Evaluation of Solitary Cold Thyroid Nodules by Echography and Thermography Orlo H. Clark, MD,” San Francisco, California Francis S. Greenspan, MD,* San Francisco, California Granville C. Coggs, MD,* San Francisco, California Leon Goldman, MD, FACS, San Francisco, California
Thyroid operations are an effective form of treatment for thyroid nodules and are associated with minimal morbidity and rare mortality [1,2]. The major indication for thyroidectomy in nontoxic goiter is the suspicion of malignant thyroid disease. Despite the excellent therapeutic effectiveness of thyroid operations, the accuracy in differentiating benign from malignant thyroid neoplasms without operation is low. Most medical centers report that the incidence of thyroid cancer in patients having thyroid operations varies between 5 and 35 per cent [3-6]. Obviously, if only 5 per cent of patients undergoing thyroid operations have cancer of the thyroid, too many persons are being subjected to thyroid procedures; conversely, if 50 per cent are found to have cancer, too few patients with thyroid disease are undergoing operation and many patients are being observed without definitive treatment. Because of the difficulty in predicting the presence of thyroid cancer in solitary nonfunctioning thyroid nodules by 1311scanning and because thyroid cancer is rare in cystic thyroid nodules less From the Surgical Service, Veterans Administration Hospital, and Departments of Surgery, Medicine, and Radiology, University of California Hospital, San Francisco, California. This work was supported in part by the Beoletto Fund, Research Evaluation and Allocation Committee, School of Medicine, University of California, San Francisco, and by research grant Cl-4C from the American Cancer Society. Reprint requests should be addressed to 0. H. Clark, MD, Department of Surgery, Veterans Administration Hospital, 4150 Clement Street, San Francisco, California 94121. Presented at the Golden Anniversary Meeting of the Pacific Coast Surgical Association, Scottsdale, Arizona. February 16-20. 1975. ’ By invitation.
206
than 4 cm in diameter [7,8], we initiated a prospective study using echography, ultrasound, and thermography in our preoperative evaluation of thyroid nodules. This was undertaken in an attempt, first, to improve accuracy in differentiating between benign and malignant thyroid nodules and, secondly, to determine the reliability of echography and thermography in distinguishing between solid and cystic thyroid nodules. From February 1973 through December 1974, at the University of California Hospitals in San Francisco, sixty-one patients with solitary cold thyroid nodules, as determined by clinical examination and 1311scanning, were evaluated by echography and thirty-one by thermography. Twenty-seven of the sixty-one patients had confirmation of the thyroid lesion by histologic examination. Two additional patients were successfully treated by aspiration. These twenty-nine patients are discussed. Methods Ultrasound or echography has recently been applied to the thyroid and has been found of value in the differentiation of solid and cystic thyroid nodules [7-Ill. This noninvasive and atraumatic technic uses ultrasonic energy of 1 mm or less in wavelength (megahertz range), which is generally considered to be harmless [12]. In fact, echography is presently the procedure of choice for examination of the pregnant uterus [12]. Ultrasound imaging is unique in that all body tissues except bone and air-filled lungs are relatively permeable to ultrasonic energy of 1 mm or less in wavelength. This permits adequate visualization of even the deepest structures in
The American Journal of Surgery
Cold Thyroid Nodules
the neck except those rendered inaccessible by the overlying trachea or vertebral column [7]. The principle of echography is based on partial reflection of ultrasonic energy at tissue boundaries or interfaces that have specific acoustic impedence differences [ I1 1. High-frequency ultrasound has many similarities to light energy, as it may be reflected, refracted, focused, and scattered. Thus, echography provides information on the physical characteristics of lesions, such as whether they are cystic or solid. The sound reflections or echoes are detected, processed electronically, and displayed on an oscilloscope screen. They may be represented by either one-dimensional, A-mode, or two-dimensional, B-mode, echography. (Figures 1 to 3.) The normal thyroid is homogeneous on ultrasonic examination at low probe sensitivity and appears as a sonolucent or echo-free zone. Fluid-filled structures or cysts are also sonolucent but they remain so at high as well as at low gain settings. Cysts also characteristically have a thin discrete posterior wall and echoes from structures immediately behind cysts are enhanced. It is important to differentiate cystic thyroid nodules from solid nodules, because cysts of the thyroid that are less than 4 cm in diameter are virtually never malignant [7]. Limitations of echography are: (1) poor resolution of lesions less than 1 cm in diameter; (2) nonvisualization of lesions in the retrosternal area because of the overlying sternum; (3) inconclusive results in lesions larger than 4 cm because of hemorrhage and degenerative changes in larger solid tumors 18,121. Rapid progress, however, has been made in the development of ultrasound equipment. The resolution of some of the newer ultrasound units is now 1 to 2 mm [13]. With this degree of resolution, purely cystic lesions may be differentiated from cystic goiters or hemorrhagic tumors. B-mode echography with increasing sensitivity was used in all of our patients. Scanning was carried out with the patient in a supine position with hyperextension of the neck. A Picker diagnostic recorder with a
2.25 megahertz transducer was used, and the results were visualized on an oscilloscope screen. Accurate positioning of the transducer over the thyroid nodule is necessary for reliable information. Thermography is similar to echography in that it is a rapid, safe, and noninvasive procedure for diagnosing thyroid lesions [14]. It has no possible hazards since it only records the infrared radiation emitted from the body [IS]. The thermal pattern is recorded by thermister-detecting cells that convert the thermal heat pattern into an electronic one [16]. The emitted pattern is a summation of thermal data for both the skin and underlying deeper structures. Lawson [17] in 1956 and Barnes and Gershon-Cohen [18] in 1963 first showed that malignant tumors produce local heat. This is attributed to their accelerated local metabolism and increased vascularity. Cystic lesions, in contrast, do not generate increased heat and therefore can be differentiated from solid lesions. The technic of thermography was similar to that described by Mansfield, Farrell, and Asbell (191, with the patient in the supine position and the neck hyperextended. An Aga thermogram was used. In all patients, the upper thorax and neck were exposed to the ambient temperature for ten minutes in the room where the technic was performed. This allowed the temperature of the skin to equilibrate with that of the environment. Alcohol was applied to the neck in some patients after the initial thermogram to enhance the temperature differential of the deeper structures. Aspiration of suspected cystic thyroid nodules was performed with the patient in a supine position with hyperextension of the neck. The skin was prepared with an antiseptic solution and the skin over the nodule was anesthetized with 1 per cent lidocaine. An 18 gauge needle was placed into the suspected cystic nodule and the fluid was aspirated. (Figures 4 and 5.) Fluid from the cyst was sent to the laboratory for cytologic examination.
