Solitary Thyroid Richard D.
Liechty, MD; Philip
T.
Nodules
Stoffel, MD; David E. Zimmerman; Steven G. Silverberg, MD
\s=b\ A study was made of 67 patients with solitary thyroid nodules in which strict clinical criteria to eliminate the probability of cancer, including a history of radiation to the neck, were used. Twelve (17.9%) were found to have histologic malignancy. This figure is threefold that of a study made by one of the authors 11 years earlier, but comparable to others more recently reported from cancer centers elsewhere. It is not certain whether the
apparent increase is actual or merely the result of more careful screening of patients for referral. Shrinking of the nodule by thyroid suppression therapy had been definite but incomplete in three nodules, one of which was found to be malignant. Excision is recommended for all persistent thyroid nodules. (Arch Surg 112:59-61, 1977)
the incidence of malignancy in solitary nodules from 5% to greater than 35%, and some indicate that the frequency, overall, is rising chiefly because of improved selection of patients. Our experience also reflects this increasing prevalence.
RESULTS
place thyroid Studies
SUBJECTS AND METHODS From a review of the medical records of all patients who underwent thyroid surgery at Colorado General Hospital during the years 1965 through 1975, we included in this study 67 patients who met the following requirements: (1) an asymptomatic solitary thyroid nodule verified clinically by two different physicians, (2) no suspicious neck nodes, (3) no prior history of thyroid disease or voice changes, (4) a normal chest roentgenogram, (5) no history of therapeutic radiation to the head and neck area. Thus, to minimize the factor of selection associated with any cancer center, we attempted to winnow from this review those paitents who were referred to our institution with the probable diagnosis of thyroid
Table 1 lists the pathologic findings. The incidence of malignancy was 17.9%. More than half (57%) of the lesions represented multinodular glands with colloid-cystic-hyperplastic disease. Table 2 shows the frequency of the nodules according the sex. Overall the female:male ratio was about 7.5:1. The ages of our patients ranged from 10 to 90 years, with a mean of 41.3 years. The Figure shows the distribution of the nodules, both benign and malignant, according to age. Fifty-three patients had '"I scintiscans. Table 3 shows the results; 70% of the benign nodules and 90% of the ma¬ lignant ones were cold. One malignant nodule was reported as normal. Sonography results are listed in Table 4 for 11
patients.
(Drs Liechty and Stoffel) and Pathology, (Dr Silverberg), University of Colorado Medical Center,
In almost all patients, our surgeons routinely performed total lobectomy and partial isthmusectomy. If rapid sections or permanent histologie sections showed invasion or positive nodes, they enlarged the operations or reoperated to include near-total thyroidectomy, and, if lymph nodes contained cancer, they added lymph node excision. There were no operative deaths or recurrent nerve injuries. One patient after total thyroidectomy has perma¬ nent hypoparathyroidism. To this date, none of the pa¬ tients with thyroid cancer has died from his disease or showed recurrences.
Reprint requests to University of Colorado Medical Center, 4200 E Ninth Ave, Denver, CO 80220 (Dr Liechty).
cation for
cancer.
We reviewed all of the pathology reports and verified the diagnoses of thyroid adenomas and malignancy after reexamining the original microscopical sections with a pathologist. We could not, from the records, determine precisely how long each patient had lived in the Rocky Mountain area, but almost all were
citizens of the state and many
were
born in Colorado.
Accepted
for publication Aug 30, 1976. From the Departments of Surgery
Denver.
Thirty-two patients received suppressive thyroid medi¬ periods varying up to six months. Only three
Downloaded From: http://archsurg.jamanetwork.com/ by a UQ Library User on 06/21/2015
( ^
>
CO
Q_ >—
O h_
CU .
12 11 10 9 8 7 6 5 4 3
Benign lesions Malignant disease
2 1
0
a
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95
Age (years)
Age
Table
distribution of
patients
with
solitary thyroid nodules.
Table 3.—Results of ,3
1.—Pathologic Diagnoses No.
