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Factors increasing the probability of malignancy in thyroid nodules
Factors Increasing the Probability of Malignancy in Thyroid Nodules R.C. Haff, LT COL USAF MC, Lackland
Air Force Base, Texas
Benjamin C. Schecter, MAJ USAF MC, Lackland Air Force Base, Texas Raymond G. Armstrong, MD, Lackland Air Force Base, Texas William E. Evans, MD,* Lackland Air Force Base, Texas
The incidence of malignancy in surgically excised thyroid nodules varies from 3 to 24 per cent in recently reported series [l-3]. Both the introduction of radioactive iodine scintiscanning of the thyroid gland and thyroid feeding as a means of diagnostic suppression have improved preoperative prediction of the probability of malignancy in thyroid nodules [4,5]. Both methods have been generally employed in most institutions for the past two decades. Despite the widely reported safety of thyroid operations [6,7], considerable disagreement exists in the surgical and medical literature as to the need for routine exploration of all thyroid nodules to rule out malignancy [8,9]. This disagreement is baaed in large part on a marked discrepancy between the incidence of malignancy in autopsy and surgical series [3,10]. Furthermore, the generally passive behavior of the majority of thyroid malignancies has led many authors to question the true classification of many of these neoplasms [a]. It is imperative in view of these arguments that every effort be made to eliminate essentially unnecessary thyroid operations by avoiding procedures when the probability of malignancy is very small. We have recently undertaken a survey of our experience with thyroid operations over a ten year period. During that time, radioactive iodine scanning and preoperative thyroid feeding were employed routinely but not universally. Specifically, patients undergoing operations for the determination of possible malignancy within the thyroid gland have From the Department of Surgery, General Surgery Servioe. Wilford Hall USAF Medical Center, Lacklend Air Force Base, Texas. Reprint requests should be addressed to R. C. Haff. LT CCL. Department of Sugsq. General Sugeq Service, Wilford USAF Medical Center, Lackland Air Force Sase, Texas 78236. * Resent address: Ohio State University Hospital, 410 West 10th Avenue, Columbus, Ohio 43210.
Vokm
u)?. Juae 1978
been evaluated. We have ascertained what features in the preoperative evaluation of patients undergoing such procedures significantly increase or decrease the probability of malignancy being present. Material and Methods
The records of all patients undergoing primary operations on the thyroid gland for causes other than symptomatic hyperthyroidism at the Wilford Hall USAF Medical Center between January 1, 1963 and December 31,1972 have been reviewed. Datahave been obtained regarding age, sex, duration of symptoms, physical characteristics on admitting examination, the presence or absence of accompanying lymphadenopathy, and findings of histologic examination at time of operation. These data were then analyzed statistically, utilizing standard chi square analysis to determine which of these characteristics were associated with an increase or decrease in the incidence of malignancy in resected thyroid tissue. Results
During the ten year period, 404 patients underwent operation for thyroid or thyroid-related masses. The primary operation for diagnosis was performed at this institution in 349 instances. These 348 (249 females, 99 males) patients are the subject of this analysis. Fifty-seven patients (16.4 per cent) with primary thyroid malignancies are present. Of the 99 males, 25 (25.3 per cent) had carcinoma; of the 249 females, 32 (12.9 per cent) had carcinoma (1 degree of freedom; X2 = 8.4; p < 0.005). The incidence of malignancy among males is nearly double that among females. This difference is of high statistical significance. The incidence of carcinoma related to age among all patients with thyroid operations is illustrated in Table I. These differences are not significant.