Figure 1. A-mode echograms demonstrating normal pattern over right lobe of thyroid. Figure 2. A-mode echogram of a thyroid cyst. Arrow identifies echo-free (sonolucent) area. Figure 3. B-mode echogram of benign thyroid cyst. Lesion disappeared compiate/y after two aspirations.
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Figure 4. 13’1 scan of thyroid with left cold thyroid nodule. Figure 5. 13’I scan of thyroid after aspiration of thyroid cyst identified in Figures 3 and 4.
Results Twenty-seven of the sixty-one patients who had thyroid echography had confirmation of the thyroid lesion by histologic examination and two patients had successful aspiration. Of thirteen patients thought to have cystic lesions on echography, ten (77 per cent) had fluid-filled lesions at operation or aspiration and three (23 per cent) had solid lesions. Five of the ten cysts were pure cysts
Figure 6. Thermogram. Arrows demonstrate site of hot thyroid nodule that was solid by ultrasound.
208
and five others were cystic or blood-filled follicular adenomas. Three patients with histologically proved cystic lesions had a cold lesion and one had an indeterminate lesion, that is, neither an increase nor a decrease in emitted heat, on thermography. Two of the three patients who had misdiagnosis of a cyst on echography had a correct diagnosis on thermography. (Figure 6.) All thirteen patients who had solid lesions diagnosed by echography had solid lesions at operation; one patient had a warm lesion, four had indeterminate lesions, and one had a cool lesion on thermography. Of two patients whose lesions were judged to be indeterminate by echography, the one patient tested by thermography was properly diagnosed by this test. Both of these,patients had solid lesions at operation and both thyroid nodules were less than 2 cm in diameter. The one patient with a mixed lesion on echography had a cold lesion on thermography and was found to have a follicular adenoma with hemorrhage at operation. The overall diagnostic accuracy for echography was 82 per cent, with 11 per cent of the results in error and 6 per cent nondiagnostic. Thermography gave a 57 per cent (eight of fourteen) overall accuracy, with 7 per cent (one of fourteen) of the results in error and 36 per cent (five of fourteen) nondiagnostic. Both patients successfully treated by aspiration required two aspirations. The fluid removed from the cyst in one of these patients was similar to straw-colored water, and in the other it was dark brown, suggesting previous hemorrhage. Cytologic examination revealed the aspirated cystic fluid to be benign in both cases.
The
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Cold Thyroid Nodules
Comments Our overall diagnostic reliability of echography of 82 per cent is similar to that reported by Rosen, Walfish, and Miskin [lo] of 92 per cent and that reported by Blum et al [7] of 98 per cent. When thermography and echography were both performed and were in agreement, they were 100 per cent reliable in differentiating between solid and cystic thyroid nodules. When these two tests gave conflicting results, the nodule was always solid. The usefulness of these tests in evaluating thyroid nodules that are possibly malignant is based on the fact that cystic thyroid nodules are rarely ever malignant. Blum et al [7] stated, “The probability of an occult neoplasm in the wall of the cyst is no greater than its probability in the remainder of the thyroid.” Miller, Zafar, and Karo [20], in a recent retrospective histologic review, found only 2 instances of cystic carcinoma in 302 consecutively removed cancerous thyroid lesions. Another important question concerning the value of these tests relates to the percentage of solitary cold thyroid nodules that are cystic. Certainly, if the incidence of cysts in solitary thyroid nodules is only 1 per cent, the usefulness of differentiation between solid and cystic lesions would be limited. The exact incidence of cysts in solitary thyroid nodules is difficult to determine; however, most reviews [21-241 report the incidence of thyroid cysts between 15 and 22 per cent. (Table I.) Goldman has concluded from his clinical experience that 20 to 25 per cent of patients with solitary cold thyroid nodules have had cysts at operation. Crile [23] has reported the successful treatment of solitary thyroid nodules thought to be cystic in forty-seven of fifty patients, or 94 per cent. Miller, Zafar, and Karo [20] have had success in fiftyseven of sixty-eight patients, or 84 per cent. They attributed their failures to viscous gelatinous material, residual nodule, and patient anxiety. Of importance is the fact that no complications have been reported in more than one hundred aspirations. Aspiration is performed easily and safely as an outpatient procedure. One might suggest needle biopsy of all thyroid nodules, as recently recommended by Crile and Hawk [25] and Wang et al [26]. Dissemination of papillary carcinoma has been reported after needle biopsy; however, this seems to be an unusual occurrence [10,25]. The major problem with thyroid biopsy for nodules is the unreliability of the procedure [24,27,28]. Boehme et al [27] performed biopsy of thyroid nodules under direct vision in the pa-
Volume 130, AugusllS75
TABLE
I
Incidence of Cysts in Solitary Thyroid Nodules
Incidence Authors
Per Cent
No. of Patients
Miller and Zafar [21] Miskin, Rosen, and Walfish [22] Crile [23]
20 22 15
...