Benign Multinodular Adenoma Follicular Hiirthle
Thyroiditis Thyroglossal Simple cyst Total (%) Malignant Papillary
38
goiter
duct
Cold Warm Hot Normal Total No. of scans
Scintillography
Benign
Malignant
Lesions 30
Lesions
43
10
cyst 1 55
Follicular Hürthle Other lymphoma Total (%) Total
1 12 67
(82.1)
(17.9)
Table 2.—Female-Male Distribution
Benign 55
Malignant 10
49
(82.1%)
Table
12
(17.9%)
Total 59 67
4.—Comparison of Ultrasonographic Interpretations With Pathologic Diagnoses
Patient Ultrasound With benign lesions 1 "Areas of sonolucence" 2 Solid mass 3 Cystic mass 4
Cystic
5 6 7 8
Solid mass Solid mass Follicular mass
Cystic
No.
No.
Female Male Total (%)
Diagnostic Impression
9 With 10 11
Solid
mass
mass mass
(?)
Pathologic Diagnosis Multinodular goiter Thyroid adenoma Multinodular goiter Multinodular goiter Colloid nodule Multinodular goiter Follicular nodules Follicular nodule; Hürthle adenoma Nodular goiter
malignant lesions Cystic mass
Follicular
cancer
Solid
Follicular
cancer
Downloaded From: http://archsurg.jamanetwork.com/ by a UQ Library User on 06/21/2015
mass
patients showed some but not complete involution; with benign and one with malignant lesions.
two
COMMENT
Eleven years ago in a study of 299 patients from a Midwestern university hospital, the senior author and his colleagues found a 5.7% incidence of malignancy in clini¬ cally benign, solitary thyroid nodules.1 Using the even more stringent criteria for the clinical elimination of malignancy in this study, we found a 17.9% incidence, a value threefold greater. Studies from Chicago,-' Boston,1 and Michigan' show about the same frequency of cancer; 13.2%, 19%, and 28.7%, respectively. However, these reports also come from cancer centers, and the subtle effect of selection, which we have rigorously tried to control, must have influenced their data. None of these reports, for example, excluded patients with a prior history of neck irradiation. The Michigan group reported that "during the five-year period, an increasing number of women in their late 20s or early 30s gave his¬ tories of irradiation to the head and neck... ."4 According to several studies, the incidence of thyroid cancer in solitary nodules has increased over the past decade. Brooks' and Hill et al"' attribute the rise, at least in part, to more careful selection of patients for whom surgical diagnosis is recommended. Because our patients were referred from many physi¬ cians within the Rocky Mountain area, we operated on these patients under no standard preoperative protocol. We did, however, attempt to screen out those patients who were likely to have thyroid cancer. For example, we ex¬ cluded four patients with clinically benign nodules who, although they met our other criteria, had received thera¬ peutic irradiation in childhood. All four proved to have
thyroid cancers, histologically. Although the scintiscans showed 90% of malignant nodules to be cold, 70% of benign nodules were also cold. Larger studies reflect an even more questionable view of the value of thyroid scans in predicting thyroid malignan¬ We lack sufficient experience with ultrasound to cy.make authoritative comments. New equipment with better discrimination promises more precision in the future. Because this is a relatively small series, we feel that we cannot make any meaningful assertions about the efficacy of thyroid suppression or our surgical and subsequent medical therapy of thyroid cancer in just 12 patients. We wish to reemphasize the central points of this study: From a review of 67 patients, referred to us from various physicians and carefully screened by us to represent "benign" solitary nodules, almost one of five patients had histologically demonstrated thyroid cancer. Comparing this high frequency of malignant nodules with the 5.7% incidence of a similar study using even less strict criteria, '"'
believe that better patient selection has contributed to the increased frequency of cancer in clinically benign, solitary thyroid nodules. One other factor peculiar to our area merits brief mention. Most Coloradans live at elevations above a mile, and ionizing irradiation increases with altitude. Eisenbud" estimates, for example, that populations living at 1,500 meters receive twice, and those at 3,000 meters six times, the radiation exposure of those at sea level. Although numerous studies link ionizing irradiation, causally with thyroid cancer,71- we lack the epidemiological data in this retrospective study that could confirm or deny such an as¬ sociation. The high incidence of cancer and low complication rate reaffirms our basic philosophy of recommending excision of virtually all solitary thyroid nodules. we
References
Liechty RD, Graham M, Freemeyer P: Benign solitary thyroid nodules. Surg Gynecol Obstet 121:571-573, 1965. 2. Kendall LA, Condon RD: Prediction of malignancy in solitary thyroid 1.