707
Haff
et al
TABLE
Incidence
I
of Carcinoma
Related
(yr)
Number of Patients
Patients with Carcinoma
o-19 20-39 40 and older
13 196 139
3 (23.1%) 36 (18.4%) 18 (12.9%) _____--_____
Age
Note:
2 degrees
TABLE
II
of freedom;
Probability Physical
X” = 2.49;
of Malignancy Characteristics
Thyroid mass Asymmetrical enlargement Diffuse enlargement Normal nodes Note:
III
gland
Related
281
to Gland Patients with Carcinoma 38
(14.6%)
70 7
10 (14.3%) 1 (14.3%)
10
8 (80.0%)
plus
3 degrees
of freedom;
X2 = 23.4;
Relationship
of Scan
to Incidence
of Carcinoma
Findings
Number of Patients Cold nodules Functional nodules Multiple nodules Diffuse enlargement Normal scan Note:
p > 0.25.
of Thyroid
Number of Patients
Table
to Age
4 degrees of freedom;
181 38 21 6 27
p > 0.005.
in All
Patients
Patients with Carcinoma 30 3 1 1 7
(15.1%) (7.9%) (4.8%) (20.0%) (13.1%)
X2 = 1.24; p > 0.25.
When patients undergoing thyroid exploration are evaluated in terms of the presence or absence of cervical adenopathy, it is found that a highly significant difference exists in the probability of malignancy: of 310 patients with no cervical adenopathy, 32 (10.3 per cent) had thyroid carcinoma; of 38 patients with cervical adenopathy 25 (65.8 per cent) had carcinoma(1 degree of freedom; X2 < 75; p < 0.001) The probability of malignancy based on the physical characteristics of the thyroid gland is summarized in Table II. A significant difference appears only in those patients operated on primarily because of cervical adenopathy. The physical characteristic of the gland itself as noted at preoperative evaluation appears to have no essential effect on the probability of malignancy. Table III demonstrates the relationship of scan findings to the incidence of malignancy in all patients in this study. There is no statistically significant
708
difference between groups, as determined by radioactive iodine scintiscan. However, there is suggestive evidence that the presence of either multiple cold nodules or functional nodules, on scan, is associated with a diminished probability of malignanCY. Comments
This series, covering ten years’ experience, is comparable to most others which have followed the introduction of routine thyroid feeding and the routine use of radioactive iodine scintiscanning on nearly all patients [5]. In this setting, we have had an incidence of 16.4 per cent primary malignancies in all patients explored because of a suspicious thyroid or parathyroid lesion. Several factors noted in the preoperative evaluation of our patients are associated with a significant increase in the probability of a malignancy being present. Most striking is the presence of cervical adenopathy associated with any abnormality on palpation of the thyroid gland. This set of findings is associated with a much better than even chance of malignancy in this series; in this regard, it is similar to several other series [5]. Suggestive evidence that certain findings on radioactive iodine scintiscanning are associated with a decreased probability of primary thyroid cancer includes the presence of functional nodules or of multiple nodules within the thyroid gland. No finding noted on scan is associated with a marked increase in incidence of carcinoma in this series. Based on the findings of this study it would appear reasonable to recommend immediate exploration in any patient with an abnormality of the thyroid gland when suspicious cervical adenopathy is present. To subject these patients to the delay necessitated by thyroid feeding appears to be unwarranted. This is true in our experience regardless of thyroid scan findings. Furthermore, the presence of any abnormality in the thyroid of the male, except for diffuse enlargement without cervical lymphadenopathy, similarly makes preoperative thyroid feeding undesirable. In contrast, we believe scan evidence of a functional nodule or multiple nodularity within the thyroid gland in the absence of cervical lymphadenopathy is a good indication that suppressive thyroid feeding can be safely undertaken. This is particularly true if these findings are present in young females. Thus, a rational approach to the abnormal thyroid gland would be as follows. (1) Operate immediately on any male patient with a thyroid gland that is abnormal on palpation. (2) Operate immediately on any female patient with an abnormal gland in the pres-