Crockford
16
17/103
and Bain [24]
88/425 1 l/50
thology laboratory; they found that the thyroid, unlike the liver or kidney, does not have a homogeneous distribution of disease, and therefore needle biopsy often does not reveal the most significant histopathologic features. Their overall diagnostic accuracy for thyroid carcinoma was only 41 per cent in cold solitary nodules and 31 per cent in multinodular goiters. They concluded that needle biopsy of cold nodules should not be performed [27]. Pathologists also may find it virtually impossible to distinguish between a benign nodule and well differentiated thyroid carcinoma on cytologic evidence [lo]. By the combined use of echography and thermography we have been able to distinguish accurately between cystic and solid thyroid nodules. Continued improvement in the resolution of ultrasonic equipment has recently been demonstrated by Jellins et al [13]. Resolution of echoes in areas smaller than 1 cm was not possible with the equipment used in our study, but with newer equipment it is possible to resolve echoes of 1 or 2 mm in size. (Figure 7.) With this degree of resolution, thermography will not be necessary. We should then be able to distinguish between pure cysts and cystic degeneration or hemorrhage within thyroid tumors. (Figure 8.)
Figure 7. Gray scale echography using compound scanning (box size represents 1.3 cm In the patient). (Reprinted with permission from Jellins et al [ 131.)
209
8. 9.
IO.
11.
12. 13.
14. 15. 16.
Figure 8. Gray scale echography using compound scanning w/th photograph of sectioned specimen. (Reprinted with permission from Jellins et al [ 131.)
17.
18. 19.
Conclusions
267, 1969. Kambal A: Carcinoma in solitary thyroid nodules. Br J Surg 58: 434, 1969. Miller JM: Carcinoma and thyroid nodules: problem in endemic goiter area. N Engl J Med 252: 247, 1955. Greenspan FS: Thyroid nodules and thyroid cancer. West J Med 121: 359, 1974. Blum A, Goldman AB, Herskovic A, Hernberg J: Clinical ap plications of thyroid echography. N Engl J Med 287: 1164, 1972. Blum M, Weiss B, Hemberg J: Evaluation of thyroid nodules by A-mode echography. Radiology 101: 651, 1971. Rasmussen SN, Christiansen MJB, Jorgensen JS, Holm HH: Differentiation between cystic and solid thyroid nodules by ultra-sonic examination. Acta Chir Stand 137: 33 1, 197 1. Rosen IB, Walfish PG, Miskin M: The use of B-mode ultrasonography in changing indications for thyroid operations. Surg Gynecol Obstet 139: 193, 1974. Thijs LG, Roos P, Wiener JD: Use of ultrasound and digital scintophoto analysis in the evaluation of solitary thyroid nodules. J Nucl Med 13: 504, 1972. Lele PP: Application of ultrasound in medicine. N Engl J Med 286: 1317, 1972. Jellins J, Kossoff G, Wiseman J, Reeve T, Hales I: Ultrasonic gray scale visualizations of the thyroid. U#rasound in Med & Bioll975 in press. Samuels BE: Thermography: a valuable tool in the detection of thyroid disease. Radiology 102: 59, 1972. Freundlich IM: Thermography. N Engl J Med 287: 880. 1972. Samuel E: Medical aspects of thermography. Br J Hosp A&d [Equip Suppl] 4: 8, 1968. Lawson RN: Implications of surface temperatures in the dii agnosis of breast cancer. Can Med Assoc J 75: 309, 1956. Barnes RB, Gershon-Cohen J: Clinical thermography. JAMA 185: 949, 1963. Mansfield CM. Farrell C, Asbell S: The use of thermography in the detection of metastatic liver disease. Bad/o&y 95: 696, 1970. Miller JM. Zafar SU, Karo JJ: The cystic thyroid nodule. Radiology 110: 257, 1974. Miller JM, Zafar SU: The cystic thyroid nodule: recognition and management. Program of the 48th Meeting of the American Thyroid Association, Chicago, September 20-23, 1972, p 70. Miskin M, Rosen IB, Walfish RG: B-mode ultrasonography in assessment of thyroid gland lesions. Ann Intern Med 79: 505, 1973. Crile G Jr: Treatment of thyrold cysts by aspiration. Surgery 189: 210, 1966. Crockford PM, Bain GO; Fine needle biopsy of the thyroid. Can MedAssoc J 110: 1029,1974. Crile 0, Hawk WA: Aspiration biopsy of thyroid nodules. Surg GynecolObstet 126: 241, 1973. Wang CA, Vickery AL, Maloof F, Nardi GL, Raker J, Hamlin E Jr: The validity of needle biopsy of the thyroid. Program of the 49th Meeting of the American Thyroid Association, Seattle, September 12-15,1973. Boehme CJ, Winship T, Lindsay S, Kypridakis G: An evaluation of needle biopsy of the thyroid gland. Surg G~IWCO/ Obstet 119: 831, 1964. Hansen JB, Kolendorf K: Fine needle biopsy of thyroid lesions. NEnglJhled291: 851, 1974.
