HYPERPLASIA. Distinction between papillary neoplasia and hyperplasia may be especially difficult, particularly in adenomatous goiter. Some nodules of adenomatous goiter may show hyperplastic papillary foci in cystic areas, and the intense hyperplasia of Graves' disease showing intrafollicular papillae may suggest cancer to the unwary. Again, because of the paucity of cellular pleomorphism and mitotic activity in both neoplastic and hyperplastic papillary lesions, the criteria of malignancy are capsular or vascular invasion. The presence of psammoma bodies is of considerable value because they are rarely seen in nonneoplastic lesions. Benign papillary adenomas are relatively rare, and it is emphasized that such a frozen section diagnosis should not be rendered to the surgeon until exhaustive examination of multiple tissue blocks has excluded capsular and vascular invasion. If a problem in diagnosis exists, the surgeon is best advised to proceed with a conservative operation for papillary cancer. UNDIFFERENTIATED TUMORS. Undifferentiated tumors less commonly present diagnostic difficulties. The small cell variant, in its diffuse form, may be confused with a lymphocytic or lymphoblastic lymphoma and, in its compact form, with medullary thyroid cancer or metastatic breast cancer. The giant cell variant may be misdiagnosed as a sarcoma though the latter are distinctly rare tumors of the thyroid. Examination of numerous tissue blocks may be required before focal areas of recognizable follicular or papillary cancer clearly indicate the primary thyroid epithelial origin of the tumor. METASTATIC TUMORS. Metastatic spread to the thyroid from malignant melanoma or from primary renal, bronchogenic, or breast cancer is not uncommon. Such lesions, however, rarely present as apparent primary neoplasms of the thyroid, and an adequate preoperative work-up should prevent the problem of deciding the cell type of the lesion in the operating suite. As with undifferentiated tumors, most lesions can be appropriately diagnosed if multiple tissue blocks are extensively examined after surgery~ NODULE CALLED BENIGN ON FROZEN SECTION, BUT CANCER ON PERMANENT SECTION AFTER SURGERY COMPLETED. Occasionally, a frozen section diagnosis of benign nodule is changed to a diagnosis of cancer one or more days after surgery when multiple permanent sections are read. This is unavoidable and should cause no consternation if the surgeon and pathologist have consulted and hedged their bets at the operating table. If the final diagnosis is papillary cancer, and the surgeon has performed a lobectomy on the side of the gross lesion, in our opinion nothing more need be done except to place the patient on suppressive
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doses of desiccated thyroid. However, if only the nodule itself has been removed at surgery, most surgeons believe that subsequent subtotal thyroidectomy is indicated. If the final diagnosis is follicular cancer, and the surgeon has performed a lobectomy on the side of the gross lesion, an adequate operation has been done unless metastatic disease develops. We have not seen a mistake made on undifferentiated cancer; the diagnosis is usually obvious grossly, and the lesion is usually unresectable. If an operation has been done on the thyroid for some other reason than to rule out cancer, but microscopic foci of cancer are found on permanent section analysis, nothing more need be done. In our experience, the patient is "cured" by whatever operation has been performed, even subtotal lobectomy. These "cancers" must therefore have a low malignant potential. We have placed all such patients on desiccated thyroid.
REQUIRED OPERATION AFTER SPECIFIC HISTOLOGIC DIAGNOSIS OF CANCER ON FROZEN SECTION
Papillary Cancer Opinions differ in this country on the correct operation for papillary cancer, but a large number of surgeons now utilize conservative operations in treating this cancer. If no extrathyroidal extension is apparent on careful inspection of the neck and histologic examination of suspicious lymph nodes, we have performed a total lobectomy on the side of the gross lesion. Up to 85 per cent of such glands have microscopic foci of cancer in the other lobe, but they are rarely palpable. We have preferred to perform a subtotal lobectomy on the contralateral side, leaving the posterior capsule and approximately 25 per cent of the posterior of this lobe intact. Even more conservative treatment may be correct, especially in children and in women under the age of 40, and in patients with a history of neck irradiation. Recurrence in the contralateral lobe after simple lobectomy on the side of the lesion is uncommon in such patients maintained on suppressive doses of thyroid for the remainder of their lives. We have seen none ourselves. If papillary cancer is found outside the thyroid gland, particularly in adjacent lymph nodes, we have utilized a modified radical neck operation similar to that described by Block and Wilson. 1 This operation leaves the sternocleidomastoid muscle intact, preserves the jugular vein except in the rare instances where it is involved, and utilizes no disfiguring vertical cervical incisions. However, in all other respects a standard neck dissection is carried out to include a total lobectomy on the side of the lesion and a near total lobectomy on the opposite side. Enlarged posterior lymph nodes are taken by simple excision and are not included in the block dissection. Recurrence is rare after apparent removal of all cancer in the neck by this operation if the patient is maintained on thyroid suppression. However, mediastinal recurrences have been reported. Where follicular and papillary elements are found in the same specimen, with no undifferentiated areas, treatment should be as for papillary cancer alone (Fig. 1). Survival after conservative operations for these
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Figure 1. Mixed pattern of papillary and follicular elements in a thyroid cancer. Since survival after surgery is similar to that for papillary cancer alone, treatment of such a lesion should be as for papillary cancer. Postoperative care should include suppressive doses of thyroid hormone.
lesions followed by desiccated thyroid medication is similar to that for papillary cancer alone. However, if undifferentiated areas are found, usually in patients over 50, total thyroidectomy seems indicated because of the extremely malignant nature of these tumors.
Follicular Cancer Follicular cancer alone is not common, is usually encapsulated, and is usually found only in one lobe. Total lobectomy is an adequate operation unless the isthmus must be removed to obtain sufficient margin around the tumor, or unless known metastases are present. Lymph node dissections are not necessary, as these tumors metastasize via the blood stream to lung and bone. Completion thyroidectomy at a later date should be reserved for those few instances where radio-iodine treatment of distant metastases is planned. Undifferentiated Cancer These tumors grow rapidly, and are usually attached to vital neck organs which cannot be sacrificed at operation. In our experience, neck recurrence has been universal after supposedly curative total thyroidectomy unless the tumor was inadvertently discovered as a microscopic foci at operation for another indication. Removal of the isthmus to preserve airway patency is all that can be accomplished in most instances. Radiation therapy can then be tried, particularly for the small cell variant, although the results are poor.
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REFERENCES 1. Block, G. E., and Wilson, S. M.: A modified neck dissection for carcinoma of the thyroid. SURG. CLIN. N. AMER., 51: 139, 1971. 2. Crile, G., Jr.: Changing end results in patients with papillary carcinoma of the thyroid. Surg., Gynec. Obstet., 132:460, 1971. Department of Surgery Yale University School of Medicine 333 Cedar Street New Haven, Connecticut 06510