The American
Journal or Surgery
Factors
ence of cervical adenopathy. (3) Obtain a radioactive iodine scan in female patients with abnormal thyroid and no cervical adenopathy. (4) In the presence of a scan finding of functional or multiple nodules, institute thyroid feeding and observation for a period of three to six months, followed by operation in patients with no decrease in mass size. (5) In patients with cold solitary lesions, institute thyroid feeding. If no decrease in the size of the mass is noted within six weeks, prompt intervention is indicated. Summary
A series of 348 patients undergoing operative intervention because of thyroid masses is reviewed. The incidence of primary malignancy among these patients is 16.4 per cent. Male sex and the presence of cervical adenopathy significantly increase the probability of malignancy. The presence of multiple nodules or a functional nodule on radioiodine thyroid scan significantly reduces the probability of cancer. A rational approach to thyroid nodules is presented
Vdwu
191, Juno 1976
in Thyroid Malignancy
based on these findings and new modalities that have become available. References 1. Tiechty RD, Graham M, Freemeyer P: Benign solitary thyroid nodules. Surg Gynecol Gbstet 121: 571, 1965. 2. Smith FW: The case for thyroidectomy for nodular goiter. Surgery 65: 603, 1969. 3. Bowens OM, Vander JB: Thyroid nodular and thyroid malig nancy; the risk involved in delay surgery. Ann /nt.sm Med 57: 245, 1962. 4. Robinson E, Horn Y, Hochman A: Incidence of cancer in thyroid nodules. Surg Gynecol Obstet 123: 1024, 1966. 5. Hill LD, Kellogg H, Crampton JH, Jones HW, Baker JW: Changing management of carcinoma of the thyroid. Am J Swg 106: 176, 1964. 6. Haff RC: Technical factors influencing morbidity in thyroid operations. Am J Surg 126: 363, 1973. 7. Colcock BP, King JL: The morbidity and mortality of thyroid surgery. Surg Gynecol Obstet 114: 13 1, 1962. 8. Astwood EB: The problem of nodules in the thyroid gland. Pediatrics 18: 501, 1956. 9. Vanderloon WP: The occurrence of carcinoma of the thyroid glan in autopsy material. N Engl J Med 237: 221, 1947. 10. Sokal JE: Occurrence of thyroid cancer. N Engl J Msd 249: 393, 1953.
709
Air Force Base, Texas
Benjamin C. Schecter, MAJ USAF MC, Lackland Air Force Base, Texas Raymond G. Armstrong, MD, Lackland Air Force Base, Texas William E. Evans, MD,* Lackland Air Force Base, Texas
The incidence of malignancy in surgically excised thyroid nodules varies from 3 to 24 per cent in recently reported series [l-3]. Both the introduction of radioactive iodine scintiscanning of the thyroid gland and thyroid feeding as a means of diagnostic suppression have improved preoperative prediction of the probability of malignancy in thyroid nodules [4,5]. Both methods have been generally employed in most institutions for the past two decades. Despite the widely reported safety of thyroid operations [6,7], considerable disagreement exists in the surgical and medical literature as to the need for routine exploration of all thyroid nodules to rule out malignancy [8,9]. This disagreement is baaed in large part on a marked discrepancy between the incidence of malignancy in autopsy and surgical series [3,10]. Furthermore, the generally passive behavior of the majority of thyroid malignancies has led many authors to question the true classification of many of these neoplasms [a]. It is imperative in view of these arguments that every effort be made to eliminate essentially unnecessary thyroid operations by avoiding procedures when the probability of malignancy is very small. We have recently undertaken a survey of our experience with thyroid operations over a ten year period. During that time, radioactive iodine scanning and preoperative thyroid feeding were employed routinely but not universally. Specifically, patients undergoing operations for the determination of possible malignancy within the thyroid gland have From the Department of Surgery, General Surgery Servioe. Wilford Hall USAF Medical Center, Lacklend Air Force Base, Texas. Reprint requests should be addressed to R. C. Haff. LT CCL. Department of Sugsq. General Sugeq Service, Wilford USAF Medical Center, Lackland Air Force Sase, Texas 78236. * Resent address: Ohio State University Hospital, 410 West 10th Avenue, Columbus, Ohio 43210.