These studies demonstrate that when results of echography and thermography were in agreement, the nature of a cold thyroid nodule was correctly predicted in every case. Used individually, each test has a small but clinically significant margin of error. It is apparent that with improved echographic equipment, ultrasound alone may be all that is required for uniform accuracy. The nature of a thyroid nodule should not be diagnosed from indeterminate studies and these indeterminate lesions must be treated as solid tumors. We agree with Rosen, Walfish, and Miskin [JO] that cysts that do not compress on aspiration and cysts that recur or show atypical cytologic features should be removed by thyroid lobe&my. Purely cystic thyroid nodules, however, may be treated by aspiration easily and safely, thus avoiding unnecessary operations.
20.
References
Discussion
1. Colcock BP, King ML: The mortality and morbidity of thyroid surgery. Surg Gynecol Obstet 114: 131. 1962. 2. Esselstyn CB Jr, Crile GC Jr: Indications for surgical therapy in thyroid disease. Semin Nucl Med 1: 474, 1971. 3. Taylor S: The solitary thyroid nodule. JR Coil Surg Edinb 14:
210
21.
22.
?3. 24. 25. 26.
27.
28.
Leonard Rosoff (Los Angeles, CA): At the Los Angeles County-USC Medical Center, B-mode echograms are obtained routinely in patients with solitary nonfunctioning nodules in the neck, 1.5 cm or more in
The American Journal of Sur9ary
Cold Thyroid Nodules
diameter. The authors’ findings, as in other reports on the subject, indicate that sonar scans have no value whatsoever in differentiating malignant from benign solid tumors of the thyroid. To date, the only reliable method of making this essential discrimination is microscopic examination after removal of the lesion by thyroid lobectomy. As everyone experienced in thyroid surgery is aware, at times even this may be difficult with rapid freezing technics at the time of operation and must await microscopic examination of paraffin sections twenty-four hours or more after operation. However, ultrasonic examination of nonfunctioning thyroid nodules does appear to be of value in differentiating solid and cystic lesions. As indicated by the authors, it is a rapid, safe, noninvasive, and readily obtained diagnostic test. Doctors Michael Shaub and Robert Wilson from our section of Diagnostic Ultrasound reported their studies at our hospital at the meeting of the American Institute of Ultrasound, held in Seattle in October 1974. One hundred patients with solitary hypofunctioning nodules in the neck were examined with ultrasound between January 1974 and September 1974. At the time of their presentation, the precise diagnosis had been established in thirty-three patients by histologic examination of the tissue after operation or by percutaneous needle aspiration of a cyst. (Slide) This slide summarizes their results and indicates the confirmation of their diagnosis of solid tumors in the twenty-three patients in whom this was made by sonar scan. Similarly, in each of the ten patients with a diagnosis of a cystic lesion, the findings were confirmed by operation or aspiration. Three of these lesions were thyroglossal duct cysts in the region of the thyroid isthmus and all were removed at operation. All seven of the remaining patients with the diagnosis of a cystic lesion of the thyroid were treated by aspiration by our medical thyroidologists. Of these, five patients had complete disappearance of the cyst after one aspiration. In one patient, a second aspiration was necessary; in another, three aspirations were needed because of reaccumulation of the cyst fluid. Over 80 ml of fluid was withdrawn at each tap. Because of the reaccumulation of fluid in the latter two cases, the lesion was removed at operation, and a diagnosis of benign colloid cyst was made on histologic examination. The cytologic features of the cyst fluid in all patients treated by aspiration were carefully examined and the patients were carefully evaluated by repeated physical examination of the neck as well as echographs. The incidence of cystic lesions of the thyroid in this series is approximately 17 per cent, similar to that of the authors. In the series of Shaub and Wilson, echo return caused by the debris of necrosis and hemorrhage, so-called “degeneration” of a solid tumor, was interpreted as indicating a “solid” tumor.
Volume130,August1975
After aspiration of a cyst is undertaken, abnormal cytologic findings in the cyst fluid, a remaining nodule, or reaccumulation of fluid in the cyst are indications for operation. I wish to repeat the admonition that removal of a solitary nodule of the thyroid by lobectomy remains the treatment of choice for noncystic lesions. I wish to ask Doctor Clark two questions: (1) What was the size of the smallest lesion identified by ultrasound scan in the series reported today; and (2) as transmission of sound through lymphomas is known to be enhanced, with diminished internal echo, has this been encountered by the authors in their use of ultrasound examination for neck lesions? Eugene J. Joergenson (Glendale, CA): I would like to ask Doctor Clark one question: What is the charge for this examination in your hospital? Orlo H. Clark (closingj: We have instituted these useful diagnostic tests at the University of California Hospitals in San Francisco not to discourage surgeons from operating but to help us select those patients who require operation because of suspected malignant thyroid nodules. Physicians frequently treat poor risk or elderly patients with solitary cold thyroid nodules conservatively despite the fact that in experienced hands thyroid operations are associated with minimal morbidity and rare mortality. When a solitary thyroid nodule is cold on radioiodine scanning, solid on echography, and hot on thermography, it would be unwise, because of the high risk of malignant disease, to treat this patient expectantly or with suppressive doses of exogeneous thyroid hormone. Conversely, not all nodular thyroids need to be removed and solitary thyroid nodules that are cystic on echography and cold on thermography can be treated safely and easily by aspiration. In answer to the second question, the resolution of the ultrasound equipment used in this investigation was 1 cm. The two patients included in this review who had indeterminate echograms were found at operation to have solid thyroid growths 1 to 2 cm in diameter. There were several other patients with nodules this size who were not included in this group because their nodules have not been diagnosed by histologic examination and it was impossible to determine whether they were solid or cystic. With the newer ultrasound equipment, considerably better resolution has been obtained. It is also important to emphasize that the person performing the ultrasound testing needs some knowledge about the thyroid since accurate placement of the probe on the gland is critical for diagnosis. As far as cost is concerned, many of the patients in this study were not charged because it was prospective investigation. However, the total charge for both thyroid echography and thermography, including the radiologist’s fee, is about $100.00.