nodules. Lancet 1:1071-1073, 1969. 3. Brooks JR: The solitary thyroid nodule. Am J Surg 125:477-481, 1973. 4. Hoffman GL, Thompson NW, Heffron C: The solitary thyroid nodule: A reassessment. Arch Surg 105:379-385, 1972. 5. Hill LD, Beebe HG, Hipp R, et al: Thyroid suppression. Arch Surg 108:403-405, 1974. 6. Eisenbud H: Environmental Radioactivity. New York, McGraw-Hill Book Inc, 1963, pp 135-170. 7. Hollingsworth DR, Hamilton HB, Tamagaki H, et al: Thyroid disease: A study in Hiroshima, Japan. Medicine 42:47-71, 1963. 8. Conrad RA, Dobryns BM, Sutow WW: Thyroid neoplasia as late effect of exposure to radioactive iodine in fallout. JAMA 214:316-324, 1970. 9. DeGroot L, Paloyan E: Thyroid carcinoma and radiation: A Chicago endemic. JAMA 225:487-491, 1973. 10. Refetoff S, Harrison J, Karanfilski BT, et al: Continuing occurrence of thyroid carcinoma after irradiation to the neck in infancy and childhood. N Engl J Med 292:171-175, 1975. 11. Becker FO, Economou SG, Southwick HW, et al: Adult thyroid cancer after head and neck irradiation in infancy and childhood. Ann Intern Med 83:347-351, 1975. 12. Winship T: Carcinoma of the thyroid in children. Pediatrics 18:459\x=req-\ 466, 1956.
Editorial Comment Of interest in this concise review of solitary thyroid nodules is an implicit challenge of thyroid suppression for discrimination of benign and malignant thyroid tumors. Of 32 patients who received suppressive doses of thyroid hormone, only three showed some regression, and one of these had thyroid cancer. Typically, the gross and microscopical appearance of a nontoxic goiter comprises an admixture of activity and regression. It is reasonable to expect that natural involution can coincide with administration of an agent. Further, the suppressive effect of thyroid hormone for differentiated thyroid cancer is well docu¬ mented. It is timely to reexamine what may well be another example of pharmacologie habituation that only delays effective operative
management.
Downloaded From: http://archsurg.jamanetwork.com/ by a UQ Library User on 06/21/2015
Jerome J. DeCosse, MD Milwaukee
Liechty, MD; Philip
T.
Nodules
Stoffel, MD; David E. Zimmerman; Steven G. Silverberg, MD
\s=b\ A study was made of 67 patients with solitary thyroid nodules in which strict clinical criteria to eliminate the probability of cancer, including a history of radiation to the neck, were used. Twelve (17.9%) were found to have histologic malignancy. This figure is threefold that of a study made by one of the authors 11 years earlier, but comparable to others more recently reported from cancer centers elsewhere. It is not certain whether the
apparent increase is actual or merely the result of more careful screening of patients for referral. Shrinking of the nodule by thyroid suppression therapy had been definite but incomplete in three nodules, one of which was found to be malignant. Excision is recommended for all persistent thyroid nodules. (Arch Surg 112:59-61, 1977)
the incidence of malignancy in solitary nodules from 5% to greater than 35%, and some indicate that the frequency, overall, is rising chiefly because of improved selection of patients. Our experience also reflects this increasing prevalence.
RESULTS
place thyroid Studies
SUBJECTS AND METHODS From a review of the medical records of all patients who underwent thyroid surgery at Colorado General Hospital during the years 1965 through 1975, we included in this study 67 patients who met the following requirements: (1) an asymptomatic solitary thyroid nodule verified clinically by two different physicians, (2) no suspicious neck nodes, (3) no prior history of thyroid disease or voice changes, (4) a normal chest roentgenogram, (5) no history of therapeutic radiation to the head and neck area. Thus, to minimize the factor of selection associated with any cancer center, we attempted to winnow from this review those paitents who were referred to our institution with the probable diagnosis of thyroid
Table 1 lists the pathologic findings. The incidence of malignancy was 17.9%. More than half (57%) of the lesions represented multinodular glands with colloid-cystic-hyperplastic disease. Table 2 shows the frequency of the nodules according the sex. Overall the female:male ratio was about 7.5:1. The ages of our patients ranged from 10 to 90 years, with a mean of 41.3 years. The Figure shows the distribution of the nodules, both benign and malignant, according to age. Fifty-three patients had '"I scintiscans. Table 3 shows the results; 70% of the benign nodules and 90% of the ma¬ lignant ones were cold. One malignant nodule was reported as normal. Sonography results are listed in Table 4 for 11
patients.