Vokm
u)?. Juae 1978
been evaluated. We have ascertained what features in the preoperative evaluation of patients undergoing such procedures significantly increase or decrease the probability of malignancy being present. Material and Methods
The records of all patients undergoing primary operations on the thyroid gland for causes other than symptomatic hyperthyroidism at the Wilford Hall USAF Medical Center between January 1, 1963 and December 31,1972 have been reviewed. Datahave been obtained regarding age, sex, duration of symptoms, physical characteristics on admitting examination, the presence or absence of accompanying lymphadenopathy, and findings of histologic examination at time of operation. These data were then analyzed statistically, utilizing standard chi square analysis to determine which of these characteristics were associated with an increase or decrease in the incidence of malignancy in resected thyroid tissue. Results
During the ten year period, 404 patients underwent operation for thyroid or thyroid-related masses. The primary operation for diagnosis was performed at this institution in 349 instances. These 348 (249 females, 99 males) patients are the subject of this analysis. Fifty-seven patients (16.4 per cent) with primary thyroid malignancies are present. Of the 99 males, 25 (25.3 per cent) had carcinoma; of the 249 females, 32 (12.9 per cent) had carcinoma (1 degree of freedom; X2 = 8.4; p < 0.005). The incidence of malignancy among males is nearly double that among females. This difference is of high statistical significance. The incidence of carcinoma related to age among all patients with thyroid operations is illustrated in Table I. These differences are not significant.
707
Haff
et al
TABLE
Incidence
I
of Carcinoma
Related
(yr)
Number of Patients
Patients with Carcinoma
o-19 20-39 40 and older
13 196 139
3 (23.1%) 36 (18.4%) 18 (12.9%) _____--_____
Age
Note:
2 degrees
TABLE
II
of freedom;
Probability Physical
X” = 2.49;
of Malignancy Characteristics
Thyroid mass Asymmetrical enlargement Diffuse enlargement Normal nodes Note:
III
gland
Related
281
to Gland Patients with Carcinoma 38
(14.6%)
70 7
10 (14.3%) 1 (14.3%)
10
8 (80.0%)
plus
3 degrees
of freedom;
X2 = 23.4;
Relationship
of Scan
to Incidence
of Carcinoma
Findings
Number of Patients Cold nodules Functional nodules Multiple nodules Diffuse enlargement Normal scan Note:
p > 0.25.
of Thyroid
Number of Patients
Table
to Age
4 degrees of freedom;
181 38 21 6 27
p > 0.005.
in All
Patients
Patients with Carcinoma 30 3 1 1 7
(15.1%) (7.9%) (4.8%) (20.0%) (13.1%)
X2 = 1.24; p > 0.25.
When patients undergoing thyroid exploration are evaluated in terms of the presence or absence of cervical adenopathy, it is found that a highly significant difference exists in the probability of malignancy: of 310 patients with no cervical adenopathy, 32 (10.3 per cent) had thyroid carcinoma; of 38 patients with cervical adenopathy 25 (65.8 per cent) had carcinoma(1 degree of freedom; X2 < 75; p < 0.001) The probability of malignancy based on the physical characteristics of the thyroid gland is summarized in Table II. A significant difference appears only in those patients operated on primarily because of cervical adenopathy. The physical characteristic of the gland itself as noted at preoperative evaluation appears to have no essential effect on the probability of malignancy. Table III demonstrates the relationship of scan findings to the incidence of malignancy in all patients in this study. There is no statistically significant
708
difference between groups, as determined by radioactive iodine scintiscan. However, there is suggestive evidence that the presence of either multiple cold nodules or functional nodules, on scan, is associated with a diminished probability of malignanCY. Comments