211
Thyroid operations are an effective form of treatment for thyroid nodules and are associated with minimal morbidity and rare mortality [1,2]. The major indication for thyroidectomy in nontoxic goiter is the suspicion of malignant thyroid disease. Despite the excellent therapeutic effectiveness of thyroid operations, the accuracy in differentiating benign from malignant thyroid neoplasms without operation is low. Most medical centers report that the incidence of thyroid cancer in patients having thyroid operations varies between 5 and 35 per cent [3-6]. Obviously, if only 5 per cent of patients undergoing thyroid operations have cancer of the thyroid, too many persons are being subjected to thyroid procedures; conversely, if 50 per cent are found to have cancer, too few patients with thyroid disease are undergoing operation and many patients are being observed without definitive treatment. Because of the difficulty in predicting the presence of thyroid cancer in solitary nonfunctioning thyroid nodules by 1311scanning and because thyroid cancer is rare in cystic thyroid nodules less From the Surgical Service, Veterans Administration Hospital, and Departments of Surgery, Medicine, and Radiology, University of California Hospital, San Francisco, California. This work was supported in part by the Beoletto Fund, Research Evaluation and Allocation Committee, School of Medicine, University of California, San Francisco, and by research grant Cl-4C from the American Cancer Society. Reprint requests should be addressed to 0. H. Clark, MD, Department of Surgery, Veterans Administration Hospital, 4150 Clement Street, San Francisco, California 94121. Presented at the Golden Anniversary Meeting of the Pacific Coast Surgical Association, Scottsdale, Arizona. February 16-20. 1975. ’ By invitation.
206
than 4 cm in diameter [7,8], we initiated a prospective study using echography, ultrasound, and thermography in our preoperative evaluation of thyroid nodules. This was undertaken in an attempt, first, to improve accuracy in differentiating between benign and malignant thyroid nodules and, secondly, to determine the reliability of echography and thermography in distinguishing between solid and cystic thyroid nodules. From February 1973 through December 1974, at the University of California Hospitals in San Francisco, sixty-one patients with solitary cold thyroid nodules, as determined by clinical examination and 1311scanning, were evaluated by echography and thirty-one by thermography. Twenty-seven of the sixty-one patients had confirmation of the thyroid lesion by histologic examination. Two additional patients were successfully treated by aspiration. These twenty-nine patients are discussed. Methods Ultrasound or echography has recently been applied to the thyroid and has been found of value in the differentiation of solid and cystic thyroid nodules [7-Ill. This noninvasive and atraumatic technic uses ultrasonic energy of 1 mm or less in wavelength (megahertz range), which is generally considered to be harmless [12]. In fact, echography is presently the procedure of choice for examination of the pregnant uterus [12]. Ultrasound imaging is unique in that all body tissues except bone and air-filled lungs are relatively permeable to ultrasonic energy of 1 mm or less in wavelength. This permits adequate visualization of even the deepest structures in
The American Journal of Surgery
Cold Thyroid Nodules
the neck except those rendered inaccessible by the overlying trachea or vertebral column [7]. The principle of echography is based on partial reflection of ultrasonic energy at tissue boundaries or interfaces that have specific acoustic impedence differences [ I1 1. High-frequency ultrasound has many similarities to light energy, as it may be reflected, refracted, focused, and scattered. Thus, echography provides information on the physical characteristics of lesions, such as whether they are cystic or solid. The sound reflections or echoes are detected, processed electronically, and displayed on an oscilloscope screen. They may be represented by either one-dimensional, A-mode, or two-dimensional, B-mode, echography. (Figures 1 to 3.) The normal thyroid is homogeneous on ultrasonic examination at low probe sensitivity and appears as a sonolucent or echo-free zone. Fluid-filled structures or cysts are also sonolucent but they remain so at high as well as at low gain settings. Cysts also characteristically have a thin discrete posterior wall and echoes from structures immediately behind cysts are enhanced. It is important to differentiate cystic thyroid nodules from solid nodules, because cysts of the thyroid that are less than 4 cm in diameter are virtually never malignant [7]. Limitations of echography are: (1) poor resolution of lesions less than 1 cm in diameter; (2) nonvisualization of lesions in the retrosternal area because of the overlying sternum; (3) inconclusive results in lesions larger than 4 cm because of hemorrhage and degenerative changes in larger solid tumors 18,121. Rapid progress, however, has been made in the development of ultrasound equipment. The resolution of some of the newer ultrasound units is now 1 to 2 mm [13]. With this degree of resolution, purely cystic lesions may be differentiated from cystic goiters or hemorrhagic tumors. B-mode echography with increasing sensitivity was used in all of our patients. Scanning was carried out with the patient in a supine position with hyperextension of the neck. A Picker diagnostic recorder with a
2.25 megahertz transducer was used, and the results were visualized on an oscilloscope screen. Accurate positioning of the transducer over the thyroid nodule is necessary for reliable information. Thermography is similar to echography in that it is a rapid, safe, and noninvasive procedure for diagnosing thyroid lesions [14]. It has no possible hazards since it only records the infrared radiation emitted from the body [IS]. The thermal pattern is recorded by thermister-detecting cells that convert the thermal heat pattern into an electronic one [16]. The emitted pattern is a summation of thermal data for both the skin and underlying deeper structures. Lawson [17] in 1956 and Barnes and Gershon-Cohen [18] in 1963 first showed that malignant tumors produce local heat. This is attributed to their accelerated local metabolism and increased vascularity. Cystic lesions, in contrast, do not generate increased heat and therefore can be differentiated from solid lesions. The technic of thermography was similar to that described by Mansfield, Farrell, and Asbell (191, with the patient in the supine position and the neck hyperextended. An Aga thermogram was used. In all patients, the upper thorax and neck were exposed to the ambient temperature for ten minutes in the room where the technic was performed. This allowed the temperature of the skin to equilibrate with that of the environment. Alcohol was applied to the neck in some patients after the initial thermogram to enhance the temperature differential of the deeper structures. Aspiration of suspected cystic thyroid nodules was performed with the patient in a supine position with hyperextension of the neck. The skin was prepared with an antiseptic solution and the skin over the nodule was anesthetized with 1 per cent lidocaine. An 18 gauge needle was placed into the suspected cystic nodule and the fluid was aspirated. (Figures 4 and 5.) Fluid from the cyst was sent to the laboratory for cytologic examination.