(Drs Liechty and Stoffel) and Pathology, (Dr Silverberg), University of Colorado Medical Center,
In almost all patients, our surgeons routinely performed total lobectomy and partial isthmusectomy. If rapid sections or permanent histologie sections showed invasion or positive nodes, they enlarged the operations or reoperated to include near-total thyroidectomy, and, if lymph nodes contained cancer, they added lymph node excision. There were no operative deaths or recurrent nerve injuries. One patient after total thyroidectomy has perma¬ nent hypoparathyroidism. To this date, none of the pa¬ tients with thyroid cancer has died from his disease or showed recurrences.
Reprint requests to University of Colorado Medical Center, 4200 E Ninth Ave, Denver, CO 80220 (Dr Liechty).
cation for
cancer.
We reviewed all of the pathology reports and verified the diagnoses of thyroid adenomas and malignancy after reexamining the original microscopical sections with a pathologist. We could not, from the records, determine precisely how long each patient had lived in the Rocky Mountain area, but almost all were
citizens of the state and many
were
born in Colorado.
Accepted
for publication Aug 30, 1976. From the Departments of Surgery
Denver.
Thirty-two patients received suppressive thyroid medi¬ periods varying up to six months. Only three
Downloaded From: http://archsurg.jamanetwork.com/ by a UQ Library User on 06/21/2015
( ^
>
CO
Q_ >—
O h_
CU .
12 11 10 9 8 7 6 5 4 3
Benign lesions Malignant disease
2 1
0
a
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95
Age (years)
Age
Table
distribution of
patients
with
solitary thyroid nodules.
Table 3.—Results of ,3
1.—Pathologic Diagnoses No.
Benign Multinodular Adenoma Follicular Hiirthle
Thyroiditis Thyroglossal Simple cyst Total (%) Malignant Papillary
38
goiter
duct
Cold Warm Hot Normal Total No. of scans
Scintillography
Benign
Malignant
Lesions 30
Lesions
43
10
cyst 1 55
Follicular Hürthle Other lymphoma Total (%) Total
1 12 67
(82.1)
(17.9)
Table 2.—Female-Male Distribution
Benign 55
Malignant 10
49
(82.1%)
Table
12
(17.9%)
Total 59 67
4.—Comparison of Ultrasonographic Interpretations With Pathologic Diagnoses
Patient Ultrasound With benign lesions 1 "Areas of sonolucence" 2 Solid mass 3 Cystic mass 4
Cystic
5 6 7 8
Solid mass Solid mass Follicular mass
Cystic
No.
No.
Female Male Total (%)
Diagnostic Impression
9 With 10 11
Solid
mass
mass mass
(?)
Pathologic Diagnosis Multinodular goiter Thyroid adenoma Multinodular goiter Multinodular goiter Colloid nodule Multinodular goiter Follicular nodules Follicular nodule; Hürthle adenoma Nodular goiter
malignant lesions Cystic mass
Follicular
cancer
Solid
Follicular
cancer
Downloaded From: http://archsurg.jamanetwork.com/ by a UQ Library User on 06/21/2015
mass
patients showed some but not complete involution; with benign and one with malignant lesions.