This series, covering ten years’ experience, is comparable to most others which have followed the introduction of routine thyroid feeding and the routine use of radioactive iodine scintiscanning on nearly all patients [5]. In this setting, we have had an incidence of 16.4 per cent primary malignancies in all patients explored because of a suspicious thyroid or parathyroid lesion. Several factors noted in the preoperative evaluation of our patients are associated with a significant increase in the probability of a malignancy being present. Most striking is the presence of cervical adenopathy associated with any abnormality on palpation of the thyroid gland. This set of findings is associated with a much better than even chance of malignancy in this series; in this regard, it is similar to several other series [5]. Suggestive evidence that certain findings on radioactive iodine scintiscanning are associated with a decreased probability of primary thyroid cancer includes the presence of functional nodules or of multiple nodules within the thyroid gland. No finding noted on scan is associated with a marked increase in incidence of carcinoma in this series. Based on the findings of this study it would appear reasonable to recommend immediate exploration in any patient with an abnormality of the thyroid gland when suspicious cervical adenopathy is present. To subject these patients to the delay necessitated by thyroid feeding appears to be unwarranted. This is true in our experience regardless of thyroid scan findings. Furthermore, the presence of any abnormality in the thyroid of the male, except for diffuse enlargement without cervical lymphadenopathy, similarly makes preoperative thyroid feeding undesirable. In contrast, we believe scan evidence of a functional nodule or multiple nodularity within the thyroid gland in the absence of cervical lymphadenopathy is a good indication that suppressive thyroid feeding can be safely undertaken. This is particularly true if these findings are present in young females. Thus, a rational approach to the abnormal thyroid gland would be as follows. (1) Operate immediately on any male patient with a thyroid gland that is abnormal on palpation. (2) Operate immediately on any female patient with an abnormal gland in the pres-
The American
Journal or Surgery
Factors
ence of cervical adenopathy. (3) Obtain a radioactive iodine scan in female patients with abnormal thyroid and no cervical adenopathy. (4) In the presence of a scan finding of functional or multiple nodules, institute thyroid feeding and observation for a period of three to six months, followed by operation in patients with no decrease in mass size. (5) In patients with cold solitary lesions, institute thyroid feeding. If no decrease in the size of the mass is noted within six weeks, prompt intervention is indicated. Summary
A series of 348 patients undergoing operative intervention because of thyroid masses is reviewed. The incidence of primary malignancy among these patients is 16.4 per cent. Male sex and the presence of cervical adenopathy significantly increase the probability of malignancy. The presence of multiple nodules or a functional nodule on radioiodine thyroid scan significantly reduces the probability of cancer. A rational approach to thyroid nodules is presented
Vdwu
191, Juno 1976
in Thyroid Malignancy
based on these findings and new modalities that have become available. References 1. Tiechty RD, Graham M, Freemeyer P: Benign solitary thyroid nodules. Surg Gynecol Gbstet 121: 571, 1965. 2. Smith FW: The case for thyroidectomy for nodular goiter. Surgery 65: 603, 1969. 3. Bowens OM, Vander JB: Thyroid nodular and thyroid malig nancy; the risk involved in delay surgery. Ann /nt.sm Med 57: 245, 1962. 4. Robinson E, Horn Y, Hochman A: Incidence of cancer in thyroid nodules. Surg Gynecol Obstet 123: 1024, 1966. 5. Hill LD, Kellogg H, Crampton JH, Jones HW, Baker JW: Changing management of carcinoma of the thyroid. Am J Swg 106: 176, 1964. 6. Haff RC: Technical factors influencing morbidity in thyroid operations. Am J Surg 126: 363, 1973. 7. Colcock BP, King JL: The morbidity and mortality of thyroid surgery. Surg Gynecol Obstet 114: 13 1, 1962. 8. Astwood EB: The problem of nodules in the thyroid gland. Pediatrics 18: 501, 1956. 9. Vanderloon WP: The occurrence of carcinoma of the thyroid glan in autopsy material. N Engl J Med 237: 221, 1947. 10. Sokal JE: Occurrence of thyroid cancer. N Engl J Msd 249: 393, 1953.
709