Figure 1. A-mode echograms demonstrating normal pattern over right lobe of thyroid. Figure 2. A-mode echogram of a thyroid cyst. Arrow identifies echo-free (sonolucent) area. Figure 3. B-mode echogram of benign thyroid cyst. Lesion disappeared compiate/y after two aspirations.
Volume130,AugustlQ75
207
Clark et al
Figure 4. 13’1 scan of thyroid with left cold thyroid nodule. Figure 5. 13’I scan of thyroid after aspiration of thyroid cyst identified in Figures 3 and 4.
Results Twenty-seven of the sixty-one patients who had thyroid echography had confirmation of the thyroid lesion by histologic examination and two patients had successful aspiration. Of thirteen patients thought to have cystic lesions on echography, ten (77 per cent) had fluid-filled lesions at operation or aspiration and three (23 per cent) had solid lesions. Five of the ten cysts were pure cysts
Figure 6. Thermogram. Arrows demonstrate site of hot thyroid nodule that was solid by ultrasound.
208
and five others were cystic or blood-filled follicular adenomas. Three patients with histologically proved cystic lesions had a cold lesion and one had an indeterminate lesion, that is, neither an increase nor a decrease in emitted heat, on thermography. Two of the three patients who had misdiagnosis of a cyst on echography had a correct diagnosis on thermography. (Figure 6.) All thirteen patients who had solid lesions diagnosed by echography had solid lesions at operation; one patient had a warm lesion, four had indeterminate lesions, and one had a cool lesion on thermography. Of two patients whose lesions were judged to be indeterminate by echography, the one patient tested by thermography was properly diagnosed by this test. Both of these,patients had solid lesions at operation and both thyroid nodules were less than 2 cm in diameter. The one patient with a mixed lesion on echography had a cold lesion on thermography and was found to have a follicular adenoma with hemorrhage at operation. The overall diagnostic accuracy for echography was 82 per cent, with 11 per cent of the results in error and 6 per cent nondiagnostic. Thermography gave a 57 per cent (eight of fourteen) overall accuracy, with 7 per cent (one of fourteen) of the results in error and 36 per cent (five of fourteen) nondiagnostic. Both patients successfully treated by aspiration required two aspirations. The fluid removed from the cyst in one of these patients was similar to straw-colored water, and in the other it was dark brown, suggesting previous hemorrhage. Cytologic examination revealed the aspirated cystic fluid to be benign in both cases.
The
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Cold Thyroid Nodules
Comments Our overall diagnostic reliability of echography of 82 per cent is similar to that reported by Rosen, Walfish, and Miskin [lo] of 92 per cent and that reported by Blum et al [7] of 98 per cent. When thermography and echography were both performed and were in agreement, they were 100 per cent reliable in differentiating between solid and cystic thyroid nodules. When these two tests gave conflicting results, the nodule was always solid. The usefulness of these tests in evaluating thyroid nodules that are possibly malignant is based on the fact that cystic thyroid nodules are rarely ever malignant. Blum et al [7] stated, “The probability of an occult neoplasm in the wall of the cyst is no greater than its probability in the remainder of the thyroid.” Miller, Zafar, and Karo [20], in a recent retrospective histologic review, found only 2 instances of cystic carcinoma in 302 consecutively removed cancerous thyroid lesions. Another important question concerning the value of these tests relates to the percentage of solitary cold thyroid nodules that are cystic. Certainly, if the incidence of cysts in solitary thyroid nodules is only 1 per cent, the usefulness of differentiation between solid and cystic lesions would be limited. The exact incidence of cysts in solitary thyroid nodules is difficult to determine; however, most reviews [21-241 report the incidence of thyroid cysts between 15 and 22 per cent. (Table I.) Goldman has concluded from his clinical experience that 20 to 25 per cent of patients with solitary cold thyroid nodules have had cysts at operation. Crile [23] has reported the successful treatment of solitary thyroid nodules thought to be cystic in forty-seven of fifty patients, or 94 per cent. Miller, Zafar, and Karo [20] have had success in fiftyseven of sixty-eight patients, or 84 per cent. They attributed their failures to viscous gelatinous material, residual nodule, and patient anxiety. Of importance is the fact that no complications have been reported in more than one hundred aspirations. Aspiration is performed easily and safely as an outpatient procedure. One might suggest needle biopsy of all thyroid nodules, as recently recommended by Crile and Hawk [25] and Wang et al [26]. Dissemination of papillary carcinoma has been reported after needle biopsy; however, this seems to be an unusual occurrence [10,25]. The major problem with thyroid biopsy for nodules is the unreliability of the procedure [24,27,28]. Boehme et al [27] performed biopsy of thyroid nodules under direct vision in the pa-
Volume 130, AugusllS75
TABLE
I
Incidence of Cysts in Solitary Thyroid Nodules
Incidence Authors
Per Cent
No. of Patients
Miller and Zafar [21] Miskin, Rosen, and Walfish [22] Crile [23]
20 22 15
...