two
COMMENT
Eleven years ago in a study of 299 patients from a Midwestern university hospital, the senior author and his colleagues found a 5.7% incidence of malignancy in clini¬ cally benign, solitary thyroid nodules.1 Using the even more stringent criteria for the clinical elimination of malignancy in this study, we found a 17.9% incidence, a value threefold greater. Studies from Chicago,-' Boston,1 and Michigan' show about the same frequency of cancer; 13.2%, 19%, and 28.7%, respectively. However, these reports also come from cancer centers, and the subtle effect of selection, which we have rigorously tried to control, must have influenced their data. None of these reports, for example, excluded patients with a prior history of neck irradiation. The Michigan group reported that "during the five-year period, an increasing number of women in their late 20s or early 30s gave his¬ tories of irradiation to the head and neck... ."4 According to several studies, the incidence of thyroid cancer in solitary nodules has increased over the past decade. Brooks' and Hill et al"' attribute the rise, at least in part, to more careful selection of patients for whom surgical diagnosis is recommended. Because our patients were referred from many physi¬ cians within the Rocky Mountain area, we operated on these patients under no standard preoperative protocol. We did, however, attempt to screen out those patients who were likely to have thyroid cancer. For example, we ex¬ cluded four patients with clinically benign nodules who, although they met our other criteria, had received thera¬ peutic irradiation in childhood. All four proved to have
thyroid cancers, histologically. Although the scintiscans showed 90% of malignant nodules to be cold, 70% of benign nodules were also cold. Larger studies reflect an even more questionable view of the value of thyroid scans in predicting thyroid malignan¬ We lack sufficient experience with ultrasound to cy.make authoritative comments. New equipment with better discrimination promises more precision in the future. Because this is a relatively small series, we feel that we cannot make any meaningful assertions about the efficacy of thyroid suppression or our surgical and subsequent medical therapy of thyroid cancer in just 12 patients. We wish to reemphasize the central points of this study: From a review of 67 patients, referred to us from various physicians and carefully screened by us to represent "benign" solitary nodules, almost one of five patients had histologically demonstrated thyroid cancer. Comparing this high frequency of malignant nodules with the 5.7% incidence of a similar study using even less strict criteria, '"'
believe that better patient selection has contributed to the increased frequency of cancer in clinically benign, solitary thyroid nodules. One other factor peculiar to our area merits brief mention. Most Coloradans live at elevations above a mile, and ionizing irradiation increases with altitude. Eisenbud" estimates, for example, that populations living at 1,500 meters receive twice, and those at 3,000 meters six times, the radiation exposure of those at sea level. Although numerous studies link ionizing irradiation, causally with thyroid cancer,71- we lack the epidemiological data in this retrospective study that could confirm or deny such an as¬ sociation. The high incidence of cancer and low complication rate reaffirms our basic philosophy of recommending excision of virtually all solitary thyroid nodules. we
References
Liechty RD, Graham M, Freemeyer P: Benign solitary thyroid nodules. Surg Gynecol Obstet 121:571-573, 1965. 2. Kendall LA, Condon RD: Prediction of malignancy in solitary thyroid 1.
nodules. Lancet 1:1071-1073, 1969. 3. Brooks JR: The solitary thyroid nodule. Am J Surg 125:477-481, 1973. 4. Hoffman GL, Thompson NW, Heffron C: The solitary thyroid nodule: A reassessment. Arch Surg 105:379-385, 1972. 5. Hill LD, Beebe HG, Hipp R, et al: Thyroid suppression. Arch Surg 108:403-405, 1974. 6. Eisenbud H: Environmental Radioactivity. New York, McGraw-Hill Book Inc, 1963, pp 135-170. 7. Hollingsworth DR, Hamilton HB, Tamagaki H, et al: Thyroid disease: A study in Hiroshima, Japan. Medicine 42:47-71, 1963. 8. Conrad RA, Dobryns BM, Sutow WW: Thyroid neoplasia as late effect of exposure to radioactive iodine in fallout. JAMA 214:316-324, 1970. 9. DeGroot L, Paloyan E: Thyroid carcinoma and radiation: A Chicago endemic. JAMA 225:487-491, 1973. 10. Refetoff S, Harrison J, Karanfilski BT, et al: Continuing occurrence of thyroid carcinoma after irradiation to the neck in infancy and childhood. N Engl J Med 292:171-175, 1975. 11. Becker FO, Economou SG, Southwick HW, et al: Adult thyroid cancer after head and neck irradiation in infancy and childhood. Ann Intern Med 83:347-351, 1975. 12. Winship T: Carcinoma of the thyroid in children. Pediatrics 18:459\x=req-\ 466, 1956.
Editorial Comment Of interest in this concise review of solitary thyroid nodules is an implicit challenge of thyroid suppression for discrimination of benign and malignant thyroid tumors. Of 32 patients who received suppressive doses of thyroid hormone, only three showed some regression, and one of these had thyroid cancer. Typically, the gross and microscopical appearance of a nontoxic goiter comprises an admixture of activity and regression. It is reasonable to expect that natural involution can coincide with administration of an agent. Further, the suppressive effect of thyroid hormone for differentiated thyroid cancer is well docu¬ mented. It is timely to reexamine what may well be another example of pharmacologie habituation that only delays effective operative
management.
Downloaded From: http://archsurg.jamanetwork.com/ by a UQ Library User on 06/21/2015
Jerome J. DeCosse, MD Milwaukee