Crockford
16
17/103
and Bain [24]
88/425 1 l/50
thology laboratory; they found that the thyroid, unlike the liver or kidney, does not have a homogeneous distribution of disease, and therefore needle biopsy often does not reveal the most significant histopathologic features. Their overall diagnostic accuracy for thyroid carcinoma was only 41 per cent in cold solitary nodules and 31 per cent in multinodular goiters. They concluded that needle biopsy of cold nodules should not be performed [27]. Pathologists also may find it virtually impossible to distinguish between a benign nodule and well differentiated thyroid carcinoma on cytologic evidence [lo]. By the combined use of echography and thermography we have been able to distinguish accurately between cystic and solid thyroid nodules. Continued improvement in the resolution of ultrasonic equipment has recently been demonstrated by Jellins et al [13]. Resolution of echoes in areas smaller than 1 cm was not possible with the equipment used in our study, but with newer equipment it is possible to resolve echoes of 1 or 2 mm in size. (Figure 7.) With this degree of resolution, thermography will not be necessary. We should then be able to distinguish between pure cysts and cystic degeneration or hemorrhage within thyroid tumors. (Figure 8.)
Figure 7. Gray scale echography using compound scanning (box size represents 1.3 cm In the patient). (Reprinted with permission from Jellins et al [ 131.)
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8. 9.
IO.
11.
12. 13.
14. 15. 16.
Figure 8. Gray scale echography using compound scanning w/th photograph of sectioned specimen. (Reprinted with permission from Jellins et al [ 131.)
17.
18. 19.
Conclusions
267, 1969. Kambal A: Carcinoma in solitary thyroid nodules. Br J Surg 58: 434, 1969. Miller JM: Carcinoma and thyroid nodules: problem in endemic goiter area. N Engl J Med 252: 247, 1955. Greenspan FS: Thyroid nodules and thyroid cancer. West J Med 121: 359, 1974. Blum A, Goldman AB, Herskovic A, Hernberg J: Clinical ap plications of thyroid echography. N Engl J Med 287: 1164, 1972. Blum M, Weiss B, Hemberg J: Evaluation of thyroid nodules by A-mode echography. Radiology 101: 651, 1971. Rasmussen SN, Christiansen MJB, Jorgensen JS, Holm HH: Differentiation between cystic and solid thyroid nodules by ultra-sonic examination. Acta Chir Stand 137: 33 1, 197 1. Rosen IB, Walfish PG, Miskin M: The use of B-mode ultrasonography in changing indications for thyroid operations. Surg Gynecol Obstet 139: 193, 1974. Thijs LG, Roos P, Wiener JD: Use of ultrasound and digital scintophoto analysis in the evaluation of solitary thyroid nodules. J Nucl Med 13: 504, 1972. Lele PP: Application of ultrasound in medicine. N Engl J Med 286: 1317, 1972. Jellins J, Kossoff G, Wiseman J, Reeve T, Hales I: Ultrasonic gray scale visualizations of the thyroid. U#rasound in Med & Bioll975 in press. Samuels BE: Thermography: a valuable tool in the detection of thyroid disease. Radiology 102: 59, 1972. Freundlich IM: Thermography. N Engl J Med 287: 880. 1972. Samuel E: Medical aspects of thermography. Br J Hosp A&d [Equip Suppl] 4: 8, 1968. Lawson RN: Implications of surface temperatures in the dii agnosis of breast cancer. Can Med Assoc J 75: 309, 1956. Barnes RB, Gershon-Cohen J: Clinical thermography. JAMA 185: 949, 1963. Mansfield CM. Farrell C, Asbell S: The use of thermography in the detection of metastatic liver disease. Bad/o&y 95: 696, 1970. Miller JM. Zafar SU, Karo JJ: The cystic thyroid nodule. Radiology 110: 257, 1974. Miller JM, Zafar SU: The cystic thyroid nodule: recognition and management. Program of the 48th Meeting of the American Thyroid Association, Chicago, September 20-23, 1972, p 70. Miskin M, Rosen IB, Walfish RG: B-mode ultrasonography in assessment of thyroid gland lesions. Ann Intern Med 79: 505, 1973. Crile G Jr: Treatment of thyrold cysts by aspiration. Surgery 189: 210, 1966. Crockford PM, Bain GO; Fine needle biopsy of the thyroid. Can MedAssoc J 110: 1029,1974. Crile 0, Hawk WA: Aspiration biopsy of thyroid nodules. Surg GynecolObstet 126: 241, 1973. Wang CA, Vickery AL, Maloof F, Nardi GL, Raker J, Hamlin E Jr: The validity of needle biopsy of the thyroid. Program of the 49th Meeting of the American Thyroid Association, Seattle, September 12-15,1973. Boehme CJ, Winship T, Lindsay S, Kypridakis G: An evaluation of needle biopsy of the thyroid gland. Surg G~IWCO/ Obstet 119: 831, 1964. Hansen JB, Kolendorf K: Fine needle biopsy of thyroid lesions. NEnglJhled291: 851, 1974.
These studies demonstrate that when results of echography and thermography were in agreement, the nature of a cold thyroid nodule was correctly predicted in every case. Used individually, each test has a small but clinically significant margin of error. It is apparent that with improved echographic equipment, ultrasound alone may be all that is required for uniform accuracy. The nature of a thyroid nodule should not be diagnosed from indeterminate studies and these indeterminate lesions must be treated as solid tumors. We agree with Rosen, Walfish, and Miskin [JO] that cysts that do not compress on aspiration and cysts that recur or show atypical cytologic features should be removed by thyroid lobe&my. Purely cystic thyroid nodules, however, may be treated by aspiration easily and safely, thus avoiding unnecessary operations.
20.
References
Discussion
1. Colcock BP, King ML: The mortality and morbidity of thyroid surgery. Surg Gynecol Obstet 114: 131. 1962. 2. Esselstyn CB Jr, Crile GC Jr: Indications for surgical therapy in thyroid disease. Semin Nucl Med 1: 474, 1971. 3. Taylor S: The solitary thyroid nodule. JR Coil Surg Edinb 14:
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22.
?3. 24. 25. 26.
27.
28.
Leonard Rosoff (Los Angeles, CA): At the Los Angeles County-USC Medical Center, B-mode echograms are obtained routinely in patients with solitary nonfunctioning nodules in the neck, 1.5 cm or more in
The American Journal of Sur9ary
Cold Thyroid Nodules
diameter. The authors’ findings, as in other reports on the subject, indicate that sonar scans have no value whatsoever in differentiating malignant from benign solid tumors of the thyroid. To date, the only reliable method of making this essential discrimination is microscopic examination after removal of the lesion by thyroid lobectomy. As everyone experienced in thyroid surgery is aware, at times even this may be difficult with rapid freezing technics at the time of operation and must await microscopic examination of paraffin sections twenty-four hours or more after operation. However, ultrasonic examination of nonfunctioning thyroid nodules does appear to be of value in differentiating solid and cystic lesions. As indicated by the authors, it is a rapid, safe, noninvasive, and readily obtained diagnostic test. Doctors Michael Shaub and Robert Wilson from our section of Diagnostic Ultrasound reported their studies at our hospital at the meeting of the American Institute of Ultrasound, held in Seattle in October 1974. One hundred patients with solitary hypofunctioning nodules in the neck were examined with ultrasound between January 1974 and September 1974. At the time of their presentation, the precise diagnosis had been established in thirty-three patients by histologic examination of the tissue after operation or by percutaneous needle aspiration of a cyst. (Slide) This slide summarizes their results and indicates the confirmation of their diagnosis of solid tumors in the twenty-three patients in whom this was made by sonar scan. Similarly, in each of the ten patients with a diagnosis of a cystic lesion, the findings were confirmed by operation or aspiration. Three of these lesions were thyroglossal duct cysts in the region of the thyroid isthmus and all were removed at operation. All seven of the remaining patients with the diagnosis of a cystic lesion of the thyroid were treated by aspiration by our medical thyroidologists. Of these, five patients had complete disappearance of the cyst after one aspiration. In one patient, a second aspiration was necessary; in another, three aspirations were needed because of reaccumulation of the cyst fluid. Over 80 ml of fluid was withdrawn at each tap. Because of the reaccumulation of fluid in the latter two cases, the lesion was removed at operation, and a diagnosis of benign colloid cyst was made on histologic examination. The cytologic features of the cyst fluid in all patients treated by aspiration were carefully examined and the patients were carefully evaluated by repeated physical examination of the neck as well as echographs. The incidence of cystic lesions of the thyroid in this series is approximately 17 per cent, similar to that of the authors. In the series of Shaub and Wilson, echo return caused by the debris of necrosis and hemorrhage, so-called “degeneration” of a solid tumor, was interpreted as indicating a “solid” tumor.
Volume130,August1975
After aspiration of a cyst is undertaken, abnormal cytologic findings in the cyst fluid, a remaining nodule, or reaccumulation of fluid in the cyst are indications for operation. I wish to repeat the admonition that removal of a solitary nodule of the thyroid by lobectomy remains the treatment of choice for noncystic lesions. I wish to ask Doctor Clark two questions: (1) What was the size of the smallest lesion identified by ultrasound scan in the series reported today; and (2) as transmission of sound through lymphomas is known to be enhanced, with diminished internal echo, has this been encountered by the authors in their use of ultrasound examination for neck lesions? Eugene J. Joergenson (Glendale, CA): I would like to ask Doctor Clark one question: What is the charge for this examination in your hospital? Orlo H. Clark (closingj: We have instituted these useful diagnostic tests at the University of California Hospitals in San Francisco not to discourage surgeons from operating but to help us select those patients who require operation because of suspected malignant thyroid nodules. Physicians frequently treat poor risk or elderly patients with solitary cold thyroid nodules conservatively despite the fact that in experienced hands thyroid operations are associated with minimal morbidity and rare mortality. When a solitary thyroid nodule is cold on radioiodine scanning, solid on echography, and hot on thermography, it would be unwise, because of the high risk of malignant disease, to treat this patient expectantly or with suppressive doses of exogeneous thyroid hormone. Conversely, not all nodular thyroids need to be removed and solitary thyroid nodules that are cystic on echography and cold on thermography can be treated safely and easily by aspiration. In answer to the second question, the resolution of the ultrasound equipment used in this investigation was 1 cm. The two patients included in this review who had indeterminate echograms were found at operation to have solid thyroid growths 1 to 2 cm in diameter. There were several other patients with nodules this size who were not included in this group because their nodules have not been diagnosed by histologic examination and it was impossible to determine whether they were solid or cystic. With the newer ultrasound equipment, considerably better resolution has been obtained. It is also important to emphasize that the person performing the ultrasound testing needs some knowledge about the thyroid since accurate placement of the probe on the gland is critical for diagnosis. As far as cost is concerned, many of the patients in this study were not charged because it was prospective investigation. However, the total charge for both thyroid echography and thermography, including the radiologist’s fee, is about $100.00.